Emergence of Phytobacter diazotrophicus carrying an IncA/C2 plasmid harboring bla NDM-1 in Tokyo, Japan.

Phytobacter diazotrophicus is an Enterobacterales species that was originally identified as a plant growth-promoting, Gram-negative bacterium. Recently, this species has been recognized as relevant to opportunistic human and nosocomial infections in clinical settings. Its frequent misidentification as other Enterobacterales species from clinical examination occasionally causes a delay in the identification of nosocomial outbreaks. Here, we report the emergence of New Delhi metallo-ß-lactamase (NDM)-producing P. diazotrophicus isolated from hospitalized pediatric patients and hospital environments in Tokyo, Japan. In our case, these isolates were found during an investigation of carbapenem-resistant Enterobacterales in relation to nosocomial infections. Whole-genome sequencing is useful for overcoming the difficulty of species identification. Furthermore, we found that bla NDM-1 was carried by an IncA/C2 plasmid (approximately 170 kbp), which was transferrable from the clinical isolates to the recipient strain Escherichia coli J53. Our study demonstrated that P. diazotrophicus behaves as a carrier of bla NDM-harboring plasmids, potentially disseminating resistance to carbapenems among Enterobacterales. IMPORTANCE Early detection of nosocomial outbreaks is important to minimize the spread of bacteria. When an outbreak is caused by multidrug-resistant bacteria such as carbapenem-resistant Enterobacterales, a delay in findings makes it difficult to control it because such bacteria often spread not only among human patients but also in hospital environments. Phytobacter diazotrophicus, an Enterobacterales species that has recently been found to be relevant to clinical settings, is often misidentified as other bacteria in clinical laboratories. Here, we found NDM-producing P. diazotrophicus in hospitalized pediatric patients and their environment in Tokyo, Japan. Given that the isolates carried bla NDM-1-harboring transferrable plasmids, the influence of such bacteria could be greater with the mediation of horizontal transfer of carbapenem resistance. Our findings suggest that P. diazotrophicus should be recognized as an NDM-carrier, for which more attention should be paid in clinical settings.

Seroprevalence of Entamoeba histolytica at a voluntary counselling and testing centre in Tokyo: a cross-sectional study.

BACKGROUND: Amebiasis, which is caused by Entamoeba histolytica, is a re-emerging public health issue owing to sexually transmitted infection (STI) in Japan. However, epidemiological data are quite limited. METHODS: To reveal the relative prevalence of sexually transmitted E. histolytica infection to other STIs, we conducted a cross-sectional study at a voluntary counselling and testing (VCT) centre in Tokyo. Seroprevalence of E. histolytica was assessed according to positivity with an ELISA for E. histolytica-specific IgG in serum samples collected from anonymous VCT clients. RESULTS: Among 2083 samples, seropositive rate for E. histolytica was 2.64%, which was higher than that for HIV-1 (0.34%, p<0.001) and comparable to that for syphilis (rapid plasma reagin (RPR) 2.11%, p=0.31). Positivity for Chlamydia trachomatis in urine by transcription-mediated amplification (TMA) was 4.59%. Seropositivity for E. histolytica was high among RPR/Treponema pallidum hemagglutination (TPHA)-positive individuals and it was not different between clients with and without other STIs. Both seropositivity of E. histolytica and RPR were high among male clients. The seropositive rate for anti-E. histolytica antibody was positively correlated with age. TMA positivity for urine C. trachomatis was high among female clients and negatively correlated with age. Regression analysis identified that male sex, older age and TPHA-positive results are independent risk factors of E. histolytica seropositivity. CONCLUSIONS: Seroprevalence of E. histolytica was 7.9 times higher than that of HIV-1 at a VCT centre in Tokyo, with a tendency to be higher among people at risk for syphilis infection. There is a need for education and specific interventions against this parasite, as a potentially re-emerging pathogen.

Molecular Characteristics of Novel Mono-Reassortant G9P[8] Rotavirus A Strains Possessing the NSP4 Gene of the E2 Genotype Detected in Tokyo, Japan.

