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Sickle Cell Trait and Sudden Death

Sickle Cell Trait and Sudden Death

The first cases identified were four US Army recruits who died during or immediately after strenuous exercise during basic training at Fort Bliss, Texas (elevation 4050 ft.), between March 1968 and February 1969 [18]. On the basis of autopsy specimens and morphologic cri- teria previously established for individuals with sickle cell disease [19, 20], the authors concluded that the sol- diers died of diffuse microvascular obstruction from sickled erythrocytes or “sickle crisis.” Although hypox- emia was modest at 4000 ft (ambient PO2, 70– 75 mmHg), investigators concluded that the decrease in arterial PO2 levels initiated events that led to acidosis, excess lactate formation, and intravascular sickling. They postulated that even though factors such as dehydration, increased blood viscosity, and hypercoagulability may have contributed to this syndrome, “the …. moderate-to- severe exercise after recent arrival at a relatively high altitude….” ultimately led to sickle crisis and sudden death. They also concluded that the variable hemoglobin S concentration (30–44%) among recruits spared some with sickle cell trait but not others.

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Biochemical and immunological mechanisms by which sickle cell trait protects against malaria

Biochemical and immunological mechanisms by which sickle cell trait protects against malaria

Malaria, especially that caused by Plasmodium falciparum, has been a major cause of morbidity and mortality through- out human history. As a result, malaria has exerted extraordinary evolutionary pressure on the human gen- ome and appears to have selected for multiple genetic polymorphisms that provide protection against severe disease [1-4]. The best-characterized human genetic poly- morphism associated with malaria results in sickle haemo- globin (HbS). The high prevalence of HbS in sub-Saharan Africa and some other tropical areas is almost certainly due to the protection against malaria afforded to heterozy- gotes [1-3,5]. Since the protective effect of sickle cell trait on malaria was first described over 60 years ago [6-8] our understanding of the epidemiology and mechanisms of protection of this genotype have continued to expand, as will be discussed below.

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The Relative Biologic Effectiveness versus Linear Energy Transfer Curve as a Cell Trait

The Relative Biologic Effectiveness versus Linear Energy Transfer Curve as a Cell Trait

The magnitude of biological response varies with different radiation types. Using Linear Energy Transfer (LET) to dif- ferentiate types of incident radiation beam, the Relative Biologic Effectiveness (RBE) as a function of LET (RBE-LET) was found to have a characteristic shape with a peak around LET values 100 - 200 eV/nm. This general feature is be- lieved to be a property of the incident beam. Our systems engineering model, however, suggests that the shape of the RBE-LET curve is a cell trait, a property of the cell. Like any other trait, phenotypic variations result from interactions of the genes and their context. State-space block diagram of the differential equation model suggests the genes are those in the DNA double strand break (dsb) repair pathway; and the context is cellular stress responsing to DNA damage by both external stimuli and internal redox state. At a deeper level, the block diagram suggests cell using mathematical cal- culations in its decision-making when facing a stress signal. The MRN protein complex, in particular, may perform ad- dition to count the degree of DNA twisting for the homeostatic regulation of DNA supercoiling. The ATM protein may act as a feedback amplifier.

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Renal Medullary Carcinoma in an Adolescent With Sickle Cell Trait

Renal Medullary Carcinoma in an Adolescent With Sickle Cell Trait

ABSTRACT. We describe the complex presentation of a patient with renal medullary carcinoma, a newly described entity primarily affecting young patients with sickle cell trait. Renal medullary carcinoma is an aggres- sive, rapidly destructive tumor associated with a delayed diagnosis and a poor outcome. The most common pre- senting signs and symptoms include hematuria, abdom- inal or flank pain, and weight loss. Sickle cell trait as the sole cause of hematuria in young black patients is a diagnosis of exclusion. Hemoglobin electrophoresis, in- travenous pyelography, and computed tomography scans should be the minimal studies performed in young black patients with hematuria. Pediatrics 1999;103(2). URL: http://www.pediatrics.org/cgi/content/full/103/2/e22; sickle cell trait, hematuria, renal medullary carcinoma, renal tumors.

