Glycolate oxidase-1 gene variants influence the risk of hyperoxaluria and renal stone development.

PURPOSE: Oxalate is an excellent calcium ion attractor with great abundance in the human body, and the liver is the major source of oxalate. The Glycolate oxidase-1 (GOX1) gene is solely responsible for the glycolate and glyoxylate metabolism and produces oxalate. This study has been designed to comprehend the association of genetic variants of the GOX1 gene with the risk of hyperoxaluria and renal stone disease in the Indian population. METHOD: The present study is a candidate gene approach prospective case-control study carried out on 300 participants (150 cases and 150 controls) at Muljibhai Patel Urological Hospital, Gujarat, India. Biochemical parameters, including serum levels of calcium, creatinine, parathyroid hormone, and 24-h urine metabolites, were performed. The genotyping of GOX1 gene variants rs6086287, rs2235250, rs2255183, and rs2294303 was performed using a customized TaqMan assay probe by RT-PCR. RESULT: Parathyroid hormone, serum creatinine, and urine metabolites were significantly elevated in nephrolithiasis compared to healthy individuals. All mutated homozygous genotypes GG (rs6086287), TT (rs2235250), GG (rs2255183), and CC (rs2294303) were significantly associated with a high risk of renal stone disease. Individuals diagnosed with hyperoxaluria and carrying TG (rs6086287), AG (rs2255183), and TT (rs2294303) genotypes have a significantly high risk of renal stone disease. Moreover, haplotype analysis and correlation analysis also confirmed the strong association between genetic variants and nephrolithiasis. CONCLUSION: Genetic variants of the GOX1 genes were associated with renal stone disease. In the presence of risk genotype and hyperoxaluria, the susceptibility to develop renal stone disease risk gets modulated.

Atraumatic splenic rupture secondary to granulocyte-colony stimulating factor medication exposure.

Hematopoietic hormones such as granulocyte-colony stimulating factors are commonly used prevent neutropenia in patients undergoing chemotherapy and to prepare patients for bone marrow donations. In rare cases, splenic injury can result from exposure to this medication. We present the case of a 30-year-old man who presented to the emergency department the day after a bone marrow donation procedure complaining of severe, acute onset left upper quadrant abdominal pain, radiating to the shoulder. Neither the patient nor his family reported any abdominal trauma prior to or following the marrow donation procedure. An initial bedside ultrasound examination was positive for peritoneal fluid and distortion of the normal splenic architecture, raising suspicion for possible intraabdominal or splenic injury. An emergent confirmatory CT with contrast of the abdomen confirmed the initial ultrasound examination suspicion of an atraumatic splenic rupture and with evidence of venous bleeding but without active arterial extravasation. An emergent trauma surgery consultation was placed, and he underwent embolization with an uneventful recovery. This case report highlights the need for a high index of suspicion for atraumatic splenic rupture in patients exposed to these types of granulocyte-colony stimulating factors.

Heart health for South Asians: improved cardiovascular risk factors with a culturally tailored health education program.

BACKGROUND/AIM: The Kaiser Permanente (KP) Northern California Heart Health for South Asians (HHSA) Program is a two-hour educational class that provides culturally relevant lifestyle and dietary recommendations to South Asian (SA) patients, in an effort to reduce their known disproportionate burden of cardiovascular (CV) disease. We evaluated the impact of the HHSA Program on CV risk factors and major adverse CV events (MACE). METHODS: A retrospective cohort study identified 1517 participants of SA descent, ≥ 18 years old from 2006 to 2019. We evaluated the change in risk factors with program attendance (median follow up of 6.9 years) for systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), LDL, HDL, BMI, and HbA1c. We also performed a propensity matched analysis to evaluate differences in MACE including stroke, myocardial infarction (MI), coronary revascularization, and all-cause mortality. RESULTS: There were significant improvements in DBP, TG, LDL-c, HDL-c, BMI, and HbA1c at one year follow up and sustained improvements in DBP (-1.01mmHg, p = 0.01), TG (-13.74 mg/dL, p = 0.0001), LDL-c (-8.43 mg/dL, p = < 0.0001), and HDL-c (3.16 mg/dL, p = < 0.0001) levels at the end of follow up. In the propensity matched analysis, there was a significant reduction in revascularization (OR 0.33, 95% CI 0.14-0.78, p = 0.011) and mortality (OR 0.41, 95% CI 0.22-0.79, p = 0.008), and a trend towards reduction in stroke. CONCLUSIONS: Our study demonstrates the efficacy of a culturally tailored SA health education program in improving CV risk factors and reducing MACE. The program highlights the importance and value of providing culturally tailored health education in primary CV disease prevention.

