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BACKGROUND: Exenatide (synthetic exendin-4;AC2993) is a 39-amino acid peptide in the new class of antidiabetic agents known as incretin mimetics. In clinical trials, exenatide exhibited glucoregulatory effects (glucose-dependent stimulation of insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying) in patients with type 2 diabetes mellitus (DM). OBJECTIVE: The goal of this study was to determine the relative bioavailability of exenatide injected subcutaneously into the abdomen, arm, or thigh. METHODS: Patients with type 2 DM were randomized in an open-label, crossover study to assess relative bioavailability of exenatide (10 microg) injected into the arm and thigh versus injection into the abdomen. Serial plasma exenatide concentrations were measured for 10 hours after injection. A sample size of >24 patients provided approximately 80% power to ensure that 90% CIs were within the 80% to 125% interval for the ratios (geometric least squares [LS] means) of AUC(0-infinity). RESULTS: Twenty-eight patients were randomized into the study (mean age, 56 [8] years; glycosylated hemoglobin, 8.0 [1.7]%; body mass index, 33 [5] kg/m2; all values given as mean [SD]). AUC(0-infinity) values (geometric LS mean SE for SC injections into the abdomen arm and thigh were 63,935 (6608), 59,573 (6157), and 62,148 (6424) pg./mL, respectively. The AUC (geometric LS mean ratio for relative bioavailability) for arm versus abdomen was 0.93 (geometric 90% CI, 0.82-1.05); for thigh versus abdomen it was 0.97 (geometric 90% CI, 0.86-1.10). Consistent with the observed data, intrasubject variability of AUC(0-infinity) was low among the 3 treatments (coefficient of variation, 26%). C(max) values (geometric LS mean [SE]) were 220 (24) pg/mL, abdomen; 218 (23) pg/mL, arm; and 193 (21) pg/mL, thigh. The C(max) (geometric LS mean ratio) for arm versus abdomen was 0.99 (geometric 90% CI, 0.85-1.15), and for thigh versus abdomen it was 0.88 (geometric 90% CI, 0.75-1.02). The most common treatment-emergent adverse events were mild to moderate nausea (36%), headache (25%), vomiting (21%), and dizziness (18%). Three patients received an inadvertent 10-fold overdose and were withdrawn from the study immediately. All experienced severe nausea and vomiting, and 1 patient experienced severe hypoglycemia requiring aid. All recovered without mishap and were excluded from statistical and tolerability results. There were no adverse events related to the injection or the injection site. CONCLUSION: In this study of patients with type 2DM, SC administration of exenatide into the abdomen, arm, or thigh resulted in comparable bioavailability. [ABSTRACT FROM AUTHOR]

The deep-sea open ocean habitat (below 200 m depth) is comprised of little-to-no light, near freezing temperatures, and vastly connected stratified waters. Bioluminescence is often linked to the success and diversification of fishes in these dark deep-sea habitats, which are host to many species-rich and morphologically diverse clades. Fish bioluminescence takes many forms and is used in a variety of behaviors including counterillumination, prey detection and luring, communication, and predator avoidance. This study focuses on lanternfishes (Myctophidae), a diverse group (252 spp. in 34 genera) of deep-sea fishes in which bioluminescence has played a critical role in their diversification. Using histological techniques, we provide new morphological analyses of the complex structure of the primary photophores of representative species from 17 genera in which photophore morphology has not previously been described. We combine this information with data from prior studies to compare primary photophore characteristics for species representing all 34 lanternfish genera. Although we find that lanternfish primary photophores are similar in many of their structural components, including the possession of a modified scale cup, photocytes, pigment, and reflector layers, we observe significant variation among species in other aspects of photophore morphology. Observed morphological differences include variation in pigmentation and in the calcification and thickness of the modified scale cup. We also find reflectors that are very thin or absent in gymnoscopeline and lampanyctine species, relative to the robust reflectors present in myctophine species. We find evidence of secondary reflectors and secondary pigment layers in six lanternfish species and observe major differences in scale-lens thickness and mineralization across the assemblage. Lastly, Scopelopsis multipunctatus is the only species analyzed lacking a photophore cup. Obtaining finer detail of light organ morphology across this species-rich lineage provides much-needed insight into the factors that have contributed to the remarkable diversity of lanternfishes in the deep open ocean., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Martin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tooth replacement rates of polyphyodont cartilaginous and bony fishes are hard to determine because of a lack of obvious patterning and maintaining specimens long enough to observe replacement. Pulse-chase is a fluorescent technique that differentially colours developing mineralized tissue. We present in situ tooth replacement rate and position data for the oral and pharyngeal detentions of Ophiodon elongatus (Pacific lingcod). We assessed over 10 000 teeth, in 20 fish, and found a daily replacement rate of about two teeth (3.6% of the dentition). The average tooth is in the dental battery for 27 days. The replacement was higher in the lower pharyngeal jaw (LPJ). We found no difference between replacement rates of feeding and non-feeding fish, suggesting feeding was not a driver of tooth replacement. Lingcod teeth have both a size and location fate; smaller teeth at one spot will not grow into larger teeth, even if a large tooth nearby is lost. We also found increased rates of replacement at the posterior of the LPJ relative to the anterior. We propose that lingcod teeth do not migrate in the jaw as they develop; their teeth are fated in size and location, erupting in their functional position.

