Prevalence of, and risk factors for, carriage of carbapenem-resistant Enterobacteriaceae among hospitalized patients in Japan.

BACKGROUND: The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been reported to be lower in Japan than in many other countries. However, extensive surveillance for CRE carriage has not been performed in Japan. AIM: To investigate the prevalence of CRE carriage in Japan among convalescent patients considered to be at high risk of being CRE carriers using an improved selective culture medium. METHODS: A cross-sectional survey was conducted in 22 acute care hospitals (ACHs) and 21 long-term care hospitals (LTCHs) in northern Osaka from December 2015 to January 2016. Patients who used incontinence aids, an enteral feeding tube or a urinary catheter were enrolled. Faecal specimens were examined using the newly developed M-ECC for imipenemase (IMP)-producing CRE, which is the most prevalent form of CRE in Japan. The positive isolates were analysed by polymerase chain reaction and sequencing. Risk factors associated with carriage were analysed by logistic regression. FINDINGS: Among 1507 patients, 184 (12.2%) carried CRE. The percentage of positive patients was significantly higher in LTCHs (14.9%) than in ACHs (3.6%) (P<0.001). Risk factors for CRE carriage were longer hospital stay [odds ratio (OR) 2.59; 95% confidence interval (CI) 1.87-3.60], enteral feeding (OR 3.03, 95% CI 2.08-4.42) and antibiotic exposure (OR 2.00, 95% CI 1.40-2.87). Among the 233 CRE isolates identified, 223 were IMP producers; the remaining isolates did not produce carbapenemase. CONCLUSIONS: This is the first Japanese report to demonstrate the significant spread of CRE in both ACHs and LTCHs using an improved selective medium. A coordinated regional approach may help to prevent further spread.

Time-Resolved Measurement of Interatomic Coulombic Decay Induced by Two-Photon Double Excitation of Ne_{2}.

The hitherto unexplored two-photon doubly excited states [Ne^{*}(2p^{-1}3s)]_{2} were experimentally identified using the seeded, fully coherent, intense extreme ultraviolet free-electron laser FERMI. These states undergo ultrafast interatomic Coulombic decay (ICD), which predominantly produces singly ionized dimers. In order to obtain the rate of ICD, the resulting yield of Ne_{2}^{+} ions was recorded as a function of delay between the extreme ultraviolet pump and UV probe laser pulses. The extracted lifetimes of the long-lived doubly excited states, 390(-130/+450) fs, and of the short-lived ones, less than 150 fs, are in good agreement with ab initio quantum mechanical calculations.

Interatomic Coulombic decay cascades in multiply excited neon clusters.

In high-intensity laser light, matter can be ionized by direct multiphoton absorption even at photon energies below the ionization threshold. However on tuning the laser to the lowest resonant transition, the system becomes multiply excited, and more efficient, indirect ionization pathways become operative. These mechanisms are known as interatomic Coulombic decay (ICD), where one of the species de-excites to its ground state, transferring its energy to ionize another excited species. Here we show that on tuning to a higher resonant transition, a previously unknown type of interatomic Coulombic decay, intra-Rydberg ICD occurs. In it, de-excitation of an atom to a close-lying Rydberg state leads to electron emission from another neighbouring Rydberg atom. Moreover, systems multiply excited to higher Rydberg states will decay by a cascade of such processes, producing even more ions. The intra-Rydberg ICD and cascades are expected to be ubiquitous in weakly-bound systems exposed to high-intensity resonant radiation.

Femtosecond charge and molecular dynamics of I-containing organic molecules induced by intense X-ray free-electron laser pulses.

