A basic science of public health Essay

According to Friis, epidemiology has to do with the distribution and determinants of health and diseases, morbidity, injuries, disability, and mortality in populations. It is considered a basic science of public health, because its studies are applied to the control of the various health problems in the population. Also, its methods are applied to various health-related fields such as health care administration and health education. Because its focus is on the amount of health and disease in the population, it is at times referred to as population medicine. There are various uses and applications of epidemiology. Some specific applications of epidemiology that Friis did not specifically mention in lesson 1are genetic epidemiology, environmental epidemiology, and occupational epidemiology. Genetic epidemiology puts an emphasis on hereditary factors that may play a role in various human diseases in families and in populations. Research in this area is focused on the risk factors and traits of the genetic basis of diseases. Members of a Psychiatry department in Virginia completed a meta-analysis on the genetic epidemiology of major depression using relevant data from previous primary studies. They concluded that major depression is as a result of genetic influence, not alone, but along with environmental influence. This conclusion was made on the basis of a review of family, adoption, and twin studies that met specific criteria for the primary studies. Environmental epidemiology studies the environmental exposures that are related to various diseases, illnesses, developmental conditions, disabilities, and deaths in populations. Some examples of these environmental exposures are air pollution, radiation through air, water, or food contamination, second-hand smoke, and hazardous waste. Health conditions such as cancer, cardiovascular disease, and reproductive problems are some of the effects of these environmental exposures. A local example of this is the pollution from the refineries here in Corpus Christi. People who reside near the refineries have a 17% higher cancer rate than the rest of the city. There are apparently many consistently sick residents in the area. They are called the ‘Black Thumb’ neighborhood, because the soil in the area is poisoned and contaminated by the pollu tion from the refineries. The application of epidemiologic methods to populations of workers is occupational epidemiology. Studies on this topic involve various work-related patterns of disease and illness. They look at workers exposed to various risk factors such as heavy metals or chemicals and determine if these exposures result in adverse health outcomes. There is also a focus on biological and physical health effects as well. Occupational Epidemiologists attempt to study how often workers are injured on the job, what groups are most affected, and the reasons for these injuries. The results from these studies are used to find ways to prevent or reduce the risks of injuries and illnesses on the job. In conclusion, the various epidemiologic methods and studies are applied to the control of health problems in populations. Three specific applications of epidemiology are genetic epidemiology, environmental epidemiology, and occupational epidemiology. Genetic epidemiology is concerned with the role of genetic factors in determining health and disease in families and in populations. Environmental epidemiology is concerned with the relationship between exposures from the environment and adverse health outcomes in populations. Occupational epidemiology studies work-related patterns of disease and illnesses. The existence of these various epidemiologic applications help to identify and prevent the causes of health and disease in our communities. Epidemiology provides us with necessary and beneficial information we need to live a healthy life. References Corpus Christi’s Refinery Row. (n.d.). Retreived from www.txpeer.org/toxictour/corpus_christi.html Friis, R. (2010). Epidemiology 101. Jones and Bartlett Publishers. Kendler, K.S., Neale, M.C., Sullivan, P.F. (2010) Genetic epidemiology of major depression: review and meta-anyalysis. Am J Psychiatry. 157(10): 1552-62 Occupational Epidemiology. (n.d.). Heartland Center for Occupational Health & Safety. Retrieved from www.public-health.uiowa.edu/heartland/academic-programs/occ-epi.html

Dementia

Dementia Dementia  has become an all-important  disease  because the population is aging rapidly and the cost of health care associated with  dementia  is ever increasing. In addition to cognitive function impairment, associated behavioral and psychological symptoms of  dementia  (BPSD) worsen patient's quality of life and increase caregiver's burden.Alzheimer's  disease  is the most common type of  dementia  and both behavioral disturbance and cognitive impairment of  Alzheimer's  disease  are thought to be associated with the N-methyl-D-aspartate (NMDA) dysfunction as increasing evidence of dysfunctional glutamatergic neurotransmission had been reported in behavioral changes and cognitive decline in  Alzheimer's  disease. We  reviewthe literature regarding  dementia  (especially  Alzheimer's  disease), BPSD and relevant findings on glutamatergic and NMDA neurotransmission, including the effects of memantine, a NMDA receptor antagonist, and NMDA-enhancing agents, such as D-serine and D-cycloserine.Literatures suggest that behavioral disturbance and cognitive impairment of  Alzheimer's  disease  may be associated with excitatory neurotoxic effects which result in impairment of neuronal plasticity and degenerative processes. Memantine shows benefits in improving cognition, function, agitation/aggression and delusion in  Alzheimer's  disease. On the other hand, some NMDA modulators which enhance NMDA function through the co-agonist binding site can also improve cognitive function and psychotic symptoms.We propose that modulating NMDA neurotransmission is effective in treating behavioral and psychological symptoms of  Alzheimer's  disease. Prospective study using NMDA enhancers in patients with  Alzheimer'sdisease  and associated behavioral disturbance is needed to verify this hypothesis. Mental disorders constitute a huge social and economic burden for health care systems worldwide [1], raising the quest ion of effective and lasting treatments. Physical activity (PA) and exercise (EX) continue to gain the attention of practitioners and researchers with regard to prevention and treatment of different psychopathological abnormalities.In the general population, several epidemiological studies have found significant cross-sectional correlations between mental health and PA levels. In an adult US population, regular PA is associated with a significantly decreased prevalence of current major depression, panic disorder, agoraphobia, social phobia, and specific phobia [2]. A study from Norway confirmed this negative cross-sectional association between depression and leisure-time PA of any intensity (not work-related PA), and pointed out that social factors such as social support, rather than biological markers, play an important role [3].Recently, a Dutch study replicated this finding, reporting lower rates of any affective, anxiety, or substance use disorder in subjects who exercised at le ast 1 h/wk, without finding a linear dose-response relationship [4]. Prospectively, the overall incidence of mental disorders and co-morbid mental disorders, as well as the incidence of anxiety, somatoform, and dysthymic disorder, decreases by PA [5]. Furthermore, a four-year prospective study revealed that PA decreases the incidence rates of depressive and anxiety disorders in older adults [6].Finally, ten Have et al. reported in their epidemiological study that patients engaging in regular PA were more likely to recover from their mental illness at a three-year follow-up In psychiatric patients, different mechanisms of action for PA and EX have been discussed: On a neurochemical and physiological level, a number of acute changes occur during and following bouts of EX, and several long-term adaptations are related to regular EX training.For instance, EX has been found to normalize reduced levels of brain-derived neurotrophic factor (BDNF) and therefore has neuroprotective or even n eurotrophic effects [7-9]. Animal studies found EX-induced changes in different neurotransmitters such as serotonin and endorphins [10,11], which relate to mood, and positive effects of EX on stress reactivity (e. g. , the hypothalamus-pituitary-adrenal axis [12,13]). Finally, anxiolytic effects of EX mediated by atrial natriuretic peptide have been reported [14].Potential psychological mechanisms of action include learning and extinction, changes in body scheme and health attitudes/behaviors, social reinforcement, experience of mastery, shift of external to more internal locus of control, improved coping strategies, or simple distraction Several prospective studies have found that a high level of PA seems to delay the onset of dementia (see [74] for a review). Since improvements in strength and endurance after training were found in cognitively impaired patients as well as healthy controls [75], PA interventions are generally feasible in this population.For Alzheimer's disease (AD) , preliminary evidence suggests that EX interventions may improve communication performance [78], Mini Mental State Examination scores and verbal fluency [79], and disruptive behavior [80]. Four studies [81-84] found that PA slowed down and partially reversed the decline in performance of activities of daily living and progression of the cognitive symptoms related to dementia, in contrast to an older study, which did not find improvements in functional ability [85]. Zschucke , E. and Gaudlitz, K.Exercise and Physical Activity in Mental Disorders: Clinical and Experimental Evidence Zschucke , E. and Gaudlitz, K. (2013) Exercise and Physical Activity in Mental Disorders: Clinical and Experimental Evidence. Journal of Preventative Medicine and Public Health  , 46 (1), p. 12-21. Available at: http://www. ncbi. nlm. nih. gov/pmc/articles/PMC3567313/ [Accessed: 6th Mar 13]. Leptin, an adipocytokine produced in the peripheral system as well as in the brain, is implicated in obesity, food intake, glucose homeostasis, and energy expenditure.Leptin expression levels and signaling pathways may also be linked to the pathophysiology of neurodegenerative diseases including Alzheimer’s disease. Epidemiological studies have demonstrated that higher circulating leptin levels are associated with lower risk of dementia including Alzheimer’s disease, and lower circulating levels of leptin have been reported in patients with Alzheimer’s disease. Leptin receptors are highly expressed in the hippocampus, a brain area involved in learning and memory and severely affected during the course of Alzheimer’s disease.In laboratory studies, several in vivo and in vitro studies have shown that leptin supplementation decreases amyloid-? (A? ) production and tau phosphorylation, two major biochemical events that play a key role in the pathogenesis of Alzheimer’s disease. In this review, we will review the structure of leptin, the type of receptors of leptin in the brain, the various biological functions attributed to this adipocytokine, the signaling pathways that govern leptin actions, and the potential role of leptin in the pathophysiology of Alzheimer’s disease.Leptin exerts its functions by binding to the leptin receptor (ObR). This binding can involve several signaling pathways including JAK/STAT pathway, ERK pathway and the PI3K/Akt/mTOR Pathway. Modulation of these pathways leads to the regulation of a multitude of functions that define the intricate involvement of leptin in various physiological tasks. In this review, we will specifically relate the potential involvement of leptin signaling in Alzheimer’s disease based on work published by several laboratories including ours.All this work points to leptin as a possible target for developing supplementation therapies for reducing the progression of Alzheimer’s disease. Leptin is a 146 amino acid protein with a molecular weight of 16 kDa encoded by the  ob   gene and primarily, but not exclusively, expressed by the white adipose tissue (WAT) and is implicated in obesity, food intake, and energy homeostasis. Leptin protein was discovered by the molecular geneticist Jeffrey Friedman in 1994 at Rockefeller University and the work was published in a landmark  Nature  paper in December 1994 [1].The human  ob  gene has been mapped to chromosome 7q31. 