Optimizing Melasma Management With Topical Tranexamic Acid: An Expert Consensus.

Because of its complex pathogenesis, chronicity, and high rates of recurrence, melasma is regarded as a challenging skin disorder. Topical treatments are often offered as first-line therapy. However, many patients are unaware that melasma is recurrent and requires long-term management. Hydroquinone is effective for controlling relapses and has become the standard of care for melasma in many countries. Nonetheless, it is limited by its side effect profile. Certain patient profiles who have had prior therapy and/or are refractory to treatment may be offered an alternative, that is topical tranexamic acid (TXA) alone or in combination with other modalities. This review provides a summary of current evidence on topical TXA as a treatment for certain case profiles. This paper aims to fill knowledge gaps in terms of currently available options, highlighting the role of topical TXA alone or in combination with other active ingredients (ie, topical TXA 2% with patented delivery technology). J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7104 Citation: Desai SR, Chan LC, Handog E, et al. Optimizing melasma management with topical tranexamic acid: An expert consensus. J Drugs Dermatol. 2023;22(4):386-392. doi:10.36849/JDD.7104.

An Intelligent Water Monitoring IoT System for Ecological Environment and Smart Cities.

Global precipitation is becoming increasingly intense due to the extreme climate. Therefore, creating new technology to manage water resources is crucial. To create a sustainable urban and ecological environment, a water level and water quality control system implementing artificial intelligence is presented in this research. The proposed smart monitoring system consists of four sensors (two different liquid level sensors, a turbidity and pH sensor, and a water oxygen sensor), a control module (an MCU, a motor, a pump, and a drain), and a power and communication system (a solar panel, a battery, and a wireless communication module). The system focuses on low-cost Internet of Things (IoT) devices along with low power consumption and high precision. This proposal collects rainfall from the preceding 10 years in the application region as well as the region's meteorological bureau's weekly weather report and uses artificial intelligence to compute the appropriate water level. More importantly, the adoption of dynamic adjustment systems can reserve and modify water resources in the application region more efficiently. Compared to existing technologies, the measurement approach utilized in this study not only achieves cost savings exceeding 60% but also enhances water level measurement accuracy by over 15% through the successful implementation of water level calibration decisions utilizing multiple distinct sensors. Of greater significance, the dynamic adjustment systems proposed in this research offer the potential for conserving water resources by more than 15% in an effective manner. As a result, the adoption of this technology may efficiently reserve and distribute water resources for smart cities as well as reduce substantial losses caused by anomalous water resources, such as floods, droughts, and ecological concerns.

HLA-B*58: 01 association in allopurinol-induced severe cutaneous adverse reactions: the implication of ethnicity and clinical phenotypes in multiethnic Malaysia.

OBJECTIVE: The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined. METHODS: We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC). RESULTS: HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive. CONCLUSION: Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.

Clinical characteristics, management, and quality of life of psoriasis patients with coexistent lupus erythematosus: Data from the Malaysian Psoriasis Registry.

OBJECTIVE: To describe the clinical characteristics, management and quality of life of psoriasis patients with and without coexistent lupus erythematosus (LE). METHODS: This retrospective cross-sectional study uses data from the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018. RESULTS: Of 21 735 psoriasis patients, 34 (0.16%) had coexistent LE. The male to female ratio among psoriasis patients with coexistent LE was 1:5.8 versus 1.3:1 in patients with psoriasis but without LE. Nearly 70% presented with LE preceding psoriasis. Psoriasis patients with LE had an earlier age of psoriasis onset (27.56 ± 11.51 versus 33.31 ± 16.94 years, P = 0.006), a higher rate of psoriatic arthropathy (26.5% versus 13.0%, P = 0.02), and a significantly greater impairment of quality of life (Dermatology Quality of Life Index >10; 57.6% versus 40.3%, P = 0.04) compared with psoriasis patients without LE. The majority (87.5%) had systemic LE. The incidences of lupus nephritis (72.7% versus 40%) and hematological abnormalities (50% versus 20%) were higher among patients with LE preceding psoriasis compared with those with psoriasis preceding LE. Antinuclear antibody and double-stranded DNA were positive in 59.4% and 28.1% of psoriasis patients with LE, respectively. Hydroxychloroquine triggered the onset of psoriasis in 7 (24.1%) patients. Patients with LE were more likely to receive systemic treatment for psoriasis compared with those without LE (30.3% versus 14.2%, P = 0.008). CONCLUSIONS: Psoriasis patients with coexistent LE were uncommon, displayed a female preponderance, were more likely to have joint involvement, and had greater quality of life impairment than those without LE. LE preceded psoriasis in most of these patients, and systemic LE was the most common subtype.

