[Application of V-Y advancement flap with facial artery perforator for the repair of midface skin defects].

Objective: To investigate the efficacy of V-Y advancement flap with facial artery perforator for the repair of midface skin defects. Methods: A retrospective analysis was performed on 18 patients with facial skin cancer, including 11 males and 7 females, aged 65-83 years, who underwent the repair of midface skin defects using V-Y advancement flap with facial artery perforator in the Department of Head and Neck Surgery, Affiliated Cancer Hospital of Nantong University from January 2020 to April 2023. Medium, large or complex midface skin defects developed after surgical resections of the primary lesions. According to the defect site, size, location information of facial vessels, a V-Y advancement flap with appropriate shape was designed for each case. During the operation, the facial vessels and their perforators were retained in the pedicle of the flap, the facial nerve branches were dissected and protected, and the further denuded pedicle was determined according to actual amount of advancement. After the flap was advanced, the facial defect area was repaired without tension, and the anatomical positions and functions of the eyes, nose and mouth were restored as far as possible. Postoperative follow-ups were conducted to observe the survival rate of the flaps, postoperative complications, recurrences and metastases of tumors. Results: Midface defects of 3.0 cm×3.5 cm-6.5 cm×7.5 cm were observed after tumor resections, which involved one or more subregions. The sizes of the flaps were 3.5 cm×9.0 cm-7.0 cm×18.0 cm. All flaps were completely alive except for one with temporary local bruising. With following-up of 4-40 months, 5 of the 12 patients with lower eyelid and inner canthus invasions had lower eyelid ectropion, but no exposed keratitis was found; one case with poorly differentiated squamous cell carcinoma had lymph node metastasis in the submandibular region and underwent neck dissection again; no recurrence or metastasis occurred in the remaining cases. Conclusion: The V-Y advancement flap with facial artery perforator can be used to repair medium, large or complex midface skin defects, with a high survival rate, and the operation method is safe and reliable.

Contact sensitization to fragrance allergen: a 5-year review in the Department of Dermatology, Hospital Kuala Lumpur.

INTRODUCTION: Fragrance allergy remains an important cause of contact dermatitis. We aim to describe the characteristics of patients with contact sensitisation to fragrances who underwent patch testing in the Department of Dermatology Hospital Kuala Lumpur. MATERIALS AND METHODS: This is a 5-year retrospective study of patients who developed positive reactions to fragrance allergens at the Department of Dermatology, Hospital Kuala Lumpur, Malaysia between January 2017 and December 2021. Patch tests were performed with European Baseline Series and relevant extended series. Patch test readings were recorded according to the International Contact Dermatitis Research Group recommendation. RESULTS: A total of 854 patients underwent patch test during the study period with 133 (15.6%) patients developing at least one positive reaction to fragrance allergens. The median age of patients at presentation was 40 years (range 16-79) old with 78.2% females. The most common initial presentation was hand eczema (55.6%). Other commonly involved sites include face (38.3%), leg (35.3%) and trunk (22.6%). The most frequent sensitising fragrance allergens were Fragrance Mix I (10.5%), Balsam of Peru (7.1%) and Fragrance Mix II (4.9%). Sixty patients (45%) developed positive reaction to more than one fragrance allergens. Twelve patients (9%) developed positive patch test reactions to their own products such as skincare, hair dye and hand wash. Current relevance was recorded in 96 patients (72.2 %). CONCLUSION: Contact sensitisation to fragrance allergens was detected in about 15% of our patients who underwent patch test. The most common sensitising allergens were Fragrance Mix I and II and Balsam of Peru.

Fungus isolated from dermatomycoses: a 9-month prospective study at Hospital Melaka.

