Annwyne Houldsworth - Academia.edu (original) (raw)

Papers by Annwyne Houldsworth

Journal of Emerging Diseases and Virology, 2021

COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two sp... more COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two spike subunits on the envelope of SARS-CoV-2, S1 and S2, where S1 binds to the Angiotensin Converting Enzyme (ACE-2), a receptor on the host cells and S2 binds to the cell surface membrane. Different immune responses to the virus are apparent, from asymptomatic to severe respiratory distress, organ failure and ultimately death. Immune responses without hyper-inflammation are essential to successful viral resolution. Pathological and environmental factors drive the immunological repertoire, in response to the virus, influencing innate immune cell activation, cytokine-balance and T cell differentiation. This is determined by age, comorbidity, Vitamin D status and ethnicity related factors. Homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. Mast cell activation and release of histamine is important to the cytokine driven T-cell differentiation a...

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MededPublish, 2021

Correction of order and content of sections-character section correctly inserted, repetition remo... more Correction of order and content of sections-character section correctly inserted, repetition removed. Corrected typos and mistakes Added educational relevance of neuroscience to education. Added introduction to review Added methodology, describing establishing concepts for sections and search methods and sources.

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Immune Dysregulation in Severe COVID-19 and the Possible Role of Mast Cell-Vitamin D Interactions. J Emerg Dis Virol 6(1): , 2021

COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two sp... more COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two spike subunits on the envelope of SARS-CoV-2, S1 and S2, where S1 binds to the Angiotensin Converting Enzyme (ACE-2), a receptor on the host cells and S2 binds to the cell surface membrane. Different immune responses to the virus are apparent, from asymptomatic to severe respiratory distress, organ failure and ultimately death. Immune responses without hyper-inflammation are essential to successful viral resolution. Pathological and environmental factors drive the immunological repertoire, in response to the virus, influencing innate immune cell activation, cytokine-balance and T cell differentiation. This is determined by age, comorbidity, Vitamin D status and ethnicity related factors. Homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. Mast cell activation and release of histamine is important to the cytokine driven T-cell differentiation as the adaptive response. This review combines the relative effects of UV-index-related Vitamin-D synthesis with immune status. Innate immune responses, T cell differentiation and renin/angiotensin system are different in patients affected by COVID-19 and their different outcomes are explored.

Understanding the differences between individuals that determine disease outcome will greatly enhance future therapy methods.

Journal of Interferon & Cytokine Research, 2005

Most people with hepatitis C virus (HCV) develop chronic infection with persistent viremia. Resol... more Most people with hepatitis C virus (HCV) develop chronic infection with persistent viremia. Resolution of infection is associated with antiviral cellular immune responses of T helper 1 (Th1) type. Interleukin-12 (IL-12) is a key cytokine in the generation of Th1 responses, and functionally relevant polymorphisms of the IL12B gene and its promoter have been described recently. We sought an association between three IL12B polymorphisms and outcome of HCV infection in 195 HCV antibody-positive patients; 123 were chronically infected with detectable HCV RNA, and 72 had spontaneously resolved infection testing repeatedly negative for HCV RNA. Genotyping was performed for a single nucleotide polymorphism (SNP) in the 3'-UTR (1188A/C) of the IL12B gene and for 4-bp insertion/deletion polymorphisms in the IL12B promoter region and in the intron 4 region of the IL12B gene. We found chronically infected patients were significantly more likely than those with resolved HCV infection to be homozygous for the 3'-UTR A allele (66% vs. 50%; chi-square = 4.12, p = 0.04 with Yates correction), which has been associated with lower IL-12 production. No other significant association was found. Our findings support the concept that an individual's genetically determined ability to produce IL-12 is another factor that can influence the outcome of HCV infection.