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Immunological Characterization in Malaria Patients with and without the Sickle Cell Trait

Immunological Characterization in Malaria Patients with and without the Sickle Cell Trait

Our observations suggest that malaria protection by HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite. A better understanding of the underlying mechanisms might yield impor- tant insights into both these processes. There was obvious increase in the total IgG, IL 6 in malaria patients with sickle cell trait and in a symptomatic and uncomplicated case compared to malaria patients without sickle cell trait and in severe cases of malaria. Meanwhile IL12 was higher in uncomplicated cases compared to those with severe cases in malaria without sickle cell and also increased in asymptomatic cases in malaria patient with sickle cell trait compared to uncomplicated cases. As regard to IL 18 it was raised in malaria patients with sickle cell trait. The presence of HbAS is associated with increased acquired immunity to mild malaria. Further work will need to be done to work out how this change in immunity occurs. It is not yet known whether these results are also true for protection against severe malaria, and in any case the protection is only partial; hence, treatment of anyone with malaria, whatever their sickle cell status, is essential.

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Hemoglobin K Woolwich (Hb KW):  Its Combination with Sickle Cell Trait

Hemoglobin K Woolwich (Hb KW): Its Combination with Sickle Cell Trait

Hemoglobin K-Woolwich (Hb KW) is a rare hemoglobin variant with very few cases reported. It is most prevalent in West African countries, particularly Nigeria, Ghana, and the Ivory Coast. Some reports suggest Hb KW may be a clinically benign trait, whereas others indicate it may behave si- milarly to a β + thalassemia. The combination of hemoglobin S and hemoglobin KW (Hb S/KW) is a rare double heterozygous disorder with little known clinical characteristics. We report the hema- tologic and clinical data on three patients with Hb S/KW to help describe the characteristics of this patient population. The first two cases represent first cousins, ages 3 and 2 years. They are clini- cally asymptomatic. They have normal hemoglobin and mean corpuscle volume (MCV) levels without reticulocytosis. The third case is of a 14-year-old male who is non-anemic with no micro- cytosis. He has been clinically well except for abdominal pain upon dehydration. On hemoglobin electrophoresis, these patients have Hb S levels slightly higher than typically observed with sickle cell trait and a delay of hemoglobin F to adult levels. There exists a need for more reports to better delineate the clinical course and management of these patients.

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An up-date on the prevalence of sickle cell trait in Eastern and Western Uganda

An up-date on the prevalence of sickle cell trait in Eastern and Western Uganda

Sickle cell disease is an inherited hemoglobinopathy aris- ing from the substitution of glutamic amino acid by valine in the sixth position of the beta globin chain [1]. Inheritance of the sickle cell trait follows a recessive auto- somal pattern. Phenotypically, only persons with double recessive genes of sickle cell (ss homozygotes) do mani- fest disease, whilst the heterozygotes (AS) are being referred to as carriers. According to Diallo, Africa is the most highly affected continent with 200,000 new born affected by sickle cell anemia (SCA) per year [1]. This constitutes approximately 66.6% of the children born with haemoglobinopathies worldwide. According to reports from Ghana, it is estimated that 15,000 children

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Relationships between sickle cell trait, malaria, and educational outcomes in Tanzania

Relationships between sickle cell trait, malaria, and educational outcomes in Tanzania

There is a large literature suggesting that malaria explains an important component of the lagging devel- opment performance of sub-Saharan Africa [6]. Using micro data, several recent papers [7–12] show long run benefits to cohorts exposed to malaria control or eradi- cation programs early in life with respect to educational attainment, cognition, employment, and/or earnings. However, these studies largely rely on ecological designs; for example several compare educational outcomes for individuals born in more versus less malarial areas prior to national eradication campaigns. As such they may be subject to confounding biases. Research which examines educational outcomes as a function of individual, rather than geographic, variation in malaria exposure is needed. The genetic variations generated by SCD provide an opportunity to identify the effect of malaria exposure in childhood on educational attainment. Using the technique of Mendelian randomization, the key assumption is that a specific genotype (in this case HbAS) is linked to a health- related characteristic (protection from malaria), but is unrelated to other confounding variables or to the out- come of interest [13]. If this assumption is valid, then indi- viduals with SCT will have reduced exposure to malaria but will otherwise be comparable to individuals without sickle cell trait. This property of SCT has been previously used, in a Mendelian randomization framework, to study the relationship between malaria and stunting [14], but has not to our knowledge been used to study the relation- ship between malaria and educational attainment. If it is true that exposure to non-severe malaria reduces children’s cognitive development and ability to learn, chil- dren with the SCT living in highly endemic malaria areas should therefore display improved educational outcomes in the long run. This study therefore utilized genetic and epidemiological data to assess the effects of exposure to malaria and SCT on children’s educational attainment in an area that was until recently holo/hyper-endemic to malaria (Korogwe district in north-eastern Tanzania.)

