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There is a growing global interest in using peptides in the health industry for pharmaceuticals, cosmetics, and natural food products. Peptides contain two or more linked amino acids, whereas more than 50 amino acids are classified as polypeptides. Although there is a growing level of interest in the use of peptides in the health and wellness industry, there is a lack of literature pertaining to a specific tripeptide derived from arginine, alanine, and lysine (RAK) that is of interest for human dietary use. Therefore, a 90-day repeated-dose toxicity study was performed in rats to evaluate the subchronic oral toxicity of RAK. Eighty Han:WIST rats were administered RAK by gavage at doses of 0, 250, 500, or 1000 mg/kg bw/day. There were no mortalities or other treatment related effects, and no target organs were identified. A no-observed-adverse-effect-level (NOAEL) of 1000 mg/kg bw/day, the highest dose tested, was determined. This study will contribute to the body of research in regard to the safety of the use of RAK., (© 2023 John Wiley & Sons Ltd.)

Microorganisms have the potential to produce nutrient-rich products that can be consumed as food or feed. The protein-rich powder derived from heat treatment of the whole-cell biomass of polyhydroxybutyrate-deficient Cupriavidus necator, a metabolically versatile organism that uses elements found in the air, is an example of such a product. To assess the safety of the protein powder for use as a nutritional ingredient in human food, in accordance with internationally accepted standards, its genotoxic potential and repeated-dose oral toxicity were investigated. A bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian micronucleus test were performed. No evidence of mutagenicity or genotoxicity was found. Additionally, a 90-day repeated-dose oral toxicity study in rats was completed, in which a total of 100 male and female Wistar rats were exposed by gavage to daily doses of 1000, 2000, or 3000 mg/kg bw/day of the test material. Following 90 days of continuous exposure, no mortality or treatment-related adverse effects were observed and no target organs were identified. Therefore, a no observed adverse effect level was determined at 3000 mg/kg bw/day, the highest dose tested., (© 2023 John Wiley & Sons Ltd.)

Gold nanocrystals (AuNC) are gold nanoparticles (AuNP) relatively homogenous in size at 8-28 nm with clean surfaces and crystalline structures. There are concerns and a lack of consensus in the scientific literature and major regulatory bodies regarding not only the safety of nanoparticles when consumed by humans, but exactly how to determine their safety and whether evidence from a nanoparticle with one set of physiochemical properties extends to one with a different set. Additionally, there are few general long-term toxicity data on AuNP. To our knowledge, the potential toxicity of AuNC specifically, with the above characteristics, or otherwise, has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test to further explore their safety. AuNC were not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 60-day, repeated-dose oral toxicity study, rats were administered 0, 2.5, 5, or 10 mg/kg bw/day of AuNC by gavage. No toxicity was identified. Therefore, a no observed adverse effect level was determined as 10 mg/kg body weight/day., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Vnd is a dual transcriptional regulator that is essential for Drosophila dorsal-ventral patterning. Yet, our understanding of the biochemical basis for its regulatory activity is limited. Consistent with Vnd's ability to repress target expression in embryos, endogenously expressed Vnd physically associates with the co-repressor, Groucho, in Drosophila Kc167 cells. Vnd exists as a single complex in Kc167 cells, in contrast with embryonic Vnd, which forms multiple high-molecular-weight complexes. Unlike its vertebrate homolog, Nkx2.2, full-length Vnd can bind its target in electrophoretic mobility shift assay, suggesting that co-factor availability may influence Vnd's weak regulatory activity in transient transfections. We identify the high mobility group 1-type protein, D1, and the novel helix-loop-helix protein, Olig, as novel Vnd-interacting proteins using co-immunoprecipitation assays. Furthermore, we demonstrate that both D1 and Olig are co-expressed with Vnd during Drosophila embryogenesis, consistent with a biological basis for this interaction. We also suggest that the phosphorylation state of Vnd influences its ability to interact with co-factors, because Vnd is extensively phosphorylated in embryos and can be phosphorylated by activated mitogen-activated protein kinase in vitro. These results highlight the complexities of Vnd-mediated regulation.