Journal of Contemporary Medical Education, 2016

The role of a university professor is multifaceted; as teacher, facilitator, assessor, evaluator,... more The role of a university professor is multifaceted; as teacher, facilitator, assessor, evaluator, models of learning themselves as self-directed learners, addressing several key competencies for the effective teacher. It is not only about the transmission of knowledge, facts and skills but also about understanding how a student learns and being able to adapt and differentiate the delivery to personalise the learning. Appropriate questioning to assess prior knowledge and testing or challenging the understanding of the student learning is also a skill for the professor. Being able to access and use a variety of resources is important to deepen the understanding of student learning, including current IT skills. The relationship between learner and mentor is essential, developing trust and confidence. The development of appropriate medical and basic science language is an important element to the learning process. The professor's collaboration and collegiate practices in a learning community enrich the learning experience, where best practice can be shared and communicated. It is important to be able to measure the impact of the teaching through assessment (formative and summative) and evaluation, which drives continued improvement in the learning experience. The innovative use of resources and environment that supports student and patient-centred learning and effectively engages with the students must be contextually and clinically relevant to the student's experience.

Journal of Medical Virology, 2014

International Journal of Endocrinology and Metabolic Disorders

Aims: A retrospective, observational, case control, pilot study investigating the relationship be... more Aims: A retrospective, observational, case control, pilot study investigating the relationship between insulin resistance (IR), renal function and maternal serum chromium (Cr) level in pregnancy. Methods: 115 pregnant women in their first 12 weeks to 40 weeks were initially recruited for the study, involving an oral glucose tolerance test (oGTT) from the Day Assessment unit at Derriford Hospital using the 75 g standard glucose load recommended by WHO. 101 patients were at least 28 weeks gestation, 10 were diagnosed with gestational diabetes mellitus (GDM), 8 of these were included in the study. 34 of these patients at over 28 weeks gestation were further tested for urine and serum Cr and creatinine (GDM, n=8; non-GDM, n=26) and insulin (n=70), IR was calculated. The diagnosed GDM group (n=8) was compared to the normoglycaemic group (n=26) and control group of non-pregnant, normoglycaemic controls (n=8). No statistical significance observed between the groups with respect to age or BMI. Results: Correlation was found between IR and serum Cr/BMI in the whole patient group (p=0.009; R=0.435, n=34) and within the non-GDM patients (R=0.416; p=0.01, n=26 two tailed) but not within the GDM patients (n=8) alone. There was significant correlation in the GDM group only for increased urine creatinine associated with urine Cr levels (p=0.049, R=0.709, n=8) at the 0.05 two-tailed level. Conclusion: Increased IR during pregnancy was related to an increase in serum Cr /BMI levels in non-GDM pregnant women. Deficiency of Cr status may be a pathogenic factor in the development of GDM. We propose a mechanism.

Several cell surface molecules have hepatitis C virus (HCV) binding properties and may serve as r... more Several cell surface molecules have hepatitis C virus (HCV) binding properties and may serve as receptors facilitating viral entry into cells. The large extracellular loop (LEL) of CD81 has been shown to bind the HCV envelope protein E2 with several critical residues for the CD81HCV-E2 interaction. It was hypothesised that variation in the CD81 LEL sequence may modify susceptibility to HCV infection. HCV RNA negative patients with spontaneous viral clearance (RNA ve); HCV RNA positive cases, who are affected chronically (RNA þve); and patients at high risk of HCV infection, exposed but uninfected patients (EU) were studied. Genomic DNA was extracted from whole blood samples and four exons of the CD81 LEL gene were amplified by PCR and sequenced. The cDNA derived from CD81 ( 700bp) was sequenced following RNA extraction from peripheral blood mononuclear cells. Patients, who are RNA positive, RNA negative, and exposed uninfected were sequenced for four DNA sections (A, B, C, and D). S...