Rotavirus A (RVA) has been detected in patients with gastroenteritis even after vaccine introduction in Japan. To investigate circulating RVA strains, RVA-positive stool specimens obtained in Tokyo in 2017 and 2018 were analyzed using next-generation sequencing. A total of 50 and 21 RVA samples were obtained in 2017 and 2018, respectively. In 2017, G2P[4] (40.0%) was the most prevalent strain, followed by G3P[8] (DS-1-like) (28.0%), G8P[8] (10.0%), G3P[8] (Wa-like) (8.0%), G9P[8]-E1 (8.0%), and mixed infection (6.0%). In 2018, G3P[8] (DS-1-like) (28.6%) and G9P[8]-E2 (28.6%) were the most prevalent strains, followed by G9P[8]-E1 (19.0%), G2P[4] (9.5%), G8P[8] (9.5%), and mixed infection (4.8%). Six G9P[8]-E2 strains detected in 2018 showed an atypical genotype constellation (G9P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1), which had not been reported previously. Phylogenetic analyses suggested that the RVA virus was generated by inter-genogroup reassortment between commonly circulating G9P[8] and G2P[4] strains in Japan. The G9P[8] strain seemed to be reassorted with only the NSP4 gene of the E2 genotype of the G2P[4] strain. Since this newly-emerged G9P[8]-E2 virus was detected in different locations in Tokyo, the virus appears to have already begun to spread to a wider area.

FRI-4 carbapenemase-producing Enterobacter cloacae complex isolated in Tokyo, Japan.

Objectives: A carbapenem-resistant Enterobacter cloacae complex isolated in Tokyo, Japan, produced a carbapenemase that was detected by a Carba NP test and a modified carbapenem inactivation method, but none of the 'Big Five' carbapenemase genes was detected by PCR. This study aimed to identify the carbapenemase. Methods: Carbapenemase genes were screened by WGS. Next, we generated a recombinant plasmid in which the carbapenemase gene was inserted. We also extracted the carbapenemase gene-carrying plasmid from the E. cloacae complex. The effects of both plasmids on the antibiotic susceptibility of Escherichia coli were then tested. The carbapenemase gene-carrying plasmid in the E. cloacae complex was completely sequenced. Results: A novel carbapenemase gene, blaFRI-4, encoded an amino acid sequence that was 93.2% identical to French imipenemase (FRI-1). E. coli transformed with blaFRI-4 showed reduced carbapenem susceptibility. A complete sequence of the blaFRI-4-carrying 98 508 bp IncFII/IncR plasmid (pTMTA61661) showed that blaFRI-4 and the surrounding region (18.7 kb) were duplicated. Conclusions: The FRI-4-producing E. cloacae complex was isolated in Japan, whereas all other FRI variants have been found in Europe, suggesting that the spread of FRI carbapenemases is global.

Molecular identification and characterization of Sarcocystis spp. in horsemeat and beef marketed in Japan.

Human Sarcocystis infections are known to be caused by the ingestion of raw or undercooked beef or pork containing mature sarcocysts of Sarcocystis hominis or S. suihominis, respectively. In addition, several cases of parasitic food poisoning in Japan have recently been reported after consumption of raw horsemeat containing sarcocysts of S. fayeri. In this study, the presence of sarcocysts in 28 horsemeat and 121 beef samples collected in Tokyo was investigated. Sarcocysts of S. fayeri were found in 16 horsemeat samples. Sarcocysts of S. hominis were not detected in beef samples, while sarcocysts of S. cruzi were detected in 60 beef samples. In addition, S. hirsuta and S. bovini were isolated only from New Zealand beef samples. Bradyzoites in sarcocysts collected from 62/73 sarcocyst-positive refrigerated horsemeat and beef samples were determined to be viable. Molecular analysis of S. fayeri 18S rRNA gene sequences revealed that intraspecific variation among eight individual bradyzoites from a single sarcocyst was as high as 9.8%. In contrast, mitochondrial cytochrome c oxidase subunit 1 (mtDNA cox1) gene sequences from the six fragments of a single sarcocyst were 100% identical. Sarcocysts of S. bovini isolated from beef also exhibited intraspecific variation in 18S rRNA gene sequences and had to be cloned before sequencing, while mtDNA cox1 gene sequences were obtained by direct sequencing. Therefore, we conclude that molecular analysis of the mtDNA cox1 gene is the most useful for identification of Sarcocystis species. This study provides the first published partial sequence of the S. fayeri mtDNA cox1 gene.

