Evaluation of the effectiveness and cost effectiveness of a Community-delivered Integrated Malaria Elimination (CIME) model in Myanmar: protocol for an open stepped-wedge cluster-randomised controlled trial.

INTRODUCTION: In the Greater Mekong Subregion, community health workers, known as malaria volunteers, have played a key role in reducing malaria in the control phase, providing essential malaria services in areas with limited formal healthcare. However, the motivation and social role of malaria volunteers, and testing rates, have declined with decreasing malaria burden and reorientation of malaria programmes from control to elimination. Provision of additional interventions for common health concerns could help sustain the effectiveness of volunteers and maintain malaria testing rates required for malaria elimination accreditation by the WHO. METHODS AND ANALYSIS: The Community-delivered Integrated Malaria Elimination (CIME) volunteer model, integrating interventions for malaria, dengue, tuberculosis, childhood diarrhoea and malaria Rapid Diagnostic Test (RDT)-negative fever, was developed based on global evidence and extensive stakeholder consultations. An open stepped-wedge cluster-randomised controlled trial, randomised at the volunteer level, will be conducted over 6 months to evaluate the effectiveness of the CIME model in Myanmar. One hundred and forty Integrated Community Malaria Volunteers (ICMVs, current model of care) providing malaria services in 140 villages will be retrained as CIME volunteers (intervention). These 140 ICMVs/villages will be grouped into 10 blocks of 14 villages, with blocks transitioned from control (ICMV) to intervention states (CIME), fortnightly, in random order, following a 1-week training and transition period. The primary outcome of the trial is blood examination rate determined by the number of malaria RDTs performed weekly. Difference in rates will be estimated across village intervention and control states using a generalised linear mixed modelling analytical approach with maximum likelihood estimation. ETHICS AND DISSEMINATION: The study was approved by Institutional Review Board, Myanmar Department of Medical Research (Ethics/DMR/2020/111) and Alfred Hospital Ethics Review Committee, Australia (241/20). Findings will be disseminated in peer-review journals, conferences and regional, national and local stakeholder meetings. TRIAL REGISTRATION NUMBER: NCT04695886.

Antiretroviral therapy (ART) coverage at public and private ART facilities in Myanmar.

Myanmar's continuum of HIV care was surveyed to assess the National AIDS Control Programme's progress; according to its reports, ART coverage was 38% in 2014, 47% in 2015, and 56% in 2016. To evaluate ART coverage and gaps in care, a serial cross-sectional study used the national programme data reported between January 2014 and December 2016, including 228 public and 62 private ART facilities. ART coverage among PLHIV under 15 years old was 89% in 2014, 93% in 2015, and 88% in 2016. Retention in ART care among women was higher than among men, although women were more likely to discontinue care. PLHIV who were enrolled in ART facilities initiated ART at the rates of 60% in 2014, 68% in 2015, and 74% in 2016. Over the 3-year study period, these facilities reported that 2.5-3.7% of PLHIV taking ART had died, and that 3.3-4.8% were lost to follow-up. PLHIV who were tested for viral load were low (2.5-3%). The continuum of HIV care at ART facilities has improved, but more information about attrition and viral suppression are still needed. The reporting system for newly diagnosed PLHIV and facilities for viral load testing need to be strengthened.

A Case of Pulmonary Epithelioid Hemangioendothelioma with Literature Review.

Pulmonary epithelioid hemangioendothelioma is a rare vascular tumor and infrequently described in medical literature as case reports and case series. Diagnosis is often incidental with high index of histopathological suspicion from clinical pathologist. The pathological pattern is quite unique with distinct immunohistochemical stains. Up to this day, there is no established standard treatment owing to the scarcity of this tumor. In this case report, we describe a case of pulmonary epithelioid hemangioendothelioma unexpectedly diagnosed with transthoracic needle biopsy, along with a review of the current literature.

A Rare Cause of Bilateral Corneal Ulcers: Vitamin A Deficiency in the Setting of Chronic Alcoholism.

Vitamin A deficiency is rarely encountered in the western world. When encountered, vitamin A deficiency is seen as a component of the malabsorption spectrum of disease. Given the infrequency of nutritional deficits in the developed world, vitamin A-associated ophthalmologic disease is rarely encountered. We report a case of a 56-year-old male with severe vitamin A deficiency in the setting of alcoholic liver cirrhosis. This case emphasizes two important points. First, it considers vitamin A deficiency as a cause of corneal ulceration in patients with chronic alcoholism. Second, it raises awareness of hepatotoxicity that can result after the supplementation of vitamin A in patients with chronic alcoholism. Although an uncommon diagnosis, it should be considered when other causes, such as infectious and autoimmune conditions, are ruled out.