Dermatology Life Quality Index in Patients with Psoriasis Treated with Biologic Versus Non-biologic Treatment in Malaysia: A Retrospective Cross-Sectional Study.

BACKGROUND: Psoriasis imposes a substantial burden on patients' social, emotional, physical, and family life. Although psoriasis has no complete cure, various treatments are available to control its symptoms and improve a patients' quality of life. OBJECTIVE: We aimed to compare the effectiveness of biologic versus non-biologic treatments on health-related quality of life among patients with psoriasis in Malaysia. METHODS: This retrospective cross-sectional study evaluated data of adult patients diagnosed with psoriasis during 2007-18 from the Malaysian Psoriasis Registry. Baseline demographics, disease, and treatment characteristics were described. For a subset of patients treated with biologics and non-biologics who had baseline and 6-month follow-up data available, changes in the mean Dermatology Life Quality Index scores and the proportion of patients with a clinically relevant improvement (≥ 4 points) post-treatment were assessed. RESULTS: Overall, 15,238 adult patients with psoriasis from the Malaysian Psoriasis Registry were included in the analysis. Patients receiving biologics showed a statistically significant reduction in the mean Dermatology Life Quality Index scores after 6 months compared with those receiving non-biologic treatment (- 5.7 vs - 0.8%; p < 0.001). The proportion of patients who achieved a ≥ 4-point improvement in Dermatology Life Quality Index scores was approximately two times greater in the biologic-treated group versus the non-biologic-treated group (56.4 vs 27.7%). CONCLUSIONS: Biologic treatment showed a greater reduction in the Dermatology Life Quality Index scores of patients with psoriasis versus non-biologic treatment. These results highlight the importance of early treatment with more efficacious treatment options, such as biologic therapies, to improve the overall health-related quality of life of patients with psoriasis.

Mutual adaptation between mouse transglutaminase 4 and its native substrates in the formation of copulatory plug.

Formation of copulatory plugs by male animals is a common means of reducing competition with rival males. In mice, copulatory plugs are formed by the coagulation of seminal vesicle secretion (SVS), which is a very viscous and self-clotting fluid containing high concentration of proteins. In its native state, mouse SVS contains a variety of disulfide-linked high-molecular-weight complexes (HMWCs) composed of mouse SVS I-III, which are the major components of mouse SVS. Further, mouse SVS I-III are the substrates for transglutaminase 4 (TGM4), a cross-linking enzyme secreted from the anterior prostate. According to activity assays, mouse TGM4 prefers a mild reducing and alkaline environment. However, under these conditions, the activity of mouse TGM4 toward SVS I-III was much lower than that of a common tissue-type TGM, TGM2. On the other hand, mouse TGM4 exhibited much higher cross-linking activity than TGM2 when native HMWCs containing SVS I-III were used as substrates under non-reducing condition. By the action of TGM4, the clot of SVS became more resistant to proteolysis. This indicates that the activity of TGM4 can further rigidify the copulatory plug and extend its presence in the female reproductive tract. Together with the properties of TGM4 and the nature of its disulfide-linked SVS protein substrates, male mice can easily transform the semen into a rigid and durable copulatory plug, which is an important advantage in sperm competition.

Disseminated sporotrichosis in a patient with a past history of lepromatous leprosy: a case report.

Disseminated sporotrichosis is uncommon and usually occurs in patients who are immunodeficient. Here we describe a male patient who was otherwise in good physical condition, who presented with disseminated sporotrichosis. The only significant event in his past medical history was lepromatous leprosy which had been treated 42 years earlier.

Scalp psoriasis and Dermatology Life Quality Index: A retrospective study based on 12-year data from the Malaysian Psoriasis Registry.

