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The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the emerging public health challenge of understanding and treating POE children. We examined two scenarios using preclinical models: offspring exposed to oxycodone (OXY) in utero (IUO) and acute postnatal OXY (PNO). We hypothesized exposure to OXY during pregnancy primes offspring for neurodevelopmental deficits and severity of deficits is dependent on timing of exposure. Notable findings include reduced head size and brain weight in offspring. Molecular analyses revealed significantly lower levels of inflammasome-specific genes in the prefrontal cortex (PFC). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) highlighted the enrichment of genes associated with mitochondrial and synapse dysfunction in POE offspring. Western blot analysis validated IPA predictions of mitochondrial dysfunction in PFC-derived synaptosomes. Behavioral studies identified significant social deficits in POE offspring. This study presents the first comparative analysis of acute PNO- and IUO-offspring during early adolescence finding acute PNO-offspring have considerably greater deficits. The striking difference in deficit severity in acute PNO-offspring suggests that exposure to opioids in late pregnancy pose the greatest risk for offspring well-being., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Renal artery stenosis (RAS) is known to co-exist with heart failure (HF), however the impact of RAS on rates of acute kidney injury during an acute HF hospitalization, and adverse events after acute HF hospitalizations has not been well studied., Methods: We performed a retrospective cohort study of subjects hospitalized for acute HF at a tertiary academic care center. We identified subjects who had a renal artery duplex ultrasound or other diagnostic study for RAS to categorize heart failure subjects as RAS+ or RAS-. AKI was defined as a rise from admission to peak creatinine of >0.3 mg/dL or >1.5 fold. In-hospital outcomes including rates of AKI were ascertained. Adverse outcomes over a two-year follow up period were also ascertained., Results: A total of 93 subjects with acute HF hospitalization met the inclusion criteria and were enrolled in this study; 27 (29%) were identified as RAS+. At admission, subjects with RAS had higher rates of diabetes and prior PCI. During the HF hospitalization, subjects with RAS were more likely to develop AKI. No significant differences were identified in baseline or hospital medication use among subjects with versus without RAS. Importantly, the rate of ACE-I/ARB use was low in both groups and no significant difference in ACE-I/ARB use was demonstrated. Subjects with RAS had higher rates of recurrent HF hospitalization during the follow-up period., Conclusions: RAS is prevalent among subjects with acute HF, associated with higher rates of AKI during HF hospitalization, and associated with higher rates of recurrent HF hospitalization during follow-up., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Immune disorders and cancer share a common pathway involving NF-κb signaling. Through involvement with GM-CSF, NF-κB can contribute to proliferation and activation of T- and B- cells as well as immune cell migration to sites of inflammation. In breast cancer, this signaling pathway has been linked to resistance with endocrine and chemotherapies. Similarly, in ovarian cancer, NF-κB influences angiogenesis and inflammation pathways. Further, BRCA1 signaling common to both breast and ovarian cancer also has the capability to induce NF-κB activity. Immunotherapy involving NF-κB can also be implemented to combat chemoresistance. The complex signaling pathways of NF-κB can be harnessed for developing cancer therapeutics to promote immunotherapy for improving patient outcomes., Competing Interests: Authors LS and JN were employed by the company Gradalis, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Devanaboyina, Kaur, Whiteley, Lin, Einloth, Morand, Stanbery, Hamouda and Nemunaitis.)

Ovarian cancer response to immunotherapy is limited; however, the evaluation of sensitive/resistant target treatment subpopulations based on stratification by tumor biomarkers may improve the predictiveness of response to immunotherapy. These markers include tumor mutation burden, PD-L1, tumor-infiltrating lymphocytes, homologous recombination deficiency, and neoantigen intratumoral heterogeneity. Future directions in the treatment of ovarian cancer include the utilization of these biomarkers to select ideal candidates. This paper reviews the role of immunotherapy in ovarian cancer as well as novel therapeutics and study designs involving tumor biomarkers that increase the likelihood of success with immunotherapy in ovarian cancer.

Radiation therapy (RT) in some cases results in a systemic anticancer response known as the abscopal effect. Multiple hypotheses support the role of immune activation initiated by RT-induced DNA damage. Optimal radiation dose is necessary to promote the cGAS-STING pathway in response to radiation and initiate an IFN-1 signaling cascade that promotes the maturation and migration of dendritic cells to facilitate antigen presentation and stimulation of cytotoxic T cells. T cells then exert a targeted response throughout the body at areas not subjected to RT. These effects are further augmented through the use of immunotherapeutic drugs resulting in increased T-cell activity. Tumor-infiltrating lymphocyte presence and TREX1, KPNA2 and p53 signal expression are being explored as prognostic biomarkers.

While ovarian cancer typically responds well to front line treatment, many patients will relapse within 5 years. Treatment options are less effective at each recurrence highlighting the need for novel maintenance therapies. PolyADP-ribose polymerase (PARP) inhibitors have recently gained approval in ovarian cancer maintenance. Niraparib was approved regardless of BRCA mutation status, however impact on overall survival is limited. Oliparib was approved for BRCA mutant and BRCA wildtype/homologous recombination deficient patients. This review will focus on current frontline ovarian cancer treatment as well molecularly based approaches to ovarian cancer management., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background : Returning to employment following moderate to severe traumatic brain injury (msTBI) is critical for a survivor's well-being, yet currently there are no systematic reviews that comprehensively describe employment outcomes following msTBI. The objective of this study was to systematically synthesize literature on employment outcomes following msTBI. Methods : Original studies published through April 2018 on MEDLINE/PubMed, PsychINFO, and CINAHL were eligible if the objective was to investigate employment outcomes following msTBI; outcome was measured ≥1 year; participants were ≥15; and size was ≥60. Post-injury employment prevalence and return to pre-injury level of work were summarized through meta-analysis. Results : Of 38 eligible studies, post-injury employment prevalence was most often reported (n = 35), followed by job stability (n = 6), and return to pre-injury level of work (n = 4). Overall post-injury employment prevalence was 42.2%; whereas the return-to-previous-work prevalence was 33.0%. Post-injury employment prevalence appeared to increase over time, from 34.9% at 1 year to 42.1% up to 5 years and 49.9% beyond 5 years. Conclusion : Nearly half of individuals with msTBI were employed post-injury, yet only a third returned to pre-injury level of work. Future researchers are recommended to standardize employment outcome measures to enable better comparison of outcomes across studies.