The First Case of Native Mitral Valve Endocarditis due to Micrococcus luteus and Review of the Literature.

Gram-positive cocci species, notably Staphylococcus, Streptococcus, and Enterococcus account for 80 to 90% of infective endocarditis cases. HACEK microorganisms (Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) account for approximately 3% of cases and Candida species account for 1-2% of cases. Micrococcus luteus is a rare cause of endocarditis. To our knowledge, only 17 cases of prosthetic valve endocarditis have been described due to M. luteus and a single case of native aortic valve endocarditis has been described. The following case is the only documented case of native mitral valve endocarditis. A review of the literature pertaining to Micrococcus endocarditis was performed to further characterize the entity.

Corrigendum to "Prevalence of Dental Caries in 5- and 6-Year-Old Myanmar Children".

[This corrects the article DOI: 10.1155/2019/5948379.].

Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition.

PURPOSE: Jatrorrhizine (JAT) is a natural protoberberine alkaloid, possesses detoxification, bactericidal and hypoglycemic activities. However, its anti-cancer mechanism is not clear. This study aimed to investigate the mechanism of JAT through which inhibits colorectal cancer in HCT-116 and HT-29 cells. METHODS: MTT assay and colony formation assay were used to check the cell proliferation ability. Cell apoptosis and cell cycle were measured by Hoechst 33342 staining and flow cytometry, respectively. Cell migration and invasion were detected by scratch wound healing assay and trans-well assay, respectively. Further, expression of related proteins was examined via Western blotting and the in vivo anti-cancer effect of JAT was confirmed by nude mice xenograft model. RESULTS: The research showed that JAT inhibited the proliferation of HCT-116 and HT-29 cells with IC50 values of 6.75±0.29 µM and 5.29±0.13 µM, respectively, for 72 hrs. It has also showed a time dependently, cell cycle arrested in S phase, promoted cell apoptosis and suppressed cell migration and invasion. In addition, JAT inhibited Wnt signaling pathway by reducing ß-catenin and increasing GSK-3ß expressions. Increased expression of E-cadherin, while decreased N-cadherin, indicating that JAT treatment suppressed the process of cell epithelial-mesenchymal transition (EMT). In HCT-116 nude mice xenograft model, JAT inhibited tumor growth and metastasis, and induced apoptosis of tumor cells. CONCLUSION: This study demonstrated that JAT efficiently inhibited colorectal cancer cells growth and metastasis, which provides a new point for clinical treatment of colorectal cancer.

Assisted Education for Specialized Medicine: A Sustainable Development Plan for Neurosurgery in Myanmar.

BACKGROUND: With only 4 active certified neurosurgeons for a population of 50 million, neurosurgical care was seriously underdeveloped in Myanmar in 2012. Together with the local neurosurgical community, Swiss Neurosurgeons International started a program of assisted education with the aim of increasing the neurosurgical capacity to 60 active neurosurgeons by 2023. METHODS: Our program included a fully sponsored fellowship at an academic hospital in Switzerland for every Myanmar neurosurgeon in training to observe contemporary neurosurgery and the organization of regular workshops, lectures, and educational surgeries in Myanmar. Halfway through the program, we performed a survey to assess its benefits and shortcomings. RESULTS: In 2019, the number of active neurosurgeons in Myanmar had increased to 20, with 50 more in training. Intracranial pressure monitoring, cervical spine surgery, transsphenoidal surgery, and intraoperative electrophysiology have become established procedures. Our survey showed an increased interest by the residents in tumor and vascular surgery and a new interest in spinal surgery. The overall rating of the fellowship was "very good," with language barriers, cultural differences, and coping with inclement weather reported as the greatest difficulties. CONCLUSIONS: Since the start of our project in 2013, a series of contemporary neurosurgical technologies and procedures have been introduced to Myanmar with the help of Swiss Neurosurgeons International. Our survey results have shown the strong points of the ongoing educational program and the weaknesses to be addressed. Midway through our 10-year project, with an expanded and improved education program, our goal of 60 active neurosurgeons in Myanmar by 2023 seems well within reach.

Prevalence of Dental Caries in 5- and 6-Year-Old Myanmar Children.

There are no national data available of the oral health in Myanmar. In this study, we examined dental caries status of 187 school children located in the suburban area of Naypyidaw, capital of Myanmar, at the age of five and six and analyzed by the individual level and tooth level. Maxillary D and B were sensitive for dental caries almost at the same level. They were less sensitive than maxillary A. Mandibular A and B were tolerant for dental caries. Prevalence of dental caries in Myanmar children was still high. By applying item response theory and multilevel modeling, tooth level analysis can be implemented to confirm the tendency for sensitivity or tolerance for dental caries by the tooth level.