Introduction: Psoriasis affects approximately 2-3% of the population worldwide, although the overall prevalence in Asia is <0.5%. Scalp psoriasis is a common initial presentation of psoriasis, which affects almost 80% of patients with psoriasis. Method: This retrospective descriptive study investigated 1,671 patients with psoriasis with scalp involvement registered with the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018. Results: A total of 21,859 patients with psoriasis were registered with the MPR during the study period; among them, scalp involvement was seen in 7.6% (n= 1,671). Female sex preponderance (61%) was observed in the majority of Malay patients (58.5%), followed by the Chinese (16.9%), Indian (17.1%) and other ethnic patients (7.5%). A positive family history of psoriasis was identified in 22.7% (n=380). Approximately 34.8% (n=581) and 11% (n=172) of the patients had nail changes and psoriatic arthropathy, respectively. The mainstay treatment modality was topical treatment (93.6%), followed by systemic therapy (10%) and phototherapy (0.5%). The comorbidities found among the patients with scalp psoriasis included hypertension (27.9%), obesity (26%), dyslipidaemia (21%), diabetes mellitus (18.4%), ischaemic heart disease (5.4%) and cerebrovascular disease (1.3%). Approximately 23% reported a Dermatology Life Quality Index (DLQI) of >10, which indicated moderate-to-severe impairment. Conclusion: The proportion of patients with psoriasis with scalp involvement in our study (7.6%) is much lower than previous reports. Scalp psoriasis markedly negatively impacts the DLQI.

A proline rich acidic protein PRAP identified from uterine luminal fluid of estrous mice is able to enhance the estrogen responsiveness of Ishikawa cells.

Using mice as experimental animals, proteins in the uterine luminal fluid (ULF) from both adults and diethylstilbestrol dipropionate (DES)-treated immature animals were resolved by 2D gel electrophoresis. Two of the protein spots, (a) and (b) around the positions of 18-20 kDa, in the adult ULF were not found in the DES-treated ULF. Automated Edman degradation established the same N-terminal sequences of AHQVPVKTKGKHVFP for the two protein spots. Two trypsin digests of spot (a) were analyzed using CID MS/MS to establish the peptide sequences DNQLGPLLPEPK and RPDAMTWVETEDILSHLR. These partial sequences were confirmed in the cDNA-deduced mouse proline rich acidic protein (PRAP). Using human Ishikawa cell line as a surrogate endometrial model, we demonstrated rapid entrance of exogenous PRAP into the cells and its ability to enhance alkaline phosphatase activity of the E(2) -stimulated cells. Further, the transcripts of five estrogen-responsive genes, including ALPP (Placental alkaline phosphtase), ALPPL (placental alkaline phosphatase-like 2), TGF (transforming growth factor), PR (progesterone receptor), and Wnt7a, were measured after the cell incubation in modified Eagle medium containing 0.1 nM E(2) , or 0-25 µM PRAP, or both together at 37°C for 48 h. As compared with the control, E(2) alone increased the transcripts of ALPP, ALPPL, TGF-α, and PR, and reduced the transcript of Wnt7a, whereas PRAP alone had a slight impact on their expression. E(2) together with PRAP greatly increased the E(2) -stimulated transcriptions of ALPP, ALPPL, TGF-α, and PR, and markedly reduced the E(2) -suppressed transcription of Wnt7a.

The findings of 18F-fluorodeoxyglucose positron emission tomography-computed tomography scan in patients with hidradenitis suppurativa in Malaysia: A multicenter study.

Hidradenitis suppurativa (HS) is known to have association with systemic diseases with chronic inflammation such as psoriasis. We aim to describe the concomitant systemic inflammation in patients with HS using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scan. This was a case-control study conducted in three tertiary hospitals in Northern Malaysia from January to December 2017, involving HS patients aged 18 years and above. Thirty-two HS patients with age- and sex-matched controls were recruited with a mean age of 31.4 years (range: 18-56). Numerous cutaneous inflammatory foci were detected on FDG-PET/CT scan in clinically unapparent sites (27/32, 84.4%). Approximately 90.6%, 93.8%, and 50.0% of the patients had significantly higher cutaneous uptake over nasal, mandibular, and scalp regions, respectively (P < 0.0001). PET/CT scan did not detect any systemic inflammation unlike those found in psoriasis. Three (9.4%) patients had thyroid nodules with high uptake (maximum standard uptake values ranging from 2.9 to 11.3). Two of them were confirmed to have papillary thyroid carcinoma, while the third patient has inconclusive finding. 18F-FDG PET/CT scan may be useful to map disease burden of HS. Nonlesional inflammatory foci on the skin of the nose, mandibular, and scalp are probably significant. The association of thyroid carcinoma in HS warrants further evaluation.

Identification of the major TG4 cross-linking sites in the androgen-dependent SVS I exclusively expressed in mouse seminal vesicle.