Bleeding Severity and Phenotype in 22q11.2 Deletion Syndrome-A Cross-Sectional Investigation.

OBJECTIVES: To prospectively quantify bleeding severity and elaborate hemorrhagic symptoms in children with 22q11.2 deletion syndrome (22q11DS) using 2 validated bleeding assessment tools (BATs), namely the Pediatric Bleeding Questionnaire and the International Society on Thrombosis and Hemostasis BAT (ISTH-BAT). We also sought to compare subjects' bleeding scores to unaffected first-degree family members. STUDY DESIGN: Children with 22q11DS and unaffected first-degree family members were recruited for the study. Two validated BATs were administered by a pediatric hematologist. Additional clinical and laboratory data were abstracted from patient medical records. Standard descriptive and nonparametric statistical methods were used. RESULTS: In total, 29 eligible subjects and controls were assessed. Median age (range) of subjects and controls was 8 (5-17) years and 38 (9-56) years, respectively. In total, 17 of 29 subjects had a positive bleeding score on ISTH-BAT compared with 1 of 29 control patients (P < .0001). Median ISTH-BAT score in subjects was 3 (0-12), compared with 2 (0-6) in control patients (P = .022). Median Pediatric Bleeding Questionnaire score in subjects was 2 (-1 to 12). The most frequent bleeding symptoms reported in subjects with 22q11DS were epistaxis (69%) and bruising (52%). Eighteen subjects had been surgically challenged, and 6 were noted to have increased perioperative hemorrhage. CONCLUSIONS: Children with 22q11DS have increased bleeding scores compared with their first-degree unaffected relatives. The majority of the bleeding symptoms described were mucocutaneous.

Pediatric Myocardial T1 and T2 Value Associations with Age and Heart Rate at 1.5 T.

The objective of the study was to determine normal global left ventricular reference values for T1 and T2 in children. This is a retrospective study that included healthy subjects, age 5-19 years, who underwent CMR for the indication of pectus excavatum from 2018 to 2019. Linear regression models were used to determine associations of native T1 and T2 values to heart rate, age, and other CMR parameters. 102 patients with a mean age of 14.0 ± 2.4 years were included (range 5.4-18.8). 87 (85%) were males and 15 (15%) were females. The mean global T1 was 1018 ± 25 ms and the mean T2 was 53 ± 3 ms. T1 was negatively correlated with age (r = - 0.39, p < 0.001) and positively correlated with heart rate (r = 0.32, p < 0.001) by univariate analysis. Multivariable analysis showed that age and heart rate were independently associated with T1. T2 demonstrated a weak negative correlation with age (r = - 0.20, p = 0.047) and no correlation with heart rate. There was no difference in T1 (p = 0.23) or T2 (p = 0.52) between genders. This study reports normal pediatric T1 and T2 values at a 1.5 Tesla scanner. T1 was dependent on age and heart rate, while T2 was less dependent on age with no correlation with heart rate.

Casting a Wider NET: An Unusual Cause of Acute Liver Failure in a Pregnant Patient.

We present a case patient in her second trimester of pregnancy who developed acute liver failure from metastatic neuroendocrine tumor (NET). Although she underwent prompt induction of a non-viable fetus due to initial concerns of hemolysis, elevated liver enzymes, and low platelet count syndrome, her liver function continued to deteriorate postpartum. She was subsequently transferred to our institution in order to undergo further evaluation that included a transjugular liver biopsy and subsequent diagnosis of high-grade NET. She was given salvage carboplatin-based chemotherapy, as she was not a liver transplant candidate. Unfortunately, the patient expired from cardiovascular collapse as a component of multiorgan failure.

