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Abstract This study aimed on the one hand to clarify the quality, authenticity, safety, and other issues related to products of the anabolic-androgenic steroid methandienone advertised on the Internet and personally imported to Japan and on the other hand to evaluate the use of two portable Raman spectrometers in identifying the active pharmaceutical ingredient (API). The study found that all n = 15 samples purchased from 14 websites were problematic regarding their package, labeling, and/or content. Specifically, one sample (6.7%) was confirmed falsified, twelve samples (80%) were found either to be falsified or unlicensed as pharmaceutical product, and two samples (13.3%) were received without information on the manufacturers’ physical address or country of origin, with one sample (6.7%) having no labeling or other accompanying information at all. Both Raman spectrometers were able to identify the API in all samples as confirmed and quantified by ultra-high-performance liquid chromatography–Fourier transform mass spectrometry. Twelve samples contained on average less than 90% of the declared API content. By contacting national regulatory authorities in 44 countries, methandienone products were found to be approved in 1 country and not approved in 21 countries. To prevent health hazards and abuse, measures against the acquisition of anabolic-androgenic steroids from unknown sources are required. Portable Raman spectrometers may be suitable for the non-destructive and quick identification of methandienone in tablets. Graphical Abstract

Purpose: We report the clinical findings and molecular identification of ocular Thelazia callipaeda from Niigata Prefecture in the Hokuriku area of Japan during winter. Observations: A 77-year-old male visited an ophthalmology clinic in Niigata Prefecture in January 2022 after a 2-week-duration of a conjunctival injection in the left eye and foreign body sensation. Slit-lamp microscopy revealed 11 active nematodes in the left conjunctival sac. Morphological characteristics included longer female body length than male, buccal cavity lacking teeth and lips, and serrated striations along the body surface. The specimens were determined to be T. callipaeda. Genetic analysis of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene revealed an h9 haplotype. Conclusions and Importance: T. callipaeda infection, especially the h9 haplotype, commonly occurs in western Japan owing to its higher incidence in warmer climates, suggesting the origin of the case. Here, we report a human case of Thelaziasis diagnosed in a cold region of Japan (the Hokuriku area) during winter. This human case of T. callipaeda infection from a cold, previously unassociated region, raises concerns about the potential geographical widening of its distribution, and further investigation may be warranted to prevent its spread.

Abstract In vitro excystation of cysts of microscopically identified Chilomastix mesnili and Retortamonas sp. isolated from Japanese macaques and Retortamonas sp. isolated from small Indian mongooses could be induced using an established protocol for Giardia intestinalis and subsequently by culturing with H2S-rich Robinson’s medium supplemented with Desulfovibrio desulfuricans. Excystation usually began 2 h after incubation in Robinson’s medium. DNA was isolated from excysted flagellates after 4 h of incubation or from cultured excysted flagellates. Phylogenetic analysis based on their 18S rRNA genes revealed that two isolates of C. mesnili from Japanese macaques belonged to the same cluster as a C. mesnili isolate from humans, whereas a mammalian Retortamonas sp. isolate from a small Indian mongoose belonged to the same cluster as that of an amphibian Retortamonas spp. isolate from a ‘poison arrow frog’ [sequence identity to AF439347 (94.9%)]. These results suggest that the sequence homology of the 18S rRNA gene of the two C. mesnili isolates from Japanese macaques was similar to that of humans, in addition to the morphological similarity, and Retortamonas sp. infection of the amphibian type in the small Indian mongoose highlighted the possibility of the effect of host feeding habitats.

Summary: At the moment of union in fertilization, sperm and oocyte are transcriptionally silent. The ensuing onset of embryonic transcription (embryonic genome activation [EGA]) is critical for development, yet its timing and profile remain elusive in any vertebrate species. We here dissect transcription during EGA by high-resolution single-cell RNA sequencing of precisely synchronized mouse one-cell embryos. This reveals a program of embryonic gene expression (immediate EGA [iEGA]) initiating within 4 h of fertilization. Expression during iEGA produces canonically spliced transcripts, occurs substantially from the maternal genome, and is mostly downregulated at the two-cell stage. Transcribed genes predict regulation by transcription factors (TFs) associated with cancer, including c-Myc. Blocking c-Myc or other predicted regulatory TF activities disrupts iEGA and induces acute developmental arrest. These findings illuminate intracellular mechanisms that regulate the onset of mammalian development and hold promise for the study of cancer.

