Recurrent umbilical varix rupture with hemoperitoneum: a case report and review of literature.

BACKGROUND: Non-traumatic hemoperitoneum was a rare event with the risk of sudden death. Spontaneous rupture of hepatocellular carcinoma is the most intuitive diagnosis when hemoperitoneum occurs in cirrhotic patients who are not regularly followed up. However, other etiologies of hemoperitoneum, such as intra-abdominal varix rupture, should be kept in mind. CASE PRESENTATION: A 44-year-old man with alcoholic liver cirrhosis, Child-Pugh B was sent to our emergency department (ED) because of recurrent abdominal pain and hypovolemic shock. He had similar symptoms one month ago and was diagnosed as hepatocellular carcinoma (HCC) rupture with hemoperitoneum, therefore he underwent trans-arterial embolization (TAE). However, the follow-up magnetic resonance imaging (MRI) showed less possibility of hepatocellular carcinoma. Contrast enhanced abdominal computed tomography (CT) showed possible umbilical vein contrast agent extravasation. Exploratory laparotomy confirmed the diagnosis of rupture umbilical varix with hemoperitoneum. CONCLUSION: Although umbilical varix rupture is a rare cause of hemoperitoneum, it should be kept in mind in cirrhotic patients with unexplained hemoperitoneum.

Who writes dermatology randomized controlled trials? The need to specify the role of medical writers.

Medical writers may make major contributions to the preparation of a manuscript, but are not listed as authors. We assessed the prevalence, affiliation and role of medical writers in dermatology randomized controlled trials (RCTs) published in 2019 in the top 7 medical and top 10 dermatology journals. Medical writers were identified in 39/83 trials (47%), all of which were exclusively industry-funded trials (39/47, prevalence 83%). Most studies stated their role as 'medical writing support' and/or 'editorial assistance' (35/39, 90%), but when more information was provided, four studies specified first draft preparation (50% of RCTs in general medical and 1.3% of RCTs in dermatology journals). Medical writers are common in dermatology trials but their role is often vaguely stated. In April 2020 the British Journal or Dermatology and Clinical and Experimental Dermatology adopted CRediT (Contributor Roles Taxonomy), which describes contributions of authors and may help clarify who writes trial manuscripts.

The status and outcomes of registered clinical trials for Janus kinase inhibitors in alopecia areata: are unpublished trials being overlooked?

Recent meta-analyses of Janus kinase (JAK) inhibitors in alopecia areata (AA) have excluded trial registries and may thus be subject to publication bias. This study assessed the potential for evidence selection bias and provides an overview of JAK inhibitor trials in AA. A broad search strategy of ClinicalTrials.gov was performed for AA. We also recorded whether results were published on PubMed. There were 26 trials identified, of which 9 were ongoing (mostly oral JAK inhibitors: 8 studies; 89%). Of completed/terminated trials, 4/17 (24%) had terminated prematurely, citing 'inefficacy/futility' or 'sponsor decision'. These were all topical JAK inhibitor trials (4/8, 50% termination rate), with a 0% termination rate (0/9) for oral JAK inhibitor trials. We conclude that topical JAK inhibitors may be less efficacious than has been apparent in the literature to date, with 50% of trials having terminated due to inefficacy/futility or sponsor decision and only one topical JAK inhibitor trial ongoing.

Simultaneous flow cytometric immunophenotyping of necroptosis, apoptosis and RIP1-dependent apoptosis.

Flow cytometry was been widely used to measure apoptosis for many decades but the researcher has no definitive way of determining other forms of cell death using this technology. The use of Western Blot technology has numerous drawbacks in that all the cells in the sample whether live, dead or maybe undergoing multiple discrete forms of cell death are analysed as one population. Flow cytometry given that it can analyse different sub-populations of cells within a sample would reveal the expression of cell death markers within these sub-populations rather than just give a single result from the entire population. Here we describe a flow cytometric assay fully realising that potential by the use of anti-RIP-3 (Receptor-interacting serine/threonine-protein kinase 3) and anti-active caspase-3 fluorescently tagged antibodies and a fixable live dead fluorescent dye. This allows the determination of the degree of necroptosis, apoptosis and RIP1-dependent apoptosis within live and dead populations. Necroptosis was identified by the up-regulation of RIP3, while RIP1-dependent apoptosis was described by double positive for RIP3/active Caspase-3 events in live and dead populations. Apoptotic cells were defined by an active-Caspase-3+ve/RIP3-ve phenotype. Pan-caspase blocker zVAD and RIP1 inhibitors GSK'481 or necrostatin-1 revealed interesting modulations of such sub-populations of Jurkat cells. This novel flow cytometric assay employing two antibodies and a fixable viability probe provides the researcher with in-depth analysis of various forms of regulated forms of cell death beyond what is currently available and is a major methodological advancement in this field.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.

