Phage Therapy: An Alternative Approach to Combating Multidrug-Resistant Bacterial Infections in Cystic Fibrosis.

Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as , , (), , and . These infections still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure to antibiotics in combination favors the development and spread of multi-resistant bacteria; thus, the development of alternative strategies is crucial to counter antimicrobial resistance.

The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division.

Aims: The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary disease. Mycobacterium abscessus is associated with chronic lung deterioration in these populations. The intrinsic resistance of M.

Prognostic factors for return to work in patients affected by chronic low back pain: a systematic review.

Chronic low back pain (LBP) represents a leading cause of absenteeism from work. An accurate knowledge of complex interactions is essential in understanding the difficulties of return to work (RTW) experienced by workers affected by chronic LBP. This study aims to identify factors related to chronic LBP, the worker, and the psycho-social environment that could predict and influence the duration of an episode of sick leave due to chronic LBP.

Structural basis for specific inhibition of salicylate synthase from Mycobacterium abscessus.

Blocking iron uptake and metabolism has been emerging as a promising therapeutic strategy for the development of novel antimicrobial compounds. Like all mycobacteria, M. abscessus (Mab) has evolved several countermeasures to scavenge iron from host carrier proteins, including the production of siderophores, which play a crucial role in these processes.

Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?

Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound.

Improving Protection to Prevent Bacterial Infections: Preliminary Applications of Reverse Vaccinology against the Main Cystic Fibrosis Pathogens.

Reverse vaccinology is a powerful tool that was recently used to develop vaccines starting from a pathogen genome. Some bacterial infections have the necessity to be prevented then treated. For example, individuals with chronic pulmonary diseases, such as Cystic Fibrosis, are prone to develop infections and biofilms in the thick mucus that covers their lungs, mainly caused by complex, , , and These infections are complicated to treat and prevention remains the best strategy.

Side Chain-Modified Benzothiazinone Derivatives with Anti-Mycobacterial Activity.

Tuberculosis (TB) is a leading infectious disease with serious antibiotic resistance. The benzothiazinone (BTZ) scaffold PBTZ169 kills (Mtb) through the inhibition of the essential cell wall enzyme decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1). PBTZ169 shows anti-TB potential in animal models and pilot clinical tests.

CanB, a Druggable Cellular Target in .

Treatment against tuberculosis can lead to the selection of drug-resistant strains. To tackle this serious threat, new targets from are needed to develop novel effective drugs. In this work, we aimed to provide a possible workflow to validate new targets and inhibitors by combining genetic, , and enzymological approaches.

Iron Acquisition and Metabolism as a Promising Target for Antimicrobials (Bottlenecks and Opportunities): Where Do We Stand?

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections is one of the most crucial challenges currently faced by the scientific community. Developments in the fundamental understanding of their underlying mechanisms may open new perspectives in drug discovery. In this review, we conducted a systematic literature search in PubMed, Web of Science, and Scopus, to collect information on innovative strategies to hinder iron acquisition in bacteria.

Infections in Cystic Fibrosis Individuals: A Review on Therapeutic Options.

is an opportunistic pathogen that mainly colonizes and infects cystic fibrosis patients' lungs. is naturally resistant to many antibiotics such as rifamycin, tetracyclines and β-lactams. The current therapeutic regimens are not very effective and are mostly based on repurposed drugs used against infections.

Targeting Siderophore-Mediated Iron Uptake in : A New Strategy to Limit the Virulence of Non-Tuberculous Mycobacteria.

Targeting pathogenic mechanisms, rather than essential processes, represents a very attractive approach for the development of new antimycobacterial drugs. In this context, iron acquisition routes have recently emerged as potentially druggable pathways. However, the importance of siderophore biosynthesis in the virulence and pathogenicity of () is still poorly understood.

Synthesis and Assessment of the In Vitro and Ex Vivo Activity of Salicylate Synthase (Mbti) Inhibitors as New Candidates for the Treatment of Mycobacterial Infections.

Tuberculosis (TB) causes millions of deaths every year, ranking as one of the most dangerous infectious diseases worldwide. Because several pathogenic strains of () have developed resistance against most of the established anti-TB drugs, new therapeutic options are urgently needed. An attractive target for the development of new anti-TB agents is the salicylate synthase MbtI, the first enzyme of the mycobacterial siderophore biochemical machinery, absent in human cells.

Development of 6-Methanesulfonyl-8-nitrobenzothiazinone Based Antitubercular Agents.

The 6-trifluoro substituted 8-nitrobenzothiazinones (BTZs) represent a novel type of antitubercular agents, and their high antimycobacterial activity is related to the inhibition of decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1), an enzyme essential for the biosynthesis of mycobacterial cell wall. While extraordinary whole-cell activity was reported for the clinically advanced compound PBTZ169, its poor aqueous solubility signals the potential low bioavailability. To ameliorate the BTZ physiochemical property, a series of 6-methanesulfonyl substituted compounds were designed and prepared, and their antitubercular activity and DprE1 inhibition ability were evaluated.

Functional investigation of the antitubercular drug target Decaprenylphosphoryl-β-D-ribofuranose-2-epimerase DprE1/DprE2 complex.

Tuberculosis (TB) is one of the leading causes of death worldwide, due to a single pathogen, Mycobacterium tuberculosis. To eradicate TB, management of drug-resistant strains is fundamental, therefore, the identification and characterization of drug targets is pivotal. In this work we aim at describing the relationships with the well-known drug target DprE1 and DprE2, working in association for the biosynthesis of the arabinogalactan precursor, essential component of mycobacterial cell wall.