SVS I was exclusively expressed in seminal vesicle in which the protein was immunolocalized primarily to the luminal epithelium of mucosal folds. The developmental profile of its mRNA expression was shown to be androgen-dependent, manifesting a positive correlation with the animal's maturation. There are 43 glutamine and 43 lysine residues in one molecule of SVS I, which is one of the seven major monomer proteins tentatively assigned on reducing SDS-PAGE during the resolution of mouse seminal vesicle secretion. Based on the fact that SVS I-deduced protein sequence consists of 796 amino acid residues, we produced 7 recombinant polypeptide fragments including residues 1-78/F1, residues 79-259/F2, residues 260-405/F3, residues 406-500/F4, residues 501-650/F5, residues 651-715/F6, and residues 716-796/F7, and measured the covalent incorporation of 5-(biotinamido)pentylamine (BPNH(2)) or biotin-TVQQEL (A25 peptide) to each of F1-to-F7 by type 4 transglutaminase (TG(4)) from the coagulating gland secretion. F2 was active to a greater extent than the other fragments during the BPNH(2)-glutamine incorporation, and a relatively low extent of A25-lysine cross link was observed with all of the seven fragments. The MS analysis of BPNH(2)-F2 conjugate identified Q(232) and Q(254) as the two major TG(4) cross-linking sites. This was substantiated by the result that much less BPNH(2) was cross-linked to any one of the three F2 mutants, including Q232G and Q254G obtained from single-site mutation, and Q232G/Q254G from double-site mutation.

The clinical, biochemical, and ultrasonographic characteristics of patients with hidradenitis suppurativa in Northern Peninsular Malaysia: a multicenter study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disorder of follicular occlusion, resulting in abscesses with tunnel formation and severe scarring. Our objectives were to identify the clinical patterns and the prevalence of metabolic syndrome (MetS) among our HS patients and to determine the role of ultrasonography in the clinical assessment of HS. METHODS: This was a cross-sectional study carried out from September 2016 to August 2017 at three tertiary hospitals in Northern Peninsular Malaysia. RESULTS: A total of 62 patients were recruited, 83.9% of whom were male. The mean age was 29.2 with the median age of onset at 18 years old. The median duration of delay in diagnosis was 3 years. A quarter of them had positive family history. Nearly three-quarters were overweight and obese. About 12/62 (19.4%) had MetS, and it was comparable to healthy controls (15/62, 24.2%). HS patients had a significant higher risk of low-high-density lipoprotein (HDL) and obesity. Based on Hurley staging, 15/62 (24.2%) were in stage I, 38/62 (61.3%) and 9/62 (14.5%) in stages II and III, respectively. However, sonographic scoring showed 50% had severe stage of disease, and 56.9% of the patients had subclinical lesions. There was only a fair agreement between ultrasonography and Hurley staging of disease severity (k = 0.25; P = 0.004). CONCLUSION: There was a male preponderance among HS patients in Northern Peninsular Malaysia with early age of onset and more severe disease. Only one-fifth had MetS, but they had significantly higher risks of obesity and low HDL. Ultrasonography examination was useful to detect subclinical lesions and providing a better understanding on disease severity.

Cutaneous sporotrichosis: a six-year review of 19 cases in a tertiary referral center in Malaysia.

BACKGROUND: Sporotrichosis is a subcutaneous fungal infection caused by a thermally dimorphic aerobic fungus, Sporothrix schenckii. It results from traumatic inoculation or contact with animals. Most cases were reported mainly in the tropics and subtropics. OBJECTIVE: The objective of our study is to assess the clinical characteristic of cutaneous sporotrichosis among our patients. METHODOLOGY: We performed a retrospective review of all cases diagnosed with cutaneous sporotrichosis from July 2004 to June 2010. Patients' medical records were retrieved and analyzed according to demography, preceding trauma, sites of lesions, clinical subtypes, treatment, and clinical response. RESULTS: Nineteen cases were diagnosed with cutaneous sporotrichosis with a male/female ratio of 9:10. Thirteen cases (68.4%) were able to recall preceding trauma, and seven of them reported cat scratches or cat bites. Lymphocutaneous sporotrichosis was observed in 13 cases (68.4%) followed by four cases of fixed cutaneous sporotrichosis and two cases of disseminated sporotrichosis. Histologically, 11 cases (57.8%) demonstrated a granulomatous reaction. Sporothrix schenckii was cultured in 12 cases (63.2%). Thirteen cases (68.4%) were successfully treated with oral itraconazole alone for a mean duration of 15.6 weeks. Two cases with disseminated cutaneous sporotrichosis were treated with intravenous amphotericin B. CONCLUSION: Lymphocutaneous sporotrichosis was the most common subtype of cutaneous sporotrichosis in our series, with cat scratches or bites being the most common preceding trauma. Oral itraconazole was highly effective for the localized subtypes, whereas intravenous amphotericin B was required in disseminated cutaneous sporotrichosis.