Overproduction of a ß-fructofuranosidase1 with a high FOS synthesis activity for efficient biosynthesis of fructooligosaccharides.

Aureobasidium melanogenum 11-1 was found to be able to produce over 281.7 ±â€¯7.1 U/mL of ß-fructofuranosidase activity. The protein deduced from the cloned ß-fructofuranosidase1 gene had the conserved motif A (IGDP), motif D (RDP) and motif E (ET) and 11 N-glycosylation sites, indicating it was a ß-fructofuranosidase with the high-level fructooligosaccharide (FOS) biosynthesis. Overexpression of the ß-fructofuranosidase1 gene in the yeast strain 11-1 made a tranformant 33 produce 557.7 U/mL of ß-fructofuranosidase activity. The molecular weight of the ß-fructofuranosidase1 in which all the carbohydrates were removed by the Endo-H was 82.4 kDa. Within 7 h of the transfructosylation reaction, the yield of FOS was 0.66 g of FOS/g of sucrose and percentages of GF2, GF3 and GF4 were 79.5%, 18.9% and 1.6%. This demonstrated that the ß-fructofuranosidase1 and the transformant 33 had highly potential applications in biotechnology for FOS production.

Comparative performance of the finite element method and the boundary element fast multipole method for problems mimicking transcranial magnetic stimulation (TMS).

OBJECTIVE: A study pertinent to the numerical modeling of cortical neurostimulation is conducted in an effort to compare the performance of the finite element method (FEM) and an original formulation of the boundary element fast multipole method (BEM-FMM) at matched computational performance metrics. APPROACH: We consider two problems: (i) a canonic multi-sphere geometry and an external magnetic-dipole excitation where the analytical solution is available and; (ii) a problem with realistic head models excited by a realistic coil geometry. In the first case, the FEM algorithm tested is a fast open-source getDP solver running within the SimNIBS 2.1.1 environment. In the second case, a high-end commercial FEM software package ANSYS Maxwell 3D is used. The BEM-FMM method runs in the MATLAB® 2018a environment. MAIN RESULTS: In the first case, we observe that the BEM-FMM algorithm gives a smaller solution error for all mesh resolutions and runs significantly faster for high-resolution meshes when the number of triangular facets exceeds approximately 0.25 M. We present other relevant simulation results such as volumetric mesh generation times for the FEM, time necessary to compute the potential integrals for the BEM-FMM, and solution performance metrics for different hardware/operating system combinations. In the second case, we observe an excellent agreement for electric field distribution across different cranium compartments and, at the same time, a speed improvement of three orders of magnitude when the BEM-FMM algorithm used. SIGNIFICANCE: This study may provide a justification for anticipated use of the BEM-FMM algorithm for high-resolution realistic transcranial magnetic stimulation scenarios.

Production, Gene Cloning, and Overexpression of a Laccase in the Marine-Derived Yeast Aureobasidium melanogenum Strain 11-1 and Characterization of the Recombinant Laccase.

Aureobasidium melanogenum strain 11-1 with a high laccase activity was isolated from a mangrove ecosystem. Under the optimal conditions, the 11-1 strain yielded the highest laccase activity up to 3120.0 ± 170 mU/ml (1.2 U/mg protein) within 5 days. A laccase gene (LAC1) of the yeast strain 11-1 contained two introns and encoded a protein with 570 amino acids and four conserved copper-binding domains typical of the fungal laccase. Expression of the LAC1 gene in the yeast strain 11-1 made a recombinant yeast strain produce the laccase activity of 6005 ± 140 mU/ml. The molecular weight of the recombinant laccase after removing the sugar was about 62.5 kDa. The optimal temperature and pH of the recombinant laccase were 40 °C and 3.2, respectively, and it was stable at a temperature less than 25 °C. The laccase was inhibited in the presence of sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), phenylmethanesulfonyl fluoride (PMSF), and DL-dithiothreitol (DTT). The Km and Vmax values of the laccase for 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was 6.3 × 10-2 mM and 177.4 M/min, respectively. Many synthetic dyes were greatly decolored by the laccase.

A Giant Right Heart Thrombus-in-Transit: The Challenge of Anticoagulation in Factor V Leiden Thrombophilia.