Foodborne Outbreaks Caused by Human Norovirus GII.P17-GII.17-Contaminated Nori, Japan, 2017.

Seven foodborne norovirus outbreaks attributable to the GII.P17-GII.17 strain were reported across Japan in 2017, causing illness in a total of 2,094 persons. Nori (dried shredded seaweed) was implicated in all outbreaks and tested positive for norovirus. Our data highlight the stability of norovirus in dehydrated food products.

Whole genomic analysis of human G8P[14] group A rotavirus detected from community gastroenteritis outbreak.

Several suspected cases of zoonotic transmission of group A rotavirus (RVA)-related gastroenteritis were reported previously. In August 2012, G8P[14] RVA was detected in fecal specimens from a community gastroenteritis outbreak occurring during a school trip. In this study, additional analyses were performed and it was found that this strain had the G8-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3 sequence, similar to bovine-like RVA strains. Some contamination by emesis and diarrheic feces was observed near a rest room in the lodging area. Contact history with animals was unknown in members of this school trip, and this case implied that the strain may have acquired the ability for person-to-person transmission.

Comparison between patients with norovirus-related gastroenteritis and asymptomatic carriers with respect to distribution of antibody-complexed viral particles and intestinal flora.

Asymptomatic carriers have a major influence on the spreading of norovirus infections. The objective of this study was to examine the characteristics of patients and asymptomatic carriers affected by norovirus-related community gastroenteritis outbreaks. No significant difference between the two groups was observed in terms of the number of norovirus-antibody complexes with respect to total numbers. Principal coordinates analysis of the intestinal flora based on ß-diversity analysis, revealed a different bacterial composition between patients and asymptomatic carriers, particularly regarding the genera Pseudomonas, Bacteroides, and Erwinia, as well as the Ruminococcaceae family. Although the proportional changes between these intestinal microorganisms were not sufficient to explain gastroenteritis symptoms, they represent possible markers shared by asymptomatic norovirus carriers.

[Molecular Epidemiological Analysis of Hepatitis A Viruses Circulating in Tokyo, 2016-2017].

Hepatitis A virus (HAV) is a common infectious agent that causes acute hepatitis worldwide. Since the incubation period of HAV infection is about one month, it is difficult to identify the source of infection based only on medical interviews. Molecular epidemiological analysis of HAV isolated from patients can help to reveal the infection route and to identify diffuse outbreaks caused by common food vehicles. In the present study, samples were collected from 108 cases notified to the active epidemiological investigation system in Tokyo between 2016 and 2017. Samples found to be HAV-positive by semi-nested RT-PCR were subjected to sequencing and phylogenetic analysis; the results were analyzed together with the epidemiological data. HAV was detected in 99 out of 108 cases. Phylogenetic analysis showed that the 99 HAV strains were divided into 91 of genotype IA, two of IB, and six of IIIA. The 91 HAV strains typed as IA were further divided into four main line-ages, IA-1, IA-2, IA-3, and IA-4, each with a unique epidemiological background. Our nucleotide sequence database of HAV and epidemiological background data will be helpful to investigate sources of infection and the epidemiology of hepatitis A cases in the future.

[Serial Food Poisoning Outbreaks Caused by Norovirus-Contaminated Shredded Dried Laver Seaweed Provided at School Lunch, Tokyo, 2017].