3 [2] and encodes a 4. 5 kb mRNA transcript that is translated into a 167 amino acid peptide and subsequently processed in the ER into the 146 amino acid mature leptin protein [1]. Antecedent to the discovery of the leptin protein and positional cloning of the  ob  gene in 1994, the  ob/ob  mouse characterized by hyperphagia and a marked obese phenotype was serendipitously discovered by animal caretakers in 1950 at Jackson Laboratories [3].It was the general consensus that the  ob/ob  mouse possessed a mutation in the  obgene, but this was not elucidated and unequivocall y established until the discovery of the leptin protein and mapping of the  ob  gene by Friedman and colleagues in 1994 who showed that the mutation resulted in the loss of leptin production. In 1966, the  db/db  mouse was discovered, again at Jackson Laboratories, which not only exhibited a similar hyperphagic, obese phenotype, but also hyperglycemia [4].Tartaglia and colleagues in 1995 showed that the  db/db  mouse phenotype can be attributed to the mutation in the  db  gene that codes for the long-form of the leptin receptor obRb [5]. However, it was the seminal work of Doug Coleman and colleagues who demonstrated by a series of parabiosis experiments using  ob/ob  mice and  db/db  mice pairs and established that the  ob/ob  mice lacked a circulating factor whereas the  db/db  mice produced the circulating factor but were not able to respond to it [6,7].The validity of these breakthroughs was affirmed by subsequent discovery of the leptin protein a nd cloning of the  ob  gene [1] as well as the cloning of the  db  gene which coded for the long-form leptin receptor obRb [5]. Further corroboration emanated from the finding that the  db  mice produced the truncated form of obRb that was incapable of transducing leptin-mediated intracellular signal transduction [8-12] and administration of exogenous leptin obviated the obese, hyperphagic, hypothermic, and hypometabolic phenotype in  ob/ob  mice [13-15]. Go to: ————————————————-Leptin – structure, expression, and secretion The crystal structure of leptin has revealed the secondary and tertiary structure of the leptin molecule. The three dimensional crystal structure of leptin depicts the presence of four antiparallel ? -helices (A, B, C, and D) [16]. Two long crossover loops connect the A-B and C-D ? -helices, while a short loop connects the B-C ? - helices [16]. The entire leptin molecule is oblong shaped with the dimensions of 20x25x45 A0[16]. The entire molecule comprising of the bundle of four ? -helical loops adopts a bilayered stratified structure with ? helices A-D in one layer contiguous with ? -helices B-C in the other layer [16]. The conformation adopted by the leptin molecule results in the surface emergence of a few key hydrophobic residues like Phe41, Phe92, Trp100, Trp138, and Leu142  which not only play an indispensable role in the regulation of solubility and aggregation kinetics of the leptin protein, but are also critically requisite for as well as modulate the binding of leptin to the leptin receptor and determine the binding kinetics of the leptin-leptin receptor interaction [16].The three dimensional four-helical bundle crystal structure of leptin exhibits an overt, conspicuous congruence with other cytokines such as growth hormone (GH) [17], leukemia inhibitory factor (LIF) [18], and G-CSF (G-colony stim ulating factor) [19], despite lack of primary sequence homology with these proteins or other proteins [1]. Leptin is expressed primarily by the white adipose tissue [1,20] and circulating leptin levels are proportional to the white adipose tissue mass [21,22]. In humans, leptin expression in the subcutaneous adipose tissue is significantly more in magnitude than omental adipose tissue [23-26].Other studies have demonstrated no difference in leptin expression between the subcutaneous and omental adipose tissue [27]. Leptin expression in humans also exhibits sexual dimorphism with circulating leptin levels about 3-fold greater in females than males [25,28,29]. It is now certain that other tissues also produce leptin, including stomach [30,31], mammary gland [32], human placenta [33], ovaries [34], heart [35], skeletal muscle [36], pituitary gland [37], and the brain [37-39]. In the brain leptin mRNA expression and immunoreactivity has been seen in the hypothalamus, cortex, dentate gyr us and the hippocampus of the rat [38,39].Leptin immunoreactivity has also been reported in the mouse and hamster brain [40]. Leptin expression and circulating leptin levels are primarily contingent on the white adipose tissue mass [21,22] and are significantly elevated in obesity [21,22,41,42]. Consistent with this observation, weight loss is associated with a decrease in leptin levels in the plasma [22]. Leptin levels in the plasma also fluctuate in an ultradian manner and exhibit diurnal rhythm [43,44]. Leptin secretion occurs in a pulsatile rhythm with ~30 pulses of leptin secretion in a 24-hour cycle [43,45].Acute caloric restriction reduces leptin levels by ~30% within 24 hours [46-48] whereas caloric excess elevates leptin levels in the plasma by ~35% within 5-8 hours [47]. Therefore, nutritional intake regulates leptin expression in an acute as well as chronic fashion. The physiological and hormonal parameters that increase leptin expression include obesity [21,22,41], overf eeding or excess caloric intake [49,50], insulin [51-55], glucocorticoids [51,52,56,57], glucose [58], tumor necrosis factor ? (TNF? ) [54,59], estradiol [60-62], and IL1 [63,64] among others.The physiological and hormonal factors that decrease leptin expression include androgens [61,65], acute caloric restriction [49,50], growth hormone [66-69], somatostatin [68,70], exposure to cold temperatures [50,71,72], ? 3  adrenergic agonists [70,73-76], long-term exercise [77,78], cAMP (51, 57), PPAR? agonists such as thizolidinediones Pioglitazone, Troglitazone, and Rosiglitazone [79], and free fatty acids [80] among others. Go to: ————————————————- Leptin receptors Leptin receptors (obR) are encoded by the  db  gene [5].The obR are transmembrane spanning proteins that transduce and mediate leptin signaling. The obR exhibit structural and functional homology to the class I cytokine receptors [81,82]. The obR along with other class I cytokine receptors are typified by the characteristic presence of four cysteine residues and a â€Å"WSXWS† motif [81,83] which are a part of multiple fibronectin Type III subdomains in their extracellular domains [84]. The obR transcript undergoes alternate splicing to generate six different receptor isoforms (obRa – ob-Rf) [11].The six isoforms of obR are distinguished by and exhibit very little homology in their intracellular domain [85]. However, all the six isoforms have the same extracellular domain of over 800 amino acids and a transmembrane domain that spans 34 amino acid residues [85]. The six isoforms of obR are pigeonholed into three different groups, namely – short form, long form, and secreted obR [85]. The short-form of obR subsuming obRa (894 amino acids), obRc (892 amino acids), obRd (901 amino acids), and obRf (896 amino acids) possess a short 30-40 amino acid residue intracellular dom ain [85]. bRb (1162 amino acids) is the only functionally active leptin receptor isoform capable of transducing leptin signaling as it contains an intracellular domain that spans ~280 amino acid residues [5]. The obRe isoform (805 amino acids) lacks the intracellular domain and is therefore classified as a secreted soluble receptor and functions as a buffering system involved in the transport of leptin and bioavailibility of free circulating leptin [86,87].The short isoforms obRa, obRc, obRd, and obRf are abundantly expressed in the choroid plexus and endothelial cells of the brain microvasculature that form the BBB and may therefore regulate the flux of leptin across the BBB [88,89]. obRb is pervasively expressed in the human and rodent brain with the highest density in the ventromedial, arcuate, and dorsomedial hypothalamic nuclei [90-93]. obRb is termed the long-form leptin receptor and is solely responsible for propagating signal transduction mechanisms initiated by leptin [5,94 ].The short forms of the leptin receptor ob-Ra, ob-Rc, obRd, and obRf are devoid of intracellular signaling motifs that are obligatory for signal transduction [5]. However the short form receptors obRa and obRc are highly expressed in the choroid plexus and it is speculated that they mediate the uptake of leptin across the BBB (88, 89). obRb expression has been reported in several regions of the rodent and human brain including the hypothalamus [90,92,93], hippocampus, brain stem (nucleus of the solitary tract and the dorsal motor nucleus of the vagus), amygdala and the substantia nigra [92,93,95,96].In the hippocampus leptin receptor immunoreactivity is observed in the CA1/ CA3 region and the dentate gyrus [95,97]. Furthermore, axonal and somato-dendritic regions and hippocampal synapses exhibit leptin receptor immunolabeling in primary hippocampal cultures [97]. Go to: ——————————————à ¢â‚¬â€Ã¢â‚¬â€- Biological and physiological functions Leptin was discovered as the endogenous hormone that precludes obesity and regulates energy homeostasis [1].Antecedent to the discovery of leptin in 1994, about two decades ago, Doug Coleman had posited the role of a circulating hormone that thwarted obesity via its action in the brain to regulate food intake and energy homeostasis and in the peripheral tissues to regulate energy catabolism, thermogenesis as well as basal metabolism [7]. This was corroborated in the mid 1990s after the