Effect of Formulation Variables on the Stability of a Live,Rotavirus (RV3-BB) Vaccine Candidate using in vitro Gastric Digestion Models to Mimic Oral Delivery

In this work, two different in vitro gastric digestion models were used to evaluate the stability of a live attenuated rotavirus vaccine candidate (RV3-BB) under conditions designed to mimic oral delivery in infants. First, a forced-degradation model was established at low pH to assess the buffering capacity of formulation excipients and to screen for RV3-BB stabilizers. Second, a sequential-addition model was implemented to examine RV3-BB stability under conditions more representative of oral administration to infants. RV3-BB rapidly inactivated at < pH 5.0 (37 °C, 1 h) as measured by an infectivity RT-qPCR assay. Pre-neutralization with varying volumes of infant formula (Enfamil®) or antacid (Mylanta®) conferred partial to full protection of RV3-BB. Excipients with sufficient buffering capacity to minimize acidic pH inactivation of RV3-BB were identified (e.g., succinate, acetate, adipate), however, they concomitantly destabilized RV3-BB in accelerated storage stability studies. Both effects were concentration dependent, thus excipient optimization was required to design candidate RV3-BB formulations which minimize acid-induced viral inactivation during oral delivery while not destabilizing the vaccine during long-term 2–8 °C storage. Finally, a statistical Design -of-Experiments (DOE) study examining RV3-BB stability in the in vitro sequential-addition model identified key formulation parameters likely affecting RV3-BB stability during in vivo oral delivery.     

Pentachlorophenol and other chlorinated phenols are substrates for human hydroxysteroid sulfotransferase hSULT2A1

Pentachlorophenol (PCP) is a persistent chemical contaminant that has been extensively investigated in terms of its toxicology and metabolism. Similar to PCP, other chlorinated phenol derivatives are also widely present in the environment from various sources. Even though some of the chlorine-substituted phenols, and particularly PCP, are well-known inhibitors of phenol sulfotransferases (SULTs), these compounds have been shown to undergo sulfation in humans. To investigate the enzymatic basis for sulfation of PCP in humans, we have studied the potential for PCP as well as the mono-, di-, tri-, and tetra-chlorinated phenols to serve as substrates for human hydroxysteroid sulfotransferase, hSULT2A1. Our results show that all of these compounds are substrates for this isoform of sulfotransferase, and the highest rates of sulfation are obtained with PCP, trichlorophenols, and tetrachlorophenols. Much lower rates of sulfation were obtained with isomers of monochlorophenol and dichlorophenol as substrates for hSULT2A1. Thus, the sulfation of polychlorinated phenols catalyzed by hSULT2A1 may be a significant component of their metabolism in humans.     

The effect of thermo-mechanical fatigue on the retentive force and dimensional changes in polyetheretherketone clasps with different thickness and undercut

PURPOSEEsthetic expectations have increased the use of polyetheretherketone (PEEK) clasps as alternatives to Cr-Co in removable partial dentures (RPDs). The objective of this study was to evaluate the retentive force and dimensional change of clasps with different thickness and undercut made from PEEK by the thermo-mechanical fatigue.MATERIALS AND METHODSPEEK clasps (N = 48) with thicknesses of 1 or 1.50 mm and 48 premolar monolithic zirconia crowns with undercuts of 0.25 mm or 0.50 mm were fabricated. Samples are divided into four groups (C1-C4) and were subjected to 7200 thermal aging cycles (at 5 - 55℃). The changes in the retentive force and dimensions of the clasps were measured by micro-stress testing and micro-CT devices from five measurement points (M1 - M5). One-way ANOVA, paired t-test, two-way repeated ANOVA, and post-hoc tests were used to analyze the data (P < .05).RESULTSThe retentive forces of C1, C2, C3, and C4 groups in initial and final test were found to be 4.389-3.388 N, 4.67 - 3.396 N, 5.161 - 4.096 N, 5.459 - 4.141 N, respectively. The effects of retentive force of all PEEK clasps groups were significant decreased. Thermo-mechanical cycles caused significant dimensional changes at points with M2, M4, and M5, and abraded the clasp corners and increased the distance between the ends of the clasp, resulting in reduced retentive forces (P^* = .016, P^* = .042, P < .001, respectively).CONCLUSIONThermo-mechanical aging decreases the retentive forces in PEEK clasps. Increasing the thickness and undercut amount of clasps decreases the amount of dimensional change. The values measured after aging are within the clinically acceptable limits.     

