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Aim: To show the potential of Invisalign in multi-segmental Le Fort I preparation with the aid of an occlusogram-like method., Methods: Nine patients treated with Invisalign before segmental osteotomy of the maxilla (study sample) were matched for diagnosis, surgical procedure, and complexity of orthodontic preparation with nine patients treated with fixed appliances (control sample). A superimposition technique was adapted to complement the Invisalign software to carry out an appropriate ClinCheck in segmental pre-surgical treatments. The correct pre-surgical positions of the maxillary teeth were guided with the use of virtual added curves that followed the lower arch. The number of impressions needed in both groups to reach adequate pre-surgical coordination of the segmented arches was compared., Conclusion: With the aid of the proposed superimposition method, during the digital simulation of presurgical movements, clear aligner therapy appears to be an effective treatment even in patients with skeletal discrepancies and craniofacial anomalies involving the need for segmental Le Fort I osteotomies. More sophisticated software will certainly be implemented in the future.

Aim: The aim of this study was to analyse the facial characteristics and the craniofacial morphology in GGS patients in order to enable an early diagnosis., Background: Gorlin-Goltz syndrome (GGS) is a autosomic dominant disease, characterised by basal cell carcinoma, palmar/plantar pits, maxillary and mandibular keratocysts and dental abnormalities., Methods: Nine out of a sample of 24 GGS patients had complete cephalometric and photographic records at an average age of 8.7 years. Cephalometric and photometric analysis were carried out with standard analyses and compared with healthy patients matched for sex and age., Conclusion: Early diagnosis of GGS based on clinical features could be useful to identify the presence of keratocysts through x-ray examination proceeding with surgical removal at an early stage, limiting space occupying damages.

Muscle and viscera (gills-liver) of the fish Prochilodus lineatus were obtained from four sites of lower course of Salado river and one site at Santa Fe river near to its confluence with Salado river from Santa Fe (Argentina) between December 2021 and February 2022. Sediment samples were also obtained from the same sites. All samples were analyzed for pesticide residues following the QuEChERS method to quantify 136 compounds by UHPLC-ESI-MS/MS and GC-EI-MS/MS. Overall, muscle fish tissue showed very high concentrations (maximum concentrations detected) of the insecticide cypermethrin (204 μg/kg), polar herbicides (glyphosate; 187 μg/kg and its degradation product (aminomethylphosphonic acid) AMPA; 3116 μg/kg, and glufosinate-ammonium; 677 μg/kg), and the fungicide pyraclostrobin (50 μg/kg). In viscera samples, high values of cypermethrin (506 μg/kg), chlorpyrifos (78 μg/kg), and lambdacyhalothrin (73 μg/kg) were the main pesticides found. Mean residues concentrations detected among sites were not significantly different neither in muscle nor viscera of P. lineatus in most of the cases. Exceptionally, the southernmost studied site of the Lower Salado river showed significant differences in concentration of residues found in muscle, due to high concentrations of glyphosate and glufosinate-amonium (KW = 11.879 and KW = 13.013, respectively, P < 0.05). Other norther Lower Salado river site showed significant higher AMPA concentration in fish viscera than in the rest of the studied sites (KW = 12.86 P < 0.05). Some sediment samples showed low levels of herbicides such as glyphosate (24 μg/kg) and fungicides. However, the world highest levels of polar herbicides were recorded in fish muscle. The results of this study highlight the need for periodic monitoring due to the high concentration of pesticides and its potential risk in a very important commercial freshwater fish from Argentina, which is consumed locally and exported to other countries for human consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Disparities in the experience of chronic musculoskeletal pain in the United States stem from a confluence of a broad array of factors. Organized within the National Institute on Aging Health Disparity Research Framework, a literature review was completed to evaluate what is known and what is needed to move chronic musculoskeletal pain research forward specific to disproportionately affected populations. Peer-reviewed studies published in English, on human adults, from 2000 to 2019, and conducted in the United States were extracted from PubMed and Web of Science. Articles were reviewed for key words that focused on underrepresented ethnic/race groups with chronic musculoskeletal pain applying health factor terms identified in the NIAHealth Disparity Research Framework four levels of analysis: 1) environmental, 2) sociocultural, 3) behavioral, and 4) biological. A total of 52 articles met inclusion criteria. There were limited publications specific to underrepresented ethnic/race groups with chronic musculoskeletal pain across all levels with particular research gaps under sociocultural and biological categories. Current limitations in evidence may be supplemented by a foundation of findings specific to the broader topic of "chronic pain" which provides guidance for future investigations. Study designs including a focus on protective factors and multiple levels of analyses would be particularly meritorious. PERSPECTIVE: Chronic musculoskeletal pain unequally burdens underrepresented ethnic/race groups. In order to move research forward and to systematically investigate the complex array of factors contributing toward health disparities, an organized approach is necessary. Applying the NIA Health Disparities Research Framework, an overview of the current state of evidence specific to chronic musculoskeletal pain and underrepresented ethnic/race groups is provided with future directions identified., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the relationship between glyphosate and phosphate fertilizer application and their contribution to surface water runoff contamination. The study was performed in Aquic Argiudoll soil (Tezanos Pinto series). Four treatments were assessed on three dates of rainfall simulation after fertilizer and herbicide application. The soluble phosphorus in runoff water was determined by a colorimetric method. For the determination of glyphosate and aminomethylphosphonic acid (AMPA), a method based on fluorenylmethyloxycarbonyl (FMOC) group derivatization, solid phase extraction (SPE) purification, and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed. The application of phosphorus fertilizer resulted in an increased loss of glyphosate by runoff after 1 day of application. These results suggest the need for further study to understand the interactions and to determine appropriate application timing with the goal of reducing the pollution risk by runoff.