Factor V Leiden (FVL) is an autosomal dominant condition resulting in thrombophilia. Factor V normally acts as a cofactor for prothrombinase, helping cleave prothrombin to thrombin. A single point mutation in it disrupts factor V, making it unreceptive to protein C and increasing the risk of thrombosis. FVL mutation associated with right heart thrombus is a rare entity. Right heart thrombus or right heart thrombus-in-transit is associated with high mortality. We present a 51-year-old male with a past medical history of FVL homozygous mutation and recurrent blood clots, who has failed multiple different oral anticoagulants. He presented to the hospital with symptoms of shortness of breath and subsequently found to have a giant right heart thrombus. He was treated with surgical embolectomy. This case underscores the challenges faced by patients with FVL and recurrent blood clots.

Analysis of osteogenic potential on 3mol% yttria-stabilized tetragonal zirconia polycrystals and two different niobium oxide containing zirconia ceramics.

PURPOSE: This study was performed to evaluate the osteogenic potential of 3mol% yttria-stabilized tetragonal zirconia polycrystals (3Y-TZP) and niobium oxide containing Y-TZPs with specific ratios, new (Y,Nb)-TZPs, namely YN4533 and YN4533/Al20 discs. MATERIALS AND METHODS: 3Y-TZP, YN4533 and YN4533/Al20 discs (15 mm diameter and 1 mm thickness) were prepared and their average surface roughness (Ra) and surface topography were analyzed using 3-D confocal laser microscope (CLSM) and scanning electron microscope (SEM). Mouse pre-osteoblast MC3T3-E1 cells were seeded onto all zirconia discs and evaluated with regard to cell attachment and morphology by (CLSM), cell proliferation by PicoGreen assay, and cell differentiation by Reverse-Transcription PCR and Quantitative Real-Time PCR, and alkaline phosphatase (Alp) staining. RESULTS: The cellular morphology of MC3T3-E1 pre-osteoblasts was more stretched on a smooth surface than on a rough surface, regardless of the material. Cellular proliferation was higher on smooth surfaces, but there were no significant differences between 3Y-TZP, YN4533, and YN4533/Al20. Osteoblast differentiation patterns on YN4533 and YN4533/Al20 were similar to or slightly higher than seen in 3Y-TZP. Although there were no significant differences in bone marker gene expression (alkaline phosphatase and osteocalcin), Alp staining indicated better osteoblast differentiation on YN4533 and YN4533/Al20 compared to 3Y-TZP. CONCLUSION: Based on these results, niobium oxide containing Y-TZPs have comparable osteogenic potential to 3Y-TZP and are expected to be suitable alternative ceramics dental implant materials to titanium for aesthetically important areas.

Analysis of osteogenic potential on 3mol% yttria-stabilized tetragonal zirconia polycrystals and two different niobium oxide containing zirconia ceramics

PURPOSE: This study was performed to evaluate the osteogenic potential of 3mol% yttria-stabilized tetragonal zirconia polycrystals (3Y-TZP) and niobium oxide containing Y-TZPs with specific ratios, new (Y,Nb)-TZPs, namely YN4533 and YN4533/Al20 discs. MATERIALS AND METHODS: 3Y-TZP, YN4533 and YN4533/Al20 discs (15 mm diameter and 1 mm thickness) were prepared and their average surface roughness (Ra) and surface topography were analyzed using 3-D confocal laser microscope (CLSM) and scanning electron microscope (SEM). Mouse pre-osteoblast MC3T3-E1 cells were seeded onto all zirconia discs and evaluated with regard to cell attachment and morphology by (CLSM), cell proliferation by PicoGreen assay, and cell differentiation by Reverse-Transcription PCR and Quantitative Real-Time PCR, and alkaline phosphatase (Alp) staining. RESULTS: The cellular morphology of MC3T3-E1 pre-osteoblasts was more stretched on a smooth surface than on a rough surface, regardless of the material. Cellular proliferation was higher on smooth surfaces, but there were no significant differences between 3Y-TZP, YN4533, and YN4533/Al20. Osteoblast differentiation patterns on YN4533 and YN4533/Al20 were similar to or slightly higher than seen in 3Y-TZP. Although there were no significant differences in bone marker gene expression (alkaline phosphatase and osteocalcin), Alp staining indicated better osteoblast differentiation on YN4533 and YN4533/Al20 compared to 3Y-TZP. CONCLUSION: Based on these results, niobium oxide containing Y-TZPs have comparable osteogenic potential to 3Y-TZP and are expected to be suitable alternative ceramics dental implant materials to titanium for aesthetically important areas.

Comparison of ovalbumin and ovalbumin epitope peptide for transdermal delivery and vaccination mediated by the photothermal effect of gold nanorods.