discovery of leptin by studies that demonstrated in rodents that administration of exogenous leptin decreased food intake and augmented energy expenditure [13-15,98,99].Leptin administration augments energy expenditure by actuating the ? -oxidation of fatty acids in the mitochondria and also inducing the expression of enzymes involved in ? -oxidation [100]. However, the notion that high levels of leptin augment weight loss and circumvent obesity must be tempered with the fact that high endogenous leptin levels have been effete in thwarting obesity in humans and other mammals [21,22,41]. This can be ascribed to a phenomenon termed â€Å"leptin resistance† [101-103]. Leptin plays a pivotal role in the induction of puberty and fertility.Leptin reinstates puberty, restores fertility in  ob/ob  mice, escalates puberty and fosters reproductive behavior in wildtype rodents [104-107]. Leptin directly regulates the hypothalamic-pituitary-gonadal (HPG) axis by inducing gonadotropin release and modulating estradiol production in the ovarian follicles [108,109]. Leptin also regulates the hypothalamic-pituitary-adrenal (HPA) axis by attenuating corticotrophin releasing hormone (CRH) production and release [110,111] as well as directly inhibiting ACTH (adrenocorticotropic hormone)-induced glucocorticoid release from the adrenal cortex [111-113].Leptin is also integrally involved in the physiological homeostasis of the circulat ory system. Emerging evidence implicates leptin in hematopoeisis as leptin is involved in proliferation and differentiation hematopoietic precursors [114-116]. Higher plasma levels of leptin (~100ng/mL), suchas those observed in obese individuals, foster and promote platelet aggregation [117]. Leptin is also one of the most potent inducers of vascular epithelial cell growth and angiogenesis and the short forms and the long-form of the leptin receptor is abundantly expressed in the vasculature [117-119].Go to: ————————————————- Leptin function in the brain Hypothalamus Leptin signaling in the hypothalamus regulates food intake and energy homeostasis in mammals. The arcuate nucleus (ARC), dorsomedial nucleus (DMH), and the ventromedial nucleus (VMH) of the hypothalamus express the obRb in the greatest density. In the ARC, the obRb is abundantly expressed in two disparate neu ronal cell types, ones that express neuropeptide Y (NPY) and agouti-related peptide (AgRP) and the others that express pro-opiomelanocortin (POMC) [92,120-122].Leptin induced activation of the obRb in the POMC neurons results in depolarization and increased biosynthesis of ? -melanocyte-stimulating hormone (? -MSH) which signals downstream by actuating the melanocortin system comprising of melanocortin-3-receptors (MC3R) and melanocortin-4-receptors (MC4R) expressed by the second order neurons downstream to evoke an anorexiogenic (decreased appetite) response [122-127]. Activation of the melanocortin pathway not only suppresses appetite but also increases energy expenditure by increasing sympathetic tone resulting in ? oxidation of fatty acids in skeletal and adipose tissue. While leptin activates the POMC-expressing neurons, the actuation of obRb by leptin in the NPY/AgRP neurons results in the decreased genesis of NPY and AgRP peptides which are orexiogenic (increase appetite) in nature [122,128]. Therefore, in conspectus, leptin signaling in the hypothalamus results in the decreased expression of orexiogenic peptides (NPY, AgRP) and increased expression of anorexiogenic peptides (? -MSH) as well as increased energy expenditure in the adipose tissue and skeletal muscle tissue.Hippocampus Leptin receptors are abundantly expressed in the CA1 and CA3 regions of the hippocampus as well as the dentate gyrus [95,97]. Leptin regulates the excitability and firing of hippocampal neurons via the modulation of BK potassium channels [97]. Leptin also improves memory processing and retention when administered directly into the CA1 region in mice [129] and rodents that are deficient in the leptin receptor (db/db  mice and  fa/fa  rats) exhibit profound deficits in spatial learning and memory [129-131].Treatment of acute hippocampal slices with leptin results in the conversion of short-term potentiation (STP) to long term potentiation (LTP) by enhancing Ca2+  influ x through NMDA receptors [132]. Leptin increases synaptogenesis and aids in memory formation in the hippocampus and is purported to be a cognitive enhancer [133]. Leptin also increases neurogenesis in the dentate gyrus of adult mice [134]. Leptin also plays a critical role in hippocampal neuronal survival by activating the PI3K-Akt and JAK2/STAT3 signal transduction pathways [135].Leptin upregulates the expression of potent endogenous antioxidant enzyme Mn-SOD (manganese superoxide dismutase) and the anti-apoptotic protein Bcl-xL (B-cell lymphoma xL) in a STAT3-dependent manner in the hippocampus [135]. Leptin stabilizes mitochondrial membrane potential and attenuates the glutamate-induced mitigation in mitochondrial membrane potential and also extenuates the free iron-induced augmentation in mitochondrial ROS [135]. Go to: ————————————————- Leptin signalingLeptin binding to its long-form receptor obRb actuates four major signal transduction pathways that are coupled to obRb – JAK/STAT pathway, ERK pathway, PI3K/Akt/mTOR pathway, as well as the AMPK/SIRT1 signal transduction pathways. JAK/STAT pathway Leptin signaling via the obRb is integrally coupled to the JAK2/STAT3, JAK2/STAT5 and JAK2/STAT6 pathways [10]. The long-form of the leptin receptor obRb is constitutively coupled to Janus kinase 2 (JAK2) via the evolutionary conserved domains proximal to the membrane [136].The binding of leptin to obRb evokes a conformational change in the receptor that actuates JAK2 by phosphorylation at Tyr1007/1008  residues [136]. Activated phosphorylated JAK2 subsequently phosphorylates evolutionary conserved tyrosine residues of obRb [94] at Tyr985, Tyr1077  and Tyr1138  [137,138]. The obRb phosphorylated at Tyr1077  and Tyr1138  serves as a docking site and recruits Srchomology 2 (SH2)- and Src-homology 3 (SH3)-domain comprising roteins that sub sume proteins such as Signal Transducer and Activator of Transcription 3 (STAT3), Signal Transducer and Activator of Transcription 5 (STAT5), and Src homology region 2 domain-containing phosphatase 2 (SHP2) [139]. The phosphorylated Tyr1138  residue of obRb recruits STAT3 and STAT5 which are subsequently phosphorylated by JAK2 at Tyr705  and Tyr694  respectively. The phosphorylation STAT3 and STAT5 causes their disengagement from the leptin receptor, results in the dimerization of STAT proteins via their phosphotyrosine residues in the SH2 domains [140-142], and culminates in their nuclear translocation [142].In the nucleus, STAT dimers bind to distinct motifs or elements in the DNA called ? -IFN-activated site (GAS) in the enhancer regions of target genes and thereby modulate and regulate gene expression of target genes [142-146]. In the nucleus, the STAT signaling is abrogated by dephosphorylation and subsequent export of STAT proteins from the nucleus to the cytosol [142,14 4,147] or by targeted degradation of the STAT proteins via the Ubiquitin Proteasomal System (UPS) [148].The JAK/STAT pathway is negatively regulated by three classes of proteins, namely – suppressors of cytokine signaling (SOCS), protein inhibitors of activated STATs (PIAS), and protein tyrosine phosphatases (PTP) [149]. There are eight members of the SOCS family and their expression is induced by JAK/STAT signaling (STAT3 in particular) thereby suggesting the existence of a negative feedback loop that abrogates JAK/STAT signaling [150].The SOCS proteins negatively regulate the JAK/STAT pathway by competitively engaging and occupying the phosphotyrosine residues in obRb via their SH2 domains and obviating the recruitment of STAT proteins to obRb, thereby precluding STAT activation [150,151]. SOCS proteins via their SH2 domains also directly bind to JAK2 and extenuate the kinase activity of JAK2 [150,151]. The PIAS proteins negatively regulate the JAK/STAT signaling pathway by impeding the binding of STAT proteins to the response elements in the DNA by physically interacting and binding with STAT proteins via their zinc-binding RING-finger domains [151].SHP1 and SHP2 are most well characterized protein tyrosine phosphatases implicated in the negative regulation of the JAK/STAT pathway [149]. SHP1 and SHP2 possess two SH2 domains and therefore bind to phosphotyrosines of JAK2 and obRb and effectuate the dephosphorylation of JAK2 and obRb thereby terminating the JAK/STAT signaling [149]. ERK pathway The extracellular regulated kinase (ERK) pathway is an integral part of a larger signaling network called mitogen activated protein kinase (MAPK) pathway that is activated by leptin signaling via the leptin receptor (obRb).While phosphorylation of Tyr1138  and Tyr1077  are both requisite and mediate the activation of STAT3 and STAT5 respectively, the phosphorylation of Tyr985  of obRb mediates the activation of ERK pathway [138]. Leptin signaling via the obRb evokes the actuation of ERK pathway, both centrally and peripherally, as well as in  in vivo  and  in vitro  experimental paradigms [85]. Leptin evokes the activation of ERK pathway by both JAK2-mediated and JAK2-independent signaling effects [94,152].Contemporary evidence has implicated the protein tyrosine phosphatase SHP2 and the adaptor protein Grb2 (growth receptor bound 2) as the requisite mediators in the leptin-induced activation of ERK signaling pathway [153]. Leptin signaling also activates other members and signaling cascades subsumed under the MAPK signaling pathway, namely p38 [154-157] and JNK pathways [156]. PI3K/Akt/mTOR pathway Leptin signaling also induces the activation of the ubiquitous, pervasive, nutrient-sensitive anabolic, and the broad spectrum PI3K/Akt/mTOR pathway [152,158-161].Empirical evidence has demonstrated that the adaptor proteins IRS1 (insulin receptor substrate 1) and IRS2 (insulin receptor substrate 2) mediate the leptin-obRb induce d activation of PI3K-Akt pathway [94,158,162]. A multitude of studies have demonstrated that leptin induces the activation of Akt via phosphorylation of Akt at Ser473[163,164]. As a consequence, Akt activation is ensued upon leptin signaling which results in inhibition of GSK3? through phosphorylation at Ser9  residue [165-167].Evidently leptin also activates the serine/threonine kinase mammalian target of Rapamycin (mTOR) in the hypothalamus and macrophages [168,169] through the PI3K-Akt pathway [170]. mTOR is an evolutionary conserved kinase that modulates translation of several mRNA transcripts involved in cell growth and proliferation. mTOR regulates translation by phosphorylation and attenuation of the inhibitor of mRNA translation, eukaryotic initiation factor 4E-binding protein (4E-BP) [171-175], as well as through the phosphorylation and activation of S6 kinase (p70S6K1) [176,177]. TOR is autophosphorylated at Ser2481  and exhibits spontaneous intrinsic kinase activity u nder the activation of Akt [178,179]. mTOR phosphorylation and