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Article ; Online: Consanguineous marriages and endemic malaria

Nagelkerke Nicolas / Denic Srdjan / Agarwal Mukesh M

Malaria Journal, Vol 7, Iss 1, p

can inbreeding increase population fitness?

2008 Volume 150

Abstract: Abstract Background The practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of α + -thalassemia, which is protective against malaria. However, it also causes an ... ...

Abstract	Abstract Background The practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of α + -thalassemia, which is protective against malaria. However, it also causes an excessive mortality amongst the offspring due to an increase in homozygosis of recessive lethal alleles. The aim of this study was to explore the overall effects of inbreeding on the fitness of a population infested with malaria. Methods In a stochastic computer model of population growth, the sizes of inbred and outbred populations were compared. The model has been previously validated producing results for inbred populations that have agreed with analytical predictions. Survival likelihoods for different α + -thalassemia genotypes were obtained from the odds of severe forms of disease from a field study. Survivals were further estimated for different values of mortality from malaria. Results Inbreeding increases the frequency of α + -thalassemia allele and the loss of life due to homozygosis of recessive lethal alleles; both are proportional to the coefficient of inbreeding and the frequency of alleles in population. Inbreeding-mediated decrease in mortality from malaria (produced via enhanced α + -thalassemia frequency) mitigates inbreeding-related increases in fatality (produced via increased homozygosity of recessive lethals). When the death rate due to malaria is high, the net effect of inbreeding is a reduction in the overall mortality of the population. Conclusion Consanguineous marriages may increase the overall fitness of populations with endemic malaria.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Subject code	333
Language	English
Publishing date	2008-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: National growth charts for United Arab Emirates children with Down syndrome from birth to 15 years of age.

Aburawi, Elhadi H / Nagelkerke, Nicolas / Deeb, Asma / Abdulla, Shahrban / Abdulrazzaq, Yousef M

Journal of epidemiology

2014 Volume 25, Issue 1, Page(s) 20–29

Abstract: Background: Specific centile growth charts for children with Down syndrome (DS) have been produced in many countries and are known to differ from those of normal children. Since growth assessment depends on the growth pattern characteristic for these ... ...

Abstract	Background: Specific centile growth charts for children with Down syndrome (DS) have been produced in many countries and are known to differ from those of normal children. Since growth assessment depends on the growth pattern characteristic for these conditions, disorder-specific charts are desirable for various ethnic groups. Aims: To provide cross-sectional weight, height, and head circumference (HC) references for healthy United Arab Emirates (UAE) children with DS. Methods: A retrospective and cross-sectional growth study of Emirati children with DS, aged 0 to 18 years old, was conducted. Height, weight, and HC were measured in each child. Cole's LMS statistical method was applied to estimate age-specific percentiles, and measurements were compared to UAE reference values for normal children. Results: Incidence of DS in the UAE population is 1 in 374 live births (267 in 10 000 live births). We analyzed 1263 growth examinations of 182 children with DS born between 1994 and 2012. The male-to-female ratio was 1.6:1. Height, weight, and HC centile charts were constructed for ages 0 to 13 years. The prevalence of overweight and obesity in DS children aged 10 to 13 years of age was 32% and 19%, respectively. The DS children were significantly shorter and heavier than normal children in the UAE. Conclusions: Weight, height, and HC growth charts were created for children with DS. These can be used as a reference standard for the UAE children with DS. Overweight and obesity are quite common in DS children ≥ 10 years of age, as DS children tend to be shorter and heavier than non-DS children.
MeSH term(s)	Adolescent ; Body Height/physiology ; Body Weight/physiology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Down Syndrome/epidemiology ; Down Syndrome/physiopathology ; Female ; Growth Charts ; Head/growth & development ; Humans ; Infant ; Infant, Newborn ; Male ; Overweight/epidemiology ; Pediatric Obesity/epidemiology ; Retrospective Studies ; United Arab Emirates/epidemiology
Language	English
Publishing date	2014-09-06
Publishing country	Japan
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1442118-5
ISSN	1349-9092 ; 0917-5040
ISSN (online)	1349-9092
ISSN	0917-5040
DOI	10.2188/jea.JE20130081
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Article ; Online: Consanguineous marriages and endemic malaria: can inbreeding increase population fitness?

Denic, Srdjan / Nagelkerke, Nicolas / Agarwal, Mukesh M

Malaria journal

2008 Volume 7, Page(s) 150

Abstract: Background: The practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of alpha+-thalassemia, which is protective against malaria. However, it also causes an ... ...