Management of traumatic patellar dislocation in a regional hospital in Hong Kong.

INTRODUCTION: The role of surgery for acute patellar dislocation without osteochondral fracture is controversial. The aim of this study was to report the short-term results of management of patellar dislocation in our institute. METHODS: Patients who were seen in our institution with patella dislocation from January 2011 to April 2014 were managed according to a standardised management algorithm. Pretreatment and 1-year post-treatment International Knee Documentation Committee score, Tegner activity level scale score, and presence of apprehension sign were analysed. RESULTS: A total of 41 patients were studied of whom 20 were first-time dislocators and 21 were recurrent dislocators. Among the first-time dislocators, there was a significant difference between patients who received conservative treatment versus surgical management. The conservative treatment group had a 33% recurrent dislocation rate, whereas there were no recurrent dislocations in the surgery group. There was no difference in Tegner activity level scale score or apprehension sign before and 1 year after treatment, however. Among the recurrent dislocators, there was a significant difference between those who received conservative treatment and those who underwent surgery. The recurrent dislocation rate was 71% in the conservative treatment group versus 0% in the surgery group. There was also significant improvement in International Knee Documentation Committee score from 67.7 to 80.0 (P=0.02), and of apprehension sign from 62% to 0% (P<0.01). CONCLUSIONS: A management algorithm for patellar dislocation is described. Surgery is preferable to conservative treatment in patients who have recurrent patellar dislocation, and may also be preferable for those who have an acute dislocation.

Detection of Wolbachia from field collected Aedes albopictus Skuse in Malaysia.

BACKGROUND & OBJECTIVES: Wolbachia-based vector control strategies have been proposed as a mean to augment the existing measures for controlling dengue vector. Prior to utilizing Wolbachia in novel vector control strategies, it is crucial to understand the Wolbachia-mosquito interactions. Many studies have only focused on the prevalence of Wolbachia in female Aedes albopictus with lack of attention on Wolbachia infection on the male Ae. albopictus which also affects the effective expression of Wolbachia induced- cytoplasmic incompatibility (CI). In this study, field surveys were conducted to screen for the infection status of Wolbachia in female and male Ae. albopictus from various habitats including housing areas, islands and seashore. METHODS: Adult Ae. albopictus (n=104) were collected using human landing catches and hand aspirator. Standard ovitraps were also set in the selected areas for five days and the larvae were identified to species level. All the collected Ae. albopictus were screened for the presence of Wolbachia using multiplex polymerase chain reaction (PCR) and gene sequencing of Wolbachia surface protein (wsp) gene. RESULTS: A 100 per cent positivity of Wolbachia infection was observed for individual Ae. albopictus screened. For pooled mosquitoes, 73 of the 76 pools (female) and 83 of the 87 pools (male) were positive with Wolbachia infection. The wsp gene sequence of the Wolbachia strain isolated from individual and pooled mosquitoes showed a 100 per cent homology with Wolbachia sp. of Ae. albopictus isolated from various geographical regions. Phylogenetic analysis based on wsp gene fragments showed that the isolates were clustered into groups A and B, respectively. INTERPRETATION & CONCLUSIONS: The results indicated that Wolbachia infection was widespread in Ae. albopictus population both in female and male Ae. albopictus. All the infected females were superinfected with both A and B strains while the infected males showed a combination of superinfection of A and B strains and single infection of B strain.

ABSENCE OF AEDES AEGYPTI (L.) ON AN ECOLOGICAL ISLAND: COMPETITIVE EXCLUSION?

Ovitrap surveillance was conducted in 2012 and 2006 in Malay and Aboriginal Villages on Carey Island. In each village, standard ovitraps were placed indoors and outdoors at randomly selected houses/locations. All L3 larvae recovered were identified up to species level. Results demonstrated that only larvae of Aedes albopictus were found in all the positive ovitraps placed indoors and outdoors. In 2012, a high ovitrap index (OI) of 66.7% indoor and 84.0% outdoor in the Malay Village; and 62.5% indoor and 88.0% outdoor in Aboriginal Village with an apparent absence of Aedes aegypti. In 2006, a 100% OI was recorded in all ovitraps set indoors and outdoors in both villages.

