Singleport retroperitoneoscopic adrenalectomy Original experience as well as standardization of the technique

In this issue of Med, Sobesky et al. investigate the translational utility of sequencing cell-free DNA to describe genetic features of classic Hodgkin Lymphoma (HL) and to evaluate minimal residual disease (MRD) for patients treated in a clinical trial1.Liquid biopsy detection of residual cancer after therapy offers to transform oncology care. Nonetheless, in the residual cancer context, signals are sparse and are hindered by technical sequencing noise. Kurtz et al.1 introduce phased variant enrichment and detection sequencing (phasED-seq) to increase the circulating tumor DNA signal-to-noise ratio and detect minimal residual disease with unprecedented sensitivity.
Malaria remains a key cause of mortality in low-income countries. RTS,S/AS01 is currently the most advanced malaria vaccine, demonstrating ∼50% efficacy in controlled human malaria infection (CHMI) studies in malaria-naive adults and ∼30%-40% efficacy in field trials in African infants and children. However, a higher vaccine efficacy is desirable.
Modification of the vaccine regimen in a CHMI trial in malaria-naive individuals resulted in significant increase in protection. While three equal monthly RTS,S/AS01 doses (RRR) were used originally, the administration of a delayed third dose with 20% of the original antigen dose (RRr) resulted in ∼87% protection, linked to enhanced antibody affinity maturation. Here, we sought to identify a novel molecular basis for this higher protective efficacy using Systems Serology.
We demonstrate that the delayed fractional dose maintains monocyte phagocytosis and NK activation mediated by NANP6-specific antibodies, key correlates of protection for the RRR regimen. However, it is also marked by a higher breadth of C-term Fc effector functions, including enhanced phagocytosis. The RRr regimen breaches immunodominance of the humoral immune response, inducing a balanced response across the C-terminal (Pf16) and NANP region of CSP, both of which were linked to protection.
Collectively, these data point to an unexpectedly concordant evolution in Fab avidity and expanded C-term Fc effector functions, providing novel insights into the basis for higher protection conferred by the delayed fractional dose in malaria-naive individuals.
This research was supported by PATH's Malaria Vaccine Initiative and the MGH Research Scholars program.
This research was supported by PATH's Malaria Vaccine Initiative and the MGH Research Scholars program.
A poorly functioning tumor vasculature is pro-oncogenic and may impede the delivery of therapeutics. Normalizing the vasculature, therefore, may be beneficial. We previously reported that the secreted glycoprotein leucine-rich α-2-glycoprotein 1 (LRG1) contributes to pathogenic neovascularization. Here, we investigate whether LRG1 in tumors is vasculopathic and whether its inhibition has therapeutic utility.
Tumor growth and vascular structure were analyzed in subcutaneous and genetically engineered mouse models in wild-type and Lrg1 knockout mice. The effects of LRG1 antibody blockade as monotherapy, or in combination with co-therapies, on vascular function, tumor growth, and infiltrated lymphocytes were investigated.
In mouse models of cancer, Lrg1 expression was induced in tumor endothelial cells, consistent with an increase in protein expression in human cancers. The expression of LRG1 affected tumor progression as Lrg1 gene deletion, or treatment with a LRG1 function-blocking antibody, inhibited tuCan 311301 and AngioMature 787181), and DFG (CRC1366).Cardiovascular and renal outcome trials (CVOTs) for glucagon-like-peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) highlight new options for people with and without type 2 diabetes (T2D). Drugs within these classes reduce rates of major adverse cardiovascular events (MACE), with SGLT2i simultaneously attenuating decline in kidney function. SGLT2i reduce rates of heart failure in people with and without T2D, whereas GLP1RA lower rates of myocardial infarction and stroke in people with T2D with or without preexisting cardiovascular disease. Mechanistically, SGLT2 and the GLP-1 receptor are expressed at low levels in the heart, and within some blood vessels and immune cells, implying indirect mechanisms of action for the preservation of ventricular function, and reduction of atherosclerosis. SGLT2i likely preserve renal function through the alteration of glomerular hemodynamics. These two drug classes enable organ protection and reduced mortality in people with T2D and represent promising therapies for some people without T2D.The therapeutic landscape of epidermal growth factor receptor (EGFR)-mutation-positive non-small cell lung cancer (NSCLC) is continually evolving. A recent manuscript in Nature by Robichaux and colleagues1 reports on a structure-based classification of EGFR mutations to help predict sensitivities to EGFR inhibitors in NSCLC that may ultimately improve patient outcomes.The long time that it is taking to achieve a fully efficacious malaria vaccine calls for developing additional control strategies. A recent paper led by the Seder group provides proof of concept that passive administration of monoclonal antibodies can prevent Plasmodium falciparum parasitemia after controlled infection in malaria-naive adults.Vascular normalization therapy has the potential to facilitate drug delivery and lymphocyte infiltration in tumors. Yet, optimal targets and dosage regimens remain elusive. In this issue of Med, O'Connor et al. show that inhibition of LRG1 stabilizes the tumor-associated vasculature to enhance tumor response to both cytotoxic and immune therapies.Adjuvant endocrine therapy has transformed outcomes for patients with early-stage, hormone receptor-positive, HER2-negative breast cancer; however, the optimal duration remains undefined. In a recent issue of The New England Journal of Medicine, Gnant et al. report the results of the ABCSG-16/SALSA trial that investigated the optimal duration of extended adjuvant aromatase inhibition and found that 5 years