INTRODUCTION: Dermatomycoses are common superficial cutaneous fungal infections which affect the skin, nails and human hairs. It affects 20 to 25% of the world population. The causative fungus varies geographically across the globe. Study on dermatomycoses is crucial to identify the aetiological fungus involved locally. The study aimed to determine the causative fungus of superficial fungal infections of the skin, nail and hair in patients presented to Hospital Melaka. METHODS: This was a prospective study conducted from 15th January 2022 till 15th October 2022 at Dermatology Clinic, Hospital Melaka. Subjects with clinical dermatomycoses were included in this study. The samples were collected from skin, nails and hairs clinically affected by tinea corporis/cruris/pedis, onychomycosis and tinea capitis respectively. A potassium hydroxide (KOH) study was performed on the sample in which the fungal hyphae/yeast positive subjects were sent for fungal culture and fungal PCR test. RESULT: A total of 222 clinical samples from skin, nails and hairs with a clinical suspicion of dermatomycoses yielded fungal hyphae/yeast in KOH. Majority of the samples were collected from skin (138, 62.2%), followed by nails (65, 29.3%) and hairs (19, 8.6%). Male to female ratio was 1.18: 1. The age ranged from 2 to 87 with the median of 55.5-yearsold. Out of 222 samples, 150 (67.6%) were fungal culture positive. From fungal culture positive samples, 87 samples were from tinea corporis, 50 samples were from onychomycoses and 13 samples were from tinea capitis. Trichophyton rubrum (39, 44.8%) was the commonest dermatophyte isolated in tinea corporis/cruris/pedis. Nondermatophyte moulds (NDM, 35, 70%) were the main fungi isolated in onychomycosis. Microsporum canis (7/53.8%) was the principal causative fungus among patients with tinea capitis. Among 150 fungal culture positive samples, 76 were fungal PCR positive. Only 38 samples consistently isolated same fungal species in both fungal culture and PCR test. CONCLUSION: Majority of tinea corporis and tinea capitis fungal culture isolated dermatophytes, especially Trichophyton rubrum and Microsporum canis, respectively. Non-dermatophyte moulds were mainly isolated in onychomycosis.

Systematic evaluation of the safety and therapeutic effects of para-aortic lymphadenectomy for advanced gastric cancer: a systematic review and meta-analysis.

OBJECTIVE: At present, there is still no definite conclusion on whether advanced gastric cancer (GC) requires additional para-aortic nodes dissection (PAND). The purpose of this study is to summarize current evidence on the potential benefits of the extended systemic lymphadenectomy (D2+) compared to D2 lymphadenectomy in the treatment of gastric cancer. MATERIALS AND METHODS: Systematic literature search was performed across PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Database for Chinese Technical Periodicals, and China Biology Medicine disc using the following terms: gastric cancer, para-aortic lymphadenectomy, D2+ lymphadenectomy and D3 lymphadenectomy. RevMan 5.3 software was used for the meta-analysis. RESULTS: A total of 20 studies involving 5,643 patients were included, consisting of 6 randomized controlled trials (RCT) and 14 non-randomized controlled trials (nRCT). Compared with the D2 group, the operating time in the D2+ group was longer [mean difference (MD)=99.45 min, 95% confidence interval (CI) (48.93, 149.97), p<0.001], with more intra-operative blood loss [MD=262.14 mL, 95% CI (165.21, 359.07), p<0.001]. There were no significant differences in five-year overall survival (OS) [HR=1.09, 95% CI (0.95, 1.25), p=0.22] and post-operative mortality [RR=0.96, 95% CI (0.59, 1.57), p=0.88] between the two groups. The rate of post-operative complications in group D2+ was higher than that in group D2 [RR=1.42, 95% CI (1.11, 1.81), p<0.001]. CONCLUSIONS: Prophylactic D2+ surgery is not recommended, since D2+ surgery is associated with an increased rate of post-operative complications and does not improve the long-term survival rate of patients with advanced gastric cancer. However, D2+ surgery (especially D2+PAND) has certain survival advantages for specific patients, and D2+PAND surgery combined with chemotherapy may potentially improve long-term survival rate.

Liver disease among patients with psoriasis: the Malaysian Psoriasis Registry.

