Tumor-infiltrating lymphocytes: Streamlining a complex manufacturing process

Adoptive cell therapy of tumor-infiltrating lymphocytes has shown promise for treatment of refractory melanoma and other solid malignancies; however, challenges to manufacturing have limited its widespread use. Traditional manufacturing efforts were lengthy, cumbersome and used open culture systems. We describe changes in testing and manufacturing that decreased the process cycle time, enhanced the robustness of critical quality attribute testing and facilitated a functionally closed system. These changes have enabled export of the manufacturing process to support multi-center clinical trials

National Register Testing At Sites 41BP585, 41BP594, And 41BP595 Three Oaks Mine, Bastrop County, Texas

Between October 2012 and July 2013, Atkins conducted National Register of Historic Places (NRHP) eligibility testing at historic sites 41BP585 and 41BP594 and prehistoric site 41BP595, located within the Three Oaks Mine in Bastrop County, Texas, which is owned and operated by Luminant. Impacts to all three sites are anticipated as a result of planned mine development. This work was conducted under the direction of Principal Investigator David L. Sherman. This report of investigations was written at Atkins and is being finalized by Blanton & Associates, with David L. Sherman remaining as the Principal Investigator. This work demonstrated that significant archeological deposits that may contribute to the overall NRHP eligibility statuses of the two historic sites are absent at both sites. Standing architecture at 41BP594, however, has previously been determined to be eligible for listing on the NRHP (Martin 2001). Archival research conducted as part of the current investigation into the histories of the historic sites remains inconclusive with respect to the identity of their 1870s and earlier occupants. Testing at prehistoric site 41BP595 indicated it resulted from multiple occupational episodes during the period from the late Paleoindian to the Late Prehistoric. Shovel testing and mechanical trenching revealed the presence of an expansive buried anthrogenic A soil horizon, or midden, replete with preserved subsistence remains. Mechanical trenching also exposed a variety of burned rock cooking facilities partially surrounding the midden area. Radiocarbon assays of burned nut shells recovered from feature contexts, along with the assemblage of diagnostic lithic artifacts, suggest the site was most intensively occupied from the Late Archaic to the early Late Prehistoric. A suite of special studies was conducted on burned rock samples recovered from four of the better-preserved burned rock features. These studies, which include residue, starch, and phytolith analysis, suggest that the burned rock features were used in part to process tubers/roots and grass seeds for subsistence. Macrobotanical analysis of flotation samples recovered from feature contexts identified spent fuel remains including oak and hickory wood and subsistence remains including oak, hickory, black walnut, and acorn burned nut shells. A small amount of burned bulb, possibly representing wild onion, was also recovered through flotation. These findings suggest that significant archeological deposits important to understanding the Late Archaic to early Late Prehistoric period have been preserved at 41BP595

Human Glial-Restricted Progenitor Transplantation into Cervical Spinal Cord of the SOD1G93A Mouse Model of ALS

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1G93A rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1G93A rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1G93A mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1G93A mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation

A retrospective analysis of clinical use of alirocumab in lipoprotein apheresis patients

BACKGROUND: The previously published ODYSSEY ESCAPE trial demonstrated a significant reduction in the use of lipoprotein apheresis for heterozygous familial hypercholesterolemia (HeFH) patients when placed on alirocumab 150 mg every 2 weeks. In patients with HeFH who have consistently elevated levels of low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin therapy, current lipid guidelines recommend apheresis. Although apheresis reduces LDL-C levels by 50%-75%, it must be repeated, as frequently as every 1-2 weeks. OBJECTIVE: To assess clinical experience with apheresis and alirocumab for patients in a real-world practice setting. METHODS: This retrospective review included patients from 5 apheresis centers who were treated with apheresis and had started alirocumab therapy. In addition to LDL-C levels, total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides, and particle numbers were evaluated if data were available. RESULTS: Eleven of the 25 (44%) patients discontinued apheresis completely after initiation of alirocumab therapy, having achieved LDL-C \u3c70 mg/dL or \u3e50% reduction from baseline levels. Among the 14 patients who remained on apheresis, seven decreased the frequency of apheresis sessions. No significant safety problems were reported. CONCLUSION: Alirocumab lowered LDL-C levels by an average of 55.5% in patients receiving apheresis for elevated LDL-C. Seventy-two percent of patients on alirocumab therapy discontinued or reduced the frequency of apheresis treatment. However, some patients continued to require apheresis due to elevated lipoprotein(a), extremely elevated LDL-C, or if alirocumab therapy was discontinued due to less than anticipated LDL-C reduction

