Siao Tan - Academia.edu (original) (raw)

Papers by Siao Tan

Photodermatology, 2021

Over the last decade, melanoma incidence rates increased by almost two-fifths in the UK and a fur... more Over the last decade, melanoma incidence rates increased by almost two-fifths in the UK and a further rise of 7% between 2014 and 2035 has been predicted [1]. Regular sunscreen use may prevent the development of melanoma [2]. The public require consistent and coherent advice from healthcare professionals. We distributed a Survey Monkey questionnaire to healthcare professionals across the United Kingdom, in 2018, to find out if they provide appropriate advice on sunscreen usage to their patients, as per the British Association of Dermatologists and WHO guidelines [3,4].

Atopic dermatitis, AD (synonym eczema) is a chronic inflammatory skin disease. It affects between... more Atopic dermatitis, AD (synonym eczema) is a chronic inflammatory skin disease. It affects between 10 to 20% of children and 1 to 3% of adults worldwide. It is an important cause of morbidity and is estimated to cost £465 million per annum to the UK. AD is part of a family of Th-2 driven diseases and is often the first of these atopic diseases to manifest. The development of AD is often followed by asthma and allergic rhinitis later in life (a phenomenon known as the 'atopic march'). Up to 50% of moderate to severe AD cases have been associated with genetic mutations affecting the epidermal barrier protein filaggrin. Filaggrin aggregates keratin filaments during terminal keratinocyte differentiation, allowing normal epidermal stratification. The role of filaggrin in maintaining a functional skin barrier is further supported by a clinical study conducted by ourselves. This is the first clinical study on a European cohort (58 participants) which showed that FLG mutations were associated with experimentally demonstrable defects of skin barrier function (increased baseline transepidermal water loss), more so following exposure to a chemical irritant. However, the majority of patients with AD, especially the milder cases, do not have FLG mutations. Some of the wild-type patients in our study were noticed to have accumulation of the large filaggrin proprotein and a lack of filaggrin monomers, indicating defective proteolysis of profilaggrin into the functional monomers. Our study also found disproportionately raised protease inhibitory activities amongst the AD participants. This inappropriately raised protease inhibition may interfere with profilaggrin proteolysis, leading to the development of AD in some wild-type patients. Having demonstrated that deficiency of filaggrin monomers is associated with a defective skin barrier, we focused on the function of filaggrin in the skin and attempted to improve the skin barrier function. In addition to keratin aggregation, filaggrin constitutes the natural moisturizing factors in the epidermis following its natural breakdown into amino acids. We note that filaggrin is disproportionately rich in amino acid histidine, implying that this amino acid may have a particular significance in maintaining a functional epidermal barrier. Using an in-house skin-equivalent model, we have shown that by increasing the histidine content in the cell culture media, we could increase the expression of filaggrin monomers and reduce the penetration of a fluorescent dye into the skinequivalents. The latter indicates improved barrier function. Finally, we conducted a pilot human study which showed that histidine, when applied to mechanically damaged skin in AD and healthy participants, was associated with a faster recovery of the skin barrier function. These studies suggest that histidine is of therapeutic benefits in AD. A histidine-based treatment may be developed as an alternative to current anti-inflammatory and immunosuppressive agents used to treat AD. III Author's Declaration This is to certify that that the work contained within has been composed by me and is entirely my own work. No part of this thesis has been submitted for any other degree or professional qualification.

Four years ago my grandmother had a stroke. When my grandfather found out he took it very badly a... more Four years ago my grandmother had a stroke. When my grandfather found out he took it very badly and had a major stroke himself. The doctors had to perform emergency surgery, but he could not give his consent because of his illness. It saved his life but left him severely disabled: unable to speak, bedridden, and paralysed for eight months before he died. Was the surgery a mistake? Knowing that the surgery carried such risk, would he have wanted it? When I was a fourth year medical student I got the opportunity to study a topic I am passionate about: the factors that affect someone's desire for active medical intervention. I intended to describe to the research participants a stroke scenario very similar to my grandfather's and ask them would they have wanted the surgery if they were a member of the victim's family or if they themselves had had the stroke. I would then relate the participants' characteristics, such as age, social support, perception of health status, ...

Clinical, cosmetic and investigational dermatology, 2017

Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions w... more Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF). In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24). In vitro studie...