TEMPORAL CHANGES OF AEDES AND ARMIGERES POPULATIONS IN SUBURBAN AND FORESTED AREAS IN MALAYSIA.

Surveillance of mosquitoes and their distribution in association with rainfall, relative humidity, and temperature were conducted in selected suburban and forested areas, namely, Sungai Penchala (Kuala Lumpur) and Taman Alam (Selangor) for 12 months. Armigeres kesseli was the most abundant species in Sungai Penchala while Aedes butleri was the most dominant species in Taman Alam. A positive correlation between mosquito distribution and rainfall was observed in selected mosquito species in Sungai Penchala (Armigeres kesseli, r = 0.75; Armigeres subalbatus, r = 0.62; and Aedes albopictus, r = 0.65) and Taman Alam (Armigeres sp, r = 0.59; Ae. butleri, r = 0.85; and Ae. albopictus, r = 0.62). However, no significant cor- relation was found either between selected mosquito species in both study areas and relative humidity or temperature. Results obtained suggested that vector control programs to be conducted based on temporal distribution of vectors in order to achieve beneficial outcomes with effective costing.

Mitochondrial DNA analyses reveal low genetic diversity in Culex quinquefasciatus from residential areas in Malaysia.

The present study explored the intraspecific genetic diversity, dispersal patterns and phylogeographic relationships of Culex quinquefasciatus Say (Diptera: Culicidae) in Malaysia using reference data available in GenBank in order to reveal this species' phylogenetic relationships. A statistical parsimony network of 70 taxa aligned as 624 characters of the cytochrome c oxidase subunit I (COI) gene and 685 characters of the cytochrome c oxidase subunit II (COII) gene revealed three haplotypes (A1-A3) and four haplotypes (B1-B4), respectively. The concatenated sequences of both COI and COII genes with a total of 1309 characters revealed seven haplotypes (AB1-AB7). Analysis using tcs indicated that haplotype AB1 was the common ancestor and the most widespread haplotype in Malaysia. The genetic distance based on concatenated sequences of both COI and COII genes ranged from 0.00076 to 0.00229. Sequence alignment of Cx. quinquefasciatus from Malaysia and other countries revealed four haplotypes (AA1-AA4) by the COI gene and nine haplotypes (BB1-BB9) by the COII gene. Phylogenetic analyses demonstrated that Malaysian Cx. quinquefasciatus share the same genetic lineage as East African and Asian Cx. quinquefasciatus. This study has inferred the genetic lineages, dispersal patterns and hypothetical ancestral genotypes of Cx. quinquefasciatus.

Eco-virological survey of Aedes mosquito larvae in selected dengue outbreak areas in Malaysia.

UNLABELLED: BACKGROUND & OBJECTIVESI: Transovarial transmission of dengue virus in the Aedes vectors is now a well-documented phenomenon reported from many parts of the endemic areas in the world, which played an important role in initiating and maintaining the outbreak in human populations. This study investigated the factors affecting breeding habitats and the relationship with transovarial dengue virus in larvae of Aedes aegypti and Ae. albopictus. METHODS: Larval surveillance was conducted in dengue outbreak areas in Malaysia from 2008 until 2009. Sampling was carried out based on habitat type, water condition (substrate type), canopy coverage, temperature and pH at breeding habitats. RT-PCR was performed to detect presence of transovarial dengue virus in larvae collected in the study areas. RESULTS: A total of 789 breeding habitats were identified during this study and the majority of these breeding sites were plastic containers (57.46%). Aedes albopictus dominated most of the water condition surveyed, while Ae. aegypti indicated preference toward habitats with clear water. Aedes aegypti was selective in selecting ovipositional sites compared to Ae. albopictus where shaded areas were shown to be the most preferred. From a total of 363 mosquito larvae pools, 23 (6.3%) pools were positive for dengue virus where 18 of them were from Ae. albopictus and five were from Ae. aegypti mosquito larvae pools. INTERPRETATION & CONCLUSION: This study indicated the presence of transovarial transmission of dengue virus in immature Ae. aegypti and Ae. albopictus in the field. This study also showed that combination of water conditions, canopy coverage, temperature and pH of breeding habitats were the factors affecting the larval population. The study suggested that larval survey programme could serve as a tool not only to monitor the local dengue vector distribution but also to provide objective information for taking appropriate action by the community against dengue vectors.