BACKGROUND: Therapeutic options may be limited for patients with psoriasis who have concomitant liver disease (PsL). OBJECTIVES: We aimed to report the frequency of liver disease among patients with psoriasis, and describe the clinical features, treatment modalities and quality of life. METHODS: This was a multicentre cross-sectional study of patients with psoriasis notified to the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018. RESULTS: Of 21 735 patients with psoriasis, 174 (0.8%) had liver disease. The three most common liver diseases were viral hepatitis (62.1%), fatty liver (14.4%) and liver cirrhosis (10.9%). The male-to-female ratio was 3.8 : 1. Mean age (SD) of onset of psoriasis was higher in those with liver disease vs. those without [37.25 years (13.47) vs. 33.26 years (16.96), P < 0.001]. Patients with PsL, compared with those without liver disease, had a higher rate of dyslipidaemia (27.5% vs. 16.4%, P < 0.001), hypertension (33.9% vs. 23.7%, P = 0.002), diabetes mellitus (22.4% vs. 15.9%, P = 0.021) and HIV infection (5.3% vs. 0.4%, P < 0.001). Those with PsL were also more likely than those without liver disease to have severe disease [body surface area > 10% and/or Dermatology Life Quality Index (DLQI) > 10] (59.3% vs. 49.9%, P = 0.027), psoriatic arthropathy (21.1% vs. 13.0%, P = 0.002) and nail involvement (78.2% vs. 56.1%, P < 0.001). Also significantly higher in the group with PsL were the use of phototherapy (8.4% vs. 2.6%, P < 0.001), acitretin (7.3% vs. 2.8%, P < 0.001) and ciclosporin (3.0% vs. 0.7%, P < 0.001). Mean DLQI was similar in both groups [9.69 (7.20) vs. 9.62 (6.75), P = 0.88]. CONCLUSIONS: The frequency of patients with PsL in the MPR was 0.8%. Patients with PsL were more likely to be male, had a higher rate of comorbidities, severe disease, and nail and joint involvement than those without liver disease.

[hsa_circ_0000231 affects the progression of tongue squamous cell carcinoma by activating Wnt/ß-catenin signaling pathway].

Objective: To explore the action mechanism of hsa_circ_0000231 in the occurrence and development of tongue squamous cell carcinoma (TSCC). Methods: Tissue samples of 60 TSCC patients were examined. The patients, including 32 males and 28 females, aged from 36 to 84 years old, underwent surgery in the Affiliated Hospital of Nantong University and Affiliated Tumor Hospital of Nantong University from December 2014 to December 2017. Saliva samples were obtained from healthy volunteers (5 males and 5 females, aged from 40 to 75 years old) and 10 TSCC patients. The TSCC cell lines (CAL-27, Tca-8113 and HN-4) were used. The expression levels of hsa_circ_0000231 in 60 pairs of freshly matched TSCC and para-carcinoma tissue samples, 10 pairs of saliva samples and 3 TSCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). hsa_circ_0000231 gene interference and lentiviral transfection were constructed, hsa_circ_0000231 in TSCC cell lines CAL-27 and Tca-8113 was knocked down, and the expressions of hsa_circ_0000231 in hsa_circ_0000231 interference group (sh-circ) and no-load lentivirus group (negative control) were tested with qRT-PCR. Cells with the highest knock-down efficiency were selected for CCK-8 test, colony formation assay, transwell invasion assay and scratch assay. The expressions of EMT-related proteins including E-cadherin, snail protein, N-cadherin and vimentin and proteins related to Wnt/ß-catenin signaling pathway including ß-catenin, C-myc, Bcl-2, MMP-9 and Cyclin D1 were measured by western blot. After TSCC cells in the interference group were co-cultured with Wnt/ß-catenin pathway activator LiCl, the expressions of above proteins were re-measured by western blot. TSCC cells in interference group and control group were subcutaneously injected into nude mice to compare the effect of hsa_circ_0000231 knockdown on the growths of the tumors grafted subcutaneously in the nude mice. Statistical analysis software 25.0 was used for data analysis, and t-test or chi-square test was used for comparison between groups. Results: hsa_circ_0000231 was highly expressed in the tissue and saliva samples of TSCC patients and cell lines CAL-27, Tca-8113 and HN-4, but lowly expressed in paired para-carcinoma tissues, saliva samples of healthy people and normal human oral keratinocytes (all P<0.05). Log-rank univariate analysis showed that hsa_circ_0000231 expression level, tumor differentiation degree and T stage were related to the survival of TSCC patients (all P<0.05). Multivariate Cox risk regression model analysis suggested that hsa_circ_0000231 expression level (χ2=5.77,P=0.016) and T stage (χ2=5.27,P=0.029) were independent factors for the poor prognosis of TSCC patients. Western blot showed the expressions of snail protein, N-cadherin and vimentin were down-regulated, but E-cadherin was up-regulated in interference group compared with control group. In interference group, the expressions of ß-catenin, C-myc, Bcl-2, MMP-9 and CyclinD1 were down-regulated, which were reversed after TSCC cells were co-cultured with LiCl. The knockdown of hsa_circ_0000231 reduced the proliferation, invasion and metastasis abilities of CAL-27 and Tca-8113 cells, which were reversed after TSCC cells were co-cultured with LiCl. The growth rate and volume of the tumors grafted subcutaneously in interference group using LiCl were greater than those in negative control group. Conclusion: hsa_circ_0000231 is an independent prognostic factor of TSCC. Highly expressed hsa_circ_0000231 can promote the proliferation, invasion and metastasis of TSCC cells.