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Increased Complement Deposition on Red Blood Cells in Children with Sickle Cell Trait

Increased Complement Deposition on Red Blood Cells in Children with Sickle Cell Trait

This study showed that the mean %C3b deposition for the HbAS was significantly higher than those for HbAA RBC under both normal and reduced oxygenation. This could translate to increased susceptibility of these cells to immune complex destruction which would lead to mopping of these cells especially if infected with malaria. This would in turn lead to destructions of the parasitized cells and can be a factor in the partial protection of HbAS cells from severe manifestations of malaria for example severe malarial anaemia. When the volunteers were grouped into 0-12, 13-48 and 49-192 months age cohorts, the same general trend was maintained but only achieved significance in the 49-192 months age group. It is possible that the general increase in complement deposition increased with age leading to greater protection as the children grew older. These data suggests that differences in susceptibility to C3b deposition between HbAS and HbAA erythrocytes may not be an important factor that determines protection from severe malarial anaemia in individuals with sickle cell traits.

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Prevalence of sickle cell disease and sickle cell trait among children admitted to Al Fashir Teaching Hospital North Darfur State, Sudan

Prevalence of sickle cell disease and sickle cell trait among children admitted to Al Fashir Teaching Hospital North Darfur State, Sudan

Sickle cell anaemia is very well documented among Albagara tribes, a study performed by Bayoumi et  al. in western Sudan [14]. Also, in a subgroup of Albagara, Messeryia, studies conducted by Ahmed and his col- leagues in 1986 showed that, the prevalence of sickle cell disease was 30% [15] and 16% among immigrants from the Blue Nile province and 18% among Nilotic tribes in the south of Sudan in separate study done by Foy et al. [16]. Furthermore, Hb S is also known to be prevalent in the White Nile (1986) and Khartoum states (1972) as documented by Ahmed and his colleagues [15] and Omer et al. [17] respectively.

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Diabetes at Sickle Cell Trait with the Treatment of Medicinal Plants: A Study

Diabetes at Sickle Cell Trait with the Treatment of Medicinal Plants: A Study

We have been fortunate to realize several key outputs from this project. The research has resulted in several ouputs that provide an opportunity for future research and policy implementation for SCD. It has produced the first national study on trends for hospital admission rates for SCD using HES data in India. It has produced the first study using HES data to assess the cost of admissions due to SCD, and it has delivered both a GP educational intervention guideline and a GP template with the potential for wider roll-out. This study also identified adolescent care as an area that needs to be addressed. When studying hospital admissions that may be avoidable, counselling the adolescent age group may be an important way to teach how this disease is passed on and that responsible choices should be made. Counselling may also be relevant for not only disease carriers, but also for trait carriers as genetic counselling becomes a part of education for prevention of the next generation of disease.

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Sickle Cell Trait Screening in Athletes: Pediatricians' Attitudes and Concerns

Sickle Cell Trait Screening in Athletes: Pediatricians' Attitudes and Concerns

The methods preferred for obtaining an athlete’s sickle cell status were var- ied. The majority of pediatricians pre- fer identification based on the pa- tient’s medical record (71%), although 21% thought this might be inaccurate (Table 4). The next most preferred method was looking up the newborn screen result (60%), but 31% would avoid this due to the time it might take to get the results. Although 23% wanted to avoid Sickledex screening due to inaccuracy, 58% supported its use. Hemoglobin electrophoresis was preferred by 49%, and 44% wanted to avoid it due to cost. Very few would prefer DNA methods or self-reporting due to cost and poten- tial inaccuracies, respectively. There were no significant differences be- tween the sections regarding meth- ods (data not shown).

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Glucose 6 phosphate dehydrogenase deficiency and hemoglobinopathy in South Western Region Nepal: a boon or burden

Glucose 6 phosphate dehydrogenase deficiency and hemoglobinopathy in South Western Region Nepal: a boon or burden

Objectives: The study was carried out to optimize the phenotypic method to characterize the sickle cell trait (SCT), sickle cell anemia (SCA), and β-thalassemia (β-TT) suspected sample from tharu community of South Western prov- ince-5, Nepal. SCT and SCA were further evaluated by genotypic method employing amplification refractory mutation system (ARMS PCR). Moreover, Glucose 6 phosphate dehydrogenase (G6PD) was estimated in those hemoglobinopa- thy to observe its prevalence. The accurate and reliable method can play an important role in reduction of morbidity and mortality rate.