Abstract Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7–14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

Abstract Background The C580Y mutation in the Plasmodium falciparum kelch13 gene is the most commonly observed variant in artemisinin-resistant isolates in the Greater Mekong Subregion (GMS). Until 2017, it had not been identified outside the GMS, except for Guyana/Amazonia. In 2017, three parasites carrying the C580Y mutation were identified in Papua New Guinea (PNG). As the C580Y allele rapidly spread in the GMS, there is concern that this mutant is now spreading in PNG. Methods In 2020, a cross-sectional survey was conducted at two clinics in Wewak, PNG. Symptomatic patients infected with P. falciparum were treated with artemether plus lumefantrine following a national treatment policy. Blood samples were obtained before treatment, and polymorphisms in kelch13, pfcrt, and pfmdr1 were determined. Parasite positivity was examined on day 3. The results were compared with those of previous studies conducted in 2002, 2003, and 2016–2018. Results A total of 94 patients were included in this analysis. The proportion of C580Y was significantly increased (2.2% in 2017, 5.7% in 2018, and 6.4% in 2020; p = 4.2 × 10–3). A significant upward trend was observed in the wild-type proportion for pfcrt (1.9% in 2016 to 46.7% in 2020; p = 8.9 × 10–16) and pfmdr1 (59.5% in 2016 to 91.4% in 2020; p = 2.3 × 10–6). Among 27 patients successfully followed on day 3, including three with C580Y infections, none showed positive parasitaemia. Conclusions Under the conditions of significant increases in pfcrt K76 and pfmdr1 N86 alleles in PNG, the increase in kelch13 C580Y mutants may be a warning indicator of the emergence of parasites resistant to the currently used first-line treatment regimen of artemether plus lumefantrine. Therefore, nationwide surveillance of molecular markers for drug resistance and assessment of its therapeutic effects are important.

The severity of Entamoeba histolytica infection is determined by host immunology, pathogen virulence, and the intestinal environment. Conventional research for assessing pathogen virulence has been mainly performed using laboratory strains, such as a virulent HM-1: IMSS (HM-1) and an avirulent Rahman, under various artificial environmental conditions because of the difficulties of axenic isolation of the clinical strains. However, it is still unclear whether scientific knowledge based on laboratory strains are universally applicable to the true pathogenesis. Hereby, we performed transcriptomic analysis of clinical strains from patients with different degrees of disease severity, as well as HM-1 under different conditions. Even after several months of axenization, Clinical strains show the distinct profile in gene expression during in vitro passage, moreover, difference between any 2 of these strains was much greater than the changes on the liver challenge. Interestingly, 26 DEGs, which were closely related to the biological functions, were oppositely up- or down regulated between virulent Ax 19 (liver abscess) and avirulent Ax 11 (asymptomatic carrier). Additionally, RNAseq using laboratory strain (HM1) showed more than half of genes were differently expressed between continuously in vitro passaged HM1 (in vitro HM1) and periodically liver passaged HM1 (virulent HM1), which was much greater than the changes on the liver passage of virulent HM1. Also, transcriptomic analysis of a laboratory strain revealed that continuous environmental stress enhances its virulence via a shift in its gene expression profile. Changes in gene expression patterns on liver abscess formation were not consistent between clinical and laboratory strains.

