Association of prior treatment with nitrogen-containing bisphosphonates on outcomes of COVID-19 positive patients.

COVID-19 infection has resulted in significant morbidity and mortality globally, especially among older adults. Repurposed drugs have demonstrated activity in respiratory illnesses, including nitrogen-containing bisphosphonates. In this retrospective longitudinal study at 4 academic medical centers, we show no benefit of nitrogen-containing bisphosphonates regarding ICU admission, ventilator use, and mortality among older adults with COVID-19 infection. We specifically evaluated the intravenous bisphosphonate zoledronic acid and found no difference compared to oral bisphosphonates. BACKGROUND: Widely used in osteoporosis treatment, nitrogen-containing bisphosphonates (N-BP) have been associated with reduced mortality and morbidity among older adults. Based on prior studies, we hypothesized that prior treatment with N-BP might reduce intensive care unit (ICU) admission, ventilator use, and death among older adults diagnosed with COVID-19. METHODS: This retrospective analysis of the PCORnet Common Data Model across 4 academic medical centers through 1 September 2021 identified individuals age >50 years with a diagnosis of COVID-19. The composite outcome included ICU admission, ventilator use, or death within 15, 30, and 180 days of COVID-19 diagnosis. Use of N-BP was defined as a prescription within 3 years prior. ICU admission and ventilator use were determined using administrative codes. Death included both in-hospital and out-of-hospital events. Patients treated with N-BP were matched 1:1 by propensity score to patients without prior N-BP use. Secondary analysis compared outcomes among those prescribed zoledronic acid (ZOL) to those prescribed oral N-BPs. RESULTS: Of 76,223 COVID-19 patients identified, 1,853 were previously prescribed N-BP, among whom 559 were prescribed ZOL. After propensity score matching, there were no significant differences in the composite outcome at 15 days (HR 1.22, 95% CI: 0.89-1.67), 30 days (HR 1.24, 95% CI: 0.93-1.66), or 180 days (HR 1.17, 95% CI: 0.93-1.48), comparing those prescribed and not prescribed N-BP. Compared to those prescribed oral N-BP, there were no significant differences in outcomes among those prescribed ZOL. CONCLUSION: Among older COVID-19 patients, prior exposure to N-BP including ZOL was not associated with a reduction in ICU admission, ventilator use, or death.

At-home determination of 24-h urine sodium excretion: Validation of chloride test strips and multiple spot samples.

Sodium intake and compliance with dietary sodium modification are typically assessed using a 24-h urine collection analyzed using flame photometry, but this is inconvenient. Spot urine samples have been investigated as alternatives to 24-h collections, but their accuracy is poor. Since sodium and chloride are present in equal concentrations in dietary salt, chloride test strips may provide a suitable proxy for at-home measurement of urine sodium concentrations. We aimed to determine whether (i) chloride test strips provide a reliable measure of urinary sodium compared to the gold standard flame photometry and (ii) multiple spot samples accurately reflect 24-h urine sodium. We recruited 43 participants (19 males) aged 23.6 ± 0.6 years to complete multiple consecutive spot samples (morning and evening) along with a 24-h urine sodium collection. Urine 24-h sodium estimates using chloride test strips (114.6 ± 7.5 mmol/day) were highly correlated (r = 0.900, p < 0.0001) with flame photometry (121.1 ± 7.7 mmol/day) with a bias of -6.53 ± 22.2 mmol/day. Use of a three-spot sample average (both morning and evening spot samples) with a correction factor applied (122.9 ± 4.1 mmol/day) provided a good approximation of 24-h sodium measured by flame photometry (125.6 ± 9.0 mmol/day), with a bias of -2.55 ± 43.9 mmol/day. Chloride test strips applied to a 24-h urine collection provide a highly accurate measure of urinary sodium excretion, permitting convenient at-home sample collection and analysis. Their application to multiple spot samples provides a reasonable approximation of sodium excretion that can be used to conveniently monitor attempts at dietary sodium manipulation, without the inconvenience of completing a 24-h urine sample.

Erratum: iPS-derived MSCs from an expandable bank to deliver a prodrug-converting enzyme that limits growth and metastases of human breast cancers.

[This corrects the article DOI: 10.1038/cddiscovery.2016.64.].

iPS-derived MSCs from an expandable bank to deliver a prodrug-converting enzyme that limits growth and metastases of human breast cancers.

