Oral immunization using whole inactivated influenza virus vaccine promises an efficient vaccination strategy. While oral vaccination was hampered by harsh gastric environment, a systematic understanding about vaccine destabilization mechanisms was not performed. Here, we investigated the separate and combined effects of temperature, retention time, pH, and osmotic stress on the stability of influenza vaccine by monitoring the time-dependent morphological change using stopped-flow light scattering. When exposed to osmotic stress, clustering of vaccine particles was enhanced in an acidic medium (pH 2.0) at ≥25°C. Fluorescence spectroscopic studies showed that hyper-osmotic stress at pH 2.0 and 37°C caused a considerable increase in conformational change of antigenic proteins compared to that in acidic iso-osmotic medium. A structural integrity of membrane was destroyed upon exposure to hyper-osmotic stress, leading to irreversible morphological change, as observed by undulation in stopped-flow light scattering intensity and transmission electron microscopy. Consistent with these analyses, hemagglutination activity decreased more significantly with an increasing magnitude of hyper-osmotic stress than in the presence of the hypo- and iso-osmotic stresses. This study shows that the magnitude and direction of the osmotic gradient has a substantial impact on the stability of orally administrated influenza vaccine.

Context Subclinical features of zinc deficiency can be challenging to recognize. The prevalence of zinc deficiency based on blood zinc concentration in an adult outpatient clinic setting has not been well-studied. Objective To estimate the prevalence of low serum zinc concentrations among community-dwelling adults, and to characterize clinical features and risk factors associated with zinc deficiency. Methods This retrospective pilot prevalence study took place from 2014 to 2017 at an outpatient clinic in southeast Ohio. Patients aged 50 years or older with a stable health status were categorized into a case group with zinc deficiency (serum zinc concentration, <0.66 µg/mL) and a control group (serum zinc concentration, ≥0.66 µg/mL). Measurements included serum zinc concentration, nutritional biomarkers (ie, magnesium, calcium, albumin, and total 25-hydroxy vitamin D levels), patient history of fractures and events such as hospitalization, antibiotic use, and self-reported falls that occurred within 1 year prior to the date serum zinc concentration was measured (index date). Patients were excluded if they had a serum zinc measurement within 2 months after a hospitalization, severe renal insufficiency (3 patients with serum creatinine concentration above 2.5 mg/dL), or serum zinc concentration above 1.20 µg/mL. Results This study included 157 patients, consisting of a case group of 41 (26%) patients with zinc deficiency and a control group of 116 (74%) without zinc deficiency. Mean (SD) zinc concentrations of the case and control groups were 0.58 (0.05) µg/mL and 0.803 (0.13) µg/mL, respectively (P<.01). Patients in the case group were more likely to have had a history of hospitalization, antibiotic use, a fall within 1 year before the index date, and a history of fractures and hip fracture (P<.01 in each case). Patients taking gastric acid suppressants had increased odds of lower zinc concentrations (odds ratio, 2.24; 95% CI, 1.08-4.63). Both logistic and multivariate linear regression models revealed that past fractures, hip fractures, and hypoalbuminemia (albumin <3.5 g/dL) were associated with zinc deficiency or lower zinc concentrations. Conclusion This study revealed that 26% of patients in an outpatient adult clinic had zinc deficiency based on serum concentrations. Patients with fracture history and low serum albumin were at higher risk for zinc deficiency.

Aqueous channels of foam represent a simplified, natural bioreactor on the micro-/nano-scale. Previous studies have demonstrated the feasibility and potential application of foams in replicating cellular process in vitro, but no research has been performed to establish a basis for designing stable and biocompatible foam formulations. Our research has been directed specifically to the evaluation of ranaspumin-2 (RSN-2), a frog foam nest protein. The strong surfactant activity of RSN-2 enabled us to produce foams using low protein concentration (1 mg ml(-1)) over a wide pH range (pH ≥ 3). Importantly, the RSN-2 formulation exhibited the best foam stability at a near neutral pH condition, which shows a potential for application to various biosynthesis applications. Model cellular systems such as liposomes and inactivated A/PR/8/34 influenza virus maintained their physicochemical stability and full hemagglutination activity, indicating biocompatibility of RSN-2 with both cellular membranes and proteins both in bulk solution and in foam. Moreover, the addition of RSN-2 did not exert any deteriorative effects on bacterial cell growth kinetics. In contrast, Tween 20, Triton X-100, and BSA did not show satisfactory performance in terms of foamability, foam stability, physicochemcial stability, and biochemical stability. Although our study has been limited to representative formulations composed of only surfactant molecules, a number of unique advantages make RSN-2 a promising candidate for in vitro foam biosynthesis.

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This is a case report of a ruptured gastrointestinal stromal tumor (GIST) presenting as spontaneous hemoperitoneum. The patient was a 63-year-old female with a past medical history of hypertension and ulcerative colitis who presented to the emergency department with worsening epigastric pain. The patient denied history of trauma, previous surgeries, or forceful vomiting. She was not on anticoagulation. Vital signs at presentation were stable. A CT scan of abdomen/pelvis revealed a large amount of fluid in the upper abdomen with high attenuation material adjacent to the greater curvature of the stomach concerning for hemoperitoneum. Diagnostic laparoscopy revealed a significant amount of blood along the upper abdominal viscera. The procedure was converted to an upper midline laparotomy after identifying a necrotic, extremely friable 7 x 6 x 3 cm pedunculated mass with active hemorrhage on the posterior aspect of the greater curvature. A wedge resection was performed to remove the mass with grossly negative margins. An intraoperative frozen section revealed a stromal tumor with spindle cells. Final pathology revealed a pT3N0M0 stromal tumor with histologic spindle cells and a high mitotic rate (24/5 mm 2) consistent with a high-grade GIST. Given tumor rupture at presentation, the patient was started on imatinib therapy for a minimum duration of three years. GISTs are often asymptomatic or cause mild abdominal pain or GI bleeding. Rarely, an exophytic GIST may rupture leading to intraperitoneal bleeding. Surgical resection with negative margins is the mainstay of treatment although patients presenting with tumor rupture are at higher risk of dissemination and recurrence.