Abstract	Background: The practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of alpha+-thalassemia, which is protective against malaria. However, it also causes an excessive mortality amongst the offspring due to an increase in homozygosis of recessive lethal alleles. The aim of this study was to explore the overall effects of inbreeding on the fitness of a population infested with malaria. Methods: In a stochastic computer model of population growth, the sizes of inbred and outbred populations were compared. The model has been previously validated producing results for inbred populations that have agreed with analytical predictions. Survival likelihoods for different alpha+-thalassemia genotypes were obtained from the odds of severe forms of disease from a field study. Survivals were further estimated for different values of mortality from malaria. Results: Inbreeding increases the frequency of alpha+-thalassemia allele and the loss of life due to homozygosis of recessive lethal alleles; both are proportional to the coefficient of inbreeding and the frequency of alleles in population. Inbreeding-mediated decrease in mortality from malaria (produced via enhanced alpha+-thalassemia frequency) mitigates inbreeding-related increases in fatality (produced via increased homozygosity of recessive lethals). When the death rate due to malaria is high, the net effect of inbreeding is a reduction in the overall mortality of the population. Conclusion: Consanguineous marriages may increase the overall fitness of populations with endemic malaria.
MeSH term(s)	Consanguinity ; Endemic Diseases/prevention & control ; Gene Frequency ; Genetics, Population ; Homozygote ; Humans ; Malaria/epidemiology ; Malaria/genetics ; Models, Theoretical ; alpha-Thalassemia/genetics
Language	English
Publishing date	2008-08-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1475-2875
ISSN (online)	1475-2875
DOI	10.1186/1475-2875-7-150
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Article: Consanguinity affects selection of alpha-thalassemia genotypes and the size of populations under selection pressure from malaria.

Denic, Srdjan / Frampton, Chris / Nagelkerke, Nicolas / Nicholls, M Gary

Annals of human biology

2007 Volume 34, Issue 6, Page(s) 620–631

Abstract: Background: In populations with alpha(+)-thalassemia gene deletion, the practice of consanguineous marriages is common.: Aim: The study explored the impact of consanguinity (inbreeding) on the selection of alpha(+)-thalassemia genotypes in a computer ...

Abstract	Background: In populations with alpha(+)-thalassemia gene deletion, the practice of consanguineous marriages is common. Aim: The study explored the impact of consanguinity (inbreeding) on the selection of alpha(+)-thalassemia genotypes in a computer model. Method: In a population under selection pressure from malaria, a single protective mutation (-alpha/alphaalpha genotype) was introduced among normal genotypes (alphaalpha/alphaalpha), and mating allowed to proceed. Heterozygote (-alpha/alphaalpha) and homozygote (-alpha/-alpha) children were 1.5 and 2.5 times more likely to survive malaria than those with normal genotypes. Using different coefficients of inbreeding (F, range 0-0.12), we examined the effect of population size, and the mean number of generations required for the homozygote frequency to reach 0.5. Results: On average, consanguineous populations were larger than randomly mating populations and the size was directly proportional to F. In more inbred populations,-alpha/-alpha homozygotes reached a frequency of 0.5 faster than in less inbred populations. As the frequency of the alpha(+)-thalassemia allele in a population increases, however, the positive effect of inbreeding on the population growth decreases. Conclusion: Under selection pressure from malaria, consanguinity may increase the speed of selection of-alpha/-alpha homozygotes and provide an advantage regarding population growth over non-consanguineous populations.
MeSH term(s)	Computer Simulation ; Consanguinity ; Genotype ; Homozygote ; Humans ; Malaria/genetics ; Models, Genetic ; Selection, Genetic ; alpha-Thalassemia/etiology ; alpha-Thalassemia/genetics
Language	English
Publishing date	2007-11
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	186656-4
ISSN	1464-5033 ; 0301-4460
ISSN (online)	1464-5033
ISSN	0301-4460
DOI	10.1080/03014460701615993
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Article ; Online: Knowledge, attitude and practices of diabetic patients in the United Arab Emirates.

Al-Maskari, Fatma / El-Sadig, Mohamed / Al-Kaabi, Juma M / Afandi, Bachar / Nagelkerke, Nicolas / Yeatts, Karin B

PloS one

2013 Volume 8, Issue 1, Page(s) e52857

Abstract: Introduction: Diabetes self-management education is a cornerstone of diabetes care. However, many diabetics in the United Arab Emirates (UAE) lack sufficient knowledge about their disease due to illiteracy. Thus, before considering any possible ... ...