One attractive strategy to treat cancers is to deliver an exogenous enzyme that will convert a non-toxic compound to a highly toxic derivative. The strategy was tested with viral vectors but was disappointing because the efficiency of transduction into tumor cells was too low. Recent reports demonstrated that the limitation can be addressed by using tissue-derived mesenchymal stromal cells (MSCs) to deliver enzyme/prodrug systems that kill adjacent cancer cells through bystander effects. Here we addressed the limitation that tissue-derived MSCs vary in their properties and are difficult to generate in the large numbers needed for clinical applications. We prepared a Feeder Stock of MSCs from induced pluripotent stem cells (iPSs) that provided an extensively expandable source of standardized cells. We then transduced the iPS-derived MSCs to express cytosine deaminase and injected them locally into a mouse xenogeneic model of human breast cancer. After administration of the prodrug (5-fluorocytosine), the transduced iPS-MSCs both limited growth of preformed tumors and decreased lung metastases.

Weight management for adolescents with intellectual and developmental disabilities: Rationale and design for an 18month randomized trial.

Adolescents with intellectual and developmental disabilities (IDD) are an underserved group in need of weight management. However, information regarding effective weight management for this group is limited, and is based primarily on results from small, non-powered, non-randomized trials that were not conducted in accordance with current weight management guidelines. Additionally, the comparative effectiveness of emerging dietary approaches, such as portion-controlled meals (PCMs) or program delivery strategies such as video chat using tablet computers have not been evaluated. Therefore, we will conduct an 18month trial to compare weight loss (6months) and maintenance (7-18months) in 123 overweight/obese adolescents with mild to moderate IDD, and a parent, randomized to a weight management intervention delivered remotely using FaceTime™ on an iPad using either a conventional meal plan diet (RD/CD) or a Stop Light diet enhanced with PCMs (RD/eSLD), or conventional diet delivered during face-to-face home visits (FTF/CD). This design will provide an adequately powered comparison of both diet (CD vs. eSLD) and delivery strategy (FTF vs. RD). Exploratory analyses will examine the influence of behavioral session attendance, compliance with recommendations for diet (energy intake), physical activity (min/day), self-monitoring of diet and physical activity, medications, and parental variables including diet quality, physical activity, baseline weight, weight change, and beliefs and attitudes regarding diet and physical activity on both weight loss and maintenance. We will also complete a cost and contingent valuation analysis to compare costs between RD and FTF delivery.

Activated human mesenchymal stem/stromal cells suppress metastatic features of MDA-MB-231 cells by secreting IFN-ß.

Our recent study showed that human mesenchymal stem/stromal cells (hMSCs) are activated to express tumor necrosis factor (TNF)-α-related apoptosis-inducing ligand (TRAIL) by exposure to TNF-α and these activated hMSCs effectively induce apoptosis in triple-negative breast cancer MDA-MB-231 (MDA) cells in vitro and in vivo. Here, we further demonstrated that activated hMSCs not only induced apoptosis of MDA cells but also reduced metastatic features in MDA cells. These activated hMSC-exposed MDA cells showed reduced tumorigenicity and suppressed formation of lung metastasis when implanted in the mammary fat pad. Surprisingly, the activated hMSC-exposed MDA cells increased TRAIL expression, resulting in apoptosis in MDA cells. Interestingly, upregulation of TRAIL in MDA cells was mediated by interferon-beta (IFN-ß) secreted from activated hMSCs. Furthermore, IFN-ß in activated hMSCs was induced by RNA and DNA released from apoptotic MDA cells in absent in melanoma 2 (AIM2) and IFN induced with helicase C domain 1 (IFIH1)-dependent manners. These observations were only seen in the TRAIL-sensitive breast cancer cell lines but not in the TRAIL-resistant breast cancer cell lines. Consistent with these results, Kaplan-Meier survival analysis also showed that lack of innate sensors detecting DNA or RNA is strongly associated with poor survival in estrogen receptor-negative breast cancer patients. In addition, cancer-associated fibroblasts (CAF) isolated from a breast cancer patient were also able to express TRAIL and IFN-ß upon DNA and RNA stimulation. Therefore, our results suggest that the crosstalk between TRAIL-sensitive cancer cells and stromal cells creates a tumor-suppressive microenvironment and further provide a novel therapeutic approach to target stromal cells within cancer microenvironment for TRAIL sensitive cancer treatment.

