Publications by authors named "Paola Salvatore"

99 Publications

A novel smaller β-defensin-derived peptide is active against multidrug-resistant bacterial strains.

FASEB J 2021 12;35(12):e22026

Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.

Antibiotic resistance is becoming a severe obstacle in the fight against acute and chronic infectious diseases that accompany most degenerative illnesses from neoplasia to osteo-arthritis and obesity. Currently, the race is on to identify pharmaceutical molecules or combinations of molecules able to prevent or reduce the insurgence and/or progression of infectivity. Attempts to substitute antibiotics with antimicrobial peptides have, thus far, met with little success against multidrug-resistant (MDR) bacterial strains. During the last decade, we designed and studied the activity and features of human β-defensin analogs, which are salt-resistant, and hence active also under high salt concentrations as, for instance, in cystic fibrosis. Herein, we describe the design, synthesis, and major features of a new 21 aa long molecule, peptide γ2. The latter derives from the γ-core of the β-defensin natural molecules, a small fragment of these molecules still bearing high antibacterial activity. We found that peptide γ2, which contains only one disulphide bond, recapitulates most of the biological properties of natural human β-defensins and can also counteract both Gram-positive and Gram-negative MDR bacterial strains and biofilm formation. Moreover, it has great stability in human serum thereby enhancing its antibacterial presence and activity without cytotoxicity in human cells. In conclusion, peptide γ2 is a promising new weapon also in the battle against intractable infectious diseases.
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http://dx.doi.org/10.1096/fj.202002330RRDOI Listing
December 2021

Pneumonia in Non-HIV Patients Recovering from COVID-19: A Single-Center Experience.

Int J Environ Res Public Health 2021 Oct 29;18(21). Epub 2021 Oct 29.

Department of Clinical Medicine and Surgery, Section of Infectious Disease, University of Naples "Federico II", 80131 Naples, Italy.

Objective: to describe a single-center experience of pneumonia (PJP) in non-HIV patients recovering from COVID-19.

Methods: We report the cases of five non-HIV patients with COVID-19 who also developed PJP at a University Hospital.

Results: With the exception of one subject, who experienced an atypical and prolonged course of COVID-19, all the patients developed PJP after the clinical resolution of COVID-19 pneumonia. All but one patient had no pre-existing immunosuppressive conditions or other risk factors for PJP development at COVID-19 diagnosis. Nonetheless, following the course of COVID-19 infection, all the patients fulfilled at least one host factor for PJP; indeed, all the patients had received at least 2 weeks of high-dose steroids and three out of five had a CD4+ cell count <200/mm.

Conclusions: The use of corticosteroids for COVID-19 respiratory impairment seems to be the most common risk factor for PJP, together with viral-induced and iatrogenic lymphopenia. The worsening in respiratory function and the characteristic radiological picture during or after COVID-19 pneumonia should raise the suspicion of PJP, even in immunocompetent patients. PJP primary chemoprophylaxis can be considered in selected high-risk COVID-19 patients, but further studies are needed.
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http://dx.doi.org/10.3390/ijerph182111399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582834PMC
October 2021

Prodromal features in first-psychotic episodes of major affective and schizoaffective disorders.

J Affect Disord 2021 12 4;295:1251-1258. Epub 2021 Sep 4.

International Consortium for Mood & Psychotic Disorders, McLean Hospital, Belmont, MA, United States; Department of Psychiatry & Behavioral Sciences, University of New Mexico, Albuquerque, New Mexico, United States.

Background: Study aims were to analyze psychopathological details of prodromes leading to first-lifetime psychotic episodes and apply them to improve prediction of final diagnoses.

Methods: Comprehensive records of subjects with final diagnoses of bipolar I (BD-I; n = 216), schizoaffective (SzAffD; n = 71), or psychotic major-depressive (MDD; n = 42) disorders in the Harvard-McLean First-Psychotic Episode Project were analyzed to identify psychopathological details of prodromes leading to first-lifetime episodes with psychotic features and their ability to predict final diagnoses tested with multivariable logistic regression modeling.

Results: While held blind to final diagnoses, we identified 84 distinct psychopathological characteristics of prodromes to first-psychotic episodes, including perceptual disturbances, affective symptoms, sleep disturbances, onset rate, and duration. Prevalence of 19 factors appeared to differ among final diagnoses, and were tested with multivariable regression modeling. Significantly and independently more associated with final diagnoses of MDD than BD-I were 7 features: suicidal ideation, somatic delusions, anorexia, lack of insomnia, older presenting age, depressive symptoms, and lack of impulsivity; 9 others were associated more with later SzAffD than MDD or BD-I: lack of insomnia, homicidal behavior, lack of excitement, visual hallucinations, command hallucinations, longer prodrome, male sex, responding to internal stimuli, and younger age at presentation.