activation is negatively regulated by the TSC1/TSC2 protein complex [170]. Akt phosphorylates TSC2 causing disintegration of the TSC1/TSC2 complex which consequently results in mTOR activation [180]. Furthermore, Akt has been shown to directly phosphorylate mTOR at Ser2448residues and consequently activate mTOR [181,182].Therefore, Akt positively regulates mTOR activation by direct phosphorylation at Ser2448  as well as by indirect means which involves relieving the repressive effects of the upstream inhibitor TSC1/2 complex. Thus leptin, by virtue of its inherent ability to activate Akt, is expected to increase mTOR phosphorylation and activity. AMPK-SIRT1 pathway The 5’AMP activated protein kinase (AMPK) is the master regulatory kinase termed the â€Å"fuel gauge† that integrates signals from upstream mediators and effectors of hormones and cytokines to maintain metabolic homeostasis [183].AMPK activati on leads to increase ? -oxidation of fatty acids in the mitochondria and inhibition of lipogenesis [184,185]. Multiple lines of evidence have cogently demonstrated that leptin activates AMPK and consequently increases fatty acid oxidation [186-188]. One exception to this is the hypothalamic neurons, where leptin inhibits AMPK activation to evoke satiety and other hypothalamic effects of leptin [189-191]. In general, AMPK plays a catabolic role and engenders energy production via effects on glucose and lipid metabolism.AMPK activation also effectuates the induction of the NAD+  Ã¢â‚¬â€œ dependent deacetylase SIRT1 (silent mating type information regulation 2 homolog) [192,193], a metabolic master regulator unequivocally implicated in ageing and the regulation of lifespan [194-198] as well as regulating metabolism [199,200]. The anorexic effect of leptin mediated by the activation of POMC neurons in the hypothalamus is contingent on SIRT1 expression and activation in the neurons of the arcuate nucleus of the hypothalamus [201]. Go to: ————————————————- Role of leptin in Alzheimer diseaseAlzheimer Disease (AD) is a progressive, debilitating and the most prevalent neurodegenerative disorder typified by memory impairment and cognitive dysfunction eventually leading to fatality. The gross pathologic hallmarks of autopsied brains of patients with AD include atrophy with widened sulci and narrowed gyri in the temporal, parietal, and frontal lobes as well as the neocortex and cingulated gyrus areas of the cerebral cortex. The entorhinal cortex, amygdala, hippocampus and the para-hippocampal gyrus also exhibit pronounced atrophy due to neuronal loss [202,203].There is a decrease in gross weight of brain by 10-15% in AD patients [202]. The thickness of the six cortical layers (cortical ribbon) is usually reduced by 10-20% in AD [202] and ventricular dilation is apparent prominently in the temporal horn as a consequence of the atrophy of the amygdala and the hippocampus. Furthermore, there is a propensity for the loss of larger neurons than the loss of smaller neurons or glial cells in AD [202]. Microscopically, AD is characterized by two most common and distinct â€Å"hallmark† microscopic lesions namely senile plaques and neurofibrillary tangles (NFT).Senile plaques are extraneuronal deposits of accumulated and aggregated amyloid-? (A? ) protein in the brain parenchyma, while the NFT are intraneuronal aggregates of protein tau in the hyperphosphorylated state. Other pathological features of the AD brain include synaptic loss, neuronal and dendritic loss, neuropil threads, granulovacuolar degeneration, dystrophic neurites, Hirano bodies, and cerebrovascular amyloid deposition. There is substantial evidence that leptin modulates A? production and metabolism. Chronic peripheral leptin administration in Tg2576 mice has been reported to reduce the brain A? evels [204]. Moreover leptin also decreases the BACE1 activity in SH-SY5Y cell line [204]. Leptin decreases tau phosphorylation explicitly at residues Ser202, Ser396, and Ser404  in retinoic acidinduced differentiated SH-SY5Y cells, differentiated human NT2 cells (NT2N), and rat primary cortical neurons [205-207]. Leptin also increases synaptogenesis and aids in memory formation in the hippocampus and is purported to be a cognitive enhancer [133]. Leptin has been shown to convert STP into LTP in hippocampal cultures and hippocampal slices [132].Recent evidence suggests that leptin facilitates spatial learning and memory [130] and also increases neurogenesis in the dentate gyrus of adult mice [134]. Recent epidemiological studies have also unequivocally implicated decreased leptin levels in the pathogenesis of AD. In the Framingham prospective study, 785 subjects were followed between 1990 and 1994 from the original Framingham cohort [208]. The study conclud ed that leptin levels were inversely related to the risk of developing dementia of the Alzheimer type [208].A year preceding the findings of Lieb and colleagues, a morphometric study in Japan conducted by Narita and group found higher leptin levels were positively correlated with higher hippocampal volumes [209]. Leptin decreases Amyloid-? (A? ) levels by attenuating the genesis and augmenting the clearance of the peptide The A? peptide is derived from a two-step successive proteolytic cleavage of Amyloid-? precursor protein (A? PP) [210]. In the first step, A? PP is cleaved by the membrane-bound protease BACE1 (? -site APP cleaving enzyme 1) (also called ? secretase) to generate CTF? (carboxy terminal fragment ? ) (also known as C99 fragment) [211-215] which in the second step is subsequently cleaved by the ? -secretase complex to generate A? peptide [216-218]. According to the â€Å"amyloid cascade hypothesis†, A? is considered as the culpable factor in the instigation and progression of all the neurodegenerative events that characterize AD [219]. A plethora of studies have demonstrated that leptin decreases A? levels in several  in vivo  and  in vitro  paradigms [204,220-223]. Leptin has been shown to mitigate A? roduction by extenuating BACE1 activity in neural cultures [204]. Recent studies have implicated the AMPK/SIRT1 pathway in the leptin-induced modulation of A? levels [222]. Emerging data from our unpublished work has not only corroborated the finding that leptin regulates A? metabolism via SIRT1, but also implicated the ubiquitous transcription factor NF-? B as a SIRT1 target downstream in the modulation of A? genesis (unpublished). Leptin decreases A? levels by targeting all facets of A? metabolism, namely – production, clearance, and degradation.We have shown that leptin increases the expression levels of insulin degrading enzyme (IDE) putatively by activating the Akt pathway [223], thus augmenting the degradation of A?. Fur thermore, leptin also increases the expression levels of LRP1 [223], suggesting that leptin may foster the uptake of A? by astrocytes and microglia or reuptake of A? by neurons and therefore target A? for intracellular degradation or for clearance across the blood-brain-barrier (BBB). Leptin also effectuates the ApoE-mediated clearance of A? [204].Specifically, leptin dose-dependently increased the LRP1-mediated uptake of ApoE-bound A? , therefore committing A? toward the endosomal/lysosomal degradation pathway [204]. Leptin attenuates BACE1 expression and activity The first line of evidence linking leptin signaling dyshomeostasis in the pathogenesis of Alzheimer disease emanated from the work of Tezapsidis and colleagues [204], who demonstrated in neural cultures from transgenic mice that leptin mitigates BACE1 activity by evoking changes in lipid composition of lipid rafts of cell membranes.Furthermore, the study also demonstrated that the lipolytic ability of leptin as a conseque nce of increased ? -oxidation of fatty acids and decrease  de novo  synthesis of fatty acids and triglycerides underlies the mechanistic link between the effects of leptin on lipid composition of membranes and BACE1 activity. Recent data from our studies [223] and other laboratories [221] cogently demonstrate that leptin negatively regulates BACE1 expression, both  in vitroand  in vitro  paradigms.Moreover, Greco and colleagues have attributed this effect of reduced BACE1 expression on the ability of leptin to induce PPAR? expression and activation [221]. Indeed, leptin is a well characterized inducer of PPAR? expression and activity [220,224]. In light of this, it is important to reiterate that multiple lines of evidence exist in current literature demonstrating the role of PPAR? as a negative regulator of BACE1 expression [225]. Another mediator of leptin induced modulation of BACE1 expression may be the transcription factor STAT3.The BACE1 promoter contains a multitude of STAT3 binding sites [226]. Multiple lines of evidence have implicated STAT3 in the regulation of BACE1 expression [226-228]. Leptin may also modulate BACE1 activity via the activation of the PI3K/Akt and ERK signaling pathways [229]. BACE1 expression is also modulated by the master transcription factor NF-? B [230]. We have found that leptin represses NF-? B transcriptional activity via induction of SIRT1 expression and activity and thereby attenuates BACE1 expression (unpublished).Furthermore, inhibition of SIRT1 activity significantly compromised the mitigating effect of leptin on BACE1 expression (unpublished). Therefore, the entire range of discrete signal transduction pathways activated by leptin may be implicated in the modulation of BACE1 expression. Leptin mitigates tau phosphorylation It is now the consensus that tau hyperphosphorylation precedes and leads to PHF formation in NFT [231] and aberrant tau hyperphosphorylation is implicated in neurodegeneration in AD [232-23 6].Recent studies by Tezapsidis and colleagues as well as our work has cogently demonstrated that leptin decreases hyperphosphorylation of tau, primarily by the activation of known canonical signal transduction pathway coupled to leptin receptors. Firstly, Greco  et al. demonstrated  in vitro, in SH-SY5Y and NTera-2 human neuronal cell lines, that leptin reduces the phosphorylation of tau at Ser202, Ser396, and Ser404  residues [205]. In the same study, it was shown that leptin was ~300-fold more potent than insulin at mitigating tau phosphorylation and the activation of AMPK pathway was implicated in mediating this effect [205].The following year, the same group systematically investigated the involvement of other signal transduction pathways activated by leptin that may contribute to the attenuation of tau phosphorylation and concluded that leptin-induced activation of Akt, p38 MAPK, as well as AMPK were all intricately involved [206]. Notably, of great mechanistic importanc e, was the revelation that all the three aforementioned pathways activated by leptin, culminated in the phosphorylation of the tau kinase GSK3? at Ser9  residue leading to the inhibition of its kinase activity.Therefore, leptin-induced activation of Akt, p38 MAPK, and AMPK signal transduction pathways converged at the focal point – GSK3? , a bona fide tau kinase [206,207]. Data from our studies carried out in organotypic slices from the hippocampi of adult rabbits has