Abstract	Introduction: Diabetes self-management education is a cornerstone of diabetes care. However, many diabetics in the United Arab Emirates (UAE) lack sufficient knowledge about their disease due to illiteracy. Thus, before considering any possible intervention it was imperative to assess present knowledge, attitudes, and practices of patients towards the management of diabetes. Methods: A random sample of 575 DM patients was selected from diabetes outpatient's clinics of Tawam and Al-Ain hospitals in Al-Ain city (UAE) during 2006-2007, and their knowledge attitude and practice assessed using a questionnaire modified from the Michigan Diabetes Research Training Center instrument. Results: Thirty-one percent of patients had poor knowledge of diabetes. Seventy-two had negative attitudes towards having the disease and 57% had HbA(1c) levels reflecting poor glycemic control. Only seventeen percent reported having adequate blood sugar control, while 10% admitted non-compliance with their medications. Knowledge, practice and attitude scores were all statistically significantly positively, but rather weakly, associated, but none of these scores was significantly correlated with HbA(1c). Conclusions: The study showed low levels of diabetes awareness but positive attitudes towards the importance of DM care and satisfactory diabetes practices in the UAE. Programs to increase patients' awareness about DM are essential for all diabetics in the UAE in order to improve their understanding, compliance and management and, thereby, their ability to cope with the disease.
MeSH term(s)	Adult ; Aged ; Diabetes Complications ; Diabetes Mellitus/epidemiology ; Diabetes Mellitus/prevention & control ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Hyperglycemia/epidemiology ; Hyperglycemia/prevention & control ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; United Arab Emirates/epidemiology
Language	English
Publishing date	2013-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0052857
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Article: Ranitidine in acute high-dose organophosphate exposure in rats: effect of the time-point of administration and comparison with pyridostigmine.

Petroianu, Georg A / Hasan, Mohamed Y / Nurulain, Syed M / Shafiullah, Mohamed / Sheen, Rajan / Nagelkerke, Nicolas

Basic & clinical pharmacology & toxicology

2006 Volume 99, Issue 4, Page(s) 312–316

Abstract: Weak and reversible inhibitors of cholinesterase, when co-administered in large doses, can act in a protective manner against more potent inhibitors such as organophosphates. The clinically widely used histamine type 2 (H2) receptor blocker ranitidine is ...

Abstract	Weak and reversible inhibitors of cholinesterase, when co-administered in large doses, can act in a protective manner against more potent inhibitors such as organophosphates. The clinically widely used histamine type 2 (H2) receptor blocker ranitidine is among H2 blockers the most potent inhibitor of acetylcholinesterase but roughly three to four orders of magnitude less potent than paraoxon (an irreversible organophosphate esterase inhibitor) or pyridostigmine (a reversible carbamate esterase inhibitor). We have previously shown that in vitro ranitidine confers some protection against inhibition of cholinesterases by paraoxon and that in vivo it both increases the number of rats surviving an acute paraoxon exposure and also protects to some degree the cholinesterases from organophosphate inhibition. The purpose of the study was to compare in a prospective non-blinded study, in a rat model of acute high-dose paraoxon exposure, ranitidine with pyridostigmine either administered simultaneously or 30 min. before exposure. There were 36 rats in each of the 5 groups. All substances were applied intraperitoneally. Additional analysis included data from a similar experiment carried out in 2005, in which 54 rats were exposed to paraoxon only (G1) and 54 to paraoxon+ranitidine simultaneously (G2). All groups (except controls; G6 & G7) received 1 micro Mol paraoxon (approximately LD75); groups 2-5 received in addition to paraoxon: G2: 50 micro Mol ranitidine within 1 min. of paraoxon, G3: 1 micro Mol pyridostigmine within 1 min. of paraoxon, G4: 50 micro Mol ranitidine 30 min. before paraoxon, G5: 1 micro Mol pyridostigmine 30 min. before paraoxon. Groups 6 & 7 received only ranitidine and pyridostigmine respectively, group G1 received only paraoxon. Mortality was recorded at 30 min., 1, 2, 3, 4, 24 and 48 hr. Mortality data were compared using Kaplan-Meier plots and logrank tests. No Bonferroni correction for multiple comparisons was applied and an alpha < or = 0.05 was considered significant. All statistical analysis was performed by using SPSS 12.0 statistical software (SPSS Inc., Chicago, IL, USA). Simultaneous administration of ranitidine or pyridostigmine with paraoxon does not significantly affect mortality. Pretreatment (30 min. before) with both ranitidine or pyridostigmine statistically and significantly reduced mortality. When administered before paraoxon, pyridostigmine is statistically significantly superior to ranitidine. Both ranitidine and pyridostigmine are protective against acute paraoxon toxicity provided they are administered before paraoxon. Pyridostigmine results are statistically significantly superior to ranitidine (< or =0.05).
MeSH term(s)	Animals ; Dose-Response Relationship, Drug ; Drug Interactions ; Erythrocytes/drug effects ; Erythrocytes/enzymology ; Organophosphorus Compounds/antagonists & inhibitors ; Organophosphorus Compounds/toxicity ; Prospective Studies ; Pyridostigmine Bromide/pharmacology ; Ranitidine/pharmacology ; Rats ; Time Factors
Chemical Substances	Organophosphorus Compounds ; Ranitidine (884KT10YB7) ; Pyridostigmine Bromide (KVI301NA53)
Language	English
Publishing date	2006-10
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2134679-3
ISSN	1742-7843 ; 1742-7835
ISSN (online)	1742-7843
ISSN	1742-7835
DOI	10.1111/j.1742-7843.2006.pto_215.x
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Article ; Online: ANP and BNP responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