We studied the electronic and nuclear dynamics of I-containing organic molecules induced by intense hard X-ray pulses at the XFEL facility SACLA in Japan. The interaction with the intense XFEL pulse causes absorption of multiple X-ray photons by the iodine atom, which results in the creation of many electronic vacancies (positive charges) via the sequential electronic relaxation in the iodine, followed by intramolecular charge redistribution. In a previous study we investigated the subsequent fragmentation by Coulomb explosion of the simplest I-substituted hydrocarbon, iodomethane (CH3I). We carried out three-dimensional momentum correlation measurements of the atomic ions created via Coulomb explosion of the molecule and found that a classical Coulomb explosion model including charge evolution (CCE-CE model), which accounts for the concerted dynamics of nuclear motion and charge creation/charge redistribution, reproduces well the observed momentum correlation maps of fragment ions emitted after XFEL irradiation. Then we extended the study to 5-iodouracil (C4H3IN2O2, 5-IU), which is a more complex molecule of biological relevance, and confirmed that, in both CH3I and 5-IU, the charge build-up takes about 10 fs, while the charge is redistributed among atoms within only a few fs. We also adopted a self-consistent charge density-functional based tight-binding (SCC-DFTB) method to treat the fragmentations of highly charged 5-IU ions created by XFEL pulses. Our SCC-DFTB modeling reproduces well the experimental and CCE-CE results. We have also investigated the influence of the nuclear dynamics on the charge redistribution (charge transfer) using nonadiabatic quantum-mechanical molecular dynamics (NAQMD) simulation. The time scale of the charge transfer from the iodine atomic site to the uracil ring induced by nuclear motion turned out to be only ∼5 fs, indicating that, besides the molecular Auger decay in which molecular orbitals delocalized over the iodine site and the uracil ring are involved, the nuclear dynamics also play a role for ultrafast charge redistribution. The present study illustrates that the CCE-CE model as well as the SCC-DFTB method can be used for reconstructing the positions of atoms in motion, in combination with the momentum correlation measurement of the atomic ions created via XFEL-induced Coulomb explosion of molecules.

Bioassay-guided isolation and evaluation of antimicrobial compounds from Ixora megalophylla against some oral pathogens.

Context Ixora megalophylla Chamch. (Rubiaceae) is a new plant species recently found in southern Thailand. Ethyl acetate extracts of its leaves and stems showed antimicrobial activities. Objectives To isolate and identify the antimicrobial compounds from I. megalophylla leaves and stems. Materials and methods The dried leaves (1.7 kg) and stems (3.5 kg) were consecutively extracted with petroleum ether (5 L × 4), ethyl acetate (5 L × 3) and ethanol (5 L × 4) under reflux conditions. The ethyl acetate extract was subjected to an antimicrobial assay guided isolation with Candida albicans and Streptococcus mutans. Compounds 1-10 were identified by (1)H NMR, (13)C NMR and EI-MS. Minimal lethal concentration (MLC) against C. albicans and Streptococcus spp. was determined using a broth microdilution method for 48 and 24 h, respectively. Results and discussion On the basis of the antimicrobial assay guided isolation, 10 known compounds, including vanillic acid (1), syringic acid (2), 4-hydroxy benzaldehyde (3), scopoletin (4), loliolide (5), syringaldehyde (6), sinapaldehyde (7), coniferaldehyde (8), syringaresinol (9) and 2,2'-dithiodipyridine (10), were identified. Compounds 1-5 were purified from the ethyl acetate extract of the leaves, while 6-9 and 10 were from the ethyl acetate and ethanol extracts of the stems, respectively. Among these isolates, 10 showed the strongest antibacterial activities against S. mutans and Streptococcus mitis, with minimum inhibitory concentrations (MICs) of 2-4 µg/mL, and MLC of 4 µg/mL, as well as having a weak antifungal activity against C. albicans (MIC of 125 µg/mL). This is the first report of the antimicrobial activities of 10.

Slow Interatomic Coulombic Decay of Multiply Excited Neon Clusters.