Limitations: Historical-retrospective and prospective assessments may have misidentified some prodromal features, and subjects with final psychotic-MDD diagnosis were relatively few.

Conclusions: Psychopathological features identified during prodromes leading to first-episodes with psychotic features predicted and distinguished among final diagnoses of MDD, BD-I, and SzAffD. The findings add to growing impressions that early psychopathology has value in predicting final diagnoses of major affective and schizoaffective disorders.
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http://dx.doi.org/10.1016/j.jad.2021.08.099DOI Listing
December 2021

Microbiological Evaluation and Sperm DNA Fragmentation in Semen Samples of Patients Undergoing Fertility Investigation.

Genes (Basel) 2021 04 27;12(5). Epub 2021 Apr 27.

Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, via S. Pansini 5, 80131 Napoli, Italy.

Fifteen percent of male infertility is associated with urogenital infections; several pathogens are able to alter the testicular and accessory glands' microenvironment, resulting in the impairment of biofunctional sperm parameters. The purpose of this study was to assess the influence of urogenital infections on the quality of 53 human semen samples through standard analysis, microbiological evaluation, and molecular characterization of sperm DNA damage. The results showed a significant correlation between infected status and semen volume, sperm concentration, and motility. Moreover, a high risk of fragmented sperm DNA was demonstrated in the altered semen samples. Urogenital infections are often asymptomatic and thus an in-depth evaluation of the seminal sample can allow for both the diagnosis and therapy of infections while providing more indicators for male infertility management.
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http://dx.doi.org/10.3390/genes12050654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145398PMC
April 2021

Estimating asymptomatic SARS-CoV-2 infections in a geographic area of low disease incidence.

BMC Infect Dis 2021 Apr 15;21(1):350. Epub 2021 Apr 15.

Department of Molecular Medicine and Medical Biotechnology, University of Napoli Federico II, Via S. Pansini 5, 80131, Naples, Italy.

Background: The SARS-CoV-2 infection has emerged as a rapidly spreading infection. Today it is relatively easy to isolate Covid-19 symptomatic cases, while remains problematic to control the disease spread by infected but symptom-free individuals. The control of this possible path of contagion requires drastic measures of social distancing, which imply the suspension of most activities and generate economic and social issues. This study is aimed at estimating the percentage of asymptomatic SARS-CoV-2 infection in a geographic area with relatively low incidence of Covid-19.

Methods: Blood serum samples from 388 healthy volunteers were analyzed for the presence of anti-SARS-CoV-2 IgG by using an ELISA assay based on recombinant viral nucleocapsid protein.

Results: We found that 7 out of 388 healthy volunteers, who declared no symptoms of Covid-19, like fever, cough, fatigue etc., in the preceding 5 months, have bona fide serum anti-SARS-CoV-2 IgG, that is 1.8% of the asymptomatic population (95% confidence interval: 0.69-2.91%).

Conclusions: The estimated range of asymptomatic individuals with anti-SARS-CoV-2 IgG should be between 26,565 and 112, 350. In the same geographic area, there are 4665 symptomatic diagnosed cases.
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http://dx.doi.org/10.1186/s12879-021-06054-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046491PMC
April 2021

Testing Surgical Face Masks in an Emergency Context: The Experience of Italian Laboratories during the COVID-19 Pandemic Crisis.

Int J Environ Res Public Health 2021 02 4;18(4). Epub 2021 Feb 4.

Presidio Tecnico/Scientifico di Ateneo per l'Emergenza COVID-19, Centro Servizi Metrologici e Tecnologici Avanzati, Università di Napoli Federico II, 80124 Naples, Italy.