UNLABELLED The effective treatment of diabetes and the prevention of diabetic complications may b... more UNLABELLED The effective treatment of diabetes and the prevention of diabetic complications may be improved by a better understanding of the antioxidant function of intracellular defences against oxidative stress. Polymorphisms in antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in diabetes and/or in its complications. SOD-2 was investigated in patients with type 1 diabetes mellitus (T1DM) to ascertain if specific genotypes have any protective influences in the pathogenic mechanisms in diabetes and/or in several different complications, including retinopathy, nephropathy and diabetic controls compared to normal healthy controls. METHOD 278 (136M:142F) T1DM patients and 135 (72M:63F) normal, healthy controls were investigated for SOD-2 polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution. RESULTS A significant difference in the C-9-T genotype was observed between patients and normal controls but not between...

The delivery of effective, high-quality patient care is a highly complex activity, demanding heal... more The delivery of effective, high-quality patient care is a highly complex activity, demanding health and social care professionals to collaborate in an effective manner. Interprofessional learning (IPL) is professionally relevant, intellectually stimulating and evidence based. New learning paradigms for healthcare professionals explore new ways to combine expertise, delivering IPL programmes where patient safety and quality of care can be improved (WHO 2010). Intervening early in the health professional’s career with collaborative activities with IPL is now considered important in healthcare training. Development of multidisciplinary student centred ideas hopefully results in the enhancement of patient-centred care. Conscious competence in understanding the benefits of IPL is needed to recognise those that are naïve to IPL and competent professionals who are able to design new curricular and deliver training to address unconscious incompetence to IPL. There are many diverse theories ...

Cellular immunity with interferon gamma production could have a role in protection from hepatitis... more Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposeduninfected individuals and 105 healthy controls. Overall, the C allele was found in 27•6% of exposed-uninfected cases compared with 16•7% of healthy controls [c 2 = 6•3, P = 0•02, odds ratio (OR) = 1•9, 95% confidence interval (CI) = 1•1-3•2]. CC genotype was found in 10•5% of exposed-uninfected cases compared with 0•9% controls (c 2 = 9•3, P = 0•01, OR = 12, 95% CI = 1•5-100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed-uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection.

Journal of Emerging Diseases and Virology, 2021

COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two sp... more COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two spike subunits on the envelope of SARS-CoV-2, S1 and S2, where S1 binds to the Angiotensin Converting Enzyme (ACE-2), a receptor on the host cells and S2 binds to the cell surface membrane. Different immune responses to the virus are apparent, from asymptomatic to severe respiratory distress, organ failure and ultimately death. Immune responses without hyper-inflammation are essential to successful viral resolution. Pathological and environmental factors drive the immunological repertoire, in response to the virus, influencing innate immune cell activation, cytokine-balance and T cell differentiation. This is determined by age, comorbidity, Vitamin D status and ethnicity related factors. Homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. Mast cell activation and release of histamine is important to the cytokine driven T-cell differentiation a...

[

MededPublish, 2021

Correction of order and content of sections-character section correctly inserted, repetition remo... more Correction of order and content of sections-character section correctly inserted, repetition removed. Corrected typos and mistakes Added educational relevance of neuroscience to education. Added introduction to review Added methodology, describing establishing concepts for sections and search methods and sources.

[

Immune Dysregulation in Severe COVID-19 and the Possible Role of Mast Cell-Vitamin D Interactions. J Emerg Dis Virol 6(1): , 2021

COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two sp... more COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two spike subunits on the envelope of SARS-CoV-2, S1 and S2, where S1 binds to the Angiotensin Converting Enzyme (ACE-2), a receptor on the host cells and S2 binds to the cell surface membrane. Different immune responses to the virus are apparent, from asymptomatic to severe respiratory distress, organ failure and ultimately death. Immune responses without hyper-inflammation are essential to successful viral resolution. Pathological and environmental factors drive the immunological repertoire, in response to the virus, influencing innate immune cell activation, cytokine-balance and T cell differentiation. This is determined by age, comorbidity, Vitamin D status and ethnicity related factors. Homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. Mast cell activation and release of histamine is important to the cytokine driven T-cell differentiation as the adaptive response. This review combines the relative effects of UV-index-related Vitamin-D synthesis with immune status. Innate immune responses, T cell differentiation and renin/angiotensin system are different in patients affected by COVID-19 and their different outcomes are explored.

