Delayed fragmentation of isolated nucleobases induced by MeV ions.

We evaluated the dissociation of isolated gas-phase nucleobase molecules induced by mega electron volt (MeV)-energy ions to gain fundamental insights into the reactions of nucleobases upon fast ion irradiation. We studied five nucleobase molecules-adenine, guanine, cytosine, thymine, and uracil-as gas-phase targets. We compared the fragmentation patterns obtained from carbon ion impacts with those obtained from proton impacts to clarify the effect of heavy ion irradiation. We also compared the results with electron impact and photoionization results. In addition, we identified several delayed fragmentation pathways by analyzing the correlation between fragment pairs generated from singly and doubly charged intermediate ions. To determine the lifetimes of delayed fragmentation from singly charged intermediate ions, we evaluated the detection efficiencies of the microchannel plate detector for the neutral fragment HCN as a function of kinetic energy using a new methodology. As the first demonstration of this method, we estimated the lifetimes of C5H5N5+ generated by 1.2-MeV C+ and 0.5-MeV H+ collisions to be 0.87 ± 0.43 and 0.67 ± 0.09 µs, respectively. These lifetimes were approximately one order of magnitude longer than those of the doubly charged intermediate ion C5H5N52+.

Successful live birth in a patient who underwent cranial radiotherapy and systemic chemotherapy by implantation of a cryopreserved blastocyst on day 7.

Preservation of fertility has been recommended for cancer-bearing patients of reproductive age before undergoing cancer treatment. However, there are many considerations and it is difficult to preserve fertility for all patients undergoing therapy for malignancies. Female cancer survivors had lower pregnancy and live birth rates compared with others that underwent assisted reproductive technologies (ARTs). We should continue to consider the issue of infertility in patients who underwent therapies for malignancies. This is the first report of a successful live birth in a patient with a cranial tumor who underwent radiotherapy and chemotherapy after implantation of an autologous embryo. The patient was a 27-year-old Japanese woman. She was diagnosed with suprasellar germinoma at 13 years of age, and she developed panhypopituitarism after radiotherapy and chemotherapy. At 27 years of age, she began infertility treatment with in-vitro fertilization (IVF). The level of anti-Mallerian hormone (AMH) was 4.29 ng/ml. After ovarian stimulation by high purified human menopausal gonadotropin (HP-hMG), she obtained two blastocysts and became pregnant by implantation of a cryopre- served blastocyst. At 37 gestational weeks, she delivered a healthy female baby by cesarean section.

A comparative analysis of micafungin and caspofungin for empirical antifungal therapy in antibiotic-unresponsive febrile patients with hematologic malignancies.

This study was retrospectively carried out to compare the efficacy of echinocandins such as micafungin (MCFG) and caspofungin (CPFG) in the treatment of antibiotic-unresponsive febrile patients with hematologic malignancies. A total of 163 patients received either MCFG or CPFG. We evaluated the efficacy of echinocandin against fever decline in all patients. Fever decline, defined as a body temperature of less than 37.5 °C sustained for more than 48 h without scheduled antipyretic medication. Efficacy assessments showed that the incidence of fever decline was not significantly different between the MCFG and CPFG groups (P=0.599). The median number of days from the start of echinocandin administration to fever decline was 5 in both the MCFG and CPFG groups. Multivariate analysis showed that the use of anti-MRSA drugs (HR, 0.64; 95%CI, 0.45-0.90; P=0.011) and a change from echinocandins to voriconazole or liposomal-amphotericin B (HR, 0.50; 95%CI, 0.30-0.74; P<0.001) are significant risk factors for sustained fever. A significant difference (P=0.002) in incidence of fever decline was however associated with differences in the timing of anti-MRSA drug administration. The median number of days from the start of echinocandin administration to fever decline was 5 when administration of the anti-MRSA drug occurred "simultaneously or prior to echinocandin start" and 11 in the "next day or later of echinocandin start" group. In other words, starting anti-MRSA drug treatment after echinocandin treatment is a risk factor. In conclusion, MCFG and CPFG have similar efficacy as empirical antifungal agents in the treatment of antibioticunresponsive febrile patients with hematopoietic malignancies.

Risk factors for neutropenia with lenalidomide plus dexamethasone therapy for multiple myeloma.