Platelet immunoreceptor tyrosine-based activation motif (ITAM) and hemITAM signaling and vascular integrity in inflammation and development.

Platelets are essential for maintaining hemostasis following mechanical injury to the vasculature. Besides this established function, novel roles of platelets are becoming increasingly recognized, which are critical in non-injury settings to maintain vascular barrier integrity. For example, during embryogenesis platelets act to support the proper separation of blood and lymphatic vessels. This role continues beyond birth, where platelets prevent leakage of blood into the lymphatic vessel network. During the course of inflammation, platelets are necessary to prevent local hemorrhage due to neutrophil diapedesis and disruption of endothelial cell-cell junctions. Surprisingly, platelets also work to secure tumor-associated blood vessels, inhibiting excessive vessel permeability and intra-tumor hemorrhaging. Interestingly, many of these novel platelet functions depend on immunoreceptor tyrosine-based activation motif (ITAM) signaling but not on signaling via G protein-coupled receptors, which plays a crucial role in platelet plug formation at sites of mechanical injury. Murine platelets express two ITAM-containing receptors: the Fc receptor γ-chain (FcRγ), which functionally associates with the collagen receptor GPVI, and the C-type lectin-like 2 (CLEC-2) receptor, a hemITAM receptor for the mucin-type glycoprotein podoplanin. Human platelets express an additional ITAM receptor, FcγRIIA. These receptors share common downstream effectors, including Syk, SLP-76 and PLCγ2. Here we will review the recent literature that highlights a critical role for platelet GPVI/FcRγ and CLEC-2 in vascular integrity during development and inflammation in mice and discuss the relevance to human disease.

Labor induction utilizing the Foley balloon: a randomized trial comparing standard placement versus immediate removal.

OBJECTIVE: To compare time to delivery between two induction procedures. The Foley balloon is a mechanical method for cervical ripening. However, the device may also result in endogenous prostaglandin release following separation of the chorionic membrane and decidua. Prolonged Foley placement may therefore be unnecessary for successful labor induction. METHOD: Randomized controlled trial of labor induction at LAC+USC Medical Center between 2010 and 2013. Subjects were assigned to either (a) standard placement of the Foley balloon or (b) Foley balloon insufflation and immediate removal. Oxytocin was administered to all subjects not in active labor after 12 h. Delivery information and neonatal outcomes were documented and all patients were followed for 6 weeks for adverse events. RESULT: A total of 79 women were included in the analysis (37 standard and 42 immediate). Induction time was 8.6 h longer in the immediate removal group (23.5 vs 32.1, P=0.002), but the difference in delivery within 24 h did not meet the statistical significance (46.0 vs 28.6%, P=0.11). Similar rates of cesarean delivery, epidural use and abnormal APGAR scores were observed. After controlling for number of vaginal exams and duration of rupture, a decreased risk of infection was observed in the immediate removal group (odds ratio=0.08, 95% confidence interval=0.007 to 0.93, P=0.04). Further, when the analysis was stratified by parity, differences in induction time only persisted in nulliparous women. CONCLUSION: Immediate removal of the Foley balloon may lead to longer overall induction time, but a lower risk of infection. Parous women may be particularly good candidates for this type of induction.

Failure to achieve normal metabolic response in non-obese diabetic mice and streptozotocin-induced diabetic mice after transplantation of primary murine hepatocytes electroporated with the human proinsulin gene (p3MTChins).

BACKGROUND: A recent study by Chen et al described a therapy for diabetes that involved electroporation of primary hepatocytes with human proinsulin cDNA, p3MTChins. Intrahepatic transplantation of treated hepatocytes into streptozotocin (STZ) murine and porcine models led to euglycemia, weight maintenance, and normal insulin production. We tested the repeatability of their basic experiments and transplantation technique and expanded the study to include an autoimmune model. METHODS: Hepatocytes were isolated from B6 mice, electroporated with p3MTChins, and glucose-challenged or were injected into hepatic or spleen parenchyma of STZ-diabetic B6 and non-obese diabetic mice. Outcomes included survival, serum glucose levels, insulin, and c-peptide release. Untransfected primary hepatocytes and mice transplanted with these cells served as controls. RESULTS: p3MTChins-hepatocytes secreted insulin during glucose challenge, but glucose levels did not change with increasing glucose concentrations. Direct hepatic injection led to high mortality rates. Mice that underwent intrasplenic injection survived for >50 days (control = 4 days) and had a mild but stable improvement in hyperglycemia. C-peptide in both mouse models was detectable but eventually declined to baseline in the non-obese diabetic mice. CONCLUSIONS: Hepatocytes can be transfected with p3MTChins to produce human insulin but may lack the proper glucose-sensing or complex storage and secretion capabilities that allow for a finely tuned dynamic insulin response. Treatment is subtherapeutic, and p3MTChins-hepatocyte function may not endure in an autoimmune model. Without successful preliminary findings, cell therapy involving electroporation of p3MTChins does not appear to be practical as a therapy for diabetes and may not be a strategy to pursue at this time.

