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On 11 March 2020, following the spread of SARS-CoV-2, WHO declared a pandemic status. The impact on national health and economic systems has been huge. Therefore, many countries took measures to restrict the spread of the virus. Many work activities have been subjected to lockdown measures. However, some production activities, continued to remain open, i.e., large-scale food distribution, food industry, pharmacies, hospitals, etc. In order to contain the spread of the pandemic, public health measures have been implemented by the States to reduce the contagion of the virus in the workplace. Therefore, it was important to implement measures to contrast and contain the spread of SARS-CoV-2/COVID-19 in workplaces. The aim of this study was to adopt and implement a safety protocol useful to restrict the spread of SARS-CoV-2 in a large-scale retail trade company located in the south of Italy, before vaccination, during the first and second pandemic phases also exploiting telemedicine services. Antibody serological test cards were also used during the first pandemic wave and rapid antigenic swabs during the second to detect workers positive for SARS-CoV-2. A population of subjects who worked for another company similar for production activity and distribution on the territory was selected as the control group. During work activities, this group followed the minimum activity protocol provided by the Italian legislation (24 April 2020, Ministry Protocol), which provided the daily monitoring of the body temperature and in the case of SARS- CoV-2 positive subjects the extraordinary sanitation of the workplace. The measures implemented identified the positive subject for SARS-CoV-2 at an early stage. The protocol made it possible to significantly reduce the spread of the virus within large-scale retail distribution, and therefore, to avoid the temporary closure of the stores with a consequent reduction of economic losses compared with the control group.

Young people living in conflict-ridden areas in the southern part of the Philippines, Mindanao, experience hostility from communities motivated by religious ideologies and political beliefs. With this premise, this study will uncover emerging themes on the way students form their views towards people who have a different faith based on three distinct religious cultures of six schools situated in conflict-ridden areas in Mindanao. Guided by the precepts of phenomenology, this study utilized focused-group discussion with art-based activities and in-depth interviews to show the three dominant religious cultures in schools have distinct influences on their students' perspectives of others.

Bacterial involvement in cancer’s development, along with their impact on therapeutic interventions, has been increasingly recognized. This has prompted the development of novel strategies to disrupt essential biological processes in microbial cells. Among these approaches, metal-chelating agents have gained attention for their ability to hinder microbial metal metabolism and impede critical reactions. Nanotechnology has also contributed to the antibacterial field by offering various nanomaterials, including antimicrobial nanoparticles with potential therapeutic and drug-delivery applications. Halloysite nanotubes (HNTs) are naturally occurring tubular clay nanomaterials composed of aluminosilicate kaolin sheets rolled multiple times. The aluminum and siloxane groups on the surface of HNTs enable hydrogen bonding with biomaterials, making them versatile in various domains, such as environmental sciences, wastewater treatment, nanoelectronics, catalytic studies, and cosmetics. This study aimed to create an antibacterial material by combining the unique properties of halloysite nanotubes with the iron-chelating capability of kojic acid. A nucleophilic substitution reaction involving the hydroxyl groups on the nanotubes’ surface was employed to functionalize the material using kojic acid. The resulting material was characterized using infrared spectroscopy (IR), thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM), and its iron-chelating ability was assessed. Furthermore, the potential for drug loading—specifically, with resveratrol and curcumin—was evaluated through ultraviolet (UV) analysis. The antibacterial assay was evaluated following CLSI guidelines. The results suggested that the HNTs–kojic acid formulation had great antibacterial activity against all tested pathogens. The outcome of this work yielded a novel bio-based material with dual functionality as a drug carrier and an antimicrobial agent. This innovative approach holds promise for addressing challenges related to bacterial infections, antibiotic resistance, and the development of advanced therapeutic interventions.

This document provides a summary of research studies on ameloblastoma, a benign odontogenic tumor that can cause bone destruction, paresthesia, and aesthetic deformity. The studies have explored the prevalence of the BRAF V600E mutation, which is frequently found in ameloblastomas and is associated with disordered cell growth. The mutation is present in various countries, with the highest incidence observed in the posterior region of the mandible. The studies also discuss the potential for therapies targeting the BRAF mutation to inhibit tumor progression. However, further research is needed to fully understand the impact of these findings on diagnosis, classification, and treatment of ameloblastoma. [Extracted from the article]

The hydrophobic effect is the main factor that drives the folding of polypeptide chains. In this study, we have examined the influence of the hydrophobic effect in the context of the main mechanical forces approach, mainly in relation to the establishment of specific interplays, such as hydrophobic and CH–π cloud interactions. By adopting three oligopeptides as model systems to assess folding features, we demonstrate herein that these finely tuned interactions dominate over electrostatic interactions, including H-bonds and electrostatic attractions/repulsions. The folding mechanism analysed here demonstrates cooperation at the single-residue level, for which we propose the terminology of "single residues cooperative folding". Overall, hydrophobic and CH–π cloud interactions produce the main output of the hydrophobic effect and govern the folding mechanism, as demonstrated in this study with small polypeptide chains, which in turn represent the main secondary structures in proteins. [ABSTRACT FROM AUTHOR]

The folding of peptides and proteins is rigidly reliant on the 'chemical information' carried by the specific amino acid sequence. In this study, three polypeptides (PDBs: 2jof, 1res and 1prv) were investigated as model systems to assess their folded features, thereby enabling further understanding of mechanisms that play a role in regulating the folding process more widely. A novel physico‐chemical approach of analysis is proposed herein, focusing on chemical interactions and their related mechanical forces that we trust are determinant to drive the folding. Through this methodology, we have predicted the conformations adopted by the three polypeptides and compared the outcomes to those experimentally determined, achieving a substantial structural agreement. Molecular dynamic simulations have been carried out to further support our calculations and structural results. Within the three models, we demonstrate that the interaction of each amino acid residue with its neighbour residues is a crucial determinant for the formation of the 3D stable native structures. This article provides initial evidence that the folding occurs by means of mechanical forces developed upon establishing chemical interactions amongst residues, which, in turn, are peculiar to each specific amino acid present in each position of the peptide chain. [ABSTRACT FROM AUTHOR]

Abstract Structural design procedures are based on simplified hypotheses that attempt to approximate the actual behaviour. Depending on the adopted hypothesis, the design procedure may not satisfactorily describe the structural actual behaviour. Such condition occurs in the design of reinforced concrete pipes, where there are uncertainties related especially on the internal forces and the installation type of the pipe. Moreover, the main design hypothesis is that the cross section is plane and perpendicular to the deformed axis. Based on materials resistance principles it is known that this hypothesis is unsatisfactory to pipes with aspect ratio lower than ten. Note that the commercial reinforced concrete pipes usually present aspect ratio well below ten. In the light of the foregoing, the main objective of this paper is to analyse the accuracy of the design procedure for reinforced concrete pipes. Therefore, statistical processes were used to compare design values with experimental results. The comparisons in this paper showed that the design procedure results in oversized pipes.

Ordinary small molecule de novo drug design is time-consuming and expensive. Recently, computational tools were employed and proved their efficacy in accelerating the overall drug design process. Molecular dynamics (MD) simulations and a derivative of MD, steered molecular dynamics (SMD), turned out to be promising rational drug design tools. In this paper, we report the first application of SMD to evaluate the binding properties of small molecules toward FABP4, considering our recent interest in inhibiting fatty acid binding protein 4 (FABP4). FABP4 inhibitors (FABP4is) are small molecules of therapeutic interest, and ongoing clinical studies indicate that they are promising for treating cancer and other diseases such as metabolic syndrome and diabetes.

It is known that the spike protein of human coronaviruses can bind to a secondary receptor, or coreceptor, to facilitate the virus entry. While HCoV-229E uses human aminopeptidase N (hAPN) as a receptor, HCoV-OC43 binds to 9-O-acetyl-sialic acid (9-O-Ac-Sia), which is linked in a terminal way to the oligosaccharides that decorate glycoproteins and gangliosides on the surface of the host cell. Thus, evaluating the possible inhibitory activity of heparan sulfate, a linear polysaccharide found in animal tissues, and enoxaparin sodium on these viral strains can be considered attractive. Therefore, our study also aims to evaluate these molecules’ antiviral activity as possible adsorption inhibitors against non-SARS-CoV. Once the molecules’ activity was verified in in vitro experiments, the binding was studied by molecular docking and molecular dynamic simulations confirming the interactions at the interface of the spike proteins.