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Linking intraspecific trait variation to community abundance dynamics improves ecological predictability by revealing a growth-defence trade-off

Linking intraspecific trait variation to community abundance dynamics improves ecological predictability by revealing a growth-defence trade-off

Trait variation within species is increasingly recognised as having im- portant impacts on the population dynamics of natural communities (Berg & Ellers, 2010; Schoener, 2011). Such variation can be driven by evolutionary selection pressures favouring certain heritable traits (Kasada, Yamamichi, & Yoshida, 2014; Thompson, 1998; Yoshida, Hairston, & Ellner, 2004). Alternatively, trait variation can be caused by phenotypic plasticity, when a single genotype produces different phe- notypes under differing environments (Agrawal, 2001; Cortez, 2011; Fordyce, 2006; Tollrian & Harvell, 1999). For example, the timing of life history events or the allocation of resources to growth and defence may depend on the density of predators and resources and on en- vironmental conditions (Finlay, 1977; Lampert, 1994; Riessen, 2015; Travis et al., 2014). Trait change can mediate significant temporal vari- ation in ecological processes such as resource consumption, growth, birth and death (Bassar et al., 2010; Bolker, Holyoak, Křivan, Rowe, & Schmitz, 2003; Pelletier, Clutton- Brock, Pemberton, Tuljapurkar, & Coulson, 2007; Preisser, Bolnick, & Bernard, 2005; terHorst, Miller, & Levitan, 2010; Turcotte, Reznick, & Hare, 2011). When the modifica- tion of ecological interactions alters the strength or direction of trait change, a feedback loop is produced between abundance (ecologically driven) and trait dynamics (evolutionary/plasticity- driven) (Agrawal, Johnson, Hastings, & Maron, 2013; Becks, Ellner, Jones, & Hairston, 2012; Pelletier et al., 2007; Schoener, 2011; Yoshida, Jones, & Ellner, 2003; Yoshida et al., 2007).

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Wielebnowski (1999) surveyed 44 adult captive born cheetahs in four North American breeding facilities and identified three major personality components (Tense-fearful, Vocal-excitable, and Aggres- sive). It was found that females scored higher on the Tense-fearful component than males, leading the authors to suggest that a high level of fearfulness maybe an important adaptive trait, particularly in an open habitat and where lion density is high. An analysis of the breeding success of the sample population revealed that non- breeders of both sexes scored significantly higher on the Tense- Fearful component than breeders. Wielebnowski suggests that the- se results may therefore also allow us to predict an individual’s abil- ity to reproduce in a captive environment; implying that animals that score more highly on the Tense-fearful may not be as adaptive to a captive environment, and may need more secluded enclosures and provision of hiding places in order to breed successfully.

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Trait Anxiety in Sickle Cell Disease: investigating and exploring links to the management of pain

Trait Anxiety in Sickle Cell Disease: investigating and exploring links to the management of pain

mechanisms that can be used to explain certain outcomes. This current study follows a perspective that rejects the traditional dualisms; constructivism did not allow for variables to be observed, which was necessary to suggest a relationship between variables i.e. to measure trait anxiety as a specific type of anxiety and to show that a relationship existed between trait anxiety and health outcomes in SCD. However, empiricism did not allow for the interpretation of subjective meaning, which is an important social construct and part of human experience and of relating to the world (Stone & Elliott, 2011). Being able to explore human experience was particularly relevant to this study – it was important to hear the participants’ voices and how they experienced their illnesses; the experience of chronic pain and chronic illness is an extremely personal one and different phenomena can emerge from this type of research question. Insight into subjective phenomena is invaluable and cannot be explored without prior indication or insight. Robson (2011) confirmed this idea by positing that the world cannot be reduced to absolutes because it can also be constructed individually, for which there are an infinite number of experiences or responses. The critical realist position understands the philosophical integration of objective and subjective meanings in a method that lends itself well to the

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Overexpression of PDK4 is associated with cell proliferation, drug resistance and poor prognosis in ovarian cancer

Overexpression of PDK4 is associated with cell proliferation, drug resistance and poor prognosis in ovarian cancer