Disseminated fusariosis in a patient with acute lymphoblastic leukaemia: A case report and literature review

Fusarium spp are molds found in the soil and may be saprophytic or fa c u l t a t ive plant p a t h ogens. These are rare but important opportunistic pathogens in immunocompromised patients especially those with hematologic malignancies. Fusarium spp usually cause local infections such as onychomycosis and infections of surgical and burn wound. However more importantly, these pathogens can lead to severe disseminated infection with invo l vement of multiple organs including skin. This disseminated form of fusariosis occurs exclusively in patients with prolonged, severe neutropaenia especially in patients with acute leukaemia or those u n d e rgoing bone marrow transplantation. Prognosis of disseminated fusariosis is usually guarded if not recognized early. We report a rare case of disseminated fusariosis in a patient with acute lymphoblastic leukaemia.

Identification of a tyrosine-phosphorylated CCCTC-binding nuclear factor in capacitated mouse spermatozoa.

The molecular basis of mammalian sperm capacitation, either in vivo in the female reproductive tract, or in vitro, is poorly understood. It is well known that sperm capacitation is associated with an increase in tyrosine phosphorylation of a subset of proteins. We resolved the phosphoproteins in the cell lysate of mouse sperm after capacitation by 2-DE. One tyrosine-phosphorylated 130-kDa spot was trypsin-digested, and six oligopeptide sequences were established from the MS data. These were confirmed in a CCCTC-binding nuclear factor (CTCF), a widely expressed and highly conserved protein. Further, both an anti-phosphotyrosine antibody and an anti-CTCF antibody showed immunoreactivity to a 130-kDa component in the immunoprecipitates obtained after incubation of the cell lysate from the capacitated sperm using another anti-CTCF antibody. The data support the presence of a tyrosine-phosphorylated CTCF in the capacitated sperm. Immunolocalization of the CTCF revealed fluorescent staining in the acrosome region in both capacitated and incapacitated sperm. The electrophoretic mobility shift assay, using a CTCF target sequence 5'-GGCGGCGCCGCTAGGGGTCTCTCT-3' found in the promoter of the amyloid beta-protein precursor, manifested that, relative to CTCF in the incapacitated sperm, the tyrosine-phosphorylated protein in the capacitated sperm had stronger affinity to the CTCF target sequence.

Antibiotic sensitivity of Propionibacterium acnes isolated from patients with acne vulgaris in Kuala Lumpur Hospital,Malaysia

Background Antibiotic therapy directed against Propionibacterium acnes has been a mainstay of treatment in acne vulgaris for more than 40 years. Prolonged antibiotic usage has been associated with emergence of antibiotic-resistant P. acnes and is linked to treatment failure. Little work has been done in Malaysia on drug resistance in P. acnes and there is no surveillance data on this aspect to guide the clinical decision. Objective This study aims to evaluate antibiotic sensitivity of P. acnes isolated from patients with acne vulgaris in Kuala Lumpur Hospital, Malaysia. Methods This is a non interventional, single centered, cross-sectional hospital-based survey of antibiotic sensitivity of P. acnes isolated from patients with acne vulgaris in Kuala Lumpur Hospital from January 2010 to June 2010. Results A total of 100 patients were recruited in our study. P. acnes was isolated in 53% of patients and 11% had gram negative organism. Antibiotic resistant P. acnes was found in 15.1% of positive isolates. Clindamycin resistance was most common (15.1%) followed by erythromycin (7.5%), doxycycline (5.7%), tetracycline (1.9%) and minocycline (0%). Isolates of antibiotic resistant P. acnes was significantly higher in patients treated with antibiotics within the last 6 months (29%) as compared with non antibiotic treated patients (0%) (p<0.05). The mean duration of prior antibiotic treatment was significantly longer in the group of antibiotic resistant P. acnes as compared with antibiotic sensitive P. acnes (17.13 weeks vs 5.74 weeks, p<0.05). Conclusion Antibiotic resistant P. acnes is present locally with clindamycin and erythromycin conferring the highest resistance. Longer duration of antibiotic treatment predisposes to antibiotic resistant P. acnes and may also induce emergence of gram negative organisms. Strategies to reduce antibiotic resistance should be emphasized when prescribing antibiotic for acne vulgaris in order to achieve optimal therapeutic results while reducing the potential for antibiotic resistance.