In February 2017, four food poisoning outbreaks occurred in Tokyo, involving ten schools. Shredded dried laver seaweed processed by a single food manufacturer in December 2016 was provided in common for the school meals that caused all four outbreaks. Of 4,209 persons exposed, 1,193 (28.3%) had symptoms of gastroenteritis. Norovirus (NoV) GII was detected in 207 (78.1%) of 265 cases by real-time RT-PCR. Thirty-one shredded dried laver seaweed samples were examined and seven (22.6%) of them were positive for NoV GII. PCR fragments of NoV ORF1/2 junction region (302 bp) from seven shredded dried laver seaweed samples and 20 clinical samples derived from the four outbreaks were sequenced. All of them displayed complete homology, and the genotype was classified as GII.17. A nearly full-length sequence (7,420 bp) of NoV RNA derived from a case was obtained by next-generation sequencer analysis and phylogenetic analysis indicated that this strain belongs to the same cluster as Hu/GII/JP/2015/GII.P17_GII.17/Kawasaki308. Thus, our investigation elucidated that the causative agent of these four serial food poisoning outbreaks was NoV GII.17 and the infectious source was a single batch of shredded dried laver seaweed. The water activity of the shredded dried laver seaweed was found to be 0.119 to 0.129. It was epidemiologically clarified that NoV does not lose infectivity for about two months even in the dry state. We conclude that a large diffuse outbreak of food poisoning caused by NoV GII.17 contamination of shredded dried laver seaweed had occurred in Tokyo. Our elucidation of the causative agent indicated that the food poisoning outbreaks in multiple areas of Japan, including Tokyo, during January to February 2017 were caused by the same contaminated food.

Test-retest reproducibility of extrastriatal binding with 123I-FP-CIT SPECT in healthy male subjects.

123I-labeled 2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) is used to assess striatal dopamine transporter (DAT) expression, but it can also quantify extrastriatal serotonin transporter (SERT) expressions. While FP-CIT uptake in extrastriatal regions has been quantified, no information exists on the reproducibility of the 123I-FP-CIT specific uptake ratio (SUR) in extrastriatal regions. We investigated test-retest reproducibility of 123I-FP-CIT binding in the striatum, the midbrain, and cortical regions in eight healthy male subjects. All subjects underwent two 123I-FP-CIT SPECT scans, and SUR was calculated using the cerebellum as the reference. We found good test-retest reproducibility of 123I-FP-CIT SUR in the midbrain, and in the lateral frontal/temporal cortex and combined cortical regions. The overall variability and intraclass correlation of SUR were, respectively, 4.9-7.8% and 0.90-0.96 in striatal regions, 8.6% and 0.79 in the midbrain, and 3.6-9.1% and 0.84-0.95 in the lateral frontal/temporal cortex and combined cortical regions. Our results provide evidence that 123I-FP-CIT SPECT is a valid technique for analyzing striatal DAT, as well as extrastriatal SERT in areas such as the SERT-enriched midbrain. In addition, our data suggest that 123I-FP-CIT could be used for analyzing SERT in regions with relatively low SERT expression (e.g., temporal or frontal cortices).

[An autochthonous outbreak of dengue type 1 in Tokyo, Japan 2014].