Journal of Medical Case Reports, 2007

Background: A carcinoma within a hernia in the groin is uncommon, with an incidence of less than ... more Background: A carcinoma within a hernia in the groin is uncommon, with an incidence of less than 0.5 percent of all excised sacs. This article describes a case of synchronous colonic carcinomas, one of which presented as an inguinoscrotal mass. Case presentation: A 69-year old man presented with a large, irreducible left inguinoscrotal hernia and symptoms of obstruction. On examination, there was an 8 cm palpable mass within the hernia sac. CT scan revealed small and proximal large bowel obstruction secondary to a large ingunoscrotal sac and synchronous colonic tumours of the transverse colon and the ascending colon. The former presented as an inguinoscrotal mass. Laparotomy revealed a large tumour mass arising from the transverse colon in the hernia sac. The procedure was followed by an extended right hemicolectomy, during which the second tumour in the ascending colon was also resected. Conclusion: This case demonstrates a rare but interesting occurrence of primary transverse colon carcinoma presenting in a hernia sac, in conjunction with a synchronous tumour of the ascending colon. Prognosis is comparable to patients with a solitary tumour of similar pathological staging when the resection is curative. The presence of an inguinal hernia itself does not signify an increased risk of colorectal malignancy. However, in the presence of obstruction, incarceration, and weight loss, malignancy should be suspected. Thorough clinical examination, flexible sigmoidoscopy or radiographic evaluation is necessary preoperatively in such patients. Surgical resection, with or without adjuvant oncological treatment, should be performed as soon as possible, using established techniques with modifications according to involvement of local structures.

Journal of Medical Case Reports, 2007

A carcinoma within a hernia in the groin is uncommon, with an incidence of less than 0.5 percent ... more A carcinoma within a hernia in the groin is uncommon, with an incidence of less than 0.5 percent of all excised sacs. This article describes a case of synchronous colonic carcinomas, one of which presented as an inguinoscrotal mass. A 69-year old man presented with a large, irreducible left inguinoscrotal hernia and symptoms of obstruction. On examination, there was an 8 cm palpable mass within the hernia sac. CT scan revealed small and proximal large bowel obstruction secondary to a large ingunoscrotal sac and synchronous colonic tumours of the transverse colon and the ascending colon. The former presented as an inguinoscrotal mass. Laparotomy revealed a large tumour mass arising from the transverse colon in the hernia sac. The procedure was followed by an extended right hemicolectomy, during which the second tumour in the ascending colon was also resected. This case demonstrates a rare but interesting occurrence of primary transverse colon carcinoma presenting in a hernia sac, in conjunction with a synchronous tumour of the ascending colon. Prognosis is comparable to patients with a solitary tumour of similar pathological staging when the resection is curative. The presence of an inguinal hernia itself does not signify an increased risk of colorectal malignancy. However, in the presence of obstruction, incarceration, and weight loss, malignancy should be suspected. Thorough clinical examination, flexible sigmoidoscopy or radiographic evaluation is necessary preoperatively in such patients. Surgical resection, with or without adjuvant oncological treatment, should be performed as soon as possible, using established techniques with modifications according to involvement of local structures.

Photodermatology, 2021

Over the last decade, melanoma incidence rates increased by almost two-fifths in the UK and a fur... more Over the last decade, melanoma incidence rates increased by almost two-fifths in the UK and a further rise of 7% between 2014 and 2035 has been predicted [1]. Regular sunscreen use may prevent the development of melanoma [2]. The public require consistent and coherent advice from healthcare professionals. We distributed a Survey Monkey questionnaire to healthcare professionals across the United Kingdom, in 2018, to find out if they provide appropriate advice on sunscreen usage to their patients, as per the British Association of Dermatologists and WHO guidelines [3,4].

Atopic dermatitis, AD (synonym eczema) is a chronic inflammatory skin disease. It affects between... more Atopic dermatitis, AD (synonym eczema) is a chronic inflammatory skin disease. It affects between 10 to 20% of children and 1 to 3% of adults worldwide. It is an important cause of morbidity and is estimated to cost £465 million per annum to the UK. AD is part of a family of Th-2 driven diseases and is often the first of these atopic diseases to manifest. The development of AD is often followed by asthma and allergic rhinitis later in life (a phenomenon known as the 'atopic march'). Up to 50% of moderate to severe AD cases have been associated with genetic mutations affecting the epidermal barrier protein filaggrin. Filaggrin aggregates keratin filaments during terminal keratinocyte differentiation, allowing normal epidermal stratification. The role of filaggrin in maintaining a functional skin barrier is further supported by a clinical study conducted by ourselves. This is the first clinical study on a European cohort (58 participants) which showed that FLG mutations were associated with experimentally demonstrable defects of skin barrier function (increased baseline transepidermal water loss), more so following exposure to a chemical irritant. However, the majority of patients with AD, especially the milder cases, do not have FLG mutations. Some of the wild-type patients in our study were noticed to have accumulation of the large filaggrin proprotein and a lack of filaggrin monomers, indicating defective proteolysis of profilaggrin into the functional monomers. Our study also found disproportionately raised protease inhibitory activities amongst the AD participants. This inappropriately raised protease inhibition may interfere with profilaggrin proteolysis, leading to the development of AD in some wild-type patients. Having demonstrated that deficiency of filaggrin monomers is associated with a defective skin barrier, we focused on the function of filaggrin in the skin and attempted to improve the skin barrier function. In addition to keratin aggregation, filaggrin constitutes the natural moisturizing factors in the epidermis following its natural breakdown into amino acids. We note that filaggrin is disproportionately rich in amino acid histidine, implying that this amino acid may have a particular significance in maintaining a functional epidermal barrier. Using an in-house skin-equivalent model, we have shown that by increasing the histidine content in the cell culture media, we could increase the expression of filaggrin monomers and reduce the penetration of a fluorescent dye into the skinequivalents. The latter indicates improved barrier function. Finally, we conducted a pilot human study which showed that histidine, when applied to mechanically damaged skin in AD and healthy participants, was associated with a faster recovery of the skin barrier function. These studies suggest that histidine is of therapeutic benefits in AD. A histidine-based treatment may be developed as an alternative to current anti-inflammatory and immunosuppressive agents used to treat AD. III Author's Declaration This is to certify that that the work contained within has been composed by me and is entirely my own work. No part of this thesis has been submitted for any other degree or professional qualification.