Understanding the differences between individuals that determine disease outcome will greatly enhance future therapy methods.

Journal of Interferon & Cytokine Research, 2005

Most people with hepatitis C virus (HCV) develop chronic infection with persistent viremia. Resol... more Most people with hepatitis C virus (HCV) develop chronic infection with persistent viremia. Resolution of infection is associated with antiviral cellular immune responses of T helper 1 (Th1) type. Interleukin-12 (IL-12) is a key cytokine in the generation of Th1 responses, and functionally relevant polymorphisms of the IL12B gene and its promoter have been described recently. We sought an association between three IL12B polymorphisms and outcome of HCV infection in 195 HCV antibody-positive patients; 123 were chronically infected with detectable HCV RNA, and 72 had spontaneously resolved infection testing repeatedly negative for HCV RNA. Genotyping was performed for a single nucleotide polymorphism (SNP) in the 3'-UTR (1188A/C) of the IL12B gene and for 4-bp insertion/deletion polymorphisms in the IL12B promoter region and in the intron 4 region of the IL12B gene. We found chronically infected patients were significantly more likely than those with resolved HCV infection to be homozygous for the 3'-UTR A allele (66% vs. 50%; chi-square = 4.12, p = 0.04 with Yates correction), which has been associated with lower IL-12 production. No other significant association was found. Our findings support the concept that an individual's genetically determined ability to produce IL-12 is another factor that can influence the outcome of HCV infection.

Journal of Contemporary Medical Education, 2016

The role of a university professor is multifaceted; as teacher, facilitator, assessor, evaluator,... more The role of a university professor is multifaceted; as teacher, facilitator, assessor, evaluator, models of learning themselves as self-directed learners, addressing several key competencies for the effective teacher. It is not only about the transmission of knowledge, facts and skills but also about understanding how a student learns and being able to adapt and differentiate the delivery to personalise the learning. Appropriate questioning to assess prior knowledge and testing or challenging the understanding of the student learning is also a skill for the professor. Being able to access and use a variety of resources is important to deepen the understanding of student learning, including current IT skills. The relationship between learner and mentor is essential, developing trust and confidence. The development of appropriate medical and basic science language is an important element to the learning process. The professor's collaboration and collegiate practices in a learning community enrich the learning experience, where best practice can be shared and communicated. It is important to be able to measure the impact of the teaching through assessment (formative and summative) and evaluation, which drives continued improvement in the learning experience. The innovative use of resources and environment that supports student and patient-centred learning and effectively engages with the students must be contextually and clinically relevant to the student's experience.

Journal of Medical Virology, 2014

International Journal of Endocrinology and Metabolic Disorders

Aims: A retrospective, observational, case control, pilot study investigating the relationship be... more Aims: A retrospective, observational, case control, pilot study investigating the relationship between insulin resistance (IR), renal function and maternal serum chromium (Cr) level in pregnancy. Methods: 115 pregnant women in their first 12 weeks to 40 weeks were initially recruited for the study, involving an oral glucose tolerance test (oGTT) from the Day Assessment unit at Derriford Hospital using the 75 g standard glucose load recommended by WHO. 101 patients were at least 28 weeks gestation, 10 were diagnosed with gestational diabetes mellitus (GDM), 8 of these were included in the study. 34 of these patients at over 28 weeks gestation were further tested for urine and serum Cr and creatinine (GDM, n=8; non-GDM, n=26) and insulin (n=70), IR was calculated. The diagnosed GDM group (n=8) was compared to the normoglycaemic group (n=26) and control group of non-pregnant, normoglycaemic controls (n=8). No statistical significance observed between the groups with respect to age or BMI. Results: Correlation was found between IR and serum Cr/BMI in the whole patient group (p=0.009; R=0.435, n=34) and within the non-GDM patients (R=0.416; p=0.01, n=26 two tailed) but not within the GDM patients (n=8) alone. There was significant correlation in the GDM group only for increased urine creatinine associated with urine Cr levels (p=0.049, R=0.709, n=8) at the 0.05 two-tailed level. Conclusion: Increased IR during pregnancy was related to an increase in serum Cr /BMI levels in non-GDM pregnant women. Deficiency of Cr status may be a pathogenic factor in the development of GDM. We propose a mechanism.