The first wave of the COVID-19 pandemic brought about a broader use of masks by both professionals and the general population. This resulted in a severe worldwide shortage of devices and the need to increase import and activate production of safe and effective surgical masks at the national level. In order to support the demand for testing surgical masks in the Italian context, Universities provided their contribution by setting up laboratories for testing mask performance before releasing products into the national market. This paper reports the effort of seven Italian university laboratories who set up facilities for testing face masks during the emergency period of the COVID-19 pandemic. Measurement set-ups were built, adapting the methods specified in the EN 14683:2019+AC. Data on differential pressure (DP) and bacterial filtration efficiency (BFE) of 120 masks, including different materials and designs, were collected over three months. More than 60% of the masks satisfied requirements for DP and BFE set by the standard. Masks made of nonwoven polypropylene with at least three layers (spunbonded-meltblown-spunbonded) showed the best results, ensuring both good breathability and high filtration efficiency. The majority of the masks created with alternative materials and designs did not comply with both standard requirements, resulting in suitability only as community masks. The effective partnering between universities and industries to meet a public need in an emergency context represented a fruitful example of the so-called university "third-mission".
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http://dx.doi.org/10.3390/ijerph18041462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915703PMC
February 2021

No Detection of SARS-CoV-2 RNA on Urethral Swab in Patients with Positive Nasopharyngeal Swab.

Adv Virol 2020 9;2020:8826943. Epub 2020 Dec 9.

Department of Clinical Medicine and Surgery, Section of Dermatology, University of Naples Federico II, Naples, Italy.

Background: The SARS-CoV-2 infection has caused one of the worst pandemics that history has ever known. SARS-CoV-2 can lead to multiple organ failure, which is life-threatening. Viral RNA is found in the lung, intestine, testicle, kidney, etc., which suggests the virus can be transmitted also via routes besides respiratory droplets. The aim of our study was to evaluate the presence of SARS-CoV-2 in urethral swabs.

Methods: We enrolled ten patients with SARS-CoV-2 infection who attended the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from March 2020 to April 2020. One urethral swab and one rhino-oropharyngeal swab were collected from each patient during SARS-CoV-2 infection.

Results: All ten patients had a negative urethral swab for SARS-CoV-2 RNA, whereas the rhino-oropharyngeal swab was positive for SARS-CoV-2 RNA. This finding demonstrates that, in our patients, the virus did not affect the urinary tract and therefore would not be found in the urine, and even more importantly, it would not be transmitted via urine. This result was independent of the stage of the disease.

Conclusion: If confirmed in larger studies, this observation could be the key to understanding the role of SARS-CoV-2 in relation to the genitourinary system.
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http://dx.doi.org/10.1155/2020/8826943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729391PMC
December 2020

Phytocompounds vs. Dental Plaque Bacteria: Effects of Myrtle and Pomegranate Polyphenolic Extracts Against Single-Species and Multispecies Oral Biofilms.

Front Microbiol 2020 5;11:592265. Epub 2020 Nov 5.

Department of Science and Technology, University of Sannio, Benevento, Italy.

In the last decades, resistant microbial infection rate has dramatically increased, especially infections due to biofilm-producing strains that require increasingly complex treatments and are responsible for the increased mortality percentages compared with other infectious diseases. Considering that biofilms represent a key factor for a wide range of chronic infections with high drug tolerance, the treatment of biofilm-causing bacterial infections represents a great challenge for the future. Among new alternative strategies to conventional antimicrobial agents, the scientific interest has shifted to the study of biologically active compounds from plant-related extracts with known antimicrobial properties, in order to also evaluate their antibiofilm activity. In this regard, the aim of this study has been to assess the antibiofilm activity of polyphenolic extracts from myrtle leaf and pomegranate peel against oral pathogens of dental plaque, an excellent polymicrobial biofilm model. In particular, the antibiofilm properties of myrtle and pomegranate extracts, also in binary combination, were highlighted. In addition to inhibiting the biofilm formation, the tested polyphenolic extracts have been proven to destroy both preformed single-species and multispecies biofilms formed by , , , and oral isolates, suggesting that the new natural sources are rich in promising compounds able to counteract biofilm-related infections.
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http://dx.doi.org/10.3389/fmicb.2020.592265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674652PMC
November 2020

Gastrointestinal tract diseases as a risk factor for SARSCoV2 rectal shedding? An Italian report on 10 COVID-19 patients.

Intest Res 2021 Jul 6;19(3):354-356. Epub 2020 Nov 6.

Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

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http://dx.doi.org/10.5217/ir.2020.00084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322022PMC
July 2021

Long-term morbidity in major affective and schizoaffective disorders following hospitalization in first psychotic episodes.

Acta Psychiatr Scand 2021 01 28;143(1):50-60. Epub 2020 Oct 28.

International Consortium for Mood & Psychotic Disorders, Mailman Research Center, McLean Hospital, Belmont, MA, USA.

