Coproduction of Low-Barrier Hepatitis C Virus and HIV Care for People Who Use Drugs in a Rural Community: Brief Qualitative Report.

BACKGROUND: People who inject drugs are experiencing syndemic conditions with increasing risk of infection with hepatitis C (HCV) and HIV. However, rates of accessing HCV and HIV testing and treatment among people who inject drugs are low for various reasons, including the criminalization of drug use, which leads to a focus on treating drug use rather than caring for drug users. For many people who inject drugs, health care becomes a form of structural violence, resulting in traumatic experiences, fear of police violence, unmet needs, and avoidance of medical care. There is a clear need for novel approaches to health care delivery for people who inject drugs. OBJECTIVE: This study aimed to analyze the process of a multidisciplinary team-encompassing health care professionals, community representatives, researchers, and people with lived experience using drugs-that was formed to develop a deep understanding of the experiences of people who inject drugs and local ecosystem opportunities and constraints to inform the cocreation of low-barrier, innovative HCV or HIV care in a rural community. Given the need for innovative approaches to redesigning health care, we sought to identify challenges and tensions encountered in this process and strategies for overcoming these challenges. METHODS: Analysis was based on an in-depth review of meeting notes from the project year, followed by member-checking with the project team to revise and expand upon the challenges encountered and strategies identified to navigate these challenges. RESULTS: Challenges and tensions included: scoping the project, setting the pace and urgency of the work, adapting to web-based work, navigating ethics and practice of payment, defining success, and situating the project for sustainability. Strategies to navigate these challenges included: dedicated effort to building personal and meaningful connections, fostering mutual respect, identifying common ground to make shared decisions, and redefining successes. CONCLUSIONS: While cocreated care presents challenges, the resulting program is strengthened by challenging assumptions and carefully considering various perspectives to think creatively and productively about solutions.

On the Heart of the Hippocratic Corpus: its meaning, context and purpose.

Though the Hippocratic text On the Heart has garnered significant attention in the twentieth and twenty-first centuries from classicists, physicians and historians of medicine alike, no commentary on this important work currently exists. There remain, however, central questions of interpretation concerning a number of important points: in particular, how the author understands the structure and functioning of the heart.The significance of this text for the history of cardiovascular medicine can be found first in its position as being radically advanced in its portrayal of the inner structure of the heart when compared with any other Hippocratic text. At the same time, the text falls dramatically short of the discoveries of the Alexandrian researchers who studied during the Hellenistic period-that is, around the same period as this text's likely composition. In addition, this work contains the first extant description of the valves of the heart, and its detailed descriptions of a cuspid valve and the chordae tendineae have led several scholars to imagine that this text even contains evidence of either a systematic dissection of an animal heart or-what seems impossible outside of Alexandria, Egypt at that time-evidence of the dissection of a human heart.This article intends to provide a full commentary on the text by consolidating, and in some cases correcting, previous interpretive attempts to understand an often referenced, and at times misinterpreted, ancient medical treatise.

Genomic Regions Associated with Virulence in Pyrenophora teres f. teres Identified by Genome-Wide Association Analysis and Biparental Mapping.

Net form net blotch (NFNB), caused by the fungal pathogen Pyrenophora teres f. teres, is an important foliar disease present in all barley-producing regions of the world. This fungus is a hemibiotrophic and heterothallic ascomycete, where sexual recombination can lead to changes in disease expression in the host. Knowledge of the genetic architecture and genes involved in virulence is vital to increase the durability of NFNB resistance in barley cultivars. We used a genome-wide association mapping approach to characterize P. teres f. teres genomic regions associated with virulence in Australian barley cultivars. One hundred eighty-eight P. teres f. teres isolates collected across five Australian states were genotyped using Diversity Arrays Technology sequence markers and phenotyped across 20 different barley genotypes. Association mapping identified 14 different genomic regions associated with virulence, with the majority located on P. teres f. teres chromosomes 3 and 5 and one each present on chromosomes 1, 6, and 9. Four of the regions identified were confirmed by quantitative trait loci (QTL) mapping. The QTL regions are discussed in the context of their genomic architecture together with examination of their gene contents, which identified 20 predicted effectors. The number of QTL shown in this study at the population level clearly illustrates a complex genetic basis of P. teres f. teres virulence compared with pure necrotrophs, such as the wheat pathogens Parastagonospora nodorum and Parastagonospora tritici-repentis.

Genetic Characterization of Resistance to Pyrenophora teres f. teres in the International Barley Differential Canadian Lake Shore.

Genetic resistance to net form of net blotch in the international barley differential Canadian Lake Shore (CLS) was characterized and mapped. A doubled haploid (DH) population generated from a cross between CLS and susceptible cultivar Harrington was evaluated at the seedling stage using eight diverse Pyrenophora teres f. teres (Ptt) isolates and at the adult stage in the field using natural inoculum. To effectively map the CLS resistance, comparative marker frequency analysis (MFA) was performed using 8,762 polymorphic DArT-seq markers, where 'resistant' and 'susceptible' groups each comprised 40 DH lines displaying the most extreme phenotypes. Five DArTseq markers were consistently detected in eight disease assays, which was designated qPttCLS and deemed to harbor the locus underpinning CLS resistance. Four of these markers were present onto the barley DArTseq physical map and spans a region between 398203862 and 435526243 bp which were found to consist several genes involved in important plant functions such as disease response and signaling pathways. While MFA only detected the 3H region, genetic analyses based on segregation patterns were inconsistent, suggesting complex inheritance or variation in phenotypic expression of qPttCLS, particularly in the field. This study represents progress toward connecting Ptt pathotype surveys with the corresponding resistance genes in barley differentials. The markers associated with qPttCLS are useful for marker-assisted selection in breeding programs.