also cogently demonstrated that leptin inhibits GSK3? -induced tau phosphorylation at AT8 (Ser202, Thr205) and PHF1 (Ser396, Ser404) epitopes via the activation of Akt [223,237]. Of greater importance and relevance, was the finding that 8-weeks of leptin treatment in CRND8 transgenic mice resulted in a ~2-fold decrease in tau phosphorylation at AT8 and PHF1 epitopes [221].Leptin fosters synaptogenesis and synaptic plasticity Several studies have shown that synaptic dysfunction and synaptic loss are the cardina l hallmarks of incipient AD [238-244]. Electron microscopy [238,241,245-248], immunohistochemical and biochemical studies [240,249-251] have demonstrated that synaptic loss in the neocortex and the hippocampus is an early episode in Alzheimer’s disease [252,253]. Synaptic loss is also the most important structural correlate of cognitive impairment in AD [250,254-260]. Synaptic dysfunction can be detected in patients diagnosed ith mild cognitive impairment (MCI), a condition which may or may not progress to AD and characterized by many as a prodromal state of AD [247,261]. Leptin plays an indispensable role in learning, memory, and maintenance of synaptic plasticity [262]. Leptin receptor mutant  db/db  mice and  fa/fa  rats have deficits in spatial memory and inadequate short term memory processing as assessed by the Morris water maze [130] and T-maze footshock avoidance test paradigms [129]. In the CA1 region of the hippocampus, leptin exclusively enhances the NMDA r eceptor-mediated synaptic transmission [132].Leptin facilitates the trafficking of NMDA receptors to the plasma membrane and this may contribute to the effect of leptin on enhancing the NMDA receptor-mediated current [133]. This was also corroborated in a  Xenopus  oocyte model system expressing recombinant NMDA receptors [132]. Leptin evokes the conversion of STP to LTP in acute hippocampal slices. Further delving into the molecular mechanism underlying this effect has implicated the PI3K/Akt and ERK signaling cascades at the nexus as the inhibitors of these signaling pathways mitigated this effect of leptin [132].Furthermore, in the CA1 region of the hippocampus, leptin also fosters the induction of a novel form of LTD and this effect was attributed to NMDA receptor activation [263]. The study by Durakoglugil also examined the signal transduction cascades involved in the induction of this novel LTD by leptin and concluded that this effect was contingent on the PI3K signaling c ascade, but independent of the ERK signaling pathway [263]. In addition to regulating synaptic strength by modulation of LTP and LTD, leptin also fosters synaptogenesis.The leptin deficient  ob/ob  mice have decreased synapse density and exogenous leptin corrects this deficit in these mice [264,265]. Leptin also induces the expression of a multitude of pre- and postsynaptic proteins such as synapsin2A and synaptophysin in the hippocampus [266]. Leptin also has a profound effect on dendritic morphology. Leptin augments filopodial stabilization, fosters mobility and boosts their density, thus promoting synapse formation [267]. Interestingly, this effect of leptin on filopodial stability and density is contingent on ERK signaling pathway and not on the PI3K signaling pathway [267].Leptin increases neuronal survival and mitigates cell death There is growing consensus that leptin is a growth and survival factor in the CNS. Leptin increases the viability of SH-SY5Y cells and suppresse s apoptosis by down-regulation of caspase-10 and TRAIL and this effect is contingent on the ability of leptin to activate the JAK-STAT, PI3K-Akt, as well as ERK signaling pathways [268]. Leptin has been shown to exert neuroprotective properties in cultured MN9D rat dopaminergic cells against 6-OHDA.Leptin also averted the 6-OHDA-induced dopaminergic cell loss in the substantia nigra of mice when administered intracranially [269]. This pro-survival effect of leptin on dopaminergic neurons was attributed to the JAK2-dependent activation of the ERK signaling pathway resulting in increased levels of survival factors p-CREB and BDNF [269]. Our recent work has unequivocally demonstrated that leptin upregulates the expression of Insulin-like Growth Factor – 1 (IGF-1), a known neurotrophic and survival factor in the brain [270].Leptin has also been shown to attenuate apoptotic cell death of cultured cortical neurons in an  in vitro  oxygen-glucose deprivation model of global isch emia [271]. Furthermore, the study by Zhang  et al. , also cogently showed that intraperitoneal administration of leptin in mice reduced the infarct volume and significantly improved behavioral parameters in a middle cerebral artery occlusion (MCAO) model of global ischemia [271]. This effect of leptin was attributed to the activation of ERK signaling pathway as the general inhibitor of ERK signaling abolished this effect of leptin, both  in vitro  and  in vivo  [271].Another study employing hippocampal cultures has demonstrated that leptin inhibits neuronal cell loss in response to growth factor withdrawal and oxidative insult by evoking JAK-STAT activation leading to enhanced expression Mn-SOD and Bcl-xL and stabilizing the mitochondrial membrane potential [135]. Leptin also mitigated neuronal loss in response to excitotoxic insult evoked by glutamate in hippocampal cultures by the aforementioned molecular mechanism [135]. Leptin also protected the hippocampal neurons fr om kainite-induced damage in response to excitotoxicity evoked seizures in a mice model of temporal lobe epilepsy [135].A recent study found that leptin also attenuates MPP+-induced cell death in neuronal cultures via the activation of STAT3 and inducing the expression of UCP-2 that culminates in the obviation of mitochondrial dysfunction by MPP+  [272]. Of particular interest is the finding that cultured cortical neurons secrete prodigious amounts of leptin in response to oxygen-glucose-serum deprivation that results in enhanced expression of IL-1? and increased intransigence to apoptotic cell death [273].Moreover, neutralization of this endogenous leptin with an antibody resulted in increased susceptibility of these cultured cortical neurons to oxygen-glucose-serum deprivation – induced cell death [273]. The salutary effects of leptin on neuronal viability and function have also been corroborated by electrophysiological studies. One such study has cogently demonstrated th at leptin combats the hypoxia-induced inhibition of spontaneously firing hippocampal neurons by activating the BK channels (large conductance Ca2+  activated K+  channels) [274].Leptin induces proliferation of neuronal progenitors – evokes neurogenesis As Alzheimer disease is typified with selective neuronal loss in the hippocampus and other regions of the brain, the debunking of the dogma that neurogenesis occurs exclusively prenatally and the revelation that neurogenesis persists in the adult mammalian brain has opened novel therapeutic avenues to combat the neuronal loss in AD. Chronic leptin treatment increases hippocampal neurogenesis in mice and induces proliferation of adult hippocampal progenitor cultures [134].This effect of leptin on adult hippocampal neurogenesis is attributed to increased cell proliferation in the dentate gyrus and not enhanced cell differentiation or cell survival [134]. The study by Garza and colleagues unequivocally implicated the JAK2-STAT 3 and PI3K-Akt signal transduction pathways in the leptin induced enhancement of hippocampal neurogenesis [134]. Furthermore, leptin rescues the attenuation in adult hippocampal neurogenesis in a mouse model of chronic unpredictable stress-evoked depression via the inhibition of GSK3? nd subsequent stabilization of ? -catenin [275]. Leptin has also been documented to evoke neurogenesis and angiogenesis in a mouse stroke model (Avraham  et al. , 2011). Go to: ————————————————- Conclusion Here we have reviewed the contemporary knowledge on the protective role of the adipokine leptin and its signaling in Alzheimer’s disease. In conspectus, leptin impinges on all facets of Alzheimer’s disease pathophysiology (Figure 1). These attributes of leptin such as the decrease in A? production and increase of A? learance, reduction in tau hyperphosphorylation as well as increased synaptogenesis, increased memory, increased spatial learning, and increased neurogenesis catapult leptin treatment as a unique therapeutic intervention and an indispensable tool in the elucidation of biochemical mechanisms involved in the etiology of the sporadic form of Alzheimer’s disease. Marwarha , G. and Ghribi, O. Leptin signaling and Alzheimer’s disease Marwarha , G. and Ghribi, O. (2012) Leptin signaling and Alzheimer’s disease. American Journal of Neurodegenerative Disease, 1 (3), p. 45-265. Lifestyle nonpharmacological interventions can have a deep effect on cognitive aging. We have reviewed the available literature on the effectiveness of physical activity, intellectual stimulation, and socialization on the incidence of dementia and on the course of dementia itself. Even though physical activity appears to be beneficial in both delaying dementia onset and in the course of the disease, more research is needed before intellectual stimulation a nd socialization can be considered as treatments and prevention of the disease.Through our paper, we found that all three nonpharmacological treatments provide benefits to cognition and overall well-being in patients with age-related cognitive impairments. These interventions may be beneficial in the management of dementia. Alzheimer's disease (AD) is a neurodegenerative disorder with devastating consequences [1]. Despite being the most common cause of dementia, affecting approximately 5. 