Objective: To evaluate morbidity during long-term follow-up with clinical treatment of affective and schizoaffective disorder subjects followed from hospitalization for first major psychotic episodes.

Methods: We followed adult subjects systematically at regular intervals from hospitalization for first-lifetime episodes of major affective and schizoaffective disorders with initial psychotic features. We compiled % of days with morbidity types from detailed records and life charts, reviewed earliest antecedent morbidities, compared both with final diagnoses and initial presenting illness types, and evaluated morbidity risk factors with regression modeling.

Findings: With final diagnoses of bipolar-I (BD-I, n = 216), schizoaffective (SzAffD, 71), and major depressive (MDD, 42) disorders, 329 subjects were followed for 4.47 [CI: 4.20-4.47] years. Initial episodes were mania (41.6%), mixed states (24.3%), depression (19.5%), or apparent nonaffective psychosis (14.6%). Antecedent morbidity presented 12.7 years before first episodes (ages: SzAffD ≤ BD-I < MDD). Long-term % of days ill ranked SzAffD (83.0%), MDD (57.8%), BD-I (45.0%). Morbidity differed by diagnosis and first-episode types, and was predicted by first episodes and suggested by antecedent illnesses. Long-term wellness was greater with BD-I diagnosis, first episode not mixed or psychotic nonaffective, rapid onset, and being older at first antecedents, but not follow-up duration.

Conclusions: Initially, psychotic BD-I, SzAffD, or MDD subjects followed for 4.47 years from first hospitalization experienced much illness, especially depressive or dysthymic, despite ongoing clinical treatment. Antecedent symptoms arose years before index first episodes; antecedents and first episode types predicted types and amounts of long-term morbidity, which ranked: SzAffD > MDD > BD-I.
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http://dx.doi.org/10.1111/acps.13243DOI Listing
January 2021

The Role of Thermal Water in Chronic Skin Diseases Management: A Review of the Literature.

J Clin Med 2020 Sep 22;9(9). Epub 2020 Sep 22.

Department of Clinical Medicine and Surgery, University "Federico II" of Naples, Via Pansini 5, 80131 Naples, Italy.

The benefits of thermal water in different diseases have been known since ancient times. Over the past decades, a re-assessment of the use of mineral water for the treatment of several pathologic conditions has taken place around the world. Today, water therapy is being practiced in many countries that have a variety of mineral springs considerably different in their hydrogeologic origin, temperature, and chemical composition. Thermal water and balneotherapy offer several advantages: this approach needs no chemicals or potentially harmful drugs; there are almost no side effects during and after treatment, and there is a low risk to the patient's general health and well-being. However, it is difficult to evaluate the efficacy of this therapeutic approach in clinical practice due to the complexity of molecular mechanisms underlying its efficacy. Here we review the current knowledge of the chemical, immunological, and microbiological basis for therapeutic effects of thermal water with a specific focus on chronic inflammatory skin diseases. We also describe recent evidence of the major dermatologic diseases that are frequently treated by balneotherapy with a remarkable rate of success. Moreover, we discuss the potential role of balneotherapy either alone or as a complement to conventional medical treatments.
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http://dx.doi.org/10.3390/jcm9093047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563194PMC
September 2020

Synergy of Polyphenolic Extracts From Honey, Myrtle and Pomegranate Against Oral Pathogens, and .

Front Microbiol 2020 24;11:1465. Epub 2020 Jul 24.

Department of Science and Technology, University of Sannio, Benevento, Italy.

The increasing incidence rate of oral diseases, the wide spread of antimicrobial resistance, and the adverse effects of conventional antibiotics mean alternative prevention and treatment options are needed to counteract oral pathogens. In this regard, our study aims to evaluate the antibacterial activity of polyphenolic extracts prepared from acacia honey, myrtle leaves, and pomegranate peel against cariogenic bacteria, such as and . The chemical-physical parameters of acacia honey and the RP-HPLC polyphenolic profile of pomegranate peel extract have been previously described in our studies, while the characterization of myrtle extract, performed by HPLC analysis, is reported here. All the extracts were used singly and in binary combinations to highlight any synergistic effects. Moreover, the extracts were tested in association with amoxicillin to evaluate their ability to reduce the effective dose of this drug The values of minimal inhibitory concentrations and minimal bactericidal concentrations have been used to quantitatively measure the antibacterial activity of the single extracts, while the fractional inhibitory concentration index has been considered as predictor of anticariogenic synergistic effects. Finally, a time-kill curve method allowed for the evaluation of the bactericidal efficacy of the combined extracts. The microbiological tests suggest that acacia honey, myrtle, and pomegranate extracts are able to inhibit the cariogenic bacteria, also with synergistic effects. This study provides useful and encouraging results for the use of natural extract combinations alone or in association with antibiotics (adjuvant therapy) as a valid alternative for the prevention and treatment of oral infectious diseases.
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http://dx.doi.org/10.3389/fmicb.2020.01465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396681PMC
July 2020

Urinary Biomarkers: Diagnostic Tools for Monitoring Athletes' Health Status.