Abstract The purpose of this study was to design a convenient, small-scale dissolution test for extracting potential substandard and falsified (SF) medicines that require full pharmacopoeial analysis. The probability of metronidazole samples complying with the US Pharmacopoeia (USP) dissolution test for immediate-release tablet formulations was predicted from small-scale dissolution test results using the following criteria: (1) 95% confidence interval lower limit (95% CIlow) of the average dissolution rate of any n = 3 of n = 24 units of each sample, and (2) average and minimum dissolution rates for any n = 3 of n = 24 units. Criteria values were optimized via bootstrap sampling with Thinkeye data-mining software. Compliant metronidazole samples in the USP first-stage and second-stage dissolution test showed complying probabilities of 99.7% and 81.0%, respectively, if the average dissolution rate of n = 3 units is equal to or greater than the monograph-specified amount of dissolved drug (Q; 85% of labeled content for metronidazole). The complying probabilities were 100.0% and 79.0%, respectively, if the average dissolution rate of n = 3 units is 91% or higher and the minimum dissolution rate is 87% or higher. Suitable compliance criteria for the small-scale dissolution test are: average dissolution rate of n = 3 units is Q + 6% or more and minimum dissolution rate is Q + 2% or more.

Abstract Background Poor quality medicines have serious implications for public health. The aim of this study was to explore the quality of the antidiabetic pioglitazone, using samples collected in China and Myanmar, and samples purchased online. Methods In this cross-sectional study, we examined samples (n = 163) collected from hospitals in Shanghai, China in 2012 (n = 44), products purchased via the internet and imported into Japan in 2013 (n = 59), and samples purchased in shops in Yangon, Myanmar in 2015 (n = 60). Collected samples were subjected to visual inspection, authenticity investigation and quality testing (potency, content uniformity and dissolution test) by high-performance liquid chromatography. Samples were rated as compliant or non-compliant based on the relevant pharmacopoeial acceptance criteria. Results Visual inspection of all samples revealed compliant products. However, responses from manufacturers during authenticity investigation were poor. Among the n = 44 samples from China, one was non-compliant in the potency test. Among the n = 59 samples personally imported into Japan, 38% of generic samples were found to be non-compliant. In Myanmar, 13.3% of samples were non-compliant. Non-compliant samples predominantly failed in the dissolution test. All non-compliant samples were generic. Conclusions Despite the apparent satisfactory outcome on the samples from China, pioglitazone samples collected in Myanmar and purchased online for personal import into Japan included many substandard products, which failed quality assessment predominantly because of poor dissolution. Internet providers did not comply with Japanese regulations in various respects.

Graphene oxide (GO), a chemically oxidized sheet of graphite, has been used as a conductive carbon carrier of microbes to boost various bioelectrochemical reactions. However, the types of microbes that can reduce GO have rarely been investigated. In this study, a strain of GO-reducing bacteria, named NIT-SL11, which was obtained from a hydrogel of microbially reduced GO and anaerobic sludge that converts sewage to electricity, was phylogenically identified as a novel strain of Geotalea uraniireducens. Considering the current lack of information on the electrogenic ability of the bacterium and its physicochemical and chemotaxonomic characteristics, the polyphasic characterization of the Geotalea uraniireducens strain NIT-SL11 was performed. NIT-SL11 utilized various organic acids, such as lactate, benzoate, and formate, as electron donors and exhibited respiration using GO, electrodes, fumarate, and malate. The strain contained C16:1ω7c and C16:0 as the major fatty acids and MK-8 and 9 as the major respiratory quinones. The complete genome of NIT-SL11 was 4.7 Mbp in size with a G+C content of 60.9%, and it encoded 80 putative c-type cytochromes and 23 type IV pili-related proteins. The possible extracellular electron transfer (EET) pathways of the strain were the porin–cytochrome (Pcc) EET pathway and type IV pili-based pathway.