Objective: The aim of this study was to introduce new approaches to conduct qualitative research that may provide valuable insight into issues related to education, training and patient care in psychiatry., Conclusions: A variety of data-collection tools is available for researchers and practitioners in psychiatry. These can be used independently or in conjunction with other quantitative and qualitative methods.

Objective: In this observational study, a modified version of the Visual Function Index (VF-14) and the Snellen Visual Acuity Test were compared in how well they correlated with self-restricted driving habits in older adults. The VF-14 was originally designed to assess vision in cataract patients; however, in this study, a modified version (mVF-14) was evaluated as a tool for predicting self-restricted driving in older drivers., Methods: During a 3-month period, 151 drivers over the age of 65 were screened at the local senior center. In addition to the Snellen Visual Acuity Test and mVF-14, each participant was given a questionnaire about their driving habits, previously used in self-restriction studies., Results: Out of 151 total participants, 134 were included and 7 nondrivers and 10 subjects who did not complete all questionnaires were excluded. One hundred one participants exhibited normal visual acuity of 20/40 or better (75%), and 110 scored over 90 on the mVF-14 (82%). Spearman's rank sum correlation coefficient was used to analyze the data and showed significant negative correlation of the mVF-14 and Snellen with self-restricted driving. Individuals with normal vision (20/40 or better on the Snellen eye test) had both high and low mVF-14 scores., Conclusions: The study shows that poor vision, as indicated by the Snellen scale and low mVF-14 scores, correlates to self-imposed driving limitations. The mVF-14 showed further distinctions of self-restriction between individuals in the same Snellen Visual Acuity category. Therefore, using the mVF-14 in addition to the Snellen Visual Acuity Test can be helpful to further differentiate visual ability within older drivers who appear to have normal vision.

Exposure of airway smooth muscle (ASM) cells to the cytokine IL-1beta results in an induction of PGE2 synthesis that affects numerous cell functions. Current dogma posits induction of COX-2 protein as the critical, obligatory event in cytokine-induced PGE2 production, although PGE2 induction can be inhibited without a concomitant inhibition of COX-2. To explore other putative regulatory features we examined the role of phospholipase A2 (PLA2) and PGE synthase (PGES) enzymes in IL-1beta-induced PGE2 production. Treatment of human ASM cultures with IL-1beta caused a time-dependent induction of both cytosolic PLA2 (cPLA2) and microsomal PGES (mPGES) similar to that observed for COX-2. Regulation of COX-2 and mPGES induction was similar, being significantly reduced by inhibition of p42/p44 or p38, whereas cPLA2 induction was only minimally reduced by inhibition of p38 or PKC. COX-2 and mPGES induction was subject to feed-forward regulation by PKA, whereas cPLA2 induction was not. SB-202474, an SB-203580 analog lacking the ability to inhibit p38 but capable of inhibiting IL-1beta-induced PGE2 production, was effective in inhibiting mPGES but not COX-2 or cPLA2 induction. These data suggest that although COX-2, cPLA2, and mPGES are all induced by IL-beta in human ASM cells, regulatory features of cPLA2 are dissociated, whereas those of COX-2 and mPGES are primarily associated, with regulation of PGE2 production. mPGES induction and, possibly, cPLA2 induction appear to cooperate with COX-2 to determine IL-1beta-mediated PGE2 production in human ASM cells.

Scabies is a common infestation for patients of all ages throughout the world. One of the standard therapies for scabies is 1% lindane lotion. Lindane has been associated with neurotoxic reactions, specifically seizures. We describe a case of a middle-aged adult man with human immunodeficiency virus (HIV) infection who was found to have typical scabies and was treated with a single topical application of lindane. Two hours after the application, the patient experienced a new-onset generalized seizure. We believe that the triad of HIV infection, medications that reduce seizure thresholds, and percutaneous absorption factors, in the aggregate, induced the seizure. We believe that lindane should not be prescribed for patients with HIV infection.

Four black children with Spitz nevi are presented. The initial clinical diagnosis was pyogenic granuloma for three patients. One child had two Spitz nevi. Histologic examination revealed melanocytic dendritic hyperplasia in all cases.