Methods: We explored the PDK4 expression according to the public database containing patients with different effect of chemotherapy. Cell proliferation and invasion assays were used to determine the function of PDK4. Mice xenograft experiment was conducted to test the pro- tumorigenesis function of PDK4 in vivo. Cell apoptosis under treatment of chemo drugs was detected by flow cytometry and TUNEL analysis. Spheroid formation assay and CD133+ cell population were used to determine the PDK4-induced stem-like traits. Immunohistochemical staining was performed to test the expression of PDK4 in ovarian cancer tissues, and Kaplan– Meier curve with log-rank test was performed to determine the association between PDK4 expression and ovarian cancer patients’ prognosis.

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The Effect of Hydroxyurea Treatment on Fetal Haemoglobin Level and Clinical Status of Sudanese Sickle Cell Anaemia Patients

The Effect of Hydroxyurea Treatment on Fetal Haemoglobin Level and Clinical Status of Sudanese Sickle Cell Anaemia Patients

In spite of Hydroxyurea was the first drug to be approved by the FDA for the treatment of patients with moderate and/or severe sickle cell anaemia through the induction of fetal haemoglobin synthesis, our results showed that there is no statistically significant difference in Hb-F level in patients who were treated by Hydroxyurea and those were not (Means: 7.6% and 8.7% respectively, P,value: 0.57). This is consistent with study by Fathallah and Atweh who reported that the response to hydroxyurea in sickle cell anaemia patients is variable and about one third of patients with SCD did not respond at all to this treatment (Fathallah H, 2006; Atweh, 2006)

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Does touch massage facilitate recovery after stroke? A study protocol of a randomized controlled trial

Does touch massage facilitate recovery after stroke? A study protocol of a randomized controlled trial

A-State: The state-trait anxiety scale, subscale state; A-Trait: The state-trait anxiety scale, subscale trait; BL: Baseline; BT: Blood pressure; DBE: Department of biomedical engineering; ECG: Electrocardiogram; fMRI: Functional magnetic resonance imaging; FU: Follow up 2 months after baseline; HRQoL: Health related quality of life; HRV: Heart rate variability; Hz: Hertz; MR: Magnetic resonance; mRS: Modified ranking scale; N: Newton; NHP: Nottingham health profile; OCSP: The oxford community stroke project classification; PBL: Pre baseline; PHF: Power of high-frequency; PLF: Power of low-frequency; PTOT: Total spectral power; SPSS: Statistical package for social science; STAI: State-trait anxiety inventory; TENS: Transcutaneous electrical nerve stimulation; TM: Touch massage; TOAST: Trial of org 10172 in acute stroke treatment; UFBI: Umeå center for functional brain imaging; VAS: Visual analogue scale; VLL: Västerbotten county council; W1: After one week intervention; W2: After two weeks intervention.

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Rumination and interoceptive accuracy predict the occurrence of the thermal grill illusion of pain

Rumination and interoceptive accuracy predict the occurrence of the thermal grill illusion of pain

Trait/state variables. In the context of pain intensity, we focused in our first LR model on the potential impact of trait pessimism/optimism, trait pain catastrophizing, trait anxiety, trait rumination, pain expectancy, and IA on the likelihood that participants experienced the TGI. The statistically significant full model [X 2 (2, N = 40) = 15.14, p < .005] showed that rumination and IA significantly contributed to the predictive ability of the model (all p < .05). The other independent variables did not add to the probabil- ity of a TGI occurrence. The model including rumination and IA explained between 31% (Cox and Snell R square) and 42% (Nagelkerke R square) of the variance in the TGI perception. 77.5% of the cases were correctly classi- fied (i.e. 76.5% of the responders and 78.5% of the non- responders to the TGI). Rumination was the strongest predictor of paradoxical pain and presented an odds ratio of 35.86 (CI 2.33, 551.67; see Table 2). This result specifies that in case the rumination characteristic is under control in the model, ruminative persons are about 35 times more likely to perceive the illusion of pain than those who ruminate less. The odds ratio for IA was 20.19 (CI 1.80, 226.81; see Table 2), which signalizes that individuals who perceived their heartbeats more accur- ately had a 20 times higher probability to feel the paradox- ical pain than less interoceptively accurate candidates. The second LR model we used included the suggestibil- ity variables. No potential predictor of the TGI could be identified in this model.

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