Genetic inactivation of the phospholipase A2 activity of peroxiredoxin 6 in mice protects against LPS-induced acute lung injury.

Peroxiredoxin 6 (Prdx6) is a multifunctional enzyme that serves important antioxidant roles by scavenging hydroperoxides and reducing peroxidized cell membranes. Prdx6 also plays a key role in cell signaling by activating the NADPH oxidase, type 2 (Nox2) through its acidic Ca2+-independent phospholipase A2 (aiPLA2) activity. Nox2 generation of O2·-, in addition to signaling, can contribute to oxidative stress and inflammation such as during sepsis-induced acute lung injury (ALI). To evaluate a possible role of Prdx6-aiPLA2 activity in the pathophysiology of ALI associated with a systemic insult, wild-type (WT) and Prdx6-D140A mice, which lack aiPLA2 but retain peroxidase activity were administered intraperitoneal LPS. LPS-treated mutant mice had increased survival compared with WT mice while cytokines in lung lavage fluid and lung VCAM-1 expression, nitrotyrosine levels, PMN infiltration, and permeability increased in WT but not in mutant mice. Exposure of mouse pulmonary microvascular endothelial cells in primary culture to LPS promoted phosphorylation of Prdx6 and its translocation to the plasma membrane and increased aiPLA2 activity as well as increased H2O2 generation, nitrotyrosine levels, lipid peroxidation, NF-κB nuclear localization, and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome assembly; these effects were not seen in Nox2 null cells, Prdx6-D140A cells, or WT cells pretreated with MJ33, an inhibitor of aiPLA2 activity. Thus aiPLA2 activity is needed for Nox2-derived oxidant stress associated with LPS exposure. Since inactivation of aiPLA2 reduced mortality and prevented lung inflammation and oxidative stress in this animal model, the aiPLA2 activity of Prdx6 could be a novel target for prevention or treatment of sepsis-induced ALI.

Density-dependent ERK MAPK expression regulates MMP-9 and influences growth.

Previous work has shown that expression of the extracellular signal-regulated kinase (ERK) is decreased by high density in normal fibroblast cells, and this was correlated with increased expression of mitogen-activated protein kinase phosphatases. Because of these differences in ERK regulation upon contact inhibition, it is likely that other cellular responses may be influenced by the attainment of a contact-inhibited state. Expression of matrix metalloproteinase-9 and cadherin cleavage were both found to be decreased upon reaching high culture density. Inhibition of ERK activity with the MEK inhibitor PD98059 resulted in increased expression of cadherins, while constitutive activation of ERK through the use of expression of an ERK construct with a D319N sevenmaker mutation resulted in decreased expression of cadherins and enhanced colony formation of HT-1080 fibrosarcoma cells. Taken together, these results corroborate a role for the regulation of ERK upon the attainment of a contact-inhibited state with increased expression of cadherins.

A Rare Case of an Intracardiac Myoepithelial Carcinoma in an Infant.

Myoepithelial carcinomas (MC) represent aggressive tumors that occur in a myriad of ages and anatomic locations. The rarity and histologic similarity with other tumors make them difficult to diagnosis. We report an extremely rare case of a right ventricular outflow tract mass identified to be an intracardiac MC in a 4-month-old male infant. Pathology revealed an EWS-KLF15 translocation. Treatment included gross total resection and intensive chemotherapy. Recurrent cardiac mass with brain metastasis was seen 16 months after primary diagnosis. We describe the rarity of intracardiac MC in pediatric patients and the challenges encountered in the multimodal management of this patient.

The devil is in the detail: current management of perioperative surgical complications after liver transplantation.