OBJECTIVES: An outbreak of autochthonous dengue fever was reported in August 2014, with cases suspected mainly from Yoyogi Park in Tokyo. This is the first epidemic of dengue fever in Japan since 1945. METHODS: From August to October 2014, the following measures were taken to control the outbreak: 1) risk communication and information sharing; 2) active case finding; 3) vector surveillance in affected sites; and 4) laboratory testing. We also reviewed the surveillance data as reported to the National Epidemiological Surveillance of Infectious Diseases during the 44 epidemiological weeks. results: An official dengue fever call center was set up temporarily for the general public and 3,005 calls were received. The Tokyo Metropolitan Government issued 39 press releases regarding patients and nine related to dengue virus (DENV) detection and vector control activities for the media. Confirmed autochthonous dengue fever cases were reported between the 35th and 44th epidemiological weeks. Out of 160 cases of outbreak, 108 (67.5%) confirmed cases were reported in Tokyo. The estimated illness onset dates were between August 9 and October 7, and estimated dates of infections were between August 3 and October 3, 2014. The data suggest that the infective mosquitoes had already been present in Yoyogi Park at the end of July 2014. During the weekly vector surveillance at Yoyogi Park, a total of 1,152 adult mosquitoes, of which 856 (73.3%) were Aedes mosquitoes, were collected over 11 weeks by a light trap with dry ice. DENV was detected from adult Aedes mosquito samples collected on the 2nd, 9th, and 16th of September, 2014. Serum samples from 240 suspected cases were examined at the Tokyo Metropolitan Institute of Public Health, and 78 were positive for the DENV NS1 antigen, DENV-specific IgM antibody, or DENV nucleic acid with reverse transcriptase polymerase chain reaction (RT-PCR) (NS1: 66 cases; IgM: 50 cases; PCR: 57 cases). Genetic analysis of DENV-positive serum and mosquito samples found all to be categorized as DENV-serotype 1 (gene type I). Phylogenetic analysis of the envelope protein genome sequence from patients and mosquitoes in Tokyo revealed more than 99% similarity with each other and with the strain from the first outbreak-associated patient in Saitama. CONCLUSION: Measures important for control of infectious disease epidemic were learned during this recent indigenous dengue outbreak in Tokyo. It also highlighted the importance of preparedness for epidemics of indigenous or imported infectious diseases, especially in light of the fact that Tokyo is in preparation for the Olympic and Paralympic Games in 2020.

Decision-making deficit of a patient with axonal damage after traumatic brain injury.

Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process.

Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination.

OBJECTIVE: 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) is known to accumulate in benign conditions such as infection and inflammation as well as in malignancy. Vaccination may cause transient inflammation of lymph nodes, which may induce false-positive findings on FDG-positron emission tomography (PET) imaging. This study investigated the influence of influenza vaccination on FDG-PET/CT imaging in normal subjects. METHODS: Between November 2008 and March 2009, a total of 172 examinees underwent FDG-PET/CT during an annual cancer-screening program at our hospital, 83 of whom had a history of recent non-adjuvanted seasonal influenza vaccination. They were asked the date and injection site of the vaccination. Examinees were divided into 2 groups based on the interval after vaccination using a cutoff value of 7 days (1 week). Two double board-certified nuclear medicine physicians and radiologists visually interpreted the FDG-PET/CT images with reference to PET/CT fusion and CT images and checked the location and the number of abnormal accumulations by consensus reading. RESULTS: Intervals between vaccination and FDG-PET were less than 7 days in 5 examinees, and 7 days or more in 78 examinees. Unexpected accumulations were visualized in 4 examinees in the axilla and medial upper arm, and all of them belonged to the group who underwent vaccination less than 7 days previously. In the second group there was no abnormal FDG accumulation. CONCLUSIONS: Recent influenza vaccination before FDG-PET/CT examination may cause ipsilateral axillary lymph node accumulations, especially within several days after vaccination. Questionnaires about vaccination can help to avoid false interpretation of FDG avid axillary lymph nodes.

Comparison of computed tomography myelography and radioisotope cisternography to detect cerebrospinal fluid leakage in spontaneous intracranial hypotension.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: To compare the usefulness of radioisotope cisternography (RIC) and computed tomography myelography (CTM) for the detection of cerebrospinal fluid (CSF) leakage in spontaneous intracranial hypotension (SIH). SUMMARY OF BACKGROUND DATA: CSF leakage sites have been generally identified by RIC in patients with SIH. Although a number of reports have recently indicated the usefulness of CTM, whether RIC or CTM more reliably detects leakage sites has not been decided because the 2 tests have not been directly compared. METHODS: Both RIC and CTM were performed, and the findings were compared in 12 patients with SIH strictly meeting the second edition of the International Classification of Headache Disorders diagnostic criteria. : On RIC, the detection rate of leakage including indirect signs, an early vesicular radioisotope (RI) accumulation and delayed ascent of the RI to the cerebral convexity, was observed in 100%, but that of the direct sign, paraspinal RI accumulation, was in 8 patients (67%). On CTM, the epidural collection of intraspinally administered contrast medium was demonstrated in all patients (100%), and the collection site was located in the cervical and thoracic vertebral regions in most cases. When RIC and CTM findings were collated, paraspinal accumulation in the cervical and thoracic regions on RIC corresponded to the entire or a part of the findings on CTM. In contrast, in 4 of 5 patients with paraspinal accumulation in the lumbosacral region, epidural collection was not noted in this region on CTM. CONCLUSION: In patients with SIH, epidural collection on CTM may more accurately demonstrate CSF leakage compared with paraspinal RI accumulation on RIC.