4 million Americans [2] and almost 50% of people over the age 85 [3], no cure has yet been discovered.Efforts are also focusing on the development of more effective strategies to slow the progression of AD to increase the quality of life of those affected. Even a two-year delay in disease onset would reduce the prevalence of AD among Americans by two million people within fifty years [4]. If an intervention that delayed the onset of AD by five years had been applied back in 1997, we would have seen a 50% reduction in AD incidence [4]. Research on strategies to slow the development and progression of AD is arguably more important now than ever before, since the number of people with AD is expected to nearly triple over he next forty years [4], and dementia is the most important contributor to disability in the elderly [5]. Among others, three nonpharmacological interventions are particularly relevant as they might positively influence cognition, general functioning, and overall quality of life. These three strategies arephysical exercise,  intellectual stimulation,  and  social interaction. While there are studies that evaluate the role of individual and multimodal interventions on AD, there is a lack of literature on the combination of all three.The purpose of this paper is to review key areas of the literature that focus on the effects of physical exercise, intellectual stimulation, and socialization strategies on AD evolution, as they collectively play an important ro le in the management of Alzheimer's disease. Physical exercise encapsulates both aerobic exercises (e. g. , walking and cycling) and nonaerobic exercises (e. g. , strength and resistance training; flexibility and balance exercises). For intellectual stimulation, we examine studies that have evaluated the prognostic effects of either cognitive hobbies (e. g. reading, word puzzles, and card games) or cognitive training (e. g. , computer training games/paradigms that target specific cognitive domains such as memory and attention). Social interaction is defined as the participation of an AD patient in group-related activities, such as mealtime conversations, support groups, or other forms of social engagement. The health benefits attributed to physical activity are numerous and well known. Exercise has been associated with a lower incidence in many chronic diseases, such as coronary heart disease [6], type 2 diabetes [7], obesity [8], cancer [9], bone loss [10], and high blood pressure [11].We have reviewed the effects of physical exercise on cognition. Higher cardiorespiratory fitness has been related to higher scores on tests of cognitive function [12]. A meta-analysis of randomized controlled trials examining the relationship between exercise and cognition showed modest improvements in attention, processing speed, executive function, and memory among older adults in the treatment arms [13]. This is highly relevant for the elderly population, as it suggests that physical activity can serve as a preventative measure against age-related cognitive decline [14].Several large longitudinal studies followed older adults without cognitive impairments at baseline and measured rate of incident dementia to clarify the relationship between physical activity and incident cognitive loss. A large prospective study by Podewils et al. identified an inverse relationship between physical activity and dementia risk [15]. Compared to no exercise, physical activity has been linked wi th reduced risks of developing cognitive impairment and dementia [16] with the risk for dementia being further reduced with increasing levels of physical activity.Larson and colleagues found that persons who exercised three or more times per week had a reduced risk of developing dementia compared to those who exercised less, and the reduction was more marked among those with the poorest physical function at baseline [17]. These results were corroborated by Buchman et al. who found that participants in the lowest percentiles of physical activity had more than twice the risk of developing dementia than those in the highest percentiles of physical activity [18].Furthermore, Lautenschlager et al. demonstrated that these results might be transferable to adults with mild cognitive impairment (MCI), and, thus, at high risk for dementia; participants who underwent exercise training showed modest improvements in cognition after six months [19]. Physical exercise has, therefore, been recommen ded as a preventative measure of mild cognitive impairment and dementia [20,  21]. There is much less research focusing on the effect of physical activity in AD patients.This may be due to the challenges of implementing an exercise regime while managing the behavioral and emotional disturbances in AD patients, particularly in the later stages of the disease. However, the results in the available literature are promising. Early research involving AD patients in nonrandomized controlled trials showed significant cognitive improvements among participants who underwent cycling training and somatic and isotonic-relaxation exercises [22,  23]. Physical exercise may have beneficial effects in AD patients beyond cognition as well.A meta-analysis on 30 randomized controlled trials that employed exercise, behavioral and environmental manipulations in patients with cognitive impairment found exercise had positive effects on strength and cardiovascular fitness in addition to improvements in behavior and cognition [24–26]. Further evidence supporting multifaceted positive effects of exercise on AD can be traced to recent randomized controlled trials of physical exercise regimes on AD patients (Table 1). Compared to controls, patients in the intervention programs showed better physical functioning (functional reach, walking, and mobility).After treatment, these patients also showed improved performance of activities of daily living (ADLs), and less cognitive decline and cognitive improvement in some cases. Physical exercise, therefore, appears to be beneficial for AD patients. While the majority of the studies did not find any differences in depression, one study by Steinberg found increased depression and decreased quality of life in patients who underwent the exercise intervention [31]. Further research into the effect of physical exercise on mood and quality of life in AD patients is, therefore, required.When considering the role of exercise on AD, it is impor tant to note that any positive results may be due to a placebo effect, even in randomized controlled trials. However, due to the varied nature of the outcome measures used in these studies, it is unlikely that every intervention group demonstrated significant gains over the controls due to a placebo effect alone. Furthermore, control group members never appeared to show any improvement and often showed higher rates of functional and cognitive decline.Enhanced neuroplasticity might be underlying the improvements seen. Colcombe and colleagues demonstrated that older adults without dementia who performed aerobic exercises had greater grey and white matter volumes compared to adults who engaged in stretching and toning exercises [38]. Exercise has also been associated with functional connectivity between brain networks often affected by age, such as the default mode, frontal parietal, and frontal executive networks, in older adults without dementia [39].While randomized controlled trial s in AD patients examining the relationship between neuroplasticity and exercise are underway, correlational studies examining brain volumes and cardiorespiratory fitness have been done. In AD patients, cardiorespiratory fitness has been associated with brain volume. VO2peak, peak oxygen consumption, has been positively correlated with greater whole brain volume and white matter volume [40], notably in the inferior parietal lobule, hippocampal, and parahippocampal regions [41].Future results of randomized controlled trials will improve our knowledge in this field of research. Overall, physical activity offers promising outcomes for cognition and physical health in the elderly population and AD patients. Engagement in intellectually stimulating activities has been linked with reduced risk of developing AD and intellectual stimulation has been widely explored as a nonpharmacological treatment option for dementia [42]. Among cognitively ormal older persons, randomized control trials em ploying intellectual training concluded that cognitive interventions produce protective and potentially long lasting positive effects in various cognitive domains as well as activities of daily living [43]. There is also evidence that frequent engagement in hobbies, including reading, puzzles, and games, for at least six hours per week reduces the risk of incident dementia [44]. The concept of intellectual stimulation as a preventative measure for dementia in healthy older adults can be parallel to the notion of building a â€Å"compensatory mechanism† or â€Å"cognitive reserve† [45–48].Cognitive reserve refers to the hypothesis that individual differences shaped by inherent characteristics and external sources including intelligence, years of education, occupation, and intellectual activities, may provide neural protective support against dementia [45–47]. It has been argued that these collective life experiences may contribute to building cognitive res erve and, thus, provide skills to compensate for AD pathology [45–47].In other words, a greater cognitive reserve might delay the appearance of dementia despite the presence of neuropathology, after which a rapid progression of cognitive decline may ensue once pathology is significant enough to result in AD diagnosis. Thus, AD patients with higher education and occupation accomplishments suffer more rapid decline in cognitive abilities when compared to AD patients with less education and occupational attainment following diagnosis [49]. Another study by Helzner and colleagues [50] investigated the relationship between premorbid leisure activity and rate of cognitive decline in AD patients.Leisure activities were classified into four categories: intellectual, social, physical, and other. Higher-frequency participation in intellectual leisure activities prior to AD diagnosis was associated with delayed AD onset followed by faster cognitive decline. The study by Helzner and coll eagues [50] provides evidence for the benefits of intellectual stimulation on slowing down AD development. Besides reducing the risk of dementia, cognitive interventions later in life may affect functional decline in AD.Treiber and colleagues [51] explored the association between engaging in cognitively stimulating activities in late life and the rate of cognitive decline in incident AD. This study included a wide range of intellectual activities that required varying levels of cognitive demand, for example, completing puzzles, reading, watching television, listening to music, and cooking. The results suggested that higher-frequency participation in stimulating activities in early stages of dementia resulted in slower cognitive decline.However, as time progressed there was an overall decrease in participation in activities, which might reflect the nature of AD in terms of functional abilities. Intellectual stimulation can be divided into several categories including cognitive stimul ation, cognitive t

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Greatness of Los Angles Essay Example | Topics and Well Written Essays - 250 words

Greatness of Los Angles - Essay Example The sun in LA is mostly blanketed by the fog. Sometimes, when the sunlight manages to make its way through the mist, the sand changes its color from grey to a pale shade of purplish pink. Shadows begin to squeeze short. As soon as the humidity increases, the brightness increases more than necessary. The sunlight falls on particles between me and the distant mountains. Millions of tiny prisms of fog droplets create a mirror like effect and reflect and refract the sunlight in every direction. The mess of bounced beams of light crowds the atmosphere until the brightness gets so intense that it causes a blinding effect. Mountains merge into the background, until they become completely unidentifiable from other features of the scenery. Cinematographers spend millions of dollars to create an effect like that artificially. All of that money can be saved by shooting in LA. In this way, LA not only enriches the movie with natural light effects, but also makes the shooting more profitable.

