Talaromyces purpurogenus による効率的色素生産とその応用

筑波大学 (University of Tsukuba)201

High-dose-rate intracavitary brachytherapy boost post-external beam radiotherapy using rotterdam’s applicator in a case of recurrent carcinoma nasopharynx

Long-term local control is possible in a highly radio-responsive tumor-like carcinoma of the nasopharynx, even in the recurrent setting. High-dose-rate brachytherapy boost with its steep dose fall-off helps achieve salvage by providing optimal dose coverage to the tumor volume which is in close anatomic proximity to critical structures at the base of the skull. Here, we report the case of a 58-year-old lady, an old case of carcinoma nasopharynx presented with recurrence of symptoms in the form of nasal blockade along with a right pre-auricular swelling. Further evaluation showed an fluorodeoxyglucose-avid nasopharyngeal mass, a biopsy from which was positive for nasopharyngeal carcinoma (NPC). She first received re-radiation with external beam radiotherapy using 6 MV photons to the face and neck along with concurrent chemotherapy with cisplatin followed by brachytherapy boost with Rotterdam’s Brachytherapy Applicator @5 Gray×2# 1 week apart. Brachytherapy is a feasible tool that allows dose escalation to achieve long-term tumor control in locally advanced NPCs

Biosynthesis of Silver Nanoparticles Mediated by Extracellular Pigment from Talaromyces purpurogenus and Their Biomedical Applications

In recent years, green syntheses have been researched comprehensively to develop inexpensive and eco-friendly approaches for the generation of nanoparticles. In this context, plant and microbial sources are being examined to discover potential reducing agents. This study aims to utilize an extracellular pigment produced by Talaromyces purpurogenus as a prospective reducing agent to synthesize silver nanoparticles (AgNPs). Biosynthesized AgNPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), electron probe micro analyser (EPMA), and zeta potential. The pigment functional groups involved in the generation of AgNPs were investigated using Fourier transform infrared spectroscopy. TEM images showed that the generated nanoparticles were spherical, hexagonal, rod-shaped, and triangular-shaped with a particle size distribution from 4 to 41 nm and exhibited a surface plasmon resonance at around 410 nm. DLS and zeta potential studies revealed that the particles were polydispersed and stable (−24.8 mV). EPMA confirmed the presence of elemental silver in the samples. Biosynthesized AgNPs exhibited minimum inhibitory concentrations of 32 and 4 μg/mL against E. coli and S. epidermidis, respectively. Further, cytotoxicity of the AgNPs was investigated against human cervical cancer (HeLa), human liver cancer (HepG2), and human embryonic kidney (HEK-293) cell lines using 5-fluorouracil as a positive control. A significant activity was recorded against HepG2 cell line with a half-maximal inhibitory concentration of 11.1 μg/m

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Talaromyces purpurogenus による効率的色素生産とその応用

この博士論文は内容の要約のみの公開（または一部非公開）になっています筑波大学 (University of Tsukuba)201

Light-Emitting-Diode-Assisted, Fungal-Pigment-Mediated Biosynthesis of Silver Nanoparticles and Their Antibacterial Activity

Nanoparticle synthesis, such as green synthesis of silver nanoparticles (AgNPs) using biogenic extracts, is affected by light, which changes the characteristics of particles. However, the effect of light-emitting diodes (LEDs) on AgNP biosynthesis using fungal pigment has not been examined. In this study, LEDs of different wavelengths were used in conjunction with Talaromyces purpurogenus extracellular pigment for AgNP biosynthesis. AgNPs were synthesized by mixing 10 mL of fungal pigment with AgNO3, followed by 24 h exposure to LEDs of different wavelengths, such as blue, green, orange, red, and infrared. All treatments increased the yield of AgNPs. The solutions exposed to blue, green, and infrared LEDs exhibited a significant increase in AgNP synthesis. All AgNPs were then synthesized to determine the optimum precursor (AgNO3) concentration and reaction rate. The results indicated 5 mM AgNO3 as the optimum precursor concentration; furthermore, AgNPs-blue LED had the highest reaction rate. Dynamic light scattering analysis, zeta potential measurement, transmission electron microscopy, and Fourier transform infrared spectroscopy were used to characterize the AgNPs. All LED-synthesized AgNPs exhibited an antimicrobial potential against Escherichia coli and Staphylococcus aureus. The combination of LED-synthesized AgNPs and the antibiotic streptomycin demonstrated a synergistic antimicrobial activity against both bacterial species