Ne clusters (∼5000 atoms) were resonantly excited (2p→3s) by intense free electron laser (FEL) radiation at FERMI. Such multiply excited clusters can decay nonradiatively via energy exchange between at least two neighboring excited atoms. Benefiting from the precise tunability and narrow bandwidth of seeded FEL radiation, specific sites of the Ne clusters were probed. We found that the relaxation of cluster surface atoms proceeds via a sequence of interatomic or intermolecular Coulombic decay (ICD) processes while ICD of bulk atoms is additionally affected by the surrounding excited medium via inelastic electron scattering. For both cases, cluster excitations relax to atomic states prior to ICD, showing that this kind of ICD is rather slow (picosecond range). Controlling the average number of excitations per cluster via the FEL intensity allows a coarse tuning of the ICD rate.

Nanoplasma Formation by High Intensity Hard X-rays.

Using electron spectroscopy, we have investigated nanoplasma formation from noble gas clusters exposed to high-intensity hard-x-ray pulses at ~5 keV. Our experiment was carried out at the SPring-8 Angstrom Compact free electron LAser (SACLA) facility in Japan. Dedicated theoretical simulations were performed with the molecular dynamics tool XMDYN. We found that in this unprecedented wavelength regime nanoplasma formation is a highly indirect process. In the argon clusters investigated, nanoplasma is mainly formed through secondary electron cascading initiated by slow Auger electrons. Energy is distributed within the sample entirely through Auger processes and secondary electron cascading following photoabsorption, as in the hard x-ray regime there is no direct energy transfer from the field to the plasma. This plasma formation mechanism is specific to the hard-x-ray regime and may, thus, also be important for XFEL-based molecular imaging studies. In xenon clusters, photo- and Auger electrons contribute more significantly to the nanoplasma formation. Good agreement between experiment and simulations validates our modelling approach. This has wide-ranging implications for our ability to quantitatively predict the behavior of complex molecular systems irradiated by high-intensity hard x-rays.

Premenstrual syndrome: management and pathophysiology.

Premenstrual syndrome (PMS) is triggered by hormonal events ensuing after ovulation. The symptoms can begin in the early, mid, or late luteal phase and are not associated with defined concentrations of any specific gonadal or non-gonadal hormone. Women with PMS experience affective or somatic symptoms that cause severe dysfunction in social or occupational realms. Although evidence for a hormonal abnormality has not been established, the symptoms of the premenopausal disorders are related to the production of progesterone by the ovary. The progesterone metabolites may bind to a neurosteroid-binding site on the membrane of the neurotransmitters. Thus, ovulation suppression is an area of focus for diagnostic and treatment options. Many treatment studies have focused on suppression of ovulation with gonadotropin-releasing hormone analogs (GnRHa), high doses of transdermal estrogen, and bilateral oophorectomy all have positive evidence as treatment options for prevention of PMS. However, because of these limitations and their substantial intensive care, these do not appear to be appropriate methods for conventional treatment of PMS. Serotonergic antidepressants, selective serotonin reuptake inhibitors, are well-established, highly effective, and first-line pharmacologic therapy.

A large ovarian leiomyoma discovered incidentally in a 76-year-old woman: case report.

BACKGROUND: Ovarian leiomyoma is very rare type of ovarian tumor. This benign tumor is seen in the pediatric age group to premenopausal women. CASE: A 76-year-old woman had a huge leiomyoma (19 x 11 x 10 cm) of the right ovary. The preoperative diagnosis was difficult to distinguish from a broad ligament leiomyoma or ovarian cancer. CONCLUSIONS: Although theses tumors are benign, its extreme rarity led us to report an additional and rather unusual case of ovarian leiomyoma, and to focus some attention on this type of tumor.

Levonorgestrel-releasing intrauterine device used for dysmenorrhea: five-year literature review.