Human Immunodeficiency Virus-infected men who have sex with men with syphilis: A 5-year multicentre study in Malaysia.

OBJECTIVES: High rates of syphilis have been reported worldwide among men who have sex with men (MSM). This study aims to describe the clinical pattern and treatment response of syphilis among human immunodeficiency virus (HIV)-infected MSM in Malaysia. METHODS: This is a retrospective study on all HIV-infected MSM with syphilis between 2011 and 2015. Data was collected from case notes in five centres namely Hospital Kuala Lumpur, Hospital Sultanah Bahiyah, Hospital Umum Sarawak, University of Malaya Medical Centre and Hospital Sungai Buloh. RESULTS: A total of 294 HIV seropositive MSM with the median age of 29 years (range 16-66) were confirmed to have syphilis. Nearly half (47.6%) were in the age group of 20-29 years. About a quarter (24.1%) was previously infected with syphilis. Eighty-three patients (28.2%) had other concomitant sexually transmitted infection with genital warts being the most frequently reported (17%). The number of patients with early and late syphilis in our cohort were almost equal. The median pre-treatment non-treponemal antibody titre (VDRL or RPR) for early syphilis (1:64) was significantly higher than for late syphilis (1:8) (p<0.0001). The median CD4 count and the number of patients with CD4 <200/µl in early syphilis were comparable to late syphilis. Nearly four-fifth (78.9%) received benzathine-penicillin only, 5.8% doxycycline, 1.4% Cpenicillin, 1% procaine penicillin, and 12.4% a combination of the above medications. About 44% received treatment and were lost to follow-up. Among those who completed 1 -year follow-up after treatment, 72.3% responded to treatment (serological non-reactive - 18.2%, four-fold drop in titre - 10.9%; serofast - 43.6%), 8.5% failed treatment and 17% had re-infection. Excluding those who were re-infected, lost to follow-up and died, the rates of treatment failure were 12.1% and 8.8% for early and late syphilis respectively (p=0.582). CONCLUSION: The most common stage of syphilis among MSM with HIV was latent syphilis. Overall, about 8.5% failed treatment at 1-year follow-up.

Minimal agreement between basophil activation test and immunoassay in diagnosis of penicillin allergy.