Bone scan can be spared in asymptomatic prostate cancer patients with PSA of <=20 ng/ml and Gleason score of <=6 at the initial stage of diagnosis.

OBJECTIVE: According to several guidelines, it is acceptable to spare a bone scan in the patients who are newly diagnosed with low-risk prostate cancer. Our aim is to clarify a suitable group whereby a bone scan could be spared at the initial staging of prostate cancer. METHODS: Consecutive 857 patients who were newly diagnosed from 2004 through 2009 and received bone scans using technetium 99m methylene diphosphonate at the initial staging were enrolled. The proportion of positive bone metastases by age distribution, prostate-specific antigen level at diagnosis, Gleason score and clinical T stage were evaluated. Univariate and multivariate logistic regression analyses were performed to identify the predictors of positive bone metastases. RESULTS: Of all 857 patients, 40 patients (4.7%) showed bone metastases. Patients with higher age, prostate-specific antigen level, clinical stage and Gleason score showed significantly higher rate of bone metastases (P < 0.001). In univariate logistic regression analyses, age, prostate-specific antigen level, clinical stage and Gleason score were independent predictors of bone metastasis. The multivariate analysis showed that both the prostate-specific antigen level >50 ng/ml and the Gleason score ≥4 + 3 were independent predictors of bone metastases. CONCLUSIONS: The incidences of bone metastases in patients with a prostate-specific antigen level of ≤20 ng/ml and Gleason score of ≤6 were reasonably low. Collectively, a bone scan is not necessary as a routine examination for these patients at their initial staging of prostate cancer.

Benzodiazepine receptor imaging in an adult with Rasmussen's encephalitis and epilepsia partialis continua.

We describe an adult with Rasmussen's encephalitis associated with widespread decreased accumulation of tracer on 123-I iomazenil (IMZ) SPECT. The patient had a form of epilepsia partialis continua and neurological deterioration associated with hemiatrophy. Cranial MRI showed cerebral atrophy in the left frontal, parietal, and temporal lobes, without abnormal intensity. Delayed IMZ SPECT showed widespread decreased accumulation of tracer in the left temporal and frontal regions. An early scan showed mildly decreased accumulation in the left temporal and frontal regions. Three-dimensional stereotactic surface projection (3D-SSP) analysis showed that the decreased regions on delayed IMZ images were slightly larger as compared with the previous IMZ study performed. Some regions without decreased accumulation of tracer on Tc-ECD or early IMZ images showed decreased accumulation on delayed IMZ images. This case study suggests that benzodiazepine receptors may be reduced in the affected hemisphere of patients with Rasmussen's encephalitis.

Detection of neoplastic meningitis in a patient with gastric cancer by thallium-201 SPECT.

We describe the usefulness of thallium-201 SPECT in a patient with neoplastic meningitis (NM) from gastric carcinoma. Thallium-201 SPECT is of value for the diagnosis of cancer; retention of thallium-201 on delayed images strongly suggests malignancy. NM is a lethal, major neurologic complication of cancer. The standard for the diagnosis of NM is cytologic confirmation of malignant cells in CSF, but cytologic results are often negative (estimated false negative rate, 50%), even when NM is strongly suspected clinically. In patients with equivocal findings, our findings suggest that thallium-201 SPECT is one helpful tool for the detection of NM, particularly when associated with signet-ring cell carcinoma.