Intrauterine devices (IUDs) provide highly effective, long-term, safe, reversible contraception, and are the most widely used reversible contraceptive method worldwide. The levonorgestrel-releasing IUD (LNG-IUD), originally designed for long-term contraceptives, is now recognized to provide non-contraceptive health benefits. These include severe dysmenorrhea and/or heavy menstrual bleeding associated with uterine myoma, endometriosis, and adenomyosis. This report aims to review the last five-year literature on the efficacy and safety of the LNG-IUD in women with dysmenorrhea. Dysmenorrhea has been reported to decrease in all women. LNG-IUD seems to be superior over copper-releasing IUD for improving dysmenorrhea. The LNG-IUD is beneficial for symptom recurrence and endometriotic cyst recurrence after conservative surgery for patients with severe pain related to endometriosis. There is also evidence to support its role in menstrual problems of severely obese adolescent females. Expulsion, one of the important factors for IUD acceptability, is rare but more common in women with distorted uterine cavity. In the treatment of dysmenorrhea, the LNG-IUD is equal or superior to treat with systemic progestins or oral contraceptives even in adolescent or menopausal women.

Deep inner-shell multiphoton ionization by intense x-ray free-electron laser pulses.

We have investigated multiphoton multiple ionization dynamics of xenon atoms using a new x-ray free-electron laser facility, SPring-8 Angstrom Compact free electron LAser (SACLA) in Japan, and identified that Xe(n+) with n up to 26 is produced at a photon energy of 5.5 keV. The observed high charge states (n≥24) are produced via five-photon absorption, evidencing the occurrence of multiphoton absorption involving deep inner shells. A newly developed theoretical model, which shows good agreement with the experiment, elucidates the complex pathways of sequential electronic decay cascades accessible in heavy atoms. The present study of heavy-atom ionization dynamics in high-intensity hard-x-ray pulses makes a step forward towards molecular structure determination with x-ray free-electron lasers.

Isolation of new monoterpene coumarins from Micromelum minutum leaves and their cytotoxic activity against Leishmania major and cancer cells.

On the basis of a leishmanicidal assay-guided isolation, two new monoterpene coumarins, minutin A and minutin B, were purified from Micromelum minutum leaves together with four known coumarins, 8,4″-dihydroxy-3″,4″-dihydrocapnolactone-2',3'-diol, 8-hydroxyisocapnolactone-2',3'-diol, 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol, and clauslactone E. Among these compounds, minutin A, minutin B, 8-hydroxyisocapnolactone-2',3'-diol and clauslactone E showed a significant cytotoxic activity against Leishmania major with IC50 values of 26.2, 20.2, 12.1, and 9.8 µM, respectively, while 8,4″-dihydroxy-3″4″-dihydrocapnolactone-2',3'-diol and 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol were not active. However, all these compounds exhibited some inhibitory activity against one or more lung adenocarcinoma (SBC3 and A549) and leukaemia (K562, and K562/ADM) cell lines. Amongst these, clauslactone E, minutin B and 8-hydroxyisocapnolactone-2',3'-diol possessed the strongest cytotoxic activity against SBC3, A549, K562, and K562/ADM cell lines, with IC50 values of 3.7, 10.4, 12.1, and 10.8 µM for clauslactone E; 9.6, 17.5, 8.7 and 6.7 µM for minutin B; 8.8, 10.1, 16.9, and 10.1 µM for 8-hydroxyisocapnolactone-2',3'-diol, respectively.

Novel [corrected] medical management of primary bladder endometriosis with dienogest: a case report.

BACKGROUND: Because of its low incidence, medical treatment of has not yet been well established although surgical excision is generally considered effective. We report the first case of primary bladder endometriosis successfully managed with a novel progestin dienogest. CASE: A 39-year-old woman, nulligravida, presented with lower urinary tract symptoms, especially during menstruation. Cystoscopy, with subsequent cold cup biopsy, revealed a solitary submucosal mass (2 x 2 cm) in the bladder on the posterior wall; histopathology revealed the diagnosis of extraperitoneal endometriosis. MRI and laparoscopy confirmed no peritoneal endometriosis implants or adenomyosis. She was treated with oral 2 mg/day dienogest for six months. The measurable lesion exhibited a remarkable reduction in its size, accompanied with immediate relief of the lesion-related symptoms. At one year after medication cessation, she is well and symptom-free. CONCLUSION: Dienogest may be a novel conservative alternative for bladder endometriosis, in particular for women who wish to avoid surgical intervention.

