Extensive Reorganization of Behavior Accompanies Ontogeny of Aggression in Male Flesh Flies

Aggression, costly in both time and energy, is often expressed by male animals in defense of valuable resources such as food or potential mates. Here we present a new insect model system for the study of aggression, the male flesh fly Sarcophaga crassipalpis, and ask whether there is an ontogeny of aggression that coincides with reproductive maturity. After establishing that reproductive maturity occurs by day 3 of age (post-eclosion), we examined the behavior of socially isolated males from different age cohorts (days 1, 2, 3, 4, and 6) upon introduction, in a test arena, with another male of the same age. The results show a pronounced development of aggression with age. The change from relative indifference to heightened aggression involves a profound increase in the frequency of high-intensity aggressive behaviors between days 1 and 3. Also noteworthy is an abrupt increase in the number of statistically significant transitions involving these full-contact agonistic behaviors on day 2. This elevated activity is trimmed back somewhat by day 3 and appears to maintain a stable plateau thereafter. No convincing evidence was found for escalation of aggression nor the establishment of a dominance relationship over the duration of the encounters. Despite the fact that aggressive interactions are brief, lasting only a few seconds, a major reorganization in the relative proportions of four major non-aggressive behaviors (accounting for at least 96% of the total observation time for each age cohort) accompanies the switch from low to high aggression. A series of control experiments, with single flies in the test arenas, indicates that these changes occur in the absence of the performance of aggressive behaviors. This parallel ontogeny of aggressive and non-aggressive behaviors has implications for understanding how the entire behavioral repertoire may be organized and reorganized to accommodate the needs of the organism

A Pilot Survey: Retention in Pain Medicine Among Fellowship Trained Anesthesiologists

BACKGROUND: We aim to explore the factors related to job satisfaction among pain physicians and identify the reasons why individuals minimize or stop practicing outpatient pain medicine. OBJECTIVES/STUDY DESIGN: This is a survey-based study with the primary goal to identify factors determining job satisfaction and dissatisfaction among pain medicine fellowship graduates who continue to practice and those who are no longer practicing interventional pain. A secondary goal is to elucidate reasons for anesthesiologists trained in pain medicine to leave pain medicine, despite an additional year of training, and to work as general anesthesiologists. METHODS: In this study, all 114 pain program directors listed on the Accreditation Council for Graduate Medical Education (ACGME) website, or their administrative assistants were directly contacted via email. All email addresses were obtained from the ACGME website. The survey opened in September 2021, with reminder emails sent before the closing of the survey in December 2021. A final reminder email was sent 4 weeks prior to the closing of the survey. RESULTS: Of all the respondents, 79 (89.77%) were currently practicing pain medicine, and 9 (10.23%) were no longer practicing pain medicine. LIMITATIONS: Our study has a major limitation as we are unable to determine the response rate and are limited in the data points gathered. CONCLUSION: We hope this study will allow for pain medicine fellowship program directors to improve recruitment and retention of pain fellows in the field while addressing the pros and cons of future career aspirations with anesthesiology residents prior to fellowship selection. A larger, more thorough study with an exact response rate can compare the various outcomes based upon different types of settings, such as private practice, partnership, and academia, as well as geographical locations

A novel knee prosthesis model of implant-related osteo- myelitis in rats

Background and purpose: There have been numerous reports of animal models of osteomyelitis. Very few of these have been prosthesis models that imitate human conditions. We have developed a new rat model of implant-related osteomyelitis that mimics human osteomyelitis, to investigate the pathology of infection after orthop edic implant surgery. Methods: 2 wild-type strains of Staphylococcus aureus, MN8 and UAMS-1, and their corresponding mutants that are unable to produce poly-N-acetyl glucosamine (PNAG) (ica::tet) were injected into the medullary canals of the femur and tibia at 3 different doses: $10^2$, $10^3$, and > $10^4$ CFU/rat. We measured clinical signs, inflammatory markers, radiographic signs, histopathology, and bacteriology in the infected animals. Results: An inoculum of at least $10^4$ cfu of either wild-type bacterial strain resulted in histological, bacteriological, and radiographic signs of osteomyelitis with loosening of the prosthesis. An inoculum of $10^3$ CFU gave signs of osteomyelitis but the prosthesis remained in situ. Bacterial inocula of $10^2$ cfu gave no signs of osteolysis. Interpretation: We have established a new knee prosthesis model that is suitable for reliable induction of experimental implant-associated osteomyelitis with the prosthesis in situ, using a small inoculum of S. aureus. At a dose of $10^3$ CFU/rat, bacteria unable to produce PNAG (ica::tet) had only minor defects in their virulence