PURPOSE OF REVIEW: Despite advances in the field, perioperative morbidity is common after liver transplantation. This review examines the current literature to provide up-to-date management of common surgical complications associated with liver transplantation. RECENT FINDINGS: Research focuses on problems with anastomoses of the vena cava, portal vein, hepatic artery, and bile ducts. Interventional endoscopic and radiological techniques are used more frequently to avoid reoperation. SUMMARY: Advances in the management of perioperative surgical complications have focused on minimally invasive measures that successfully treat technical problems with implantation of liver allografts from both living and deceased donors.

Inhalable dry powder product (DPP) of mRNA lipid nanoparticles (LNPs) for pulmonary delivery.

Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated successful development of an mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes for the DPP were accomplished by varying the excipients, lipid composition, concentration of LNPs, and weight percentage of mRNA. Leucine alone or in combination with mannitol improved the formulation by increasing the mRNA yield as well as decreasing the particle size. Intratracheal administration of the DPP in mice resulted in luciferase expression in the trachea and lungs indicating successful delivery of functional mRNA. Our results show formulation optimization of mRNA LNPs administered in the form of DPP results in an efficacious functional delivery with great promise for future development of mRNA therapeutics for lung diseases.

Roflumilast alleviates adenine-induced chronic kidney disease by regulating inflammatory biomarkers.

The present investigation was carried out to explore the role of roflumilast, a PDE4 inhibitor, as a potential treatment option for chronic kidney disease. Forty-six male Wistar rats were divided into five groups: Control, Disease control (50 mg/kg Adenine p.o.), Adenine + Roflumilast (0.5, 1 and 1.5 mg/kg, p.o.). Various urinary and serum biomarkers, antioxidant status, histopathology, and protein expression of inflammatory markers were measured to investigate the effects of roflumilast on kidney functions. Adenine was found to elevate the levels of serum creatinine, urea, uric acid, sodium, potassium, chloride, magnesium, and phosphorus and reduce the level of serum calcium. Further, adenine significantly increased the serum TGF-ß levels and reduced the anti-oxidant indices. Significant elevation was observed in protein expression of IL-1ß, TNF-α, MCP-1, ICAM-1, and Fibronectin. Histopathologically, adenine caused thickening of the glomerular basement membrane, inflammatory cells infiltration, atrophy, and glomeruli deterioration. However, Roflumilast administration (1 mg/kg) remarkably decrease serum creatinine, urea, uric acid, sodium, potassium, chloride, magnesium, phosphorus by 61%, 40%, 44%, 41%, 49%, 58%, 59% and 42% respectively, and increase in calcium by 158%. Moreover, Roflumilast (1 mg/kg) significantly reduced serum TGF-ß levels by 50% and elevated anti-oxidant indices by 257%, 112%, and 60%, respectively. The protein expression was significantly reduced by 5.5-fold, 7-fold, 5.7-fold, 6.2-fold, and 5.1-fold individually. Roflumilast noticeably improved the structure of glomeruli, tubules, and cellular functioning. The study confirmed that Roflumilast has the potential to ameliorate renal injury by reducing and regulating inflammatory responses.

Roflumilast ameliorates diabetic nephropathy in rats through down-regulation of JAK/STAT signaling pathway.