Virtual screening and crystallographic studies reveal an unexpected γ-lactone derivative active against MptpB as a potential antitubercular agent.

Mycobacterial resistance is a rapidly increasing phenomenon requiring the identification of new drugs effective against multidrug-resistant pathogens. The inhibition of protein tyrosine phosphatase B (MptpB), which interferes with host immune responses, may provide a new strategy to fight tuberculosis (TB), while preventing cross-resistance issues. On this basis, starting from a virtual screening (VS) campaign and subsequent structure elucidation studies guided by X-ray analyses, an unexpected γ-lactone derivative (compound 1) with a significant enzymatic activity against MptpB was identified.

The Veterinary Anti-Parasitic Selamectin Is a Novel Inhibitor of the DprE1 Enzyme.

Avermectins are macrocyclic lactones with anthelmintic activity. Recently, they were found to be effective against , which accounts for one third of the worldwide deaths from antimicrobial resistance. However, their anti-mycobacterial mode of action remains to be elucidated.

Structural and Activity Relationships of 6-Sulfonyl-8-Nitrobenzothiazinones as Antitubercular Agents.

The benzothiazinone (BTZ) scaffold compound PBTZ169 kills by inhibiting the essential flavoenzyme DprE1, consequently blocking the synthesis of the cell wall component arabinans. While extraordinarily potent against with a minimum inhibitory concentration (MIC) less than 0.2 ng/mL, its low aqueous solubility and bioavailability issues need to be addressed.

Synthesis, Characterization, and Biological Evaluation of New Derivatives Targeting MbtI as Antitubercular Agents.

Tuberculosis (TB) causes millions of deaths every year, ranking as one of the most dangerous infectious diseases worldwide. Because several pathogenic strains of (Mtb) have developed resistance against most of the established anti-TB drugs, new therapeutic options are urgently needed. An attractive target for the development of new antitubercular agents is the salicylate synthase MbtI, an essential enzyme for the mycobacterial siderophore biochemical machinery, absent in human cells.

2019 Rome Marathon, hamstring injuries in long distance runners: influence of age, gender, weight, height, number of marathons and impact profile.

Background: Hamstring diseases are one of the most widespread diseases in athletes, especially in runners, sprinters, and endurance athletes. Notwithstanding the importance of the problem, risk factors are still marginally known. This transversal study analyzes the correlation between hamstring tendinopathy and hamstring strains and age, gender, weight, height, number of marathons, and impact profile in athletes who took part in the 2019 Rome Marathon.

Less Invasive Fixation of Acute Avulsions of the Achilles Tendon: A Technical Note.

Nowadays, surgical treatment of acute avulsions of the Achilles tendon represents a hard challenge. There is often the possibility that the calcaneus remains completely uncovered from the tendon, making the reinsertion of its distal stub complex. At the same time, the standard open surgical technique could cause difficult wound healing because of the weak blood supply, the increasing possibility of rupture, and the bacterial contamination.

Shedding X-ray Light on the Role of Magnesium in the Activity of Salicylate Synthase (MbtI) for Drug Design.

The Mg-dependent salicylate synthase (MbtI) is a key enzyme involved in the biosynthesis of siderophores. Because iron is essential for the survival and pathogenicity of the microorganism, this protein constitutes an attractive target for antitubercular therapy, also considering the absence of homologous enzymes in mammals. An extension of the structure-activity relationships of our furan-based candidates allowed us to disclose the most potent competitive inhibitor known to date (, = 4 μM), which also proved effective on mycobacterial cultures.

Erratum: Longo, U.G., et al. Scapular Dyskinesis: From Basic Science to Ultimate Treatment. 2020, , 2974.

The authors would like to correct the names and surnames of the following authors of their previous paper [...

Scapular Dyskinesis: From Basic Science to Ultimate Treatment.

: This study intends to summarize the causes, clinical examination, and treatments of scapular dyskinesis (SD) and to briefly investigate whether alteration can be managed by a precision rehabilitation protocol planned on the basis of features derived from clinical tests. : We performed a comprehensive search of PubMed, Cochrane, CINAHL and EMBASE databases using various combinations of the keywords "Rotator cuff", "Scapula", "Scapular Dyskinesis", "Shoulder", "Biomechanics" and "Arthroscopy". : SD incidence is growing in patients with shoulder pathologies, even if it is not a specific injury or directly related to a particular injury.

Cost-Effectiveness of Supervised versus Unsupervised Rehabilitation for Rotator-Cuff Repair: Systematic Review and Meta-Analysis.

Background: The objective of the present study was to compare the efficacy between supervised and unsupervised rehabilitation after rotator-cuff (RC) repair in terms of clinical outcomes, visual-analog-scale (VAS) score, range of motion (ROM), and risk of retear.

Material: a comprehensive search of Pubmed, CINAHL, Cochrane, EMBASE, Ovid, and Google Scholar databases through a combination of the following keywords with logical Boolean operators: "informed", "uninformed", "unsupervised", "supervised", "rehabilitation", "physical therapy", "physical therapies", "postoperative period", "physical-therapy techniques", "physical-therapy technique", "exercise", "exercise therapy", "rotator cuff", "rotator-cuff tear", and "rotator-cuff repair". For each article included in the study, the following data were extracted: authors, year, study design, sample size and demographic features, RC tear characteristics, clinical outcomes, ROM, VAS score, retear rate, and time of follow-up.