Neutropenia may develop as an adverse event in patients with multiple myeloma receiving lenalidomide (LEN) plus dexamethasone (DEX) therapy. In the present study, we examined the risk factors associated with grade 3/4 neutropenia during the first cycle of LEN plus DEX therapy. We observed that hemoglobin level (≤ 8.5 g/dl) was a significant risk factor for grade 3/4 neutropenia during the first cycle of therapy (odds ratio: 19.40; 95% confidence interval: 2.68-141.00; p < 0.01). thus, our findings suggest that determining the hemoglobin level could be useful in the risk management for neutropenia in patients receiving LEN plus DEX therapy.

Rapamycin Prolongs Cardiac Allograft Survival in a Mouse Model by Inducing Myeloid-Derived Suppressor Cells.

Mammalian target of rapamycin (mTOR) inhibitors are the main immunosuppressive drugs for organ transplant recipients. Nevertheless, the mechanisms by which mTOR inhibitors induce immunosuppression is not fully understood. Myeloid-derived suppressor cells (MDSCs) maintain host immunity; however, the relationship between mTOR inhibitors and MDSCs is unclear. Here, the results from a murine cardiac transplantation model revealed that rapamycin treatment (3 mg/kg, intraperitoneally on postoperative days 0, 2, 4, and 6) led to the recruitment of MDSCs and increased their expression of inducible nitric oxide synthase (iNOS). Immunohistochemical analysis revealed that rapamycin induced the migration of iNOS-expressing MDSCs into the subintimal space within the allograft vessels, resulting in a significant prolongation of graft survival compared with that in the untreated group (67 days vs. 7 days, respectively). These effects were counterbalanced by the administration of an anti-Gr-1, which reduced allograft survival to 21 days. Moreover, adoptive transcoronary arterial transfer of MDSCs from rapamycin-treated recipients prolonged allograft survival; this increase was reversed by the anti-Gr-1 antibody. Finally, co-administration of rapamycin and a mitogen-activated protein kinase kinase (MEK) inhibitor trametinib reversed rapamycin-mediated MDSC recruitment. Thus, the mTOR and Raf/MEK/extracellular signal regulated kinase (ERK) signaling pathways appear to play an important role in MDSC expansion.

Testing the validity and acceptability of the diagnostic criteria for Hoarding Disorder: a DSM-5 survey.

BACKGROUND: The DSM-5 Obsessive-Compulsive Spectrum Sub-Workgroup is recommending the creation of a new diagnostic category named Hoarding Disorder (HD). The validity and acceptability of the proposed diagnostic criteria have yet to be formally tested. METHOD: Obsessive-compulsive disorder/hoarding experts and random members of the American Psychiatric Association (APA) were shown eight brief clinical vignettes (four cases meeting criteria for HD, three with hoarding behaviour secondary to other mental disorders, and one with subclinical hoarding behaviour) and asked to decide the most appropriate diagnosis in each case. Participants were also asked about the perceived acceptability of the criteria and whether they supported the inclusion of HD in the main manual. RESULTS: Altogether, 211 experts and 48 APA members completed the survey (30% and 10% response rates, respectively). The sensitivity and specificity of the HD diagnosis and the individual criteria were high (80-90%) across various types of professionals, irrespective of their experience with hoarding cases. About 90% of participants in both samples thought the criteria would be very/somewhat acceptable for professionals and sufferers. Most experts (70%) supported the inclusion of HD in the main manual, whereas only 50% of the APA members did. CONCLUSIONS: The proposed criteria for HD have high sensitivity and specificity. The criteria are also deemed acceptable for professionals and sufferers alike. Training of professionals and the development and validation of semi-structured diagnostic instruments should improve diagnostic accuracy even further. A field trial is now needed to confirm these encouraging findings with real patients in real clinical settings.

Characteristics of prolonged luteal phase identified by milk progesterone concentrations and its effects on reproductive performance in Holstein cows.