Adem, Abdu / Al Haj, Mahmoud / Benedict, Sheela / Yasin, Javed / Nagelkerke, Nicolas / Nyberg, Fred / Yandle, Tim G / Frampton, Chris M / Lewis, Lynley K / Nicholls, M Gary / Kazzam, Elsadig

PloS one

2013 Volume 8, Issue 3, Page(s) e57806

Abstract: The objectives of this study were to investigate and compare the responses of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the circulation of hydrated, dehydrated, and dehydrated losartan - treated camels; and to document the ... ...

Abstract	The objectives of this study were to investigate and compare the responses of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the circulation of hydrated, dehydrated, and dehydrated losartan - treated camels; and to document the cardiac storage form of B-type natriuretic peptide in the camel heart. Eighteen male camels were used in the study: control or hydrated camels (n = 6), dehydrated camels (n = 6) and dehydrated losartan-treated camels (n = 6) which were dehydrated and received the angiotensin II (Ang II) AT-1 receptor blocker, losartan, at a dose of 5 mg/kg body weight intravenously for 20 days. Control animals were supplied with feed and water ad-libitum while both dehydrated and dehydrated-losartan treated groups were supplied with feed ad-libitum but no water for 20 days. Compared with time-matched controls, dehydrated camels exhibited a significant decrease in plasma levels of both ANP and BNP. Losartan-treated camels also exhibited a significant decline in ANP and BNP levels across 20 days of dehydration but the changes were not different from those seen with dehydration alone. Size exclusion high performance liquid chromatography of extracts of camel heart indicated that proB-type natriuretic peptide is the storage form of the peptide. We conclude first, that dehydration in the camel induces vigorous decrements in circulating levels of ANP and BNP; second, blockade of the renin-angiotensin system has little or no modulatory effect on the ANP and BNP responses to dehydration; third, proB-type natriuretic peptide is the storage form of this hormone in the heart of the one-humped camel.
MeSH term(s)	Angiotensin II Type 1 Receptor Blockers/pharmacology ; Animals ; Atrial Natriuretic Factor/blood ; Atrial Natriuretic Factor/metabolism ; Camelus/physiology ; Dehydration/drug therapy ; Dehydration/metabolism ; Losartan/pharmacology ; Male ; Myocardium/metabolism ; Natriuretic Peptide, Brain/blood ; Natriuretic Peptide, Brain/metabolism ; Renin-Angiotensin System/drug effects ; Renin-Angiotensin System/physiology
Chemical Substances	Angiotensin II Type 1 Receptor Blockers ; Natriuretic Peptide, Brain (114471-18-0) ; Atrial Natriuretic Factor (85637-73-6) ; Losartan (JMS50MPO89)
Language	English
Publishing date	2013-03-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0057806
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Article ; Online: Responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

Ali, Mahmoud Alhaj / Adem, Abdu / Chandranath, Irwin S / Benedict, Sheela / Pathan, Javed Y / Nagelkerke, Nicolas / Nyberg, Fred / Lewis, Lynley K / Yandle, Tim G / Nicholls, Gary M / Frampton, Chris M / Kazzam, Elsadig

PloS one

2012 Volume 7, Issue 5, Page(s) e37299

Abstract: Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with ... ...

Abstract	Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.
MeSH term(s)	Aldosterone/blood ; Analysis of Variance ; Animals ; Arginine Vasopressin/blood ; Body Weights and Measures ; Camelus/physiology ; Creatinine/blood ; Dehydration/physiopathology ; Dehydration/veterinary ; Losartan/pharmacology ; Male ; Renin-Angiotensin System/drug effects ; Renin-Angiotensin System/physiology ; Sodium/blood ; United Arab Emirates ; Urea/blood
Chemical Substances	Arginine Vasopressin (113-79-1) ; Aldosterone (4964P6T9RB) ; Urea (8W8T17847W) ; Sodium (9NEZ333N27) ; Creatinine (AYI8EX34EU) ; Losartan (JMS50MPO89)
Language	English
Publishing date	2012-05-18
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0037299
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