Several cell surface molecules have hepatitis C virus (HCV) binding properties and may serve as r... more Several cell surface molecules have hepatitis C virus (HCV) binding properties and may serve as receptors facilitating viral entry into cells. The large extracellular loop (LEL) of CD81 has been shown to bind the HCV envelope protein E2 with several critical residues for the CD81HCV-E2 interaction. It was hypothesised that variation in the CD81 LEL sequence may modify susceptibility to HCV infection. HCV RNA negative patients with spontaneous viral clearance (RNA ve); HCV RNA positive cases, who are affected chronically (RNA þve); and patients at high risk of HCV infection, exposed but uninfected patients (EU) were studied. Genomic DNA was extracted from whole blood samples and four exons of the CD81 LEL gene were amplified by PCR and sequenced. The cDNA derived from CD81 ( 700bp) was sequenced following RNA extraction from peripheral blood mononuclear cells. Patients, who are RNA positive, RNA negative, and exposed uninfected were sequenced for four DNA sections (A, B, C, and D). S...

UNLABELLED The effective treatment of diabetes and the prevention of diabetic complications may b... more UNLABELLED The effective treatment of diabetes and the prevention of diabetic complications may be improved by a better understanding of the antioxidant function of intracellular defences against oxidative stress. Polymorphisms in antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in diabetes and/or in its complications. SOD-2 was investigated in patients with type 1 diabetes mellitus (T1DM) to ascertain if specific genotypes have any protective influences in the pathogenic mechanisms in diabetes and/or in several different complications, including retinopathy, nephropathy and diabetic controls compared to normal healthy controls. METHOD 278 (136M:142F) T1DM patients and 135 (72M:63F) normal, healthy controls were investigated for SOD-2 polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution. RESULTS A significant difference in the C-9-T genotype was observed between patients and normal controls but not between...

The delivery of effective, high-quality patient care is a highly complex activity, demanding heal... more The delivery of effective, high-quality patient care is a highly complex activity, demanding health and social care professionals to collaborate in an effective manner. Interprofessional learning (IPL) is professionally relevant, intellectually stimulating and evidence based. New learning paradigms for healthcare professionals explore new ways to combine expertise, delivering IPL programmes where patient safety and quality of care can be improved (WHO 2010). Intervening early in the health professional’s career with collaborative activities with IPL is now considered important in healthcare training. Development of multidisciplinary student centred ideas hopefully results in the enhancement of patient-centred care. Conscious competence in understanding the benefits of IPL is needed to recognise those that are naïve to IPL and competent professionals who are able to design new curricular and deliver training to address unconscious incompetence to IPL. There are many diverse theories ...

Cellular immunity with interferon gamma production could have a role in protection from hepatitis... more Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposeduninfected individuals and 105 healthy controls. Overall, the C allele was found in 27•6% of exposed-uninfected cases compared with 16•7% of healthy controls [c 2 = 6•3, P = 0•02, odds ratio (OR) = 1•9, 95% confidence interval (CI) = 1•1-3•2]. CC genotype was found in 10•5% of exposed-uninfected cases compared with 0•9% controls (c 2 = 9•3, P = 0•01, OR = 12, 95% CI = 1•5-100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed-uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection.