Synthesis and biological investigation of peptidomimetic SARS-CoV-2 main protease inhibitors bearing quinoline-based heterocycles at P.

In the last few years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the cause of a worldwide pandemic, highlighting the need for novel antiviral agents. The main protease (M) of SARS-CoV-2 was immediately identified as a crucial enzyme for viral replication and has been validated as a drug target. Here, we present the design and synthesis of peptidomimetic M covalent inhibitors characterized by quinoline-based P moieties.

Evaluating the Impact of Pre-Fermentative and Post-Fermentative Vinification Technologies on Bioactive Compounds and Antioxidant Activity of Teran Red Wine By-Products.

This study aimed to evaluate bioactive properties of Teran red wine by-products (grape skins, seeds, and wine lees) from six vinification treatments, including a control (7-day standard maceration). Pre-fermentative cryomaceration (8 °C; 48 h) and hot maceration (50 °C; 48 h), followed by the 13-day (CS15; C15; H15) and 28-day (C30; H30) period, considering fermentation/maceration and extended post-fermentative maceration, were conducted. In CS15, the saignée procedure was applied before fermentation/maceration.

The Brain-Heart Axis: An Umbrella Review on Impact of Psychiatric Disease on Incidence, Management, and Outlook of Cardiovascular Disease.

Psychiatric conditions, such as depression, anxiety, bipolar disorder, and schizophrenia, are increasingly recognized as significant risk factors for cardiovascular disease (CVD). This review systematically analyzes evidence from various databases to provide a comprehensive understanding of the impact of psychiatric illnesses on the incidence, management, and prognosis of CVD. Key findings suggest a bidirectional relationship between psychiatric disorders and CVD, indicating that mental health conditions can predispose individuals to CVD, while CVD can exacerbate or trigger psychiatric symptoms.

A Network Analysis of Perinatal Depression, Anxiety, and Temperaments in Women in the First, Second, and Third Trimesters of Pregnancy.

Although depression and anxiety are found to be affected by temperaments, little research has studied these relationships in pregnancy. The present study explored the associations among perinatal depression (PD), anxiety dimensions (state, trait, and generalized anxiety disorder (GAD)), and temperaments between women in the three trimesters of pregnancy through a network analysis approach. Moreover, differences in the severity of PD and anxiety between women in the three trimesters were evaluated.

This pain drives me crazy: Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome.

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic, abdominal, and/or pelvic pain. Although the term cystitis suggests an inflammatory or infectious origin, no definite cause has been identified. It occurs in both sexes, but women are twice as much affected.

Is Antipsychotic Drug Use During Pregnancy Associated with Increased Malformation Rates and Worsening of Maternal and Infant Outcomes? A Systematic Review.

There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR "birth defect*" OR "congenital abnormality" OR "congenital abnormalities" OR "brain changes" OR "behavioral abnormalities" OR "behavioral abnormalities") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023.

Metalloenzyme Inhibitors against Zoonotic Infections: Focus on and .

The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61% of human pathogens and causing an estimated 2.7 million deaths annually.

A case report of unusual recurrent bronchopneumonia infections in Mounier-Kuhn syndrome.

Mounier-Kuhn syndrome is a rare airway disease characterized by tracheal and bronchial dilatation, primarily affecting middle-aged men. We present a case of Mounier-Kuhn syndrome in a 40-year-old man with a history of recurrent respiratory infections since adolescence. The diagnostic journey involved a multidisciplinary approach incorporating clinical evaluation, radiological imaging, and bronchoscopy.

A novel potent class I HDAC inhibitor reverses the STAT4/p66Shc apoptotic defect in B cells from chronic lymphocytic leukemia patients.

Chronic Lymphocytic Leukemia (CLL) patients have a defective expression of the proapoptotic protein p66Shc and of its transcriptional factor STAT4, which evoke molecular abnormalities, impairing apoptosis and worsening disease prognosis and severity. p66Shc expression is epigenetically controlled and transcriptionally modulated by STAT4; epigenetic modifiers are deregulated in CLL cells and specific histone deacetylases (HDACs) like HDAC1, are overexpressed. Reactivation of STAT4/p66Shc expression may represent an attractive and challenging strategy to reverse CLL apoptosis defects.

Applying Different Vinification Techniques in Teran Red Wine Production: Impact on Bioactive Compounds and Sensory Attributes.

Six different vinification treatments, including a control treatment (7-day standard maceration) (K7), were performed to study the effects of non-standard techniques on bioactive compounds and sensory attributes of Teran red wine. Pre-fermentative mash cooling (8 °C; 48 h) and heating (50 °C; 48 h) followed by prolonged post-fermentative maceration of 13 days (C15;H15) or 28 days (C30;H30) were applied. In another treatment, after cooling, saignée was performed followed by 13-day prolonged maceration (CS15).

Development of Quinazolinone Derivatives as Modulators of Virulence Factors of Cystic Fibrosis Strains.

(PA), one of the ESKAPE pathogens, is an opportunistic Gram-negative bacterium responsible for nosocomial infections in humans but also for infections in patients affected by AIDS, cancer, or cystic fibrosis (CF). Treatment of PA infections in CF patients is a global healthcare problem due to the ability of PA to gain antibiotic tolerance through biofilm formation. Anti-virulence compounds represent a promising approach as adjuvant therapy, which could reduce or eliminate the pathogenicity of PA without impacting its growth.