It is well known that skin wound healing could be severely impaired in space. In particular, the skin is the tissue at risk of injury, especially during human-crewed space missions. Here, we propose a hybrid system based on the biocompatible poly 2-hydroxyethyl methacrylate (pHEMA) to actively support a nanocontainer filled with the drug. Specifically, during the cryo-polymerization of HEMA, halloysite nanotubes (HNTs) embedded with thymol (Thy) were added as a component. Thy is a natural pharmaceutical ingredient used to confer wound healing properties to the material, whereas HNTs were used to entrap the Thy into the lumen to ensure a sustained release of the drug. The as-obtained material was characterized by chemical–physical methods, and tests were performed to assess its ability for a prolonged drug release. The results showed that the adopted synthetic procedure allows the formation of a super absorbent system with good swelling ability that can contain up to 5.5 mg of Thy in about 90 mg of dried sponge. Releasing tests demonstrated the excellent material’s ability to perform a slow controlled delivery of 62% of charged Thy within a week. As humans venture deeper into space, with more extended missions, limited medical capabilities, and a higher risk of skin wounds, the proposed device would be a versatile miniaturized device for skin repair in space.

A pielonefrite é uma infecção do trato urinário superior que envolve os rins, na qual a maioria dos episódios são considerados não complicados em adultos saudáveis. Diferentes fatores de risco estão associados como, diabetes, obstrução do trato urinário, presença de cateter uretral por período prolongado, nefrostomia, anormalidades funcionais ou anatômicas do trato urinário, transplante renal, terapia imunossupressora e gravidez. As manifestações clínicas mais frequentes são febre, calafrios, dor na região de flanco e enjoo. Em pacientes idosos as manifestações clínicas podem ser atípicas. O objetivo é relatar o atendimento de paciente idosa com suspeita de pielonefrite aguda posterior a realização de litotripsia renal. Paciente do sexo feminino, 76 anos, viúva, aposentada, procurou atendimento com queixa de dor lombar, calafrios, febre intermitente, disúria, polaciúria e náuseas há 4 dias. Apresentava dor lombar de forte intensidade e dor leve em abdome inferior, sem fatores de melhora ou piora, de caráter contínuo com irradiação para fossa ilíaca esquerda. História mórbida pregressa de infecção do trato urinário de repetição, nefrolitíase à esquerda, hidronefrose moderada à esquerda e leve à direita. Realizou litotripsia renal a laser aproximadamente há um mês. Ao exame físico se encontrava em estado geral regular, lúcida e orientada. Temperatura axilar: 38° C. PA:100 x 70 mmHg. FC: 85 bpm. SAT O2 96% ar ambiente. FR: 18 irpm. Aparelho respiratório sem anormalidades. ABD: sem dor à palpação superficial ou profunda. Apresentava sinal de Giordano positivo bilateral. A hipótese diagnóstica principal foi pielonefrite aguda. Para confirmação foram solicitados exames laboratoriais. Hemograma: leucócitos: 11.320/ mm3 . Hb 10,6 g/dL. Plaquetas: 179 mil/mm3 . Urina 1: Leucocitúria. Hematúria. Proteinúria. Nitrito positivo. Urocultura: indicava presença de Klebsiella spp sensível a Imipenem e Meropenem. O diagnóstico diferencial mais provável considerado foi cistite complicada, entretanto, a presença de sinal de Giordano positivo bilateral, febre e rebaixamento no estado geral da paciente são indicativos de pielonefrite aguda. Confirmado o diagnóstico, o tratamento inicial foi efetuado por meio do uso de Cloridrato de Ondansetrona, Butilbrometo de Escopolamina e Dipirona Sódica em caso de dor abdominal ou febre. Ao receber os resultados da urocultura foi iniciado o tratamento com Imipenem. A paciente evoluiu sem complicações, se manteve estável e recebeu alta após 7 dias com recomendação de acompanhamento por serviço de nefrologia. Conclui-se, desse modo, que o diagnóstico foi correto e o tratamento foi efetivo sendo baseado na urocultura indicativa de sensibilidade da Klebsiella spp. ao Imipenem.