Background: Falsified medical products have been reported worldwide. Falsified medicines with poor quality are a potential health hazard. Some Internet sites advertise fluconazole (Diflucan ® ), an antifungal medicine used to treat deep mycoses, as “female Viagra ® .” Aim: The aim of this study was to investigate the authenticity and quality of Diflucan ® tablets distributed on the Internet. Methods: We ordered Diflucan ® tablets via the Internet and evaluated them by visual observation, authenticity investigation, quality evaluation (quantity of the active pharmaceutical ingredient, content uniformity, and dissolution), and near-infrared and Raman scattering spectroscopy. Results: We obtained 11 samples of Diflucan ® tablets from all 11 Japanese Internet sites identified in our search. Of 11 sites, 7 advertised fluconazole as having effects on female sexual function. Ten of the Diflucan ® samples were confirmed as genuine and one sample was falsified. The genuine Diflucan ® samples met the specifications of all quality evaluations. The packaging, size, and color of the falsified Diflucan ® sample obtained in this study differed from the authentic Diflucan ® tablet. The falsified Diflucan ® sample obtained in this study did not contain fluconazole and instead contained what appeared to be sildenafil citrate. The spectra of the falsified Diflucan ® tablet obtained in this study differed from the authentic Diflucan ® tablet in near-infrared and Raman scattering spectroscopy. Conclusion: We confirmed that one falsified Diflucan ® tablet was distributed online. Thus, continued measures against falsified medicines are required.

Intestinal parasitic infections, including those caused by Entamoeba species, are a persistent problem in rural areas of Thailand. The aims of this study were to identify pathogenic Entamoeba species and to analyze their genotypic diversity. Stool samples were collected from 1,233 students of three schools located in the Thai-Myanmar border region of Tak Province, Thailand. The prevalence of Entamoeba infection was measured by polymerase chain reaction (PCR) using species-specific primers. Thirty-one (2.5%) positive cases were detected for E. histolytica, 55 (4.5%) for E. dispar, and 271 (22.0%) for E. coli. Positive samples for E. histolytica and E. dispar were exclusively obtained from a few school classes, whereas E. coli was detected in all grades. No infections caused by E. moshkovskii, E. nuttalli, E. chattoni, and E. polecki were detected in the students studied. The D-A locus of tRNA-linked short tandem repeats was analyzed in samples of E. histolytica (n = 13) and E. dispar (n = 47) to investigate their diversity and potential modes of transmission. Five genotypes of E. histolytica and 13 genotypes of E. dispar were identified. Sequences of the D-A were divergent, but several unique genotypes were significantly prevalent in limited classes, indicating that intra-classroom transmission has occurred. As it was unlikely that infection would have been limited within school classes if the mode of transmission of E. histolytica and E. dispar had been through the intake of contaminated drinking water or food, these results suggest a direct or indirect person-to-person transmission mode within school classes. Positive rates for three Entamoeba species were 2-fold higher in students who had siblings in the schools than in those without siblings, suggesting that transmission occurred even at home due to heavy contacts among siblings.

During influenza epidemics, Japanese clinicians routinely conduct rapid influenza diagnostic tests (RIDTs) in patients with influenza-like illness, and patients with positive test results are treated with anti-influenza drugs within 48 h after the onset of illness. We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children (6 months-15 years old, N = 4243), using a test-negative case-control design based on the results of RIDTs in the 2018/19 season. The VE against influenza A(H1N1)pdm and A(H3N2) was analyzed separately using an RIDT kit specifically for detecting A(H1N1)pdm09. The adjusted VE against combined influenza A (H1N1pdm and H3N2) and against A(H1N1)pdm09 was 39% (95% confidence interval [CI], 30%-46%) and 74% (95% CI, 39%-89%), respectively. By contrast, the VE against non-A(H1N1)pdm09 influenza A (presumed to be H3N2) was very low at 7%. The adjusted VE for preventing hospitalization was 56% (95% CI, 16%-77%) against influenza A. The VE against A(H1N1)pdm09 was consistently high in our studies. By contrast, the VE against A(H3N2) was low not only in adults but also in children in the 2018/19 season.

