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AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.

This study aimed to explore the use of chemical and physical enhancement strategies for the intradermal delivery of cromolyn sodium (CS) for treatment of atopic dermatitis. CS gels were formulated to individually contain 2.5 and 9% salcaprozate sodium (SNAC) as a potential chemical enhancer. The effect of microneedles, alone and in combination with SNAC, was investigated via in vitro permeation studies. Skin impedance and FTIR evaluation of SNAC-treated stratum corneum (SC) was done and compared to the control. The amount of drug delivered in the dermis after 24 h by the 2.5% and 9% SNAC gels was 23.29 ± 1.89 µg/cm

We report a late presentation of adenovirus-induced renal allograft and bladder infection causing azotemia and hemorrhagic cystitis in a patient 5 years after simultaneous kidney-pancreas transplantation. Adenovirus has been increasingly recognized as a cause of morbidity and mortality in both solid organ and stem cell transplant recipients. We wish to emphasize the importance of early detection, as treatment options involve reduction of immunosuppression, followed by the addition of antiviral agents and supportive care.

Calciphylaxis is a major cause of morbidity and mortality in end-stage renal disease (ESRD). Intravenous sodium thiosulfate (STS) is the mainstay of therapy for calciphylaxis. In peritoneal dialysis (PD) patients with calciphylaxis, intravenous STS poses logistic and financial challenges. Even though pharmacokinetic studies show poor bioavailability of oral STS, we report successful use of oral STS in 2 PD patients with calciphylaxis.A 55-year-old Latina American woman with diabetes was initiated on PD after access failure and chronic hypotension. She developed painful ischemic lesions in the left middle finger and left big toe 4 months later. The ischemia in the left hand progressed, requiring amputation of two fingers. She later developed extensive painful calcific areas in the abdominal wall. She was initially started on oral STS 1500 mg twice daily that was subsequently increased to 3750 mg daily, which resulted in substantial pain relief and a decrease in the size of the calcific plaques.Another diabetic patient with ESRD who was on PD presented with a painful ischemic finger for 2 years. He was treated with oral STS 1500 mg twice daily, resulting in prompt pain relief.Oral STS can be an effective treatment for calciphylaxis.

Although almost all pathological diagnoses made from a native kidney biopsy come from careful examination of the renal cortex, certain diseases have a characteristic medullary component. Medullary angiitis has histological features of interstitial hemorrhage in the medulla with an associated polymorphonuclear leukocyte infiltrate. These findings are primarily found in the setting of antineutrophil cytoplasmic antibody-associated vasculitis. Medullary angiitis identified in the setting of negative immunofluorescence is most suggestive of pauci-immune crescentic glomerulonephritis, as presented in this case.

Renal cell carcinoma (RCC) has a high incidence in the kidney transplant population and annual surveillance detects these tumors early in their natural history. Minimal guidelines exist regarding RCC surveillance in ESRD patients awaiting transplant. A retrospective review of our kidney transplant database examined the outcomes of annual ultrasonographic surveillance during initial kidney transplant evaluation and upon annual reassessment. Of 2642 patients listed for transplant, 145 patients were found to have masses during initial kidney transplant evaluation or annual imaging consistent with new complex cystic disease or RCC. A total of 71 patients had RCC identified, with 52 found on initial kidney transplant evaluation and 19 identified on annual surveillance. Male gender and African-American race were independently associated with RCC (P

Oocyte donation affords women with ovarian failure, advanced reproductive age, heritable conditions or recurrent implantation failure the ability to conceive. Recipients must be medically screened carefully prior to attempting pregnancy. Egg donors should also be healthy and pose no infectious or genetic risk to the recipient or offspring. Donor and recipient menstrual cycles are synchronized so that embryos are transferred to a receptive endometrium. Donors are prescribed injectible gonadotrophins to achieve multifollicular growth. Recipient endometrial priming begins with 2 weeks (or more) of oestradiol, with progesterone added to the regimen 3-4 days prior to the transfer of embryos. Pregnancy rates following egg donation are among the highest observed following assisted reproduction. Despite advanced reproductive age, perinatal and obstetric outcomes are generally good. Techniques (i.e. germinal vesicle transfer, donor ooplasm, and ovarian cryopreservation and transplantation techniques) may permit the recipient to provide some genetic contribution to offspring and are currently under investigation.