L-type calcium channels in sympathetic α3ß2-nAChR-mediated cerebral nitrergic neurogenic vasodilation.

AIM: Nicotine stimulation of α3ß2-nicotinic acetylcholine receptors (α3ß2-nAChRs) located on sympathetic nerves innervating basilar arteries causes calcium-dependent noradrenaline release, leading to activation of parasympathetic nitrergic nerves and dilation of basilar arteries. This study aimed to investigate the major subtype of calcium channels located on cerebral peri-vascular sympathetic nerves, which is involved in nicotine-induced α3ß2-nAChR-mediated nitrergic vasodilation in basilar arteries. METHODS: Nicotine- and transmural nerve stimulation (TNS)-induced dilation of isolated porcine basilar arteries was examined using in vitro tissue bath. Nicotine-induced calcium influx, nicotine-induced noradrenaline release and nicotine-induced inward currents were evaluated in rat superior cervical ganglion (SCG) neurones, peri-vascular sympathetic nerves of porcine basilar arteries and α3ß2-nAChRs-expressing oocytes respectively. mRNA and protein expression of Cav 1.2 and Cav 1.3 channels were detected by RT-PCR, Western blotting and immunohistochemistry. RESULTS: Nicotine-induced vasodilation was not affected by ω-agatoxin TK (selective P/Q-type calcium channel blocker) or ω-conotoxin GVIA (N-type calcium channel blocker). The vasodilation, however, was inhibited by nicardipine (L-type calcium channel blocker) in concentrations which did not affect TNS-induced vasodilation, suggesting the specific blockade. Nicardipine concentration-dependently inhibited nicotine-induced calcium influx in rat SCG neurones and reduced nicotine-induced noradrenaline release from peri-vascular sympathetic nerves of porcine basilar arteries. Nicardipine (10 µm), which significantly blocked nicotine-induced vasorelaxation by 70%, did not appreciably affect nicotine-induced inward currents in α3ß2-nAChRs-expressing oocytes. Furthermore, the mRNAs and proteins of Cav 1.2 and Cav 1.3 channels were expressed in porcine SCG and peri-vascular nerve terminals. CONCLUSION: The sympathetic neuronal calcium influx through L-type calcium channels is modulated by α3ß2-nAChRs. This calcium influx causes noradrenaline release, initiating sympathetic-parasympathetic (axo-axonal) interaction-induced nitrergic dilation of porcine basilar arteries.

Concerning the time dependence of the decay rate of 137Cs.

The decay rates of eight nuclides ((85)Kr, (90)Sr, (108)Ag, (133)Ba, (137)Cs, (152)Eu, (154)Eu, and (226)Ra) were monitored by the standards group at the Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany, over the time frame June 1999 to November 2008. We find that the PTB measurements of the decay rate of (137)Cs show no evidence of an annual oscillation, in agreement with the recent report by Bellotti et al. However, power spectrum analysis of PTB measurements of a (133)Ba standard, measured in the same detector system, does show such evidence. This result is consistent with our finding that different nuclides have different sensitivities to whatever external influences are responsible for the observed periodic variations.

Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen.