The Drosophila embryonic CNS arises from the neuroectoderm, which is divided along the dorsal-ventral axis into two halves by specialized mesectodermal cells at the ventral midline. The neuroectoderm is in turn divided into three longitudinal stripes--ventral, intermediate, and lateral. The ventral nervous system defective, or vnd, homeobox gene is expressed from cellularization throughout early neural development in ventral neuroectodermal cells, neuroblasts, and ganglion mother cells, and later in an unrelated pattern in neurons. Here, in the context of the dorsal-ventral location of precursor cells, we reassess the vnd loss- and gain-of-function CNS phenotypes using cell specific markers. We find that over expression of vnd causes significantly more profound effects on CNS cell specification than vnd loss. The CNS defects seen in vnd mutants are partly caused by loss of progeny of ventral neuroblasts-the commissures are fused and the longitudinal connectives are aberrantly positioned close to the ventral midline. The commissural vnd phenotype is associated with defects in cells that arise from the mesectoderm, where the VUM neurons have pathfinding defects, the MP1 neurons are mis-specified, and the midline glia are reduced in number. vnd over expression results in the mis-specification of progeny arising from all regions of the neuroectoderm, including the ventral neuroblasts that normally express the gene. The CNS of embryos that over express vnd is highly disrupted, with weak longitudinal connectives that are placed too far from the ventral midline and severely reduced commissural formation. The commissural defects seen in vnd gain-of-function mutants correlate with midline glial defects, whereas the mislocalization of interneurons coincides with longitudinal glial mis-specification. Thus, Drosophila neural and glial specification requires that vnd expression by tightly regulated., (Copyright 2002 John Wiley & Sons, Inc. J Neurobiol 50: 118-136, 2002; DOI 10.1002/neu.10022)

Videolaryngostroboscopy, psychoacoustic and spectrographic analyses were performed to evaluate vocal function in two groups of male patients who had undergone CO2Laser (n = 23) and laryngofissure cordectomy (n = 21) for the treatment of T1a glottic carcinoma. None of the patients used their voices professionally. This study revealed a good correlation between the anatomical features and voice quality. Psychoacoustic and spectrographic analysis showed that the functional results were significantly worse in the patients treated by laryngofissure (p < 0.003). In this group videolaryngostroboscopy showed a higher rate of compensation in both ventricular folds than shown in the laser-treated group (p < 0.02). The authors conclude that the functional results obtained after cordectomy depend on the various combinations of scarring patterns and compensatory hyperkinesia of the ventricular or vocal folds. The better anatomical and functional results achieved following laser cordectomy may be explained by the fact that such procedures result in better, more rapid healing processes.

The "New Table indicating the percentage of disability resulting from injury and disabling diseases" approved by the Italian Ministerial Decree dated February 5, 1992 gives a superficial, highly disorganized handling of laryngeal pathologies. This Table only considers phonatory function disorders which are included in a special section; it totally neglects dyspnea and dysphagia of laryngeal origin. This omission cannot even be overcome on the basis of similarities since there are no analogous items listed for reference. In fact, the parameters applied to evaluate dyspnea (CV, VEMS, O2 consumption) apply to ventilation disorders of a pulmonary nature and cannot, therefore, be used in cases of laryngeal dyspnea. Moreover, the Table does not deal with dysphagia at all. In addition, the basis for the Table--the concept of permanent functional damage--is not always adhered to in giving indications for evaluation of phonatory tract damage. The purpose of the present work is not, however, to propose a different way to determine the percentages for the individual items in the tables; rather, the aim is to suggest a different, highly standardized procedure for evaluating laryngeal dysfunctions which is easy to apply.

The role of head size to determine the inter-subject variability of the auditory brainstem response (ABR) was investigated in 32 normally hearing adults (19 females, 13 males, aged 18 to 52). The ABRs were evaluated in respect to the absolute latency of waves I, III and V and the interpeak latencies I-III, III-V and I-V. Plain films of the skull (3 views) were also taken of each subject and several measures were calculated in order to obtain an evaluation of the dimensions of both the most rostral parts of the skull and of the posterior fossa. The radiographic data as well as the ABR parameters showed significantly shorter values in females than in males. There was a strong positive correlation between the two variables when a linear regression procedure was applyed. The highest value of the correlation coefficient (r = 0.8) was found in the relationship between the wave V latency and the posterior fossa measures. High r values and similar factors in the regression equation were also found after considering the subjects separately according to sex. These results show that the ABR latencies linearly increase together with the skull size as it appears in the X-rays, regardless of the subject's sex. We can consequently deduce that the length of the neural pathway is the main factor of inter-sex variability of the response.