was not more beneficial than a 2-year extension.1.The discovery of insulin 100 years ago was one of the most important achievements of all time. The plan from the scientists involved was easy access for all. Unfortunately, a century later that idealistic goal was not to be in many places around the world, including the US.RNA nanomedicines present a promising class of therapeutics, with broad applications in protein replacement therapy, gene editing, immunotherapy, and vaccines, owing to their versatility and precise nature. Although recent years have seen dramatic improvements in the safety and efficacy of RNA-based therapies, their functional delivery to target tissues and cells in vivo remains challenging. Here, we discuss many of these challenges, as well as the methods and materials that have been developed to overcome them, with a focus on polymeric and lipid-based nanoscale delivery systems. In addition, we provide an overview of recent clinical and pre-clinical developments in RNA nanomedicines that have been made possible by advances in delivery.Epstein-Barr virus (EBV) is a putative trigger for multiple sclerosis (MS). Bjornevik et al. utilized longitudinal analysis of 10 million adults to strongly link MS to EBV infection1 and Lanz et al. identified clonally expanded B cells in MS that bind EBV EBNA1 and GlialCam.2.Immune-related adverse events (irAEs) occur in almost every organ system in a seemingly unpredictable fashion, causing substantial morbidity and mortality. Lozano et al.1 report peripheral blood profiling from patients receiving immune checkpoint inhibitors, identifying that diverse CD4+ effector memory T cells present prior to treatment are associated with severe irAEs.
Previous research suggests that exposure to alcohol primes (i.e., stimuli associated with alcohol) affects drinkers' perceptions and behaviors. The present study investigated the effects of an environmental alcohol prime (being in a simulated bar setting) and a safe sex message prime (a public health safe sex message) on sexually active alcohol drinkers.
Participants (
= 80) were assigned to one of four conditions according to priming allocation and engaged in a simulated video chat with a potential partner. They reported their sex-related self-perceptions and perceptions of a potential partner upon procedural completion.
The alcohol-related environmental prime led participants to rate their potential partner as being significantly less inhibited and more sexual. selleck chemicals The safe sex message significantly reduced reported sex-related self-perceptions and perceptions of their partners' disinhibition. There was a significant effect of primes on participants' perceptions of their partner's friendliness--participants exposed to either or both prime(s) perceived their partner as being friendlier than participants exposed to no prime.
Results suggest that environmental alcohol primes may strengthen sexually active drinkers' perceptions of a potential partner's disinhibition and sexuality even before alcohol consumption begins, and that a safe sex message may moderate these effects. The presence of safe sex messages in alcohol-related environments may positively influence sexual risk decision making among sexually active drinkers.
Results suggest that environmental alcohol primes may strengthen sexually active drinkers' perceptions of a potential partner's disinhibition and sexuality even before alcohol consumption begins, and that a safe sex message may moderate these effects. The presence of safe sex messages in alcohol-related environments may positively influence sexual risk decision making among sexually active drinkers.
The acquired preparedness model (APM) posits that high sensitivity to reward biases individuals to learn and maintain positive outcome expectancies, which in turn increase substance use, and that high sensitivity to punishment biases individuals to learn and maintain negative outcome expectancies, decreasing use. Little work has applied the APM to cannabis use, particularly with longitudinal data and methods that separate within- and between-person associations. The current study addressed these gaps.
The sample comprised 314 emerging adults (age range 19.13-21.39 years; 52% female; predominantly non-Hispanic White [76%] or African American [15%]) recruited using random-digit dialing. Data were taken from three annual assessments. Latent curve models with structure residuals were used to distinguish between- and within-person associations. We controlled for bidirectional associations and demographic covariates.
At the between-person level, high sensitivity to reward was related to high positive expectano punishment and negative expectancies. However, our findings did not support the notion that the proposed learning processes unfold within individuals across annual assessments. Most notably, the findings emphasize the importance of disaggregating within- and between-person associations using a longitudinal design to better understand pathways to cannabis use in the developmental period of emerging adulthood.
The relationship between smoking and adolescents' peer relationships is complex, with studies showing increased risk of smoking for adolescents of both very high and very low social position. A key question is whether the impact of social position on smoking depends on an adolescent's level of coping motives (i.e., their desire to use smoking to mitigate negative affect).
We assessed how social position predicts nicotine dependence in a longitudinal sample (
= 3,717; 44.8% male; mean age = 13.41 years) of adolescent lifetime smokers measured between 6th and 12th grades. Using both social network analysis and multilevel modeling, we assessed this question at the between-person and within-person level, hypothesizing that within-person decreases in social position would lead to increased risk of nicotine dependence among those with high levels of coping motives.
In contrast to our hypotheses, only interactions with the between-person measures of social position were found, with a slight negative relationship at low levels of coping motives.