A database of milk progesterone profiles consisting 497 lactations in 3 dairy herds from northern and western regions of Japan was used to identify the characteristics and associated risk factors for prolonged luteal phase (PLP) and its effects on subsequent reproductive performance in high-producing Holstein cows. Milk samples were collected twice weekly and progesterone concentrations in whole milk were determined by ELISA. Herds were visited monthly and examined by vaginoscopy and transrectal palpation. Resumption of ovarian cyclicity within 35 d postpartum followed by regular cycles was considered normal. Prolonged luteal phase was defined when progesterone concentrations were ≥5 ng/mL for ≥20 d of duration in any cycle postpartum. Delay of first ovulation to 35 to 60 d (delayed first ovulation type I), >60 d (delayed first ovulation type II), a luteal phase of <14 d except in the first cycle (short luteal phase), and the absence of luteal activity >14 d between 2 cycles (cessation of cyclicity) were the other categories of abnormal ovarian resumptions considered. The overall incidence of PLP in the 3 herds was 11.9% and a significantly higher proportion of PLP was observed in the first cycle postpartum compared with the second and third cycles. Approximately 83% of the PLP were 20 to 28 d in duration, and maximum progesterone concentration was significantly higher when PLP lasted >35 d compared with PLP of 20 to 35 d in duration. Higher parity, commencement of luteal activity≤28 d postpartum, and postpartum complications significantly increased the occurrence of PLP within 90 d postpartum. Cows with PLP showed reduced conception rate to first artificial insemination (AI) and reduced pregnancy proportions within 100, 150, and 210 d postpartum. Based on survival analysis, PLP was associated with a 56% reduction in relative pregnancy rate and a 36% reduction in AI submission rate. Cows that experienced PLP had a longer interval from calving to first AI (74 d) and from calving to pregnancy (141 d) than cows without PLP (53 and 80 d), respectively. In conclusion, 11.9% of lactations had PLP, of which approximately two-thirds were seen in the first cycle postpartum. Most of the PLP were 20 to 28 d in duration. Higher parity, postpartum complications, and early commencement of luteal activity postpartum increased the risk for PLP. Occurrence of PLP adversely affected fertility by reducing pregnancy proportions and extending calving to conception interval.

Plasma cortisol concentrations after CIDR insertion in beef cows.

The objective of this study was to show plasma cortisol concentration after treatment with controlled internal drug release (CIDR) in non-suckling beef cows. On day 9 after oestrus, two cows were inserted with CIDR into the vagina for 24 h and the other two cows were treated as a control group. Four days later, the two control cows were treated with CIDR and the other two CIDR-treated cows were used as controls. Cortisol concentrations were determined by ELISA in plasma samples collected before, during and after insertion of CIDR. There was a significant increase in plasma cortisol concentrations (p<0.01) after insertion of CIDR. Mean (± SEM) plasma cortisol concentrations increased from 1.3 ± 0.4 to a peak of 8.8 ± 1.1 ng/ml at 5 h and then decreased to basal concentrations at 7 h after insertion of the device. In conclusion, the insertion of intra-vaginal device causes an increase in plasma cortisol concentrations in beef cows, although the pathophysiological significance of the elevation of cortisol is not known.

Adrenocortical response in cows after intramuscular injection of long-acting adrenocorticotropic hormone (tetracosactide acetate zinc suspension).

The objectives of this study were first to show adrenocortical response to a long-acting adrenocorticotropic hormone preparation (tetracosactide acetate zinc suspension) (ACTH-Z) and its effect on adrenocortical function in beef cows (Experiment 1) and second to apply the ACTH-Z challenge in dairy cows based on cortisol concentrations in milk collected at routine milking (Experiment 2). In Experiment 1, four beef cows in luteal phase were challenged with ACTH-Z, and plasma cortisol concentrations were determined for 48 h after the injection at 30-min to 2-h intervals. A rapid ACTH test was conducted 3 days before and 2 h after the completion of ACTH-Z injection for 48 h to investigate the effect on adrenocortical function. Plasma cortisol concentrations increased significantly 30 min after ACTH-Z injection (p < 0.001), and the high cortisol levels were maintained for approximately 10 h after the injection. In Experiment 2, eight dairy cows were subjected to ACTH-Z challenge 1-2 weeks and 4-5 weeks post-partum. Blood and milk samples were taken at morning and afternoon milking. All the cows showed a significant increase in cortisol concentrations in plasma as well as in skim milk 8 h after ACTH-Z injection 1-2 weeks and 4-5 weeks post-partum (p < 0.001). There was a significant correlation between plasma and skim milk cortisol concentrations 8 h after ACTH-Z challenge (r = 0.74, p < 0.001). The results obtained in this study suggest that elevated levels of plasma cortisol are maintained for approximately 10 h after ACTH-Z treatment without adverse effect on adrenocortical function and a long-acting ACTH-Z challenge based on cortisol concentrations in milk, which were collected at the morning and the afternoon milking, can be a useful tool to monitor adrenocortical function in cows.