hMena and the epithelial specific isoform hMena(11a) are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena(11a) expression and phosphorylates hMena(11a), suggesting cross-talk between the ErbB receptor family and hMena/hMena(11a) in breast cancer. The aim of this study was to determine whether the hMena/hMena(11a) overexpression cooperates with HER-2 signalling, thereby affecting the HER2 mitogenic activity in breast cancer. In a cohort of breast cancer tissue samples a significant correlation among hMena, HER2 overexpression, the proliferation index (high Ki67), and phosphorylated MAPK and AKT was found and among the molecular subtypes the highest frequency of hMena overexpressing tumors was found in the HER2 subtype. From a clinical viewpoint, concomitant overexpression of HER2 and hMena identifies a subgroup of breast cancer patients showing the worst prognosis, indicating that hMena overexpression adds prognostic information to HER2 overexpressing tumors. To identify a functional link between HER2 and hMena, we show here that HER2 transfection in MCF7 cells increased hMena/hMena(11a) expression and hMena(11a) phosphorylation. On the other hand, hMena/hMena(11a) knock-down reduced HER3, AKT and p44/42 MAPK phosphorylation and inhibited the EGF and NRG1-dependent HER2 phosphorylation and cell proliferation. Of functional significance, hMena/hMena(11a) knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena(11a) as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients.

Epithelial V-like antigen (EVA) is an immunoglobulin-like adhesion molecule identified in a screen for molecules developmentally regulated at the DN to DP progression in thymocyte development. We show that EVA is expressed during the early stages of thymus organogenesis in both fetal thymic epithelia and T cell precursors, and is progressively downregulated from day 16.5 of embryonic development. In the postnatal thymus, EVA expression is restricted to epithelial cells and is distributed throughout both cortical and medullary thymic regions. Transgenic overexpression of EVA in the thymus cortex resulted in a modified stromal environment, which elicited an increase in organ size and absolute cell number. Although peripheral T lymphocyte numbers are augmented throughout life, no imbalance either in the repertoire, or in the different T cell subsets was detected. Collectively, these data suggest a role for EVA in structural organisation of the thymus and early lymphocyte development.