This study compared the performance of two microbial fuel cells (MFCs) equipped with separators of anion or cation exchange membranes (AEMs or CEMs) for sewage wastewater treatment. Under chemostat feeding of sewage wastewater (hydraulic retention time of approximately 7 h and polarization via an external resistance of 1 Ω), the MFCs with AEM (MFCAEM) generated a maximum current that was 4–5 times greater than that generated by the MFC with CEM (MFCCEM). The high current in the MFCAEM was attributed to the approximately neutral pH of its cathode, in contrast to the extremely high pH of the MFCCEM cathode. Due to the elimination of the pH imbalance, the cathode resistance for the MFCAEM (13–19 Ω·m2) was lower than that for the MFCCEM (41–44 Ω·m2). The membrane resistance measured as the Cl− mobility of AEMs for the MFCAEM operated for 35, 583, and 768 days showed an increase with operation time and depth, and this increase contributed minimally to the cathode resistance of the MFCAEM. These results indicate the advantage of the AEM over the CEM for air-cathode MFCs. The membrane resistance may increase when the AEM is applied in large-scale MFCs on a meter scale for extended periods.

In this study, a novel electrogenic bacterium denoted as strain NIT-T3 of the genus Desulfuromonas was isolated from a graphene-oxide-reducing enrichment culture that was originally obtained from a mixture of seawater and coastal sand. Strain NIT-T3 utilized hydrogen and various organic acids as electron donors and exhibited respiration using electrodes, ferric iron, nitrate, and elemental sulfur. The strain contained C16:1ω7c, C16:0, and C15:0 as major fatty acids and MK-8, 9, and 7 as the major respiratory quinones. Strain NIT-T3 contained four 16S rRNA genes and showed 95.7% similarity to Desulfuromonasmichiganensis BB1T, the closest relative. The genome was 4.7 Mbp in size and encoded 76 putative c-type cytochromes, which included 6 unique c-type cytochromes (Desulfuromonas versatilis’ sp. nov.

The apparent degradation rate constant of fluticasone propionate (FLT) in 0.1 M NaOH:methanol=1:1 at 37 °C was previously reported to be 0.169±0.003 h−1, and four degradation products (products 1–4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0.05 M NaOH and 0.1 M NaOH:CH3CN=1:1 were 0.472±0.013 h−1 and 0.154±0.000 h−1 (n=3), respectively. The chemical structures of products 1–4 in 0.1 M NaOH:methanol=1:1 were revealed by nuclear magnetic resonance (NMR) and mass spectrometry data. The chemical structure of products 2 was that the 17-position of the thioester moiety of FLT was substituted by a carboxylic acid. The degradation product in 0.1 M NaOH:CH3CN=1:1 was found to be product 2 based on 1H NMR data. The degradation product in 0.05 M NaOH was considered to be product 2 based on the retention time of HPLC. These results are useful for detecting the degradation products of FLT by enzymes of the intestinal bacterial flora in the large intestine after dosing FLT as an enema.

Abstract Background Poor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was carried out to investigate the cause of quality failure of omeprazole in Cambodia in 2010 and Myanmar in 2014. Methods We conducted pharmacopoeial quantity, content uniformity and dissolution tests of 156 samples of omeprazole capsules collected in Cambodia in 2010 and Myanmar in 2014. High failure rates were found, especially in dissolution testing, and detailed investigation of several unacceptable samples was carried out by means of in-vitro dissolution profiling, scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT) to identify the cause of failure. Results Dissolution profiling with and without the acid stage showed that acid caused premature omeprazole release, indicating that the enteric coating of the omeprazole granules was ineffective. SEM examination of two failed samples revealed cracked and broken granules mixed with apparently intact omeprazole granules in the capsule. X-ray CT examination indicated that some granules of failed samples completely lacked enteric coating, and others had incomplete and non-uniform enteric coating or malformation. Conclusions Omeprazole capsules collected in Myanmar and Cambodia showed high failure rates in pharmacopoeial tests, especially dissolution tests. Some samples were found to have ineffective or absent enteric coating of the granules, resulting in premature dissolution and degradation in acidic conditions. This is a potentially serious public health issue that needs to be addressed by regulatory authorities in Cambodia and Myanmar, possibly through a collaborative initiative with manufacturers.