Deconstructing Haptic Feedback Information in Robot-Assisted Needle Insertion in Soft Tissues.

This paper evaluates the role and effectiveness of different types of haptic feedback in presenting relevant feedback information during needle insertion in soft tissues through a remotely operated robot. We carried out three experiments with human subjects to analyze the effect of grounded kinesthetic feedback, cutaneous vibrotactile feedback, and cutaneous pressure feedback for rendering the elastic and the viscous force components of a simplified needle-tissue interaction model in a simulated environment. Results showed that providing the two pieces of feedback information through different channels, i.

Imaging Diagnosis of Hepatocellular Carcinoma: A State-of-the-Art Review.

Hepatocellular carcinoma (HCC) remains not only a cause of a considerable part of oncologic mortality, but also a diagnostic and therapeutic challenge for healthcare systems worldwide. Early detection of the disease and consequential adequate therapy are imperative to increase patients' quality of life and survival. Imaging plays, therefore, a crucial role in the surveillance of patients at risk, the detection and diagnosis of HCC nodules, as well as in the follow-up post-treatment.

Severe Shoot Trimming and Crop Size as Tools to Modulate Cv. Merlot Berry Composition.

Viticulture production is challenged by climate change and the consequent higher accumulation of carbohydrates in grapevine berries, resulting in high-alcoholic wines. This study investigates the application of severe shoot trimming performed at three different stages and crop size management as tools for the modulation of cv. Merlot berry composition, aimed at reducing the sugar content in the berry.

The green chemistry of chalcones: Valuable sources of privileged core structures for drug discovery.

The sustainable use of resources is essential in all production areas, including pharmaceuticals. However, the aspect of sustainability needs to be taken into consideration not only in the production phase, but during the whole medicinal chemistry drug discovery trajectory. The continuous progress in the fields of green chemistry and the use of artificial intelligence are contributing to the speed and effectiveness of a more sustainable drug discovery pipeline.

Leveraging geo-referenced malaria information to increase domestic financial support for malaria elimination in Thailand.

Thailand's National Malaria Elimination Strategy 2017-2026 seeks to increase domestic support and financing for malaria elimination. During 2018-2020, through a series of training sessions, public health officials in Thailand utilized foci-level malaria data to engage subdistrict-level government units known as Local Administrative Organizations (LAOs) with the aim of increasing their understanding of their local malaria situation, collaboration with public health networks, and advocacy for financial support of targeted interventions in villages within their jurisdictions. As a result of these efforts, total LAO funding support for malaria nearly doubled from the 2017 baseline to 2020.

Bioactive Compounds and Antioxidant Activity of Red and White Wines Produced from Autochthonous Croatian Varieties: Effect of Moderate Consumption on Human Health.

Moderate wine consumption is often associated with healthy lifestyle habits. The role of wine as a healthy drink is mainly due to its bioactive compounds, which differ according to various viticultural and enological factors. The aim of the present study was to observe the differences in bioactive compounds of white and red autochthonous Croatian wines, differing in terms of the grape variety and production technology.

Covalent Reversible Inhibitors of Cysteine Proteases Containing the Nitrile Warhead: Recent Advancement in the Field of Viral and Parasitic Diseases.

In the field of drug discovery, the nitrile group is well represented among drugs and biologically active compounds. It can form both non-covalent and covalent interactions with diverse biological targets, and it is amenable as an electrophilic warhead for covalent inhibition. The main advantage of the nitrile group as a warhead is mainly due to its milder electrophilic character relative to other more reactive groups (e.

Strengthening Management, Community Engagement, and Sustainability of the Subnational Response to Accelerate Malaria Elimination in Namibia.

Leadership and management skills are critical for health programs to deliver high-quality interventions in complex systems. In malaria-eliminating countries, national and subnational health teams are reorienting strategies to address focal transmission while preventing new cases and adapting to decentralization and declines in external financing. A capacity-strengthening program in two regions in Namibia helped malaria program implementers identify and address key operational, political, and financial challenges.

Total Synthesis of the Natural Chalcone Lophirone E, Synthetic Studies toward Benzofuran and Indole-Based Analogues, and Investigation of Anti-Leishmanial Activity.

The potential of natural and synthetic chalcones as therapeutic leads against different pathological conditions has been investigated for several years, and this class of compounds emerged as a privileged chemotype due to its interesting anti-inflammatory, antimicrobial, antiviral, and anticancer properties. The objective of our study was to contribute to the investigation of this class of natural products as anti-leishmanial agents. We aimed at investigating the structure-activity relationships of the natural chalcone lophirone E, characterized by the presence of benzofuran B-ring, and analogues on anti-leishmania activity.

Civilian-military malaria outbreak response in Thailand: an example of multi-stakeholder engagement for malaria elimination.

Background: In April 2017, the Thai Ministry of Public Health (MoPH) was alerted to a potential malaria outbreak among civilians and military personnel in Sisaket Province, a highly forested area bordering Cambodia. The objective of this study was to present findings from the joint civilian-military outbreak response.

Methods: A mixed-methods approach was used to assess risk factors among cases reported during the 2017 Sisaket malaria outbreak.