Effect of subinhibitory concentrations of four commonly used biocides on the conjugative transfer of Tn916 in Bacillus subtilis

OBJECTIVES: Large amounts of biocides are used to reduce and control bacterial growth in the healthcare sector, food production and agriculture. This work explores the effect of subinhibitory concentrations of four commonly used biocides (ethanol, hydrogen peroxide, chlorhexidine digluconate and sodium hypochlorite) on the conjugative transposition of the mobile genetic element Tn916. METHODS: Conjugation assays were carried out between Bacillus subtilis strains. The donor containing Tn916 was pre-exposed to subinhibitory concentrations of each biocide for a defined length of time, which was determined by an analysis of the transcriptional response of the promoter upstream of tet(M) using β-glucuronidase reporter assays. RESULTS: Ethanol significantly (P = 0.01) increased the transfer of Tn916 by 5-fold, whereas hydrogen peroxide, chlorhexidine digluconate and sodium hypochlorite did not significantly affect the transfer frequency. CONCLUSIONS: These results suggest that exposure to subinhibitory concentrations of ethanol may induce the transfer of Tn916-like elements and any resistance genes they contain

Targeted natural killer cell–based adoptive immunotherapy for the treatment of patients with NSCLC after radiochemotherapy: a randomized phase II clinical trial

Purpose: Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo–activated NK cells in patients with NSCLC after radiochemotherapy (RCT). Patients and Methods: Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60–70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses. Results: The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%–90%] for the INT arm and 33% (95% CI, 5%–68%) for the CTRL arm (P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood

African herbal medicines in the treatment of HIV: Hypoxis and Sutherlandia. An overview of evidence and pharmacology

In Africa, herbal medicines are often used as primary treatment for HIV/AIDS and for HIV-related problems. In general, traditional medicines are not well researched, and are poorly regulated. We review the evidence and safety concerns related to the use of two specific African herbals, which are currently recommended by the Ministry of Health in South Africa and member states for use in HIV: African Potato and Sutherlandia. We review the pharmacology, toxicology and pharmacokinetics of these herbal medicines. Despite the popularity of their use and the support of Ministries of Health and NGOs in some African countries, no clinical trials of efficacy exist, and low-level evidence of harm identifies the potential for drug interactions with antiretroviral drugs. Efforts should be made by mainstream health professionals to provide validated information to traditional healers and patients on the judicious use of herbal remedies. This may reduce harm through failed expectations, pharmacologic adverse events including possible drug/herb interactions and unnecessary added therapeutic costs. Efforts should also be directed at evaluating the possible benefits of natural products in HIV/AIDS treatment

Metal stressors consistently modulate bacterial conjugal plasmid uptake potential in a phylogenetically conserved manner.

Published onlineJOURNAL ARTICLEThe environmental stimulants and inhibitors of conjugal plasmid transfer in microbial communities are poorly understood. Specifically, it is not known whether exposure to stressors may cause a community to alter its plasmid uptake ability. We assessed whether metals (Cu, Cd, Ni, Zn) and one metalloid (As), at concentrations causing partial growth inhibition, modulate community permissiveness (that is, uptake ability) against a broad-host-range IncP-type plasmid (pKJK5). Cells were extracted from an agricultural soil as recipient community and a cultivation-minimal filter mating assay was conducted with an exogenous E. coli donor strain. The donor hosted a gfp-tagged pKJK5 derivative from which conjugation events could be microscopically quantified and transconjugants isolated and phylogenetically described at high resolution via FACS and 16S rRNA amplicon sequencing. Metal stress consistently decreased plasmid transfer frequencies to the community, while the transconjugal pool richness remained unaffected with OTUs belonging to 12 bacterial phyla. The taxonomic composition of the transconjugal pools was distinct from their respective recipient communities and clustered dependent on the stress type and dose. However, for certain OTUs, stress increased or decreased permissiveness by more than 1000-fold and this response was typically correlated across different metals and doses. The response to some stresses was, in addition, phylogenetically conserved. This is the first demonstration that community permissiveness is sensitive to metal(loid) stress in a manner that is both partially consistent across stressors and phylogenetically conserved.The ISME Journal advance online publication, 2 August 2016; doi:10.1038/ismej.2016.98.We thank J Magid for access to the CRUCIAL field plot, LK Jensen for technical assistance in the laboratory and SM Milani for assistance in FACS sorting. This work was funded by the Villum Kann Rasmussen Foundation Center of Excellence CREAM (Center for Environmental and Agricultural Microbiology). UK is currently supported through an MRC/BBSRC grant (MR/N007174/1)