Why Golf Is a Sport Essay Example for Free

Why Golf Is a Sport Essay A matter of opinion has separated a variety of sports enthusiasts apart, due to the ongoing debate of whether golf is a sport or simply a skill. Famed golfer Arnold Palmer declared, â€Å"Golf is deceptively simple and endlessly complicated; it satisfies the soul and frustrates the intellect. It is at the same time rewarding and maddening – and it is without a doubt the greatest game mankind has ever invented. (ThinkQuest. com)† These words state what every athlete experiences and feels when he/she is turning a double play, making the game winning three point shot, or throwing a hail mary pass for a touchdown. Golfers are athletes too, they train for that big moment just like any other athlete, but they do it individually and gain the glory for themselves. Golf has increasingly become known not as a sport, but as a skill, which is a huge misconception that I intend to set the facts straight. The definition of a sport is narrowly defined, and to one its own opinion, but Golf is a competition just like every other sport, winning is its pinnacle. Golf requires the number one characteristic that is vital to all sports – hand-eye coordination. These men and women use their athletic ability to reach the top of their game. Golf takes sports to a different level and is played on its own terms. To each his own opinion, but why has the definition of â€Å"a sport† being termed as so narrowly? The NCAA defines a sport as: An institutional activity involving physical exertion with the purpose of competition versus other teams or individuals within a collegiate competition structure. Furthermore, sport includes regularly scheduled team and/or individual, head-to-head competition (at least five) within a defined competitive season(s); and standardized rules with rating/scoring systems ratified by official regulatory agencies and governing bodies. Baseball, basketball, football, hockey, and even golf display these qualities of what is defined as a sport. There has been a considerable amount of people who tend to disclose golf as a sport, only a skill or activity. Yet, many people object the physical exertion aspect with golf, that it does not require any. These objectors who say golf should not be included in that defined group are ignorant to athletics and its regulations. My definition of a sport is a competition that involves athletes who play to win within a certain structure of rules and regulations. Anyone can be an athlete; they do not have to be good to play a sport, as long as they try with some effort. A sport requires certain qualities of an individual too that it can not be without. Hand-eye coordination is vital to every sport out there. A basketball player has to shoot the ball into the hoop, a football player has to throw the ball to an open receiver, a baseball player has to swing a bat to hit a 95 mile per hour fastball, and golfers have to swing their club and hit a tiny ball a couple hundred yards. It is the number one aspect that is required in all sports. Although it is common to associate sports with many other qualities. The â€Å"manly† qualities of other sports such as cheerleaders and fights usually are not included in golf, some figure because it is missing these qualities, that it should not even be considered a sport. â€Å"Cheerleaders are important to sports. They keep the crowd excited; they keep the participants enthused about winning; and they give you something else to look at when the action on the field of play grinds to a halt. With golf theres not a lot of action to begin with. (Irvin)† Although golf is missing the appendages that invigorate other sports with such audacity, the onlookers respect their golfers need for silence and concentration. It is a sport which requires a massive amount of concentration, just like any other sport. Irvin states his idea that cheerleaders are important to sports, when in fact; cheerleading has nothing to do at all with the style of play. He is right that they keep the crowd excited, but that is the only reason why they are there, they do not play, they yell and dance. It makes me wonder why one would think that Golf needs to have cheerleaders to keep the crowd excited when the golfers need a massive amount of concentration. Yet regular sports fans forget that each sport is different, and that is what makes them stand out and appeal to others. Golf does not appeal to some, but a lot of people play the sport religiously, reason being – one does not have to be the typical in shape athlete that most are. Golfers are athletes too, and train to be good ones. Swinging a club and hitting a ball three hundred plus yards requires muscle strength in the torso and upper body. Golfers are just the kind of athletes who do not need to negotiate long-term big money contracts, and scratch themselves while being interviewed after play is over (Lowe). Golf is not a team sport either; it is an individual sport and the glory is captured for them, and they take pride and honor after an amazing feat as any athlete would. The honor and competitiveness of this sport has trickled down to the much supportive fan base. After exposing the truths and presenting evidence about one of the greatest sports ever to be played, we can no longer dispute golf as just a skill or activity, but declare Golf a real sport. It is important to sports enthusiasts everywhere that they have to look beyond the typical definition of a sport and expand their minds. Golfers are athletes too, playing for the top prize every time they step onto the course. Golf is gaining popularity by the second, no longer can it be said to be â€Å"not a real sport†. Golf justifies what every sport should be, the way it is played, the professional maturity that every golfer shows, and competition. Merriam Webster defines a sport as 1): physical activity engaged in for pleasure (2): a particular activity (as an athletic game) so engaged in. Golf qualifies as a sport according to this definition and until it is changed, it will remain one of the legendary sports to play.

Victorian Society in The Strange Case of Dr Jekyll and Mr Hyde Essay Example for Free

Victorian Society in The Strange Case of Dr Jekyll and Mr Hyde Essay The Strange Case of Dr Jekyll and Mr Hyde is a Horror story written by Robert Louis Stevenson. The novella explores the divided nature of human personality and Victorian society by telling the story of a respectable gentleman named Dr Jekyll, who devolves into a beast by the name of Mr Hyde. The dominant theme of the novella is the theme of the double. Stevenson explores this in many different ways throughout the novella. Some of the characters in the book turn out to be very different from what they at first appear to be. For instance, Gabriel Utterson has a very rough countenance and looks quite ugly but he is a very nice, respectable gentleman of the novella and he is also a lawyer that helps down-going men. Also, Dr Jekyll, one of the main characters of the book, is very different from what he appeared to be. He becomes the most hideous character of the novella, Mr Hyde. The first time we encounter Mr Hyde, is during Enfields terrible sight of a little girl being trampled over. Stevenson conveys how dark the streets are by focusing on the lamps which can be seen onstreet after street. Stevenson also draws our attention to the emptiness of the streets, emphasising this by using the simile all as empty as a church. Stevenson builds up a sense of mounting fear by adding that Enfield is so frightened that he listens and listens and begins to long for the sight of a policeman. Stevenson uses the character of Mr Hyde because he is everything a monster is. He is the definition of a monster and his appearance is very easy to picture. Mr Hyde is often described using animal imagery. An example of this is when Mr Enfield witnesses first hand a terrible sight of a little girl being trampled over, for the man calmly trampled over the girls body. Elsewhere, in the novella, he is compared to a hissing snake, a snarling dog and an athletic monkey and this reinforces the idea that he is some way sub-human. It is also significant that Hyde is only ever seen in the shadow, darkness or fog because he represents the hidden and mysterious side of mans personality. Stevenson uses language in a way that reveals to us the characters insincerity or sincerity by the way they speak. In the novella, there are many different characters which use their language in different ways. For example, Dr Jekyll speaks in a very indirect, reserved and cagey way of speech. He proves this in chapter three, when he become quite angry and tries to dissuade Utterson from pursuing the topic of his will, You do not understand my position, and this shows that he is reserved and unwilling to express his emotions. Utterson is also reserved and indirect. However Mr Hyde speaks with short simple and direct words like What do you want, this shows that he is very straight-forward, direct and emotional because he is not afraid to show his emotions or tell people what he thinks. Mr Hyde does speak quite aggressively also, which reveals that he is open minded and doesnt think properly before speaking. He is honest and straight to the point because he doesnt mind to tell people his thoughts. In a strange way, then, the villain of the story is more honest than its hypocritical hero. Poole is the lower-classed disreputable character in the novella as he is Dr Jekylls butler. His use of language shows that he is willing to express his emotions. For example, he also uses short direct way of speech. Through the use of different types of speech, Stevenson seems to suggest that the more respectable and self-restrained the person the more insincere and emotionally dishonest they are. In his exploration of the divided personality, Stevenson draws our attention to the divided nature of London in the 1880s. Throughout the novella, we are aware of the fact that the main respectable characters such as Utterson, Enfield, Lanyon and Jekyll all live in and around Cavendish Square. They live in that citadel of medicine, in ancient, handsome houses, which have a great air of wealth and comfort. However, we learn that the shadowy character, Edward Hyde, lives in the less respectable part of London, Soho. We also learn that he lives on a dingy street in villainous, blackguardly Surroundings. Stevenson, then, by connecting Cavendish Square with Soho, connects the rich characters in the book to the poor ones. Towards the end of the Nineteenth century, Soho was one of the least respectable areas of London. Soho was the kind of area where you would find crowded, shabby streets, people of all different nationalities, cheap eating houses, music halls, brothels or criminals making crooked deals. By connecting these two areas, Stevenson seems to be saying that the two are actually inseparable, that the rich cannot exist without the poor, that Jekyll cannot exist without Hyde. The reason that Mr Hyde who lives in Soho is in the novella at the time of dark is to show that his personality is a dark person inside. However, Jekyll and the others that live in and around Cavendish Square are in the novella at the time of light because they are bright characters who appear to be wholly good and removed from evil. Victorian society was highly moralistic and encouraged respectable gentleman to keep their private lives carefully hidden away. Stevenson makes this point by including numerous symbols of privacy and secrecy throughout the novella. For instance, Dr Jekylls laboratory is at the back of his houses which showed no window. This suggests that Dr Jekyll does not want people to know what he does in his own time because the simple reason that Victorian society was too highly moralistic. This kind of secrecy carries on through the novella with other characters as well. For example, Mr Utterson receives a package from Dr Lanyon which he examined in his office. Before opening the package he locks the door of his own office which shows that Utterson is very secretive about his business and does not want to be associated with down going men. The package was then put in a safe so that no one could have seen it. Taken as a whole, these symbols of secrecy reinforce the idea that Victorian gentlemen were compelled to keep their private lives hidden away. I think that the themes of the novel are not relevant now because the society is not so strict and people dont have to cover up their different types of living or their utmost desires.