Peptide YY producing strumal carcinoid tumor of the ovary.

BACKGROUND: Primary ovarian carcinoid tumor is uncommon and represents less than 0.1% of ovarian malignancies. The strumal carcinoid may be complicated by carcinoid syndrome induced by peptide YY (PYY). CASE REPORT: We describe a 45-year-old woman with a bilateral ovarian tumor diagnosed through periodical gynecological examination. She presented with severe constipation. Right ovarian cyst laparoscopically resected was diagnosed as a strumal carcinoid tumor; the left one was mature cystic teratoma. No metastatic findings were seen macroscopically on the ovarian surface and pelvic peritoneum. Constipation was drastically improved by resecting the tumor. The carcinoid tumor cells were positive for tumor-producing PYY by mRNA analysis. CONCLUSION: It is important to be aware of this entity in the pathological diagnosis of ovarian tumors, in the presence of any clinical indicator of carcinoid tumor/syndrome, as it carries a markedly better prognosis and clinical outcome in comparison with most other malignant ovarian tumors.

Ovarian torsion; early diagnosis by MRI to prevent irreversible damage.

BACKGROUND: Early diagnosis of ovarian torsion can help prevent irreversible damage to the adnexal structures in women desiring to maintain fertility. CASE: The patient was transferred by ambulance for a six-hour history of severe lower abdominal pain. Magnetic resonance imaging (MRI) revealed bilateral enlarged ovaries measuring 5 x 6 cm (right) and 4 x 5 cm (left) with a right twisted and thickened peduncle. Ultrasonography failed to detect the peduncle changes. At surgery, the right adnexa was twisted 180 degrees in a clockwise direction with no findings suggestive of gangrenous change, hemorrhagic infarction or ischemic change. Detorsion of the twisted ovary was performed. CONCLUSION: Detection of tube torsion at MRI may be useful in the preoperative evaluation for surgical detorsion of twisted adnexa encountered in enlarged ovaries.

Cervical cancer metastasis to the scalp: case report and literature review.

BACKGROUND: Distant metastasis in carcinoma of the uterine cervix is a rare manifestation, with scalp metastasis being an exceptional event. CASE: We describe a 48-year-old woman with Stage IIb, squamous cell carcinoma of the cervix who was initially treated with radical hysterectomy and lymphadenectomy followed by concurrent chemoradiotherapy. The patient presented eight months later with swelling over the top of the scalp. The scalp was involved in the disease as the sole anatomic site of distant metastasis. CONCLUSION: A search of the literature revealed only seven cases of such distant metastatic involvement of the scalp from cervical cancer. More frequent reports and better understanding on these rare events may give new insight to clear strategies to prevent scalp metastases.

Uterovaginal duplication with blind hemivagina and ipsilateral renal agenesis: review of unusual presentation.

Congenital abnormalities of the Müllerian duct system can result in various urogenital anomalies, including uterus didelphys with blind hemivagina and ipsilateral renal agenesis (Herlyn-Werner-Wunderlich syndrome). It usually presents after the menarche with progressive pelvic pain during periods secondary to haematocolpos. However, rarely presentation is unusual with consequent diagnostic delay. This paper attempts to review the medical literature for rare presentations that make diagnosis and treatment difficult, including our cases. Clinicians must be aware of the importance of this rare congenital anomaly of the female genital tract, especially many years after the menarche. This condition should be considered to prevent misdiagnosis or suboptimal treatment.

Sequential methotrexate treatment with and estrogen and progestin in a retained adhesive placenta.