INTRODUCTION: Basophil activation test (BAT) and immunoassays are the most widely used in vitro tests to diagnose IgE-mediated allergic reactions to penicillin. However, studies to determine if one test is interdependent from another are limited. OBJECTIVE: The present study aimed to measure the agreement between BAT and immunoassay in diagnosis of penicillin allergy. METHOD: BAT was performed using penicillin G (Pen G), penicillin V (Pen V), penicilloyl-polylysine (PPL), minor determinant mix (MDM), amoxicillin (Amx) and ampicillin (Amp) in 25 patients. Immunoassay of total IgE (tIgE) and specific IgE (sIgE) antibodies to Pen G, Pen V, Amx and Amp were quantified. Skin prick test (SPT) using PPL-MDM, Amx, Amp and Clavulanic acid were also performed. RESULTS: Minimal agreement was observed between BAT and immunoassay (k=0.25). Of two BAT-positive patients, one patient is positive to Amx (59.27%, SI=59) and Amp (82.32%, SI=82) but sIgE-negative to all drug tested. This patient is also SPT-positive to both drugs. Another patient is BAT-positive to Pen G (10.18%, SI=40), Pen V (25.07%, SI=100) and Amp (19.52%, SI=79). In sIgE immunoassay, four patients were sIgE-positive to at least one of the drugs tested. The sIgE level of three patients was between low and moderate and they were BAT-negative. One BAT-positive patient had a high level of sIgE antibodies (3.50-17.5kU/L) along with relatively high specific to total IgE ratio ≥0.002 (0.004-0.007). CONCLUSIONS: The agreement between BAT and immunoassay is minimal. Performing both tests provides little increase in the sensitivity of allergy diagnosis work-up for immediate reactions to penicillin.

Effect of atorvastatin on pulmonary hypertension rats through regulating notch signaling pathway.

OBJECTIVE: To study the effect of atorvastatin on pulmonary hypertension (PAH) rats through regulating the Notch signaling pathway. MATERIALS AND METHODS: The rat model of PAH was established via hypoxic feeding and the Control group (n=10), PAH model group (Model group, n=10) and atorvastatin treatment group (ATO group, n=10) were set up. The right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in each group were determined, the wet/dry weight (W/D) ratio of lung tissues was determined, and the tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) and interleukin-6 (IL-6) were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the pathological changes in lung tissues of rats were detected via hematoxylin-eosin (HE) staining and the apoptosis level was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Finally, the Notch signaling pathway and apoptosis level in tissues were detected via quantitative Polymerase Chain Reaction (qPCR), and the protein expression level of Notch pathway in lung tissues was determined through Western blotting. RESULTS: Both RVSP and RVHI in Model group were significantly higher than those in Control group and ATO group (p<0.05). In Model group, the levels of inflammatory factors MPO, IL-6, and TNF-α were significantly increased, and the W/D ratio was also significantly increased compared with those in Control group (p<0.05). The results of HE staining showed that the lung tissue injury in Model group was severe (p<0.05). According to the TUNEL staining results, the number of apoptotic cells in lung tissues was markedly larger in Model group than that in ATO group (p<0.05), and the expression levels of Caspase-3 and IL-6 in Model group were remarkably higher than those in ATO group (p<0.05), while the expression level of B-cell lymphoma-2 (Bcl-2) in Model group was remarkably lower than that in ATO group (p<0.05). Besides, the gene and protein expression levels of Notch1 in ATO group were evidently lower than those in Model group (p<0.05), indicating that atorvastatin can effectively suppress the expression of Notch. CONCLUSIONS: Atorvastatin can inhibit PAH in rats by suppressing the Notch pathway.

Gene polymorphism of adiponectin in restenosis after coronary stenting.