Influence of Obstructive Sleep Apnea on the Risk of Dental Caries: Insights from a 13-Year Population-Based Retrospective Study.

KNOWLEDGE TRANSFER STATEMENT: Obstructive sleep apnea has been proven to have a great negative impact on patients, and the relationship between sleep apnea and dental caries is still inconclusive. Our study shows that patients with sleep apnea and those older than 45 y have a significant risk of dental caries.

Intra-articular injection of the selective cyclooxygenase-2 inhibitor meloxicam (Mobic) reduces experimental osteoarthritis and nociception in rats.

OBJECTIVE: To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. METHODS: OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. RESULTS: OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. CONCLUSIONS: Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.

MicroRNA-17-5p post-transcriptionally regulates p21 expression in irradiated betel quid chewing-related oral squamous cell carcinoma cells.

BACKGROUND AND PURPOSE: Betel nut chewing is associated with oral cavity cancer in Taiwan. OC3 is an oral carcinoma cell line that was established from cells collected from a long-term betel nut chewer who does not smoke. After we found that microRNA-17-5p (miR-17-5p) is induced in OC3 cells, we used this cell line to examine the biological role(s) of this microRNA in response to exposure to ionizing radiation. MATERIALS AND METHODS: A combined SYBR green-based real-time PCR and oligonucleotide ligation assay was used to examine the expression of the miR-17 polycistron in irradiated OC3 cells. The roles of miR-17-5p and p21 were evaluated with specific antisense oligonucleotides (ODN) that were designed and used to inhibit their expression. Expression of the p21 protein was evaluated by Western blotting. The clonogenic assay and annexin V staining were used to evaluate cell survival and apoptosis, respectively. Cells in which miR-17-5p was stably knocked down were used to create ectopic xenografts to evaluate in vivo the role of miR-17-5p. RESULTS: A radiation dose of 5 Gy significantly increased miR-17-5p expression in irradiated OC3 cells. Inhibition of miR-17-5p expression enhanced the radiosensitivity of the OC3 cells. We found that miR-17-5p downregulates radiation-induced p21 expression in OC3 cells and, by using a tumor xenograft model, it was found that p21 plays a critical role in increasing the radiosensitivity of OC3 cells in vitro and in vivo. CONCLUSION: miR-17-5p is induced in irradiated OC3 cells and it downregulates p21 protein expression, contributing to the radioresistance of OC3 cells.

Mating compatibility and competitiveness of transgenic and wild type Aedes aegypti (L.) under contained semi-field conditions.

We conducted the world's first experiments under semi-field conditions (ACL-2 field house) to assess the mating competitiveness of genetically sterile RIDL male mosquitoes (513A strain). The field house is a state-of-the-art, fully-contained trial facility, simulating the living space for a household of 2-4 people in Peninsular Malaysia. Ten genetically sterile RIDL male A. aegypti mosquitoes competed with ten wild type males inside this field house to mate with ten wild type females. Hatched larvae from mated females were screened under a fluorescent microscope for genetic markers to determine if they were fathered by RIDL male or wild type male, and all results were cross-checked by PCR. Two such experiments were conducted, each repeated sufficient number of times. All strains were on a Malaysian lab strain background for the first experiment, while the RIDL males alone were on a recently-colonised Mexican strain background for the second experiment. A total of 52 % of the matings were with RIDL males in the first experiment, while 45 % of the matings were with RIDL (Mexican) males in the second experiment. Statistically, this is not significantly different from 50 % of the matings expected to take place with RIDL males if the latter were as competitive as that of the wild type males. This shows that A. aegypti RIDL-513A has excellent mating competitiveness under semi-field conditions, verifying earlier trends obtained in small lab cages. We also observed high mating compatibility between recently-colonised Mexican RIDL males and lab-reared Malaysian wild type females.

Current susceptibility status of Malaysian Culex quinquefasciatus (Diptera: Culicidae) against DDT, propoxur, malathion, and permethrin.

A nationwide investigation was carried out to determine the current susceptibility status of Culex quinquefasciatus Say populations against four active ingredients representing four major insecticide classes: DDT, propoxur, malathion, and permethrin. Across 14 study sites, both larval and adult bioassays exhibited dissimilar trends in susceptibility. A correlation between propoxur and malathion resistance and between propoxur and permethrin resistance in larval bioassays was found. The results obtained from this study provide baseline information for vector control programs conducted by local authorities. The susceptibility status of this mosquito should be monitored from time to time to ensure the effectiveness of current vector control operations in Malaysia.