Perioperative immunomodulation with Flt3 kinase ligand or a whole tumor cell vaccine is associated with a reduction in lung metastasis formation after laparotomy in mice.

INTRODUCTION: Laparotomy has been associated with temporary postoperative immunosuppression and accelerated tumor growth in experimental models. In a previous murine study, a whole cell vaccine plus the adjuvant monophosphoryl-lipid A was shown to be effective in decreasing the number of lung metastases that develop after laparotomy. This study was conducted to assess the impact of the adjuvant fetal liver tyrosine kinase 3 (Flt3) ligand on perioperative tumor growth when used alone or with a tumor cell vaccine. METHODS: An intravenous tumor cell injection lung metastases model was used. Sixty female A/J mice were divided into six equal groups designated (1) anesthesia control (AC), (2) AC with Flt3 ligand (ACFlt3), (3) sham laparotomy (OP), (4) OP with Flt3 ligand (OPFlt3), (5) OP with vaccine (OPVac), and (6) OP with Flt3 ligand and vaccine (OPFlt3Vac). Groups 2, 4, and 6 received daily intraperitoneal injections of Flt3 ligand (10 microg/dose with carrier) for 5 days before and 5 days after surgery. Groups 1 and 3 received similar injections of saline on the same schedule. Groups 5 and 6 were vaccinated with irradiated whole Ta3Ha tumor cells intraperitoneally three times before and twice after surgery. Immediately after surgery, all mice were injected with 10(5) Ta3Ha tumor cells via a tail vein. After 14 days, the mice were sacrificed and their lungs and tracheas were excised en bloc. Specimens were stained and counterstained with India ink and Fekete solution, and surface metastases were counted by a blinded observer. Differences between study groups were determined by analysis of variance. The peritumoral inflammatory cell infiltrate of some Flt3 and control specimens was also assessed. RESULTS: Regarding laparotomy, Flt3 ligand (mean, 1.22 metastases), whole cell vaccine (1.12 metastases), and the combination of these two agents (0.1 metastases) were each effective in significantly decreasing the number of surface lung metastases compared with surgery alone (9.88 metastases, P < .05 for all comparisons). There were no differences between the various treatment groups in regards to number of metastases. Only the combination of Flt3 and the vaccine significantly lowered the incidence of tumors (number of mice with > or =1 tumors). Histologic analysis revealed that the Flt3-treated mice demonstrated increased numbers of antigen-presenting cells surrounding the tumors compared with controls. CONCLUSIONS: Perioperative treatment with either Flt3 ligand or a whole cell tumor vaccine significantly reduced the number of lung metastases after laparotomy. The combination of the Flt3 ligand and the vaccine also decreased the incidence of metastases and was the most effective treatment. Further studies regarding perioperative immune modulation in the setting of cancer appear warranted.

Laparoscopic-assisted cecectomy is associated with decreased formation of postoperative pulmonary metastases compared with open cecectomy in a murine model.

BACKGROUND: It was shown in a murine model that sham laparotomy is associated with a higher incidence of postoperative lung metastases when compared with results seen after carbon dioxide pneumoperitoneum. Using the same tumor model, the present study was undertaken to determine if the addition of bowel resection to the operative procedure would impact the results. METHODS: Sixty mice underwent anesthesia alone (anesthesia control [AC]), laparoscopic-assisted cecectomy (LC), or open cecectomy (OC). After surgery, all animals received tail vein injections of 105 TA3-Ha tumor cells. On postoperative day 14, the lungs and trachea were excised en bloc and processed, and surface lung metastases were counted and recorded by a blinded observer. RESULTS: The mean number of surface lung metastases in the AC, LC, and OC groups was 30.9, 76.3, and 134.5, respectively. Significantly more metastases were documented after OC (P<.001) and LC (P<.05) than after anesthesia alone. Mice in the LC group had significantly fewer lung metastases (43% less) than mice in the OC group (P<.01). CONCLUSIONS: OC was associated with significantly more lung metastases than either LC or AC. Surgery-related immune suppression or trophic tumor cell stimulation occurring after surgery may contribute to this phenomenon.

Naturally occurring antibodies to epithelial cell adhesion molecule (EpCAM).

Epithelial cell adhesion molecule (Ep-CAM) is an epithelial tumor-associated antigen that is expressed by a number of normal tissues and has been used as a target in many immunotherapy studies. The purpose of this study was to determine the incidence of serum anti-EpCAM IgG (immunoglobulin G) antibodies in colon cancer and tumor-free patients and to assess the tumor protective value of anti-EpCAM antibodies. One third of both the cancer (16/48) and the control (9/27) patients had detectable antibodies. Although the mean antibody concentration was higher in cancer patients (0.048 +/- 0.120 U) than in controls (0.038 +/- 0.064 U) the difference was not statistically significant. Western blot analysis revealed reactivity to multiple HT29 cell proteins including a 40-kDa protein (presumed to be Ep-CAM). Monoclonal anti-EpCAM 323/A3 antibody did not have a tumor-protective effect in murine Ep-CAM expressing colocarcinoma. We conclude that Ep-CAM is immunogenic not only for cancer patients, but also for tumor-free individuals.