OBJECTIVE: The objective of the present study was to investigate the relationship between adiponectin (APN)+45T/G and +276G/T polymorphisms and in-stent restenosis (ISR). PATIENTS AND METHODS: A total of 150 patients treated with percutaneous coronary intervention (PCI) were divided into the ISR group and non-ISR group. The levels of blood biochemical indicators were measured, and APN+45T/G and +276G/T polymorphisms were detected by TaqMan probes. RESULTS: Cholesterol levels in the IRS group were significantly higher than those in the non-ISR group (p<0.05). The frequency of the GG genotype and G allele of the APN+45T/G locus in the ISR group were significantly higher than those in the non-ISR group (p<0.05). The frequency of the GG genotype and G allele of the APN+276G/T locus in the ISR group were significantly higher than those in the non-ISR group (p<0.05). CONCLUSIONS: APN+45T/G and +276G/T polymorphisms were associated with susceptibility to ISR, and carrying the G allele of the APN+45T/G and +276G/T loci can significantly increase the risk of ISR.

The utilization of phototherapy in the department of dermatology, Hospital Kuala Lumpur: A 5-year audit.

INTRODUCTION: Ultraviolet phototherapies are important treatment modalities for a wide range of dermatological conditions. We aim to describe the utilization of phototherapy in the Department of Dermatology Hospital Kuala Lumpur. METHODS: This is a 5-year retrospective audit on patients who underwent phototherapy between 2011 and 2015. RESULTS: There were 892 patients, M:F=1.08:1, aged from 4- 88 years, with a median age of 38.8 years who underwent phototherapy. Majority (58.9%) had skin phototype IV, followed by type III (37.7%) and type II (0.7%). There were 697(78.1%) who underwent NBUVB, 136 (15.2%) had topical PUVA, 22(2.5%) had oral PUVA, 12(1.4%) had UVA1 and 23(2.6%) had NBUVB with topical or oral PUVA/UVA1 at different time periods. The indications were psoriasis (46.6%), vitiligo (26.7%), atopic eczema (9.8%), pityriasis lichenoides chronica (5.3%), mycosis fungoides (3.9%), lichen planus (2.5%), nodular prurigo (2.2%), scleroderma (1.2%), alopecia areata (0.7%) and others. The median number of session received were 27 (range 1-252) for NBUVB, 30 (range 1-330) for topical PUVA, 30 (range 3-190) for oral PUVA and 24.5 (range 2-161) for UVA1. The acute adverse effects experienced by patients were erythema (18%), pruritus (16.3%), warmth (3.3%), blister formation (3.1%), cutaneous pain (2.4%), and xerosis (0.8%), skin swelling (0.7%) and phototoxicity (0.2%). CONCLUSION: Narrow-band UVB was the most frequently prescribed phototherapy modality in our center. The most common indication for phototherapy in our setting was psoriasis. Acute adverse events occurred in a third of patients, although these side effects were mild.

Cutaneous adverse drug reactions: A four-year audit from a district hospital in Johor, Malaysia.

Cutaneous adverse drug reactions (cADR) are common. However, only very few audits reported the clinical characteristics of cADR captured at district hospitals. We performed a 4-year audit on cADR reported to the Department of Pharmacy in Hospital Pakar Sultanah Fatimah between May 2012 and March 2016. It showed that the main adverse drug reaction (ADR) reporters were pharmacists (84.9%) where the majority of the reactions were clinical descriptions without dermatological diagnosis. Antibiotics (46.4%) were the commonest culprit drug followed by NSAIDs (22%). The most common reactions were immediate reactions, i.e. urticaria and angioedema contributing 55.7% of the cases; followed by maculopapular eruptions (41.8%). There were only six cases (1%) of severe cADR reported in this cohort. Reporting bias and the incomplete dermatological diagnosis were the main limitation of the reports.

Mycology of Onychomycosis: A 5-year retrospective review (2011 - 2015) in Hospital Kuala Lumpur.

Onychomycosis is a common nail disease with numerous etiological pathogens. In order to determine and trend the local mycological pattern of culture-positive diseased nail samples sent from the Department of Dermatology, Hospital Kuala Lumpur, a five-year retrospective audit was carried out, which revealed that non-dermatophyte molds were the predominant fungi isolated, followed by yeasts and dermatophytes. This is similar to two previous studies in Malaysia, but varies greatly from other studies around the world which showed a dermatophyte-predominant prevalence. This could be due to the nature of the environment our patients encountered.

Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress-related metabolic pathways.

Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs (such as clozapine, risperidone and aripiprazole) on stress, we compared neurochemical profile variations in the PFC and hippocampus between rat models of chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS)-based metabolomic approach and a multicriteria assessment. We identified a number of stress-induced biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid, allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines (PEs), corticosterone and progesterone. Specifically, pathway enrichment and correlation analyses suggested that stress induces oxidative damage by disturbing the creatine-phosphocreatine circuit and purine pathway, leading to excessive membrane breakdown. Moreover, our data suggested that the AAPDs tested partially restore stress-induced deficits by increasing the levels of creatine, progesterone and PEs. Thus, the present findings provide a theoretical basis for the hypothesis that a combined therapy using adenosine triphosphate fuel, antioxidants and omega-3 fatty acids as supplements may have synergistic effects on the therapeutic outcome following AAPD treatment.

Contact sensitisation in adults: a 5-year retrospective review in hospital Kuala Lumpur.

BACKGROUND: The pattern of contact sensitisation should be monitored in order to detect the changing trend of sensitising allergens. We aim to evaluate contact sensitisation in adults suspected to have allergic contact dermatitis. METHODS: This is a five-year retrospective review on contact sensitisation in adults patch-tested with the European Standard and extended series between 2011 and 2015 in the Department of Dermatology, Hospital Kuala Lumpur. RESULTS: There were 689 adults (M:F= 1:2.04; mean age 40.5 years) who were patch-tested. The majority (175, 25.4%) were white collar workers and 118 (17.1%) were healthcare workers. The provisional diagnoses of patients included contact dermatitis (80.8%); endogenous eczema (7.9%); hand eczema (3.2%); hand and foot eczema (3.5%); foot eczema (1.4%) and photodermatitis (1.2%). The allergens selected for testing were based on past and present history of exposure. Almost all (688, 99.8%) were patch-tested with the European standard allergens and 466 (67.6%) were tested with the extended series. About three quarter (528, 76.6%) developed at least one positive reaction. The top five most frequent reactions were to nickel sulphate (35.3%); potassium dichromate (16.5%); methylchloroisothiazolinone (12.9%), fragrance mix I (12.6%), and cobalt chloride (10.2%). The commonest sensitisations identified in the extended series were palladium chloride (23/105, 21.9%), stannous chloride (18/85, 21.2%), miconazole (7/44, 15.9%), gold(I)sodium thiosulfate (16/105, 15.2%) and thimerosal (29/202, 14.4%). CONCLUSION: Contact sensitisation was detected in 76.6% of adults patch-tested. Nickel sulphate was found to be the most frequently sensitising allergen. The rising prevalence of methylchloroisothiazolinone/methylisothiazolinone sensitization poses significant concern.

A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.

Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.

Langerhans Cell Histiocytosis in an Adult - a rare, life-threatening and not to be missed.

Langerhans Cell Histiocytosis (LCH) is an uncommon neoplastic disorder characterized by accumulation of histiocytes in various tissues. The clinical manifestation is highly variable, ranging from an isolated skin rash or a single bony lesion, to fatal multi-organ failure. Due to its rarity and systemic involvement, the epidemiology of LCH is still not fully understood and most studies focus on the paediatric population. The extent of clinical involvement has important prognostic implications. Treatment options may be local or systemic depending on disease extent. Here we describe a rare case of adult onset LCH who presented with recurrent pneumothoraces, diabetes insipidus and papules and plaques over the scalp and forehead.

Innate immune cells express IL-17A/F in acute generalized exanthematous pustulosis and generalized pustular psoriasis.

Acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) are rare pustular skin disorders with systemic involvement. IL-17A/F is a proinflammatory cytokine involved in various neutrophilic inflammatory disorders. Here we show that IL-17A/F is highly expressed by innate immune cells such as neutrophils and mast cells in both AGEP and GPP.