Genomic Dissection of Travel-Associated Extended-Spectrum-Beta-Lactamase-Producing Salmonella enterica Serovar Typhi Isolates Originating from the Philippines: a One-Off Occurrence or a Threat to Effective Treatment of Typhoid Fever?

One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing Salmonella enterica serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of S. Typhi. The reported strain was similar to a previously published strain harboring bla_SHV-12 from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing S. Typhi.     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

Disabled and nondisabled infants' interactions with their mothers

This study investigated social interactions between infants and mothers, comparing dyads with physically disabled infants and dyads with nondisabled infants. The groups were matched on mental and motor development, sex, socioeconomic status, birth order, and maternal education. Each infant-mother dyad was videotaped at home during a 10-minute period of free play, and blind observers subsequently transcribed infants' and mothers' behaviors. In general, the groups were remarkably similar in their interaction patterns. However, a few differences emerged: Mothers of infants with physical disabilities were significantly more commanding than were comparison mothers. Nondisabled infants tended to engage in more eye contact than did infants with physical disabilities. And whereas mothers of nondisabled infants responded to interactive play with interactive play, mothers of infants with physical handicaps tended to respond with commands and verbalizations. These results suggest reciprocal influences between infants and mothers in both groups and highlight emerging maternal behavior patterns that may interfere with the development of communication and independence in handicapped young children.     

Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial).

AIMS: Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). METHODS AND RESULTS: We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. CONCLUSION: Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.     

Epididymal cystadenomas in von Hippel-Lindau disease

Objectives. Epididymal cystadenomas (ECs) are frequently found in association with von Hippel-Lindau disease (VHL), but little has been reported about their sonographic appearance. We review the sonographic appearance of ECs, the relationship of ECs to other manifestations of VHL, and the specific genetic mutations associated with ECs.Methods. Fifty-six male patients with VHL were examined with scrotal sonography and physical examination as part of a larger screening program for VHL. The head of the epididymis was measured in two planes on sonography and compared with age-matched normal controls. All VHL patients with palpable epididymal abnormalities or enlargement (more than two standard deviations) of the head of the epididymis on ultrasound were considered positive for EC.Results. Thirty of 56 (54%) male patients with VHL demonstrated a unilateral (n = 10; 33%) or bilateral (n = 20; 67%) solid abnormality in the head of the epididymis suggestive of EC. Sonographic appearances ranged from a solid mass with multiple tiny cysts to an almost completely solid mass. The most common appearance was a 15- to 20-mm solid mass with small cystic components. Dilated efferent ductules were seen within the testicle in 7 men, evidently a result of chronic obstruction. There was no association between the clinical subtype of VHL and the presence of ECs (P >0.10, chi square). Mutations resulting in a truncated gene product were associated with the development of ECs but the association did not reach statistical significance (P = 0.06).Conclusions. ECs are a common manifestation of VHL in men and exhibit a range of appearances on ultrasound. Sonography can be used to identify ECs and determine the extent of cystic dilation of the rete testes. The benign course of ECs and the usual absence of clinical symptoms favor a conservative approach to their management.     

Validation of a self-administered diet history questionnaire using multiple diet records

The validity of a self-administered diet history questionnaire has been estimated using as the reference data the mean of three 4-day diet records collected over the year prior to the administration of the questionnaire, in 1985–1986. Subjects were women ages 45–70 years, participants in the Women's Health Trial Feasibility Study, a multi-center clinical trial in which some women were randomized to be taught to adopt and maintain a low-fat diet, while others maintained their usual diet. The questionnaire produced group mean nutrient estimates closely approximating the values obtained by three 4-day records, e.g. in the usual-diet group, 37.7% of calories from fat by both food records and by questionnaire, and in the low-fat, group, 21.3% of calories from fat by food records and 23.7% of calories from fat by questionnaire. Correlations between questionnaire and diet records for per cent of calories from fat were 0.67 and 0.65 respectively in the two groups; most correlations were in the 0.5–0.6 range, and were similar to those achievable by a single 4-day food record.