Delirium is associated with increased mortality in the geriatric population

Objective: The aim of this study was to investigate the prevalence of delirium and its association with mortality rates in elderly inpatients.

Methods: The medical records of 1435 patients over 65 years old who were treated at a regional university hospital and were referred to the university’s Consultation and Liaison Psychiatry Clinic for psychological evaluation were retrospectively analyzed. Patients with and without a diagnosis of delirium were compared. The National Survival Database was used to determine mortality rates.

Results: The prevalence of delirium was 25.5%. The delirium group was older (p?p?p?Conclusions: Independent of all other factors, delirium is associated with higher mortality risk.     

Adipocytokines and ghrelin level of bipolar patients from manic episode to euthymic episode

Purpose: Obesity and metabolic syndrome (MeS) are more frequently observed in bipolar patients than the general population. This may result from the differences of adipocytokines and ghrelin levels in bipolar disorder.

Material and methods: We evaluated the leptin, adiponectin, resistin and ghrelin levels in bipolar patients (n?=?30) in manic episode and in a control group (n?=?30). After treatment, the same patients were evaluated again during the euthymic episode. We also measured the insulin, glucose, insulin resistance (HOMA), trygliceride (TG), total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) in relation to the (MeS).

Results: When controlling for age, BMI and glucose, leptin levels were higher in the bipolar disorder manic episode group (BD-ME) and bipolar euthymic episode group (BD-EE) than the control group; resistin levels were higher in the BD-ME compared to the control group and it had a positive correlation with Young Mania Rating Scale (YMRS). After treatment, ghrelin levels were higher in the BD-EE compared to the BD-ME group. There was no difference among the groups with respect to adiponectin.

Conclusions: The present results point that high leptin, resistin and ghrelin levels may be involved in the early pathophysiological process which can lead to later obesity and MeS in patients with bipolar disorder.     

Basal cell carcinoma presenting as an excoriated cicatricial plaque: A case report

Basal cell carcinoma (BCC) is the most common skin cancer with several clinical and histopathological subtypes. Trauma and scar tissue have been implicated as possible etiological causes of BCC. Here, we report a case of a 37-year-old man with BCC arising on a longstanding cicatricial plaque with nearly 30 years' duration. Intractable pruritus, which had started two months ago and gradually intensified, was the patient's main complaint upon admission. The lesion presented as a linear, erythematous, excoriated cicatricial plaque in the left supraclavicular region. Pearly borders and the mildly atrophic center of the plaque, that were recognized upon close examination, were notable features and may indicate BCC. We believe that a detailed patient history and meticulous clinical examination are essential for diagnosing BCC arising in longstanding scars.     

Are predictive factors in sperm retrieval and pregnancy rates present in nonobstructive azoospermia patients by microdissection testicular sperm extraction on testicle with a history of orchidopexy operation?

The aim in this study is to evaluate predictive factors on sperm retrieval and pregnancy rates by microdissection testicular sperm extraction in non obstructive azoospermia patients with a history of orchidopexy operation. A total of 148 patients were included, and their medical files were evaluated. Data related to possible predictive factors on sperm retrieval and pregnancy rates such as age at orchidopexy operation, unilateral or bilateral presence of undescended testis before orchidopexy, testis volumes and hormone levels were statistically analysed. It revealed that the mean ages in patients with unilateral and bilateral orchidopexy operations were 35.37 (±4.84) and 33.94 (±5.91) respectively. Mean testis volume in the unilateral orchidopexy group was 7.59 (±3.12) ml on the right testis and 7.37 (±2.86) ml on the left testis. Mean FSH levels were detected as 22.71 (±11.86) mIU/ml in the unilateral group and 28.19 (±12.40) mIU/ml in the bilateral group. In our study, we have shown that the age at which patients undergo orchidopexy and the unilateral or bilateral presence of cryptorchidism has no correlation with sperm retrieval and pregnancy rates.