hMena (ENAH), an actin regulatory protein involved in the control of cell motility and adhesion, is modulated during human breast carcinogenesis. In fact, whereas undetectable in normal mammary epithelium, hMena becomes overexpressed in high-risk benign lesions and primary and metastatic tumors. In vivo, hMena overexpression correlates with the HER-2(+)/ER(-)/Ki67(+) unfavorable prognostic phenotype. In vitro, neuregulin-1 up-regulates whereas Herceptin treatment down-modulates hMena expression, suggesting that it may couple tyrosine kinase receptor signaling to the actin cytoskeleton. Herein, we report the cloning of hMena and of a splice variant, hMena(+11a), which contains an additional exon corresponding to 21 amino acids located in the EVH2 domain, from a breast carcinoma cell line of epithelial phenotype. Whereas hMena overexpression consistently characterizes the transformed phenotype of tumor cells of different lineages, hMena(+11a) isoform is concomitantly present only in epithelial tumor cell lines. In breast cancer cell lines, epidermal growth factor (EGF) treatment promotes concomitant up-regulation of hMena and hMena(+11a), resulting in an increase of the fraction of phosphorylated hMena(+11a) isoform only. hMena(+11a) overexpression and phosphorylation leads to increased p42/44 mitogen-activated protein kinase (MAPK) activation and cell proliferation as evidenced in hMena(+11a)-transfected breast cancer cell lines. On the contrary, hMena knockdown induces reduction of p42/44 MAPK phosphorylation and of the proliferative response to EGF. The present data provide new insight into the relevance of actin cytoskeleton regulatory proteins and, in particular, of hMena isoforms in coupling multiple signaling pathways involved in breast cancer.

An automated biosensor system designed for measuring molecular interactions in real-time and without labelling of the reactants has been used to evaluate the association/dissociation rate and affinity constants of bivalent monoclonal antibodies and a monovalent bispecific monoclonal antibody. Observed differences in affinity between parental and bispecific antibody produced were related to the association rate constants, since the dissociation rate constants were in the same range. Values were also closely related to radioimmunochemical data. These results indicate that the biosensor system, besides presenting several advantages for characterizing antigen-antibody interaction, is valuable for selecting monoclonal antibodies with properties which might be useful in the development of bispecific monoclonal antibodies.

The recent development of improved production techniques for bispecific monoclonal antibodies (biMAbs) has significantly increased interest in specific purification procedures. In this investigation, a general high-performance liquid chromatographic (HPLC) purification method is proposed that allows highly purified biMAbs to be obtained from mouse ascites fluid containing a mixture of different antibodies, i.e., parental MAbs, active biMAb and a mixture of randomly assembled heavy and light chains. Proteins from ascites fluid were precipitated with ammonium sulphate and applied to a high-performance protein A column to separate the total immunoglobulin fraction. BiMAbs were isolated from other immunoglobulins by two subsequent passages through a high-performance hydroxyapatite (HPHT) column. This purification protocol combines specificity of protein A for immunoglobulin G (IgG) and high selectivity of hydroxyapatite for different IgG idiotypes. All purification steps were performed rapidly and reliably by HPLC. This method was applied to the purification of six different biMAbs with consistently high yields, purity and homogeneity. This general purification method may prove extremely valuable when highly pure preparation of biMAbs is required, as for in vivo use.

This review reports the characteristics of the human surface molecule CD38, a structure not linked to a definite line and predominantly expressed in early and activated phenotypes. The CD38 molecule consists of a single chain of 46 kDa, spanning the membrane and with the carboxyl terminus located in the extracellular compartment. The CD38 molecule is also involved in the transduction of activation and proliferation signals, which are line unrestricted. The gene coding for the CD38 antigen has been cloned and used for the construction of simian and mouse transfectants expressing the human molecule. These cell models are used for the analysis of several unanswered issues, mainly concerning the in vivo function of CD38, the existence of a natural ligand and of polymorphism in the population.

Mouse monoclonal antibodies specific for CD3, FcR and a melanoma associated antigen have been produced. Drug resistence of such hibrydomas has been obtained tranfecting them with plasmids containing genes conferring specific resistence. Retrovirus derived shuttle vectors with high transfection efficiency have been used for transfection. Hybrydomas were than fused and bispecific antibody producing cells selected. Purification was performed by HPLC. Such bispecific antibodies can be used in ex vivo and in vivo immunotherapy.