We report here in silico repurposing studies on 52 new pyridazinone-based small-molecules through inverse virtual screening (iVS) methodologies. These analogues were originally designed as formyl peptide receptor (FPR) ligands. As it is sometimes the case in drug discovery programmes, subsequent biological screening demonstrated the inefficacy of the molecules in binding FPRs, failing in the identification of new hits. Through a focussed drug-repurposing approach we have defined a variety of potential targets that are suitable to interact with this library of pyridazinone-based analogues. A two-step approach has been conducted for computational analysis. Specifically, the molecules were initially processed through a pharmacophore-based screening. Secondly, the resulting features of binding were investigated by docking studies and following molecular dynamic simulations, in order to univocally confirm “pyridazinone-based ligand-target protein” interactions. Our findings propose aspartate aminotransferase as the most favourable repurposed target for this small-molecule series, worth of additional medicinal chemistry investigations in the field.

Glucagon-like peptide-1 (GLP-1) is involved in a range of central and peripheral pathways related to appetitive behavior. Hence, this study explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on substance and behavioral addictions, including alcohol, caffeine, nicotine, cannabis, psychostimulants, compulsive shopping, and sex drive/libido. Data were collected from various social platforms. Keywords related to GLP-1 RAs and substance/behavioral addiction were used to extract relevant comments. The study employed a mixed-methods approach to analyze online discussions posted from December 2019 to June 2023 and collected using a specialized web application. Reddit entries were the focus here due to limited data from other platforms, such as TikTok and YouTube. A total of 5859 threads and related comments were extracted from six subreddits, which included threads about GLP-1 RAs drugs and associated brand names. To obtain relevant posts, keywords related to potential substance use and compulsive behavior were selected. Further analysis involved two main steps: (1) manually coding posts based on users' references to the potential impact of GLP-1 RAs on substance use and non-substance habits, excluding irrelevant or unclear comments; (2) performing a thematic analysis on the dataset of keywords, using AI-assisted techniques followed by the manual revision of the generated themes. Second, a thematic analysis was performed on the keyword-related dataset, using AI-assisted techniques followed by the manual revision of the generated themes. In total, 29.75% of alcohol-related; 22.22% of caffeine-related; and 23.08% of nicotine-related comments clearly stated a cessation of the intake of these substances following the start of GLP-1 RAs prescription. Conversely, mixed results were found for cannabis intake, and only limited, anecdotal data were made available for cocaine, entactogens, and dissociative drugs' misuse. Regarding behavioral addictions, 21.35% of comments reported a compulsive shopping interruption, whilst the sexual drive/libido elements reportedly increased in several users. The current mixed-methods approach appeared to be a useful tool in gaining insight into complex topics such as the effects of GLP-1 RAs on substance and non-substance addiction-related disorders; some GLP-1 RA-related mental health benefits could also be inferred from here. Overall, it appeared that GLP-1 RAs may show the potential to target both substance craving and maladaptive/addictive behaviors, although further empirical research is needed. [ABSTRACT FROM AUTHOR]

The therapeutic potential of fatty acid binding protein 4 (FABP4) is widely acknowledged. Currently, there are numerous clinical studies that indicate how fatty acid binding protein 4 inhibitors could be useful in the treatment of various diseases. To identify new and more potent inhibitors, we utilized a two-step computational approach to design novel structures. Through the use of this approach, we were able to identify a new class of FABP4 inhibitors (FABP4i IC50 2.97 to 23.18 µM) that are capable of inhibiting the activity of FABP4 as low as Arachidonic acid (FABP4i IC50 3.42 ± 0.54 µM). In this study, we present the detailed structural and biological evaluation, and the synthetic procedures of the new pyridazinone-based scaffold FABP4i.

Cryogels are macroporous hydrogels prepared by cryo-gelation: a green technique that involves radical polymerization using water as a solvent [...]

Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series.