Jump Shot In Handball

Jump Shot In Handball The jump shot is one of the most important elements of handball as in the game, motor behavior are performed in specific conditions with the presence of players of the opposing team and while adhering to the regulations. However which areas can be controlled and are used to make the handball action more efficient? Thus we will look into the jump shot in which handball is analyzed in its different phases to find out its efficiency. The goals of the run, jump, shoot are ball velocity and accuracy. Maximum ball velocity and precision is required to minimize the chance of the opponent or goal keeper intercepting the shot. In team handball, shooting to score goals is one of the most important aspects of the game. In order for a shot to be successful, it must have maximum ball velocity and precision for an element of surprise for the goalkeeper (Wagner Muller, 2008). Wagner, Buchecker, Duvillard, and Mulller (2010) state that 67% of ball velocity at ball release was explained by the summation effects from the velocity of elbow extension and internal rotation of the shoulder. Thus we divide them into Approach, Take-off, Shoot, Land. Logically speaking, the faster the ball is thrown at the goal the goalkeeper will have a lesser time to save the shot. In order for a throw to be successful, the highest velocity at ball release together with aiming accuracy is required therefore during the game, thus the athlete has to keep up with the optimal efficiency of these two factors (Zapartidis, Gouvali, Bayios, Boudolos, 2007). Accuracy is something defined as variable. We didnt want to make it become a close-system where the subject keeps hitting at the same spot. Thus in the analyzing performance stage, we came out with a table to judge the subject throwing effectiveness in performing the skill. Zapartidis, Toganidis, Vareltzis, Christodoulidis, Kororos, and Skoufas (2009) reported that players during the game are notably affected by time as aiming accuracy or ball velocity gradually decrease. In all sports tasks, most coaches apply eight biomechanical principles when analyzing their athletes (Bartlett, 2007). These eight principles can be separated into two broad categories. The 3 basic universal principles; use of the stretch-shortening cycle, minimization of energy used, control degrees of freedom. The other 5 general principles; sequential action of muscles, minimization of inertia, impulse generation, maximizing the acceleration path, stability. These apply to sports tasks which are usually used by speed generation. However not all of the principles can be used to apply in every sport. For example, the stability is a one of the biomechanical principle which is applicable to sumo wrestling. Whereas it is not applicable in the game of handball, as there is a lesser emphasis on having a wide base of support for stability when preparing for a shot (Knudson, 2007). In handball, the biomechanical principles that can be applied are use of the stretch-shortening cycle, minimization of energy used, control degrees of freedom, sequential action of muscles, minimization of inertia, impulse generation and maximizing the acceleration path. The recruitment of each part of the body is important by allowing the development of maximal velocity of these parts. This begins from the proximal parts then to the distal parts of the body. The larger proximal joint starts the action by accelerating, thus a transfer of momentum results in a high velocity to the smaller distal joints. Each segments of the kinetic chain is linked to the stoppage of the proximal part results in the increase of angular velocity (Pori, Bon, Sibila, 2005). When performing the shot, certain physiological characteristics are taken into considerations. Therefore, at least for some muscular groups there should be the shortest possible time between extension and contraction for muscles involved in this phase (Pori et al., 2005). Pori et al. (2005) concluded that better players make use of extensors in the wrist better than worse players. Components of Skill 1. Approach (Run-up) Physique We assume there will be significant differences to the speed of ball release in our goal of skill regarding to body height and body weight between handball players of different performance levels (Hasan, Reilly, Cable, Ramadan, 2007). Are tall athletes better than shorter ones? Thus we have physique. Taller handball players with greater body weight have the ability to achieve a higher ball release speed (Wagner et al., 2010). Maximizing acceleration path is a critical factor Using the work-energy relationship which shows that a moving object is equals to work done. This is important for the handballer maximizing use of the run-up which to apply force (Bartlett, 2007). Using the formula: Velocity/Time Acceleration for an increase in velocity, acceleration also increases. 2. Take-off Contact Maximize force generation is a critical factor This is where the Angle, Speed, Height of Jump comes. Further increase in speed at take-off is required by generating more impulse just at take-off. Using the impulse-momentum relationship where change of momentum, I=Ft, increased in I= increased Force exerted on the ground multiply by increased Time of force. From an increased in F we have F=Mass of the athlete multiply by increasing Acceleration of the athlete. This movement requires being fast and powerful at take-off. 4. Shoot Sequence of trunk joint and muscle group in throw Ball velocity at ball release was explained by the summation effects from order of the proximal parts to the distal parts of the body (Wagner et al., 2010). High release point is a critical factor A high elbow release point needed to generate much velocity. The time of the take-off contact would point to fast and elastic strength of the subject and indirectly affect the height of a throw and ball velocity. 5. Land Contact with the ground is a critical factor Decreased force over a period of time by bending knees when landing to reduce the mean impact force which also can prevent further injury. Deterministic Model Run, Jump, Shoot Figure 1 Important considerations for videotaping the skill The points below have been well thought-out to minimize errors recorded during two-dimensional filming, thus improving the accuracy of all data (Bartlett, 2007). Perspective and parallax errors were paid carefully attention to. 1) Position of camera The camera is mounted on a fixed tripod, on a level ground and aiming at the subject. The camera is positioned as far away from the action in order to reduce perspective error. The field of view (FOV) is adjusted to match with the performance of the subjects which as is recorded. As this take advantage of the performer on the projected image and increases the accuracy of digitizing. Once the FOV is in place and it is kept constant at all time. The camera is placed perpendicular to capture the movement of the subjects, horizontal scale of 7m and vertical reference from the goal post. The set-up is shown below, Figure 2. Figure 2 A line was marked out 7 meters from the goalpost and subject use the take off area as point of jump. The camera was place 10 meters perpendicular to the take off area. 2) Lighting Filming is done outdoors, a location with a dull and non-reflective background was use to allow the athlete and the ball to standout. This will make it easier to assess the movement patterns and biomechanics of the jump shot. In contrast, if the background or backdrop was to be too bright, the athlete would be hard to spot. 3) Background The background is as neat as possible, simple and non-reflective as it provides a good contrast which allows the viewing and estimating of the axes of rotation from the subjects anatomical landmarks. 4) Shutter Speed A shutter speed of 1/2000 was selected as this shutter speed would allow for slow motion playback and ease the motion analysis process. Using a lower shutter speed would cause blurriness when the video is playback, while a higher shutter speed comes with a decrease in image quality, thus making analysis impossible. 5) Subject Preparation The recording of the movement is as unpretentious as possible. The subject is briefed that he is performing in front of a camera in an experimental perspective and had little clothing to minimize errors in locating body landmarks. A verbal consent is obtained from the athlete participating in the analysis. The subject was told to throw the ball as fast as possible into the net for the initial 4 shots. After which, he was given coaching cues to correct his technique and delivery of the skill. Results of the Videotaping Session The male subject is a national basketball player who trains 5 times a week (Height-189 cm; body mass 82kg; age 24 years old). He does not have prior experience to playing handball therefore is a suitable candidate. In order to evaluate the over arm throwing performance, according to the International Handball Federation, (IHF), rules of the game a standard handball was used: (Circumference 58-60cm and Weight 425-475g, IHF Size 3, for Men and Male Youth (over age 16). The subject was told to throw as fast as possible; no coaching cues were given for the first 4 shots. Therefore we came up an evaluation of the quality of the execution skill for the subject in Table 3. Table 3 Mark Run-up Take-Off Shoot Land 3 Optimal speed of stride and synchronized lowering of CG, Execution is smooth, in cadenced Planting of takeoff leg accurately, take-off is vertical, explosiveness The elbow is high and moving along height of the head, correct use of sequential muscle groups into the throw, explosive finishing Land on take-off leg or on both legs simultaneously with knees bend 2 Fairly too short or too long stride, Execution still fluent, in cadenced Placement of takeoff leg rather far from the goal, take-off going a little too forward The elbow still moving low, technique of execution better Average execution, with slight unbalance 1 Lack of speed, hasty lowering of CG, not in cadenced, poor execution, execution is poor Placement of takeoff leg is too far from the goal, take-off oriented too forward, lack of explosiveness Placement of takeoff leg is significantly away from the goal, take-off directed markedly forward Land on non-take- off leg, poor execution Legend: CG centre of gravity; Mark: 1 Poor, 2 Average, 3 Good As for the first 4 jumps shots, the subject attainted 10.6  ± 0.2 m/sec for the ball velocity at release. The following are the results of the first 4 jump shots, Table 4. Table 4 Attempt Run-up Take-Off Shoot Land Total Score 1 2 1 1 1 5 2 1 2 1 2 6 3 2 1 2 1 6 4 2 1 3 1 7 Attempts to give too many cues to the subject will paralyze the subject. After letting him explore the jump shot on the initial 4 shots, this time the subject was then told to aim for the top right hand corner of the goalpost, using the jump shot technique. We gave him coaching cues to correct his technique starting from the run-up phrase, take-off, shoot and then leading to landing phrase, Table 5. Table 5 Critical Features Coaching Cues Run-up Take a long third step Take-off Explosiveness-gain vertical height Optimize height of release Release at the top Angle of release Draw a semi circle Summation of forces Smooth-jump and shoot Rotation of ball Flip wrist Land Bend knees The following are the results of the jump shots with coaching cues given to him in Table 6. The subject attainted an improved 12.6  ± 0.4 m/sec for the ball velocity at release. Table 6 Attempt Run-up Take-Off Shoot Land Total Score 5 2 2 3 1 8 6 3 3 2 2 10 7 2 3 2 2 9 8 3 3 3 3 12 Qualitatively analysis Evaluation of performance After taking the video for the running jump shot, we compare it to a elite athlete jump shot. There are a few features which are important in the sequence, the run up (3 steps), the jump and the throw. The run up The 3 steps run up will provide the athlete impulse for the jump shot. As impulse = change in momentum (Blazevich, 2007). F.t = m.v m.u Momentum is the quantity of motion possessed by the body. Therefore a run up is important in this aspect. After assessment, we found out that the subject did a 1 step run up which did not create enough impulse. Therefore the rating is poor -good for the run up Critical Features Rating The run up Poor 1 step run up The jump The height of the jump is determined by a few factors, the weight of the athlete and the acceleration. F = ma The reason for the bending of the knees for a higher jump is that the time it takes for the athletes to leave the floor (Muller, 2009). v = u + at Vavg = s/t Presume the jump height is the same, the less time, he takes to jump the same distance, the more velocity the person create, the higher the person will go. By contracting the quadriceps, will stretch the tendon, by doing this, it is possible to jump higher. The assessment for the subject is poor-good as he did not bend his knee, and straighten his leg after that. Critical Feature Rating Bend Knees Poor-Good Straighten leg Poor Bend Knee? Straighten leg? The throw The speed of the throw is determined by the speed difference and the time it take for the ball to leave the hand. It is similar to the theory of the jump, where the more distance and less time you take the faster the ball will travel. The difference is that there is a twist to the body; therefore there is an angular motion to it. ÃŽÂ ±= (à Ã¢â‚¬ °f à Ã¢â‚¬ °f)/t à Ã¢â‚¬ ° = Ó ¨/t Since the mass of the ball is the constant. The only factor that can influence the amount of force being exacted on it is acceleration. T = I ÃŽÂ ± (angular) Critical Features Rating The pull back Poor Good The follow through Poor Good Pull back? Follow through Correcting the performance The whole sequence of the running throw will be broken to parts to teach the subject. Critical Features Rating Picture Remarks / Strategies Coaching Cues The run up Poor The run up will be done in 3 steps, the subject will attempt to take 3 wide steps to gain speed. Wide Step; More Force Bend Knees Poor Good The subject will jump on the spot, with the knees bend before the jump. Squat more Straighten leg Poor The subject will jump and straighten the leg to gain more height. Explode; Stretch The pull back Poor Good The subject will try to shoot with the jump. By pulling the arm further back. Arc back; Roll Shoulder The follow through Poor Good With the pull back, the subject will attempt the follow through with the same action. Follow through; Swing arm Discussion There are mainly two factors in shooting technique of handball, the first is speed ball velocity of shoot, and the second factor is that no clear prediction of direction to shoot for goal keeper. This approach gives a good evaluation on the kinematic structure in analyzing handball. Thus, this model can be used in detecting the efficiency of the jump shot. An examination of individuals information and its comparison with the model allow us to identify weakness in the execution of jump shot. The use of biomechanical analysis maybe helpful in correcting or perfecting techniques, however the efficiency of the player in a game does not depend solely on performing a perfect kinematics structure during an isolated testing environment.