Four years ago my grandmother had a stroke. When my grandfather found out he took it very badly a... more Four years ago my grandmother had a stroke. When my grandfather found out he took it very badly and had a major stroke himself. The doctors had to perform emergency surgery, but he could not give his consent because of his illness. It saved his life but left him severely disabled: unable to speak, bedridden, and paralysed for eight months before he died. Was the surgery a mistake? Knowing that the surgery carried such risk, would he have wanted it? When I was a fourth year medical student I got the opportunity to study a topic I am passionate about: the factors that affect someone's desire for active medical intervention. I intended to describe to the research participants a stroke scenario very similar to my grandfather's and ask them would they have wanted the surgery if they were a member of the victim's family or if they themselves had had the stroke. I would then relate the participants' characteristics, such as age, social support, perception of health status, ...

Clinical, cosmetic and investigational dermatology, 2017

Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions w... more Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF). In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24). In vitro studie...

Journal of Medical Case Reports, 2007

Background: A carcinoma within a hernia in the groin is uncommon, with an incidence of less than ... more Background: A carcinoma within a hernia in the groin is uncommon, with an incidence of less than 0.5 percent of all excised sacs. This article describes a case of synchronous colonic carcinomas, one of which presented as an inguinoscrotal mass. Case presentation: A 69-year old man presented with a large, irreducible left inguinoscrotal hernia and symptoms of obstruction. On examination, there was an 8 cm palpable mass within the hernia sac. CT scan revealed small and proximal large bowel obstruction secondary to a large ingunoscrotal sac and synchronous colonic tumours of the transverse colon and the ascending colon. The former presented as an inguinoscrotal mass. Laparotomy revealed a large tumour mass arising from the transverse colon in the hernia sac. The procedure was followed by an extended right hemicolectomy, during which the second tumour in the ascending colon was also resected. Conclusion: This case demonstrates a rare but interesting occurrence of primary transverse colon carcinoma presenting in a hernia sac, in conjunction with a synchronous tumour of the ascending colon. Prognosis is comparable to patients with a solitary tumour of similar pathological staging when the resection is curative. The presence of an inguinal hernia itself does not signify an increased risk of colorectal malignancy. However, in the presence of obstruction, incarceration, and weight loss, malignancy should be suspected. Thorough clinical examination, flexible sigmoidoscopy or radiographic evaluation is necessary preoperatively in such patients. Surgical resection, with or without adjuvant oncological treatment, should be performed as soon as possible, using established techniques with modifications according to involvement of local structures.

Journal of Medical Case Reports, 2007

A carcinoma within a hernia in the groin is uncommon, with an incidence of less than 0.5 percent ... more A carcinoma within a hernia in the groin is uncommon, with an incidence of less than 0.5 percent of all excised sacs. This article describes a case of synchronous colonic carcinomas, one of which presented as an inguinoscrotal mass. A 69-year old man presented with a large, irreducible left inguinoscrotal hernia and symptoms of obstruction. On examination, there was an 8 cm palpable mass within the hernia sac. CT scan revealed small and proximal large bowel obstruction secondary to a large ingunoscrotal sac and synchronous colonic tumours of the transverse colon and the ascending colon. The former presented as an inguinoscrotal mass. Laparotomy revealed a large tumour mass arising from the transverse colon in the hernia sac. The procedure was followed by an extended right hemicolectomy, during which the second tumour in the ascending colon was also resected. This case demonstrates a rare but interesting occurrence of primary transverse colon carcinoma presenting in a hernia sac, in conjunction with a synchronous tumour of the ascending colon. Prognosis is comparable to patients with a solitary tumour of similar pathological staging when the resection is curative. The presence of an inguinal hernia itself does not signify an increased risk of colorectal malignancy. However, in the presence of obstruction, incarceration, and weight loss, malignancy should be suspected. Thorough clinical examination, flexible sigmoidoscopy or radiographic evaluation is necessary preoperatively in such patients. Surgical resection, with or without adjuvant oncological treatment, should be performed as soon as possible, using established techniques with modifications according to involvement of local structures.