Efficacy and safety of concurrent chemoradiotherapy with or without Nimotuzumab in unresectable locally advanced squamous cell carcinoma of head and neck: Prospective comparative study - ESCORT-N study

Background: Nimotuzumab is an anti-epidermal growth factor receptor monoclonal antibody which can be added to chemoradiotherapy (CRT) to improve efficacy for management of locally advanced squamous cell carcinoma of the head and neck (LASCCHN). We prospectively evaluated the efficacy and safety of nimotuzumab with CRT for LASCCHN and compared with CRT alone. Materials and Methods: In this prospective study, 29 LASCCHN (Stage III–IVb) patients received Nimotuzumab plus CRT or CRT alone. Treatment included six cycles of cisplatin (40–50 mg/week) or carboplatin (area under the curve-based), nimotuzumab (200 mg/week), and radiotherapy (60–70 Gy). Tumor response was evaluated as per response evaluation criteria in solid tumors criteria. MoS was estimated using the Kaplan–Meier method. Toxicity and adverse events (AE's) were assessed as per CTCAE v 4.0. Results: At 24 weeks after completion of treatment, the tumor response rate (complete response, partial response, stable disease) was 53.3% and 35.7% favoring nimotuzumab arm while progression of disease was 40% and 35.7% in Nimotuzumab plus CRT and CRT groups, respectively. However, the objective response rate was 57% and 30% in favor of nimotuzumab arm. At median follow-up of 45.5 months, MoS was 33 months in Nimotuzumab plus CRT and 27 months in CRT group. The 5-year survival rate was 33.3% in Nimotuzumab plus CRT versus 7.1% in CRT group. Nimotuzumab was observed to be safe with no additional AE's such as hypersensitivity, hypomagnesemia, and allergic reaction was reported. Conclusion: Addition of Nimotuzumab to standard CRT showed improved survival rate in unresectable, LASCCHN patients without producing additional toxicity

Biosynthesis of Silver Nanoparticles Mediated by Extracellular Pigment from Talaromyces purpurogenus and Their Biomedical Applications

In recent years, green syntheses have been researched comprehensively to develop inexpensive and eco-friendly approaches for the generation of nanoparticles. In this context, plant and microbial sources are being examined to discover potential reducing agents. This study aims to utilize an extracellular pigment produced by Talaromyces purpurogenus as a prospective reducing agent to synthesize silver nanoparticles (AgNPs). Biosynthesized AgNPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), electron probe micro analyser (EPMA), and zeta potential. The pigment functional groups involved in the generation of AgNPs were investigated using Fourier transform infrared spectroscopy. TEM images showed that the generated nanoparticles were spherical, hexagonal, rod-shaped, and triangular-shaped with a particle size distribution from 4 to 41 nm and exhibited a surface plasmon resonance at around 410 nm. DLS and zeta potential studies revealed that the particles were polydispersed and stable (&minus;24.8 mV). EPMA confirmed the presence of elemental silver in the samples. Biosynthesized AgNPs exhibited minimum inhibitory concentrations of 32 and 4 &mu;g/mL against E. coli and S. epidermidis, respectively. Further, cytotoxicity of the AgNPs was investigated against human cervical cancer (HeLa), human liver cancer (HepG2), and human embryonic kidney (HEK-293) cell lines using 5-fluorouracil as a positive control. A significant activity was recorded against HepG2 cell line with a half-maximal inhibitory concentration of 11.1 &mu;g/mL