In vitro antibacterial activity and physicochemical properties of a crude methanol extract of the larvae of the blow fly Lucilia cuprina.

The emergence of multidrug-resistant bacterial strains has prompted the reintroduction of maggot therapy in the treatment of chronic, infected wounds. Many previous studies have demonstrated the potent antibacterial activity of larval excretions/secretions of the blowfly Lucilia sericata (Meigen) (Diptera:Calliphoridae) against bacteria. However, the antibacterial activity of its sibling species, Lucilia cuprina (Wiedemann) (Diptera:Calliphoridae) against a wide range of pathogenic bacteria has never been determined. The aim of this study was to develop a new procedure to produce whole body extract of larvae of L. cuprina via methanol extraction as well as to demonstrate the in vitro antibacterial activity of this extract against seven selected wound pathogens (Staphylococcus aureus, methicillin-resistant S. aureus, S. epidermidis, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli). The turbidimetric assay demonstrated that L. cuprina larval extract was significantly potent against all bacteria tested (P < 0.001). Additionally, colony-forming unit (CFU), agar well diffusion and minimum inhibitory concentration assays have confirmed the apparent potency of larval extract against P. aeruginosa. The reconstituted larval extract was highly robust and thermally stable. These observations substantiated the feasibility of the methanol extraction method in the production of larval extract.

First molecular genotyping of voltage gated sodium channel alleles in Culex quinquefasciatus populations in Malaysia.

A nationwide investigation was performed to detect the presence of 1014 mutation(s) in voltage gated sodium channel (kdr) gene of Culex quinquefasciatus from 14 residential areas across 13 states and a federal territory in Malaysia. Molecular genotyping of kdr mutation was performed via a modified three tubes allele-specific-polymerase chain reaction (AS-PCR) and direct sequencing of kdr gene. Based on the results of AS-PCR, homozygous susceptible (SS) genotype was found in nine out of 14 populations with 38 individuals from a total sample size of 140. Heterozygous (RS) genotype was most predominant (99 individuals) and distributed across all study sites. Homozygous resistance (RR) genotype was detected in Perak (one individual) and Selangor (two individuals). The resistance kdr allele frequencies ranged from 0.1 to 0.55, with the highest being detected in Cx. quinquefasciatus population from Selangor. This study has documented the first field-evolved instance of 1014F mutation in Malaysian mosquitoes and the findings of this study could be utilized in the implementation of strategic measures in vector control programs in Malaysia.

Perioperative antithrombotic management in joint replacement surgeries.

OBJECTIVES: To determine optimal perioperative antithrombotic management for patients with cardiac diseases undergoing joint replacement surgeries. DATA SOURCES: MEDLINE and PubMed database search up to January 2013. STUDY SELECTION: Those dealing with perioperative antithrombotic management of patients undergoing orthopaedic operations, especially joint replacement, and also those undergoing general surgery. Various combinations of the following key words were used in our search: "antiplatelet", "antithrombotic", "anticoagulant", "coronary stent", "perioperative", "venous thromboembolism", "cardiovascular", "surgery", "orthopaedic", "knee replacement", "hip replacement", "joint replacement", and "arthroplasty". DATA EXTRACTION: Literature review, original articles, and best practice guidelines. DATA SYNTHESIS: Patients should be stratified according to their risk of developing arterial thromboembolism in order to decide the most appropriate perioperative antiplatelet or anticoagulant regimen for them. After recent coronary stenting, including bare-metal stents implanted within 6 weeks and drug-eluting stents implanted within 6 months, surgery should be deferred. For venous thromboembolism prophylaxis in patients already on aspirin, the dosage should be adjusted as necessary or additional low-molecular-weight heparin administered. CONCLUSION: The perioperative management of patients with cardiac diseases in receipt of antithrombotic agents is based upon a delicate balance between the perceived risk of arterial thromboembolism and the perceived risk of perioperative bleeding. One must exercise good judgement in deciding the most appropriate perioperative antithrombotic regimen. Venous thromboembolism is also a common problem after joint replacement surgeries. For patients already on aspirin, optimal venous thromboembolism prophylaxis is still being debated.