Transdermal protein delivery is a powerful and attractive method for protein therapy and dermal vaccination compared with other administrations. However, this delivery method is restricted by the low permeability of the stratum corneum (SC), a hydrophobic barrier that restricts the entry of hydrophilic molecules such as proteins. In this study, we developed an improved gel patch system carrying ovalbumin and ovalbumin epitope peptide, and then compared their permeability into the skin. First, the gel patch was placed on mouse skin to allow contact with the polymer coated gold nanorods and then irradiated by a continuous-wave laser. Thermal ablation of the SC improved the permeability and translocation of ovalbumin and the peptide. Fluorescence images showed the translocation was enhanced when the skin was treated with the FITC-modified ovalbumin epitope peptide. However, induction of anti-OVA IgG production after treatment with the FITC-modified ovalbumin epitope peptide was lower than that with FITC-OVA.

Gold Nanorods as Nanodevices for Bioimaging, Photothermal Therapeutics, and Drug Delivery.

Gold nanorods are promising metals in several biomedical applications such as bioimaging, thermal therapy, and drug delivery. Gold nanorods have strong absorption bands in near-infrared (NIR) light region and show photothermal effects. Since NIR light can penetrate deeply into tissues, their unique optical, chemical, and biological properties have attracted considerable clinical interest. Gold nanorods are expected to act not only as on-demand thermal converters for photothermal therapy but also as mediators of a controlled drug-release system responding to light irradiation. In this review, we discuss current progress using gold nanorods as bioimaging platform, phototherapeutic agents, and drug delivery vehicles.

Enhancement of transdermal protein delivery by photothermal effect of gold nanorods coated on polysaccharide-based hydrogel.

Transdermal protein delivery is a useful and attractive method for protein therapy and dermal vaccination. However, this delivery method is restricted by the low permeability of the stratum corneum. The purpose of this study was to develop a transdermal delivery system for enhancement of protein permeability into the skin. First, we prepared a transparent gel patch made of polysaccharides with gold nanorods on the gel surface and fluorescein isothiocyanate-modified ovalbumin (FITC-OVA) inside. Next, the gel patch was placed on mouse skin to allow contact with the coated gold nanorods, and irradiated by a continuous-wave laser. The laser irradiation heated the gold nanorods and the skin temperature increased to 43°C, resulting in enhanced translocation of FITC-OVA into the skin. These results confirmed the capability of the transdermal protein delivery system to perforate the stratum corneum and thus facilitate the passage of proteins across the skin.

Lambl's Excrescence Associated with Cryptogenic Stroke: A Case Report and Literature Review.

BACKGROUND: In 1856, a Bohemian physician, Vilém Dusan Lambl, first described the presence of filiform lesions in aortic valve leaflets. Lambl's excrescences are tiny filiform strands that arise on the line of valve closure, and result from valvular wear and tear. It is a rare cause of cardioembolic stroke that can be detected by transesophageal echocardiogram. CASE REPORT: We encountered a 51-year-old, African-American woman with a history of recurrent strokes that we suspect may be the result of Lambl's excrescence. The patient was treated with dual antiplatelet therapy and was recommended to have surveillance transesophageal echocardiograms at 6 months and 1 year from the time of discharge. CONCLUSIONS: As there are no definitive guidelines for the management of patients with Lambl's excrescences, we present a review of the current medical literature and a specific case report in an attempt to provide a better strategy for managing this condition. In our case report, we focus on the management and treatment for Lambl's excrescence because no clear evidence has been published in the literature. Our review indicates that Lambl's excrescence, despite its relative scarcity, should be considered in the differential diagnosis of a patient with cryptogenic stroke.

Paraspinal and Extensive Epidural Abscess: The Great Masqueraders of Abdominal Pain.

Paraspinal and epidural abscesses are rare conditions often diagnosed later in the disease process that can have significant morbidity and mortality. Predisposing risk factors include diabetes, human immunodeficiency virus, intravenous drug abuse, and previous history of spinal surgery or injection. They can threaten the spinal cord by compressive effect, leading to sensory motor deficits and ultimately paralysis and death. Diagnosis may be a challenge due to the delayed presentation of nonspecific back pain or radicular pain such as chest pain or abdominal pain. We present a rare case on a patient with periumbilical pain, constipation, and urinary retention who was ultimately diagnosed with a paraspinal abscess extending into the epidural space from T1 to S2. He underwent decompressive laminectomy with incision and drainage of the abscesses. The patient made an excellent recovery postoperatively, and repeat magnetic resonance imaging at six weeks showed resolution of the abscess.