This study evaluated the performance of a tubular microbial fuel cell (MFC) having a core of air-chamber wrapped with an anion exchange membrane in sewage wastewater treatment. Three MFCs were vertically assembled into one module and floated in sewage water channels before and after treatments in the primary sedimentation tank. The two MFC-modules exhibited nearly similar electricity production in the range of 1.3–5.7 Wh·m−3-MFC while the bottom MFCs (60–90 cm) showed a decrease in electricity compared with the top (0–30 cm) and the middle MFCs (30–60 cm) due to the water leakage into air-cathode. One MFC module was then evaluated for its chemical oxygen demand (COD) removal efficiency with two external resistances of 27 and 3Ω in a chemostat reactor (MFC:reactor = 1:5, v/v) using three hydraulic retention times (HRTs), i.e., 3, 6, and 12 h. The best COD removal efficiency (COD-REMFC), 54 ± 14%, and BOD removal efficiency, 37 ± 17%, were observed with a resistance of 3Ω and a 12 h HRT, which resulted in 3.8 ± 2.0 A·m−3 of current recovery and 15 ± 7.5% of Coulombic efficiency. The electricity generation efficiency (EGEMFC) was the best with a resistance of 27Ω and a 12 h HRT, accounting for 0.19 ± 0.12 kWh·kg-COD−1 with a 17 ± 6.4% COD-REMFC and 0.65 ± 0.10 Wh·m−3 electricity production. Based on calculations using the COD-REMFC and EGEMFC, the integration of MFC treatments prior to aeration can reduce wastewater treatment electricity consumption by 55%.

To make the Japanese version of the CESD-R—a revised version of the Center for Epidemiologic Studies depression scale (CES-D)—in the assessment of depressive symptoms in a general population. The English version of CESD-R was translated into Japanese, and back-translated into English by three native speakers of Japanese and English; then, we selected the version most completely consistent with the original items. The CESD-R was applied to 398 community-dwelling people (191 men: 48.0%, and 207 women: 52.0%) who were over 40 years old. The Japanese version of the CES-D was also carried out in the same population. Factor analysis was performed. Additionally, the correlations between the CESD-R and CES-D results were identified. The CESD-R scores showed a significantly positive correlation with CES-D scores (r = 0.74, p < 0.0005). Analysis of the CESD-R yielded a Cronbach’s alpha result of 0.90. Factor analysis revealed one principal factor in the CESD-R, whereas the original CES-D had two factors because of reversed items. The Japanese version of the CESD-R appears to have the reliability to be applicable for assessing depressive symptoms in population-based samples. However, because the Japanese expressions for some items might be unusual, our study population was also limited; further studies on other populations and on incorporating improved Japanese terminology will be needed.

Substandard and falsified medicines are often reported worldwide. An accurate and rapid detection method for falsified medicines is needed to prevent human health hazards. Raman scattering spectroscopy has emerged as a non-destructive analysis method for the detection of falsified medicines. In this laboratory study, Raman spectroscopy was performed to evaluate the applicability of the ultra-compact Raman scattering spectrometer (C13560). Principal component analysis (PCA) was also performed on the Raman spectra. This study analyzed tadalafil (Cialis), vardenafil (Levitra), and sildenafil (Viagra) tablets. We tested the standard product and products purchased from the internet (genuine or falsified). For Cialis and Levitra, all falsified tablets were identified by the Raman spectra and PCA score plot. For Viagra, the Raman spectra of some falsified tablets were almost comparable to the standard tablet. The PCA score plots of falsified tablets were dispersed, and some plots of falsified tablets were close to the standard tablet. In conclusion, C13560 was useful for the discrimination of falsified Cialis and Levitra tablets, whereas some falsified Viagra tablets had Raman spectra similar to that of the standard tablet. The development of detection methods that can be introduced in various settings may help prevent the spread of falsified products.