OBJECTIVE: Meniscal regeneration was previously shown to be enhanced by injection of mesenchymal stem/stromal cells (MSCs) but the mode of action of the MSCs was not established. The aim of this study was to define how injection of MSCs enhances meniscal regeneration. DESIGN: A hemi-meniscectomy model in rats was used. Rat-MSCs (rMSCs) or human-MSCs (hMSCs) were injected into the right knee joint after the surgery, and PBS was injected into the left. The groups were compared macroscopically and histologically at 2, 4, and 8 weeks. The changes in transcription in both human and rat genes were assayed by species-specific microarrays and real-time RT-PCRs. RESULTS: Although the number of hMSCs decreased with time, hMSCs enhanced meniscal regeneration in a manner similar to rMSCs. hMSCs injection increased expression of rat type II collagen (rat-Col II), and inhibited osteoarthritis progression. The small fraction of hMSCs was activated to express high levels of a series of genes including Indian hedgehog (Ihh), parathyroid hormone-like hormone (PTHLH), and bone morphogenetic protein 2 (BMP2). The presence of hMSCs triggered the subsequent expression of rat-Col II. An antagonist of hedgehog signaling inhibited the expression of rat-Col II and an agonist increased expression of rat-Col II in the absence of hMSCs. CONCLUSIONS: Despite rapid reduction in cell numbers, intra-articular injected hMSCs were activated to express Ihh, PTHLH, and BMP2 and contributed to meniscal regeneration. The hedgehog signaling was essential in enhancing the expression of rat-Col II, but several other factors provided by the hMSCs probably contributed to the repair.

Adenosine trisphosphate appears to act via different receptors in terminals versus somata of the hypothalamic neurohypophysial system.

ATP-induced ionic currents were investigated in isolated terminals and somata of the hypothalamic neurohypophysial system (HNS). Both terminals and somata showed inward rectification of the ATP-induced currents and reversal near 0 mV. In terminals, ATP dose-dependently evoked an inactivating, inward current. However, in hypothalamic somata, ATP evoked a very slowly inactivating, inward current with a higher density, and different dose dependence (EC(50) of 50 µm in somata versus 9.6 µm in terminals). The ATP-induced currents, in both the HNS terminals and somata, were highly and reversibly inhibited by suramin, suggesting the involvement of a purinergic receptor (P2XR). However, the suramin inhibition was significantly different in the two HNS compartments (IC(50) of 3.6 µm in somata versus 11.6 µm in terminals). Also, both HNS compartments show significantly different responses to the purinergic receptor agonists: ATP-γ-S and benzoyl-benzoyl-ATP. Finally, there was an initial desensitisation to ATP upon successive stimulations in the terminals, which was not observed in the somata. These differences in EC(50) , inactivation, desensitisation and agonist sensitivity in terminals versus somata indicate that different P2X receptors mediate the responses in these two compartments of HNS neurones. Previous work has revealed mRNA transcripts for multiple purinergic receptors in micropunches of the hypothalamus. In the HNS terminals, the P2X purinergic receptor types P2X2, 3, 4 and 7 (but not 6) have been shown to exist in AVP terminals. Immonohistochemistry now indicates that P2X4R is only present in AVP terminals and that the P2X7R is found in both AVP and oxytocin terminals and somata. We speculate that these differences in receptor types reflects the specific function of endogenous ATP in the terminals versus somata of these central nervous system neurones.

Associating changes in output behavior with changes in parameter values in spiking and bursting neuron models.

Several recent studies have demonstrated that neuronal models allow multiple parameter value solutions for a given output. In the face of this variability of parameter values, what can be learned about neural function through parameter value differences? Here, in two different models, we examine this question by attempting to reconstruct the source of model output changes based on simple statistical analyses of parameter distributions generated by automated searches. We conclude that changes to parameter values or their associated distributions do not reliably reflect the specific mechanisms responsible for a given change in output.

Pre-pregnancy weight and excess weight gain are risk factors for macrosomia in women with gestational diabetes.

OBJECTIVE: To determine whether women with gestational diabetes mellitus (GDM) whose weight gain exceeded the 2009 Institute of Medicine (IOM) recommendations were more likely to have macrosomia. STUDY DESIGN: Retrospective cohort study of the association of weight gain in women with Class A1 GDM, with term (≥37 weeks) singleton liveborns and macrosomia (birthweight ≥4000 g). Multivariate logistic regression models were used to adjust for covariates and test for interactions. RESULT: Of 1502 women studied, pre-pregnancy body mass index (BMI) categories were: normal (39.6%), overweight (28.5%) and obese (31.9%). The mean (±standard deviation ) weight gain (lbs) for these groups was: 27.6±10.9, 24.2±13.0 and 18.8±16.3 (P<0.0001), whereas the occurrence of macrosomia was 7.4, 11.4 and 19.0%, respectively. Women with an obese BMI were twice as likely to have a macrosomic infant compared with women in the normal BMI group (odds ratio, OR 2.0; 95% CI 1.4-3.0; P=0.0005). Independently, women who exceeded the IOM guidelines were three times more likely to have a macrosomic infant (OR 3.0, 95% CI 2.2-4.2, P<0.0001). CONCLUSION: Maternal pre-pregnancy weight and weight gain during pregnancy appear to be significant and independent risk factors for macrosomia in women with GDM.