BACKGROUND: Hysterectomy is the definite and recommended treatment of a retained adhesive placenta. CASE: A 33-year-old woman at 38 weeks plus one day of gestation had a cesarean delivery due to previous history of myomectomy. On ultrasound placental retention was noted thus curettage was attempted two weeks postpartum but it induced moderate fresh bleeding. A contrast-enhanced computed tomography scan depicted the multiple vessels within the intrauterine mass and the absence of deep myometrial invasion. The patient received four doses of 50 mg of methotrexate intramuscularly every other day, alternating with four doses of 15 mg of folic acid. An attempt to evacuate the necrotic tissue along with withdrawal bleeding was successful after three courses of sequential conjugated estrogen (0.25 mg)-progestin (5 mg) therapy. CONCLUSION: The use of estrogen and progestogen together with methotrexate in combination may be simple and potentially effective for placenta accreta and placenta increta.

Isolation and sequencing of pig Blm and Ubl-1/SUMO-1 genes that relate to the recombination machinery.

BACKGROUND: The gene knockout technique is important in xenotransplantation research. Herein we have described the molecular cloning of two genes that are candidates to overcome the poor rate of homologous recombination. METHODS: Candidate cDNA fragments were amplified by polymerase chain reaction (PCR) with the corresponding primer sets deduced from a multiple alignment analysis of other mammalian genes from a cDNA library prepared from pig spleen tissue. To obtain the full-length cDNA, a 5'- and 3'-RACE PCR experiments was performed. RESULTS: We successfully isolated the cDNA sequences of two pig genes--BLM, a Bloom's syndrome-related gene, and UBL-1/SUMO-1--which are closely related to homologous recombination events. As a result, we verified the sequences of pig BLM and pig UBL-1/SUMO-1. The nucleic acid and amino acid coding sequence homologies of pig BLM gene with the corresponding human gene were 87.3% and 82.9%, respectively. The nucleic acid and amino acid coding sequence homologies of the pig UBL-1/SUMO-1 gene with the human gene were 96.4% and 100%, respectively. CONCLUSION: Current research into homologous recombination provides the possibility for improvement of gene knockout efficiency by regulating the gene expression profiles of recombination-related genes. Transient interference with the expression of pig UBL-1/SUMO-1 and BLM is expected to improve gene targeting. The results of the present study provided important information to design siRNA knockdown vectors. They were also useful for ex ante evaluation of expression profiles of these genes in primary cultures of somatic cells, which may enhance the production of gene knockout pigs.

Molecular cloning of pig Rad51, Rad52, and Rad54 genes, which are involved in homologous recombination machinery.

BACKGROUND: The low rate of homologous recombination in somatic cells is considered to be an urgent issue. Therefore, we molecularly cloned three genes that relate to efficient homologous recombination. METHODS: Polymerase chain reaction (PCR) was performed to isolate candidate cDNA fragments from a pig spleen cDNA library with the corresponding primer sets deduced from multiple alignment analysis of other mammalian genes. A 5'- and 3'-RACE PCR experiment was performed to determine the complete cDNA sequences. RESULTS: The complete cDNA sequences of the pig RAD51, RAD52, and RAD54 genes, which are closely related to homologous recombination events, were identified using molecular cloning technique. The cDNA sequences of three genes were successfully isolated by PCR-based methods. As a result, we determined the sequences of pig RAD51 (1663 bp, 339 aa), RAD52 (1884 bp, 406 aa), and RAD54 (2884 bp, 747 aa). The nucleic acid sequence homologies of the pig RAD51, RAD52, and RAD54 genes compared with the corresponding human genes were 92.9%, 77.3%, and 90.0%; the corresponding amino acid sequence homologies were 98.8%, 71.1%, and 95.0%, respectively. CONCLUSION: The knockout of alpha-1,3-galactosyltransferase in pigs resulted in a drastic reduction in xenoantigenicity. However, other xenoantigens, in particular, the non-Gal antigens, also need to be down-regulated. Gene transfer to alter expression levels of these recombination-related molecules and/or ex ante evaluation of expression profiles of these genes in primary cultures of somatic cells constitute a new approach to enhancing homologous recombination events during the production of gene knockout pigs.