Roflumilast is a potent selective inhibitor of the phosphodiesterase-4 enzyme which greatly manifest an anti-inflammatory activity in chronic obstructive pulmonary patients. Inflammation is a prominent factor in the prevalence of diabetic nephropathy, one of the most prevalent microvascular complications of Diabetes Mellitus. The present study was undertaken to assess the potential role of roflumilast in diabetic nephropathy. The model was developed by feeding a high-fat diet for four weeks and following streptozotocin (30 mg/kg) injection intraperitoneally. The rats with > 13.8 mmol/L blood glucose were treated with roflumilast (0.25, 0.5, 1 mg/kg) and standard metformin (100 mg/kg) orally once a day for eight weeks. Roflumilast (1 mg/kg) remarkably improved renal damage, indicated by an increase in 16% albumin, a decrease in 5% serum creatinine, 12% BUN, 19% HbA1c, and 34% blood glucose. It also significantly improves the oxidative stress levels, which was indicated by a decrease in 18% MDA level and an increase in GSH, SOD, and catalase by 6%, 4%, and 5%, respectively. In addition, Roflumilast (1 mg/kg) decreased the HOMA-IR index by 28% and increased the pancreatic ß-cells functioning by 30%. Moreover, significant improvement in histopathological abnormalities were observed in roflumilast treatment groups. Roflumilast treatment was shown to down-regulate the gene expressions of TNF-α (2.1-fold), NF-kB (2.3-fold), MCP-1 (2.5-fold), fibronectin (2.7-fold), collagen IV (2.7-fold), STAT 1(1.06-fold), and STAT 3 (1.20-fold) and upregulated the expression of the Nrf2 (1.43-fold) gene. Roflumilast manifested a potential role in diabetic nephropathy as a renoprotective agent. Roflumilast effectively down-regulates the JAK/STAT pathway and restores renal functions.

SHP1 loss augments DLBCL cellular response to ibrutinib: a candidate predictive biomarker.

SHP1, a tyrosine phosphatase, negatively regulates B-cell receptor (BCR) signaling. Ibrutinib selectively inhibits BTK and has been approved for the treatment of several types of B-cell lymphomas, but not yet in diffuse large B-cell lymphoma (DLBCL). A phase 3 clinical trial of ibrutinib-containing regimen has been completed to evaluate its activity in subtypes or subsets of DLBCL patients. Although the subtype of activated B-cell like (ABC) DLBCL is characterized by chronic active BCR signaling, only a fraction of ABC-DLBCL patients seem to benefit from ibrutinib-containing regimen. New alternative predictive biomarkers are needed to identify patients who better respond. We investigated if SHP1 plays a role in defining the level of the BCR activity and impacts the response to ibrutinib. A meta-analysis revealed that lack of SHP1 protein expression as well as SHP1 promoter hypermethylation is strongly associated with NHL including DLBCL. On a tissue microarray of 95 DLBCL samples, no substantial difference in SHP1 expression was found between the GCB and non-GCB subtypes of DLBCL. However, we identified a strong reverse correlation between SHP1 expression and promoter methylation suggesting that promoter hypermethylation is responsible for SHP1 loss. SHP1 knockout in BCR-dependent GCB and ABC cell lines increased BCR signaling activities and sensitize lymphoma cells to the action of ibrutinib. Rescue of SHP1 in the knockout clones, on the other hand, restored BCR signaling and ibrutinib resistance. Further, pharmacological inhibition of SHP1 in both cell lines and patient-derived primary cells demonstrate that SHP1 inhibition synergized with ibrutinib in suppressing tumor cell growth. Thus, SHP1 loss may serve as an alternative biomarker to cell-of-origin to identify patients who potentially benefit from ibrutinib treatment. Our results further suggest that reducing SHP1 pharmacologically may represent a new strategy to augment tumor response to BCR-directed therapies. Schematic diagram summarizing the major findings. Left panel. When SHP1 is present and functional, it negatively regulates the activity of the BCR pathway. Right pane. When SHP1 is diminished or lost, cells depend more on the increased BCR signaling and making them vulnerable to BTK inhibitor, ibrutinib. Diagram was generated using BioRender.

The Role of a Clinical Psychologist in Pediatric Nephrology.

Renal disease in pediatric patients tends to have a broad clinical spectrum from milder disease to severe progressive renal dysfunction requiring renal replacement therapy. Patients with chronic kidney disease (CKD) can have additional comorbidities including hypertension, diabetes, and obesity, which can add to the disease burden. The psychosocial or the mental component of the pediatric CKD patient is often overlooked by health care professionals due to a lack of resources and training in identifying psychological disorders. In addition, many components of kidney disease like fatigue from anemia and cognitive impairment make it difficult for the untrained physician to identify underlying psychological disorders. This review explores the complex psychosocial issues in patients with kidney disease and the need of more comprehensive multidisciplinary approach for treatment.