Background: substandard and falsified medicines (SFMs) are a threat to public health. The availability of SFMs in Myanmar was reported by the World Health Organization (WHO) in 1999, but there have been few systematic surveys on falsified medicines in Myanmar since then. The aim of this study is to examine the extent of SFMs for sale in Myanmar. Methods: target medicines were tablets of candesartan, metformin, and pioglitazone, and infusions of ciprofloxacin and levofloxacin. Samples were collected from hospitals, pharmacies, and wholesalers located in the Mandalay region in 2015. We carried out observation testing, authenticity investigation, and quality testing to search for SFMs, and analyzed the relationship between SFMs and the price and store type. Results: There were no falsified medicines found in the authenticity check, though there remained a problem due to low response rates from manufacturers and regulatory authorities. In the quality test, some tablets of metformin and pioglitazone made in India failed the dissolution test. Conclusions: although no serious problems were found, some substandard medicines were detected. Regular surveys to monitor SFMs are therefore recommended, together with further regulatory guidance to improve conditions in all medicine manufacturers, distributors, and pharmacies.

Medicine falsification is a global issue. Viagra, an erectile dysfunction therapeutic (EDT) medicine consisting primarily of sildenafil citrate, is the most commonly falsified medicine worldwide. Recently falsified EDTs have been reported multiple times in developing countries. The globalization of falsified EDTs has become a concern. In the present study, we selected sildenafil citrate tablets as an indicator and examined samples from a developing country, Cambodia, to investigate the availability of falsified sildenafil tablets in Cambodia and verify the current globalization status of falsified medicines from the standpoint of a developing country. Six samples of the originator Viagra, and 68 samples of generic sildenafil products were purchased from private drug outlets and wholesalers in Phnom Penh, Svay Rieng, and Battambang. The samples’ manufacturers were contacted to authenticate the samples. The quantities and dissolution rates of active ingredients were measured by a high-performance liquid chromatography system with photodiode array. Five generic samples were strongly suspected to be falsified medicines because of their extremely low quality; however, there was little distribution and no falsified medicine alleged to be produced by the originator of Viagra, which charges high prices. That finding indicates that falsification reflects local economic circumstances.

Studies concerning patient demands are mainly conducted at hospitals and pharmacies, whereas few surveys have been conducted on drug stores. The demand for drug stores is estimated to be increasing with growing needs for self-medication. Thus, conducting a customer survey at drug stores is thought to be valuable. The aim of the current study was to clarify the structure of customers’ demands for drug stores. The survey was conducted on 190 customers of 19 drug stores in Japan. The questionnaire consisted of 24 items using a 9-point Likert scale. The IBM SPSS Statistics version 23 (IBM Japan, Tokyo, Japan) and Amos version 5 (IBM Japan, Tokyo, Japan) were utilized to perform factor analysis. Gender did not influence the response to each question. Factor analysis showed that the structure of customers’ demands consisted of three factors: (1) an explanation about medicine, (2) staff’s manners, and (3) location of drug stores. Because fit indices suggested a good fit, this three-factor solution was adopted as the final factor structure. This study demonstrated the structure of customers’ demands for drug stores, with the potential for use in promotion of self-medication.

Many poor-quality medicines are supplied to patients mainly in developing countries. No systematic survey on counterfeit medicines has been conducted in Myanmar since 1999. The purpose of this study was to investigate the current situation of substandard or counterfeit medicines in Myanmar. Samples of oral medicines, cefuroxime axetil (CXM), donepezil hydrochloride (DN) and omeprazole (OM), and injections, ceftriaxone sodium (CTRX), and gentamicin sulfate (GM), were collected from pharmacies, hospitals, and wholesalers in Yangon, Myanmar in 2014. Authenticity and quality were verified. There were 221 (94%) foreign medicines among 235 collected samples. Five samples of GM and 1 DN sample were not registered with the Food and Drug Administration, Myanmar. In quality analysis, 36 samples out of 177 (20.3%) did not pass quantity tests, 27 samples out of 176 (15.3%) did not pass content uniformity tests, and 23 out of 128 samples (18.0%) did not pass dissolution tests. Three of the unregistered GM samples failed in both identification and microbial assay tests. Counterfeit GM is being sold in Yangon. Also, the quality of OM is a matter of concern. Poor-quality medicines were frequently found among the products of a few manufacturers. Regular surveys to monitor counterfeit and substandard medicines in Myanmar are recommended.

We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013-14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38 °C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39-52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56-69), 77% (95% CI, 59-87), and 26% (95% CI, 14-36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B.