Height, adiposity and body fat distribution and breast density in young women

INTRODUCTION: Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown. METHOD: Associations of height, adiposity and body fat distribution with percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25-29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy x-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging (MRI). Associations were evaluated using linear mixed effects models. All tests of statistical significance are 2-sided. RESULTS: Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percent fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) each was associated significantly with a 44.4% - 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. However, after adjustment for childhood BMI only the DXA measures percent fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8% - 19.6% decrease in ADBV . In mutually adjusted analysis, percent fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in A:G ratio was associated with a 18.5% decrease in ADBV. CONCLUSIONS: Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations

Does Proximity to Retailers Influence Alcohol and Tobacco Use Among Latino Adolescents?

Despite decades of research surrounding determinants of alcohol and tobacco (A&T) use among adolescents, built environment influences have only recently been explored. This study used ordinal regression on 205 Latino adolescents to explore the influence of the built environment (proximity to A&T retailers) on A&T use, while controlling for recognized social predictors. The sample was 45% foreign-born. A&T use was associated with distance from respondents’ home to the nearest A&T retailer (−), acculturation (+), parents’ consistent use of contingency management (−), peer use of A&T (+), skipping school (+), attending school in immediate proximity to the US/Mexico border (+), and the interaction between the distance to the nearest retailer and parents’ consistent use of contingency management (+). The association between decreasing distance to the nearest A&T retailer and increased A&T use in Latino adolescents reveals an additional risk behavior determinant in the US–Mexico border region

HIV and adolescents: focus on young key populations

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138345/1/jia20076.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138345/2/jia20076-sup-0001.pd

Mongooses (\u3ci\u3eUrva auropunctata\u3c/i\u3e) as reservoir hosts of leptospira species in the United States Virgin Islands, 2019–2020

During 2019–2020, the Virgin Islands Department of Health investigated potential animal reservoirs of Leptospira spp., the bacteria that cause leptospirosis. In this cross-sectional study, we investigated Leptospira spp. exposure and carriage in the small Indian mongoose (Urva auropunctata, syn: Herpestes auropunctatus), an invasive animal species. This study was conducted across the three main islands of the U.S. Virgin Islands (USVI), which are St. Croix, St. Thomas, and St. John. We used the microscopic agglutination test (MAT), fluorescent antibody test (FAT), real-time polymerase chain reaction (lipl32 rt-PCR), and bacterial culture to evaluate serum and kidney specimens and compared the sensitivity, specificity, positive predictive value, and negative predictive value of these laboratory meth-ods. Mongooses (n = 274) were live-trapped at 31 field sites in ten regions across USVI and humanely euthanized for Leptospira spp. testing. Bacterial isolates were sequenced and evaluated for species and phylogenetic analysis using the ppk gene. Anti-Leptospira spp. antibodies were detected in 34% (87/256) of mongooses. Reactions were observed with the following serogroups: Sejroe, Icterohaemorrhagiae, Pyrogenes, Mini, Cynopteri, Australis, Hebdomadis, Autumnalis, Mankarso, Pomona, and Ballum. Of the kidney specimens exam-ined, 5.8% (16/270) were FAT-positive, 10% (27/274) were culture-positive, and 12.4% (34/ 274) were positive by rt-PCR. Of the Leptospira spp. isolated from mongooses, 25 were L. borgpetersenii, one was L. interrogans, and one was L. kirschneri. Positive predictive values of FAT and rt-PCR testing for predicting successful isolation of Leptospira by culture were 88% and 65%, respectively. The isolation and identification of Leptospira spp. in mongooses highlights the potential role of mongooses as a wildlife reservoir of leptospirosis; mongooses could be a source of Leptospira spp. infections for other wildlife, domestic animals, and humans