Beneficial effects of roots of Argyreia nervosa (Brum.f.) Bojer on testosterone biosynthesis in testis and spermatogenesis in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Argyreia nervosa (Burm.f.) Bojer is used traditionally as an aphrodisiac and mentioned in the indigenous system of medicine as spermatogenic. The roots of the plant are also used as bitter, tonic, and alternative. AIM OF THE STUDY: To study the effect of n-butanol fraction (BTF) and ethyl acetate fraction (ETF) of methanol extract prepared from the roots of Argyreia nervosa and scopoletin isolated from ETF on testosterone biosynthesis in testis and spermatogenesis using rats. MATERIALS AND METHODS: The effect of BTF, ETF, and scopoletin on the testosterone biosynthesis was evaluated by determining the alteration in expression of mRNA corresponding to steroidogenic enzymes and concentration of testosterone using TM-3 cell line. The ability of BTF and ETF in altering the level of testicular cholesterol and testosterone along with mRNA expression corresponding to 3ß-Hydroxy-Δ5-steroid dehydrogenase (3ß-HSD) and Acute Steroid Regulatory Protein (StAR) was evaluated using rats as experimental animals. The sperm concentration in the seminal fluid was determined, and histological studies of testicular tissues were also carried out. RESULTS: Test solutions containing BTF, ETF, and scopoletin showed a dose-dependent and statistically significant increase in the testosterone content when incubated with TM-3 cells. The test solutions also increased the fold expression of mRNA corresponding to StAR and 3ß-HSD enzymes from TM-3 cells. BTF and ETF elevated testicular testosterone levels by 3.57 and 3.84-fold as compared to control animals, while the fractions showed 9.04 and 10.41-fold alteration in expression of mRNA corresponding to StAR, respectively. BTF and ETF altered the expression of mRNA corresponding to 3ß-HSD by 13.43 and 15.04-fold in testicular tissues; moreover, they elevated the activity of 3ß-HSD by 7.11 and 7.73 fold, respectively. The animals treated with BTF and ETF showed increased sperm concentration. Histological observations showed that the lumen of seminiferous tubules was densely populated with spermatozoa and Leydig cells were intensely stained. Extract prepared from fruits of Tribulus terrestris Linn and testosterone served as positive controls. CONCLUSION: BTF, ETF, and scopoletin could promote testosterone biosynthesis by elevating mRNA expression corresponding to StAR, 3ß-HSD, and by increasing 3ß-HSD activity in the testicular tissues. Elevated testosterone concentration in testis promoted spermatogenesis. The studies provided the probable mechanism through which the roots of A. nervosa act as spermatogenic.

Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE).

Current nucleoside-modified RNA lipid nanoparticle (modmRNA-LNP) technology has successfully paved the way for the highest clinical efficacy data from next-generation vaccinations against SARS-CoV-2 during the COVID-19 pandemic. However, such modmRNA-LNP technology has not been characterized in common pre-existing inflammatory or immune-challenged conditions, raising the risk of adverse clinical effects when administering modmRNA-LNPs in such cases. Herein, we induce an acute-inflammation model in mice with lipopolysaccharide (LPS) intratracheally (IT), 1 mg kg-1, or intravenously (IV), 2 mg kg-1, and then IV administer modmRNA-LNP, 0.32 mg kg-1, after 4 h, and screen for inflammatory markers, such as pro-inflammatory cytokines. ModmRNA-LNP at this dose caused no significant elevation of cytokine levels in naive mice. In contrast, shortly after LPS immune stimulation, modmRNA-LNP enhanced inflammatory cytokine responses, Interleukin-6 (IL-6) in serum and Macrophage Inflammatory Protein 2 (MIP-2) in liver significantly. Our report identifies this phenomenon as inflammation exacerbation (IE), which was proven to be specific to the LNP, acting independent of mRNA cargo, and was demonstrated to be time- and dose-dependent. Macrophage depletion as well as TLR3 -/- and TLR4-/- knockout mouse studies revealed macrophages were the immune cells involved or responsible for IE. Finally, we show that pretreatment with anti-inflammatory drugs, such as corticosteroids, can partially alleviate IE response in mice. Our findings characterize the importance of LNP-mediated IE phenomena in gram negative bacterial inflammation, however, the generalizability of modmRNA-LNP in other forms of chronic or acute inflammatory and immune contexts needs to be addressed.

Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation.

This study shows that the supramolecular arrangement of proteins in nanoparticle structures predicts nanoparticle accumulation in neutrophils in acute lung inflammation (ALI). We observed homing to inflamed lungs for a variety of nanoparticles with agglutinated protein (NAPs), defined by arrangement of protein in or on the nanoparticles via hydrophobic interactions, crosslinking and electrostatic interactions. Nanoparticles with symmetric protein arrangement (for example, viral capsids) had no selectivity for inflamed lungs. Flow cytometry and immunohistochemistry showed NAPs have tropism for pulmonary neutrophils. Protein-conjugated liposomes were engineered to recapitulate NAP tropism for pulmonary neutrophils. NAP uptake in neutrophils was shown to depend on complement opsonization. We demonstrate diagnostic imaging of ALI with NAPs; show NAP tropism for inflamed human donor lungs; and show that NAPs can remediate pulmonary oedema in ALI. This work demonstrates that structure-dependent tropism for neutrophils drives NAPs to inflamed lungs and shows NAPs can detect and treat ALI.

SEROPREVALENCE OF TOXOPLASMA GONDII IN MARKET HOGS COLLECTED FROM U.S. SLAUGHTERHOUSES.

Foodborne pathogens continue to pose a public health risk and can cause serious illness and outbreaks of disease in consumers. The consumption of raw or undercooked infected meat, such as pork containing infectious stages of Toxoplasma gondii, may be a major route of transmission to humans. Given the occasional presence of T. gondii in pork meat and the frequent use of pork for products not intended to be cooked, such as dry-cured ham, a potential risk exists for T. gondii transmission to consumers of these products. The purpose of this study was to determine the seroprevalence of T. gondii in U.S. market hogs and sows at slaughter. A total of 20,209 sera samples collected from 22 U.S. slaughterhouses, including 15 of the top 25 largest slaughter plants in the United States, were tested for T. gondii antibodies using a commercial ELISA assay. Seroprevalence in this study was 0.74%, with a herd prevalence of 10.86%. We compared seroprevalence of T. gondii in market hogs vs. sows from a separate but geographically similar set of slaughterhouse locations, with serum samples screened using the T. gondii modified agglutination test. This set of market hogs demonstrated 0% seroprevalence for T. gondii, while sows from geographically similar but separate slaughter facilities demonstrated a seroprevalence of 1.03%. Overall, both analyses show low seroprevalence of T. gondii in U.S market hogs and sows, respectively, and a marked drop in prevalence in market hogs and sows compared to previous studies.

Melt Dispersion Adsorbed onto Porous Carriers: An Effective Method to Enhance the Dissolution and Flow Properties of Raloxifene Hydrochloride.

The objective of the present investigation is to enhance the dissolution and flow properties of raloxifene hydrochloride (RXH), a biopharmaceutical classification system class II drug. Melt dispersion of RXH with polyethylene glycol (PEG) 6000 was prepared by the fusion method. The melt dispersion was then adsorbed onto a porous adsorbent, Neusilin, by the melt adsorption method. Response surface methodology was employed to establish the design space for formulation variables such as the ratio of RXH to PEG 6000 in melt dispersion and amount of porous adsorbent to melt dispersion. Differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and accelerated stability techniques were utilized to characterize formulations. Negative Gibbs free energy values indicated spontaneous solubilization of RXH in PEG 6000. The time required for 80% of drug release from optimized formulation was <20 min compared with plain RXH. Accelerated stability studies confirmed the stabilization of amorphous melt dispersion in nanopores (nanoconfinement) of inorganic silicate Neusilin. Melt dispersion, adsorbed on porous carriers, is a promising technique to improve the dissolution characteristic as well as flow properties of drug molecules.