Because current supplies will not adequately meet its needs beyond 2010, the city of Wichita, KS, applied the integrated resource planning (IRP) process to develop a long-term water resource plan. The plan is environmentally, socially, and economically acceptable to the community and holistically uses the city`s local water resources on an ``as-available`` basis. Key elements of the plan in addition to water conservation and watershed management are use of trichloroethylene-remediated and high-chloride groundwater, above-base (excess) flow from the Little Arkansas River, expansion of a local wellfield, and recharge of a primary existing water source called the Equus Beds Wellfield. Overpumping by irrigators, industries, and municipalities during the last 40 years caused a drawdown storage volume in the Equus Bed Wellfield, which can hold 100 bil gal of water. Recharging the aquifer replenishes groundwater storage and minimizes flow of chloride-contaminated water into the wellfield.

We describe the cryostat and supporting electronics for the EBEX experiment. EBEX is a balloon-borne polarimeter designed to measure the B-mode polarization of the cosmic microwave background radiation. The instrument includes a 1.5 meter Gregorian-type telescope and 1432 bolometric transition edge sensor detectors operating at 0.3 K. Electronics for monitoring temperatures and controlling cryostat refrigerators is read out over CANbus. A timing system ensures the data from all subsystems is accurately synchronized. EBEX completed an engineering test flight in June 2009 during which the cryogenics and supporting electronics performed according to predictions. The temperatures of the cryostat were stable, and an analysis of a subset of the data finds no scan synchronous signal in the cryostat temperatures. Preparations are underway for an Antarctic flight., Comment: 11 pages, 6 figures, Proceedings of the 12th Marcel Grossman Conference

During T-cell development and activation, dramatic changes occur in glycan structures that decorate cell-surface glycoproteins. These changes have been considered to be general cellular events that affect many glycans on many glycoproteins. For example, loss of sialic acid from core 1 O-glycans on T-cell surface glycoproteins CD45, CD43 and CD8, detected with peanut agglutinin (PNA), is a hallmark of immature thymocytes and activated peripheral T cells. Loss of cell-surface sialic acid during T-cell activation has been proposed to enhance TCR reactivity with antigen. However, CD4 T-cell activation also results in increased binding of the CZ-1 antibody that recognizes a sialic acid-containing epitope on CD45RB. This indicates that increased sialylation of the CZ-1 epitope occurs during CD4 T cell activation, and that loss of cell surface sialic acid during T-cell activation is a selective event rather than affecting all cell surface glycans. As specific glycans on specific glycoprotein backbones control critical events in T-cell maturation and survival, understanding mechanisms of selective glycoprotein glycosylation is important for regulating T-cell development and function. We define the sialylated O-glycan epitope recognized by CZ-1, and find that, paradoxically, CZ-1 and PNA binding are simultaneously increased on activated CD4(+) T cells, demonstrating site-specific changes in CD45 sialylation. Moreover, we identify ST3Gal I as the sialyltransferase responsible for creating the CZ-1 epitope. Thus, changes in glycan structure during T-cell activation are microheterogeneous and unique to individual glycans on specific glycoproteins, implying that these glycans have precise functions in T-cell biology.

The vascular supply of the liver and gallbladder is characterized by a striking degree of polymorphism. The occurrence of variants that differ from the usual pattern is both surprisingly common and unpredictable. Knowledge of this variable anatomy is particularly important during surgical interventions in which preoperative imaging studies are not available, such as in organ procurements. In this report we consider various anatomical arterial configurations, and describe an unusual variant.

Cardiac resynchronization therapy (CRT) by means of biventricular pacing is a fairly new procedure that has recently been approved by the United States Food and Drug Administration. Many promising studies have been published that suggest CRT improves patient quality of life (based on the Minnesota Living with Heart Failure Quality of Life Questionnaire), increases distance walked in 6 minutes, improves oxygen uptake, lowers New York Heart Association classification, decreases QRS duration, increases left ventricular ejection fraction, and increases peak oxygen consumption. These studies include the Multisite Stimulation in Cardiomyopathies (MUSTIC), the Multicenter InSync Randomized Clinical Evaluation (MIRACLE), the Pacing Therapy for Congestive Heart Failure (PATH-CHF) multicenter trial, the Medtronic Inc. InSync study, the Ventak CHF/Contak CD study, Vigor CHF and a small study conducted by Alonso and colleagues. There are also a number of studies that are still being conducted, such as the COMPANION trial, which will provide further insight into the effectiveness of cardiac resynchronization therapy.

Instruments and drains left in the abdomen following surgery may be responsible for bizarre and varied complications. The patient may remain asymptomatic for months or even years. Complications include adhesion formation, intestinal obstruction, abscesses, and erosion into the gastrointestinal tract. We report 3 patients in whom retained surgical material eroded into the duodenum and colon, respectively, and produced unusual radiologic findings and complications.