Effect of 17-alpha hydroxyprogesterone caproate on the production of tumor necrosis factor-alpha and the expression of cyclooxygenase-2 in lipopolysaccharide-treated gravid human myometrial explants.

OBJECTIVE: To determine whether 17-alpha hydroxyprogesterone (17-OHPC) alters tumor necrosis factor-alpha (TNF-alpha) production and the expression of cyclooxygenase type 2 (COX-2) in myometrium exposed to lipopolysaccharide (LPS). STUDY DESIGN: Lower segment myometrial biopsies were obtained from non-laboring patients at term. Tissues were cultured in serum-free media with 17-OHPC (1 microM) and LPS (1 microg/ml), either alone or in combination. At 24 h, the production of tumor necrosis factor-alpha (TNF-alpha) and the expression of COX-2 was determined using enzyme linked immunosorbent assay and real-time (RT-PCR). Statistical analysis was performed using non-parametric testing. A P-value of <0.05 was considered significant. RESULT: 17-OHPC had no effect on TNF-alpha production and COX-2 expression when compared with untreated myometrial explants (P=0.61 and P=0.95). LPS induced production of TNF-alpha (P=0.03) and expression of COX-2 (P=0.02). Treatment with 17-OHPC did not block LPS-induced TNF-alpha production (P=0.37) or COX-2 expression (P=0.12). CONCLUSION: In this pilot study, 17-OHPC did not affect the production of TNF-alpha or COX-2 expression in human myometrium.

Development and characterization of in vivo flexible electrodes compatible with large tissue displacements.

Electrical activity is the ultimate functional measure of neuronal tissue and recording that activity remains a key technical challenge in neuroscience. The mechanical mismatch between rigid electrodes and compliant brain tissue is a critical limitation in applications where movement is an inherent component. An electrode that permits recording of neural activity, while minimizing tissue disruption, is beneficial for applications that encompass both normal physiological movements and those which require consistent recording during large tissue displacements. In order to test the extreme of this range of movement, flexible electrodes were developed to record activity during and immediately following cortical impact in the rat. Photolithography techniques were used to fabricate flexible electrodes that were readily insertable into the brain using a parylene C base and gold conduction lines and contact pads, permitting custom geometry. We found that this electrode configuration retained mechanical and electrical integrity following both durability studies and large movements within the cortex. This novel flexible electrode configuration provides a novel platform for experimentally examining neuronal activity during a range of brain movements.

Human albumin preserves islet mass and function better than whole serum during pretransplantation islet culture.

OBJECTIVE: Human islet transplant protocols frequently include a brief period of islet culture before transplantation. Some investigators have suggested that medium supplementation with human serum might quench collagenase activity and provide better culture conditions when compared with human albumin. We studied the effect of whole serum on islet count, islet equivalence, insulin secretion, and DNA content in human islets. METHODS: Adult human islets isolated from a single pancreas with purity >50% were cultured in identical 150 islet equivalent samples at 37 degrees C using CMRL 1066-based islet medium (Mediatech) supplemented with either 0.5% human albumin or 10% human AB serum. Prior to culture and after 3 days, islets were assessed in vitro using dithizone staining (n = 4), insulin release after static glucose stimulation (n = 8), and DNA content (n = 8). RESULTS: After 3 days, islet mass (defined by the number of islets and islet equivalents counted after dithizone staining) was better preserved in islets cultured in 0.5% human albumin. Although the stimulation index and total DNA content were similar between groups, islets cultured in human albumin demonstrated greater absolute insulin secretion (p = .02) and insulin secretion per cell (p = .02). CONCLUSIONS: When used to supplement CMRL 1066-based islet culture medium, human albumin preserves islet mass and secretory capacity better than whole human serum. Human serum offers no advantage in islet preservation or function.