Int J Environ Res Public Health 2020 08 20;17(17). Epub 2020 Aug 20.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Acute or intense exercise is sometimes related to infections of the urinary tract. It can also lead to incorrect hydration as well as incorrect glomerular filtration due to the presence of high-molecular-weight proteins that cause damage to the kidneys. In this context, our study lays the foundations for the use of a urine test in a team of twelve male basketball players as a means of monitoring numerous biochemical parameters, including pH, specific weight, color, appearance, presence of bacterial cells, presence of squamous cells, leukocytes, erythrocytes, proteins, glucose, ketones, bilirubin, hemoglobin, nitrite, and leukocyte esterase, to prevent and/or treat the onset of pathologies, prescribe personalized treatments for each athlete, and monitor the athletes' health status.
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http://dx.doi.org/10.3390/ijerph17176065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503896PMC
August 2020

[Validation of surgical masks during COVID19 emergency: activities at the University of Napoli Federico II].

G Ital Med Lav Ergon 2020 06;42(2):73-81

CeSMA Centro Servizi Metrologici e Tecnologici Avanzati, Università degli Studi di Napoli Federico II, Corso Nicolangelo Protopisani, 80146 Napoli, Italy.

Summary: During COVID-19 pandemic crisis, Italian Government has approved Law Decree no. 18 of 17 march 2020, in which art. 15 allows enterprises to produce, import and commercialize surgical masks notwithstanding the current rules of product certification. It is just required that the interested enterprises send to the Italian National Institute of Health a selfcertification in which they declare the technical characteristics of the masks and that masks are produced according to the safety requirements. In this context, a technical-scientific unit was established at the University of Napoli Federico II to provide interested enterprises with state-of-the-art consultancy, testing and measurement services, adhering to rigorous scientific protocols. Characterization tests were carried out on 163 surgical masks and/or materials for their construction and they have enabled the identification of pre-screening criteria to simplify the procedure for evaluating surgical masks using methods for assessing the filtration efficiency of particles and aerosols. Based on experimental results, it has been observed that a filtration efficiency for particles with sizes larger that 650 nm (PFE>650) exceeding 35% might guarantees a bacterial filtration efficiency (BFE) higher than 95% while BFE values higher than 98% are obtained when the PFE>650 is larger than 40%. PFE measurement is extremely simpler with respect to BFE, the latter being time-consuming and requiring specific equipment and methods for its realization. Many tested materials have shown the capability to assure high filtration efficiencies but Spundonded-Meltblown-Spunbonded (SMS), that are layers of non-woven fabric with different weights of Meltblown, can simultaneously guarantee high particle filtration efficiencies with pressure drop values (breathability) in the limits to classify the surgical masks as Type II/IIR. In fact, the fabric products analyzed so far have not been able to simultaneously guarantee adequate BFE and breathability values. On the contrary, Spunbonds of adequate weights can virtually verify both requirements and accredit themselves as possible materials for the production of surgical masks, at least of Type I. Further studies are needed to verify the possibility of producing low-cost, reusable surgical masks that could meet the criteria of circular economy.
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June 2020

Methicillin-Resistant : Risk for General Infection and Endocarditis Among Athletes.

Antibiotics (Basel) 2020 Jun 18;9(6). Epub 2020 Jun 18.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S.Pansini 5, 80131 Naples, Italy.

The first studies on (SA) infections in athletes were conducted in the 1980s, and examined athletes that perform in close physical contact, with particular attention to damaged or infected skin. Recent studies have used molecular epidemiology to shed light on the transmission of SA in professional athletes. These studies have shown that contact between athletes is prolonged and constant, and that these factors influence the appearance of infections caused by SA. These results support the need to use sanitary measures designed to prevent the appearance of SA infections. The factors triggering the establishment of SA within professional sports groups are the nasal colonization of SA, contact between athletes and sweating. Hence, there is a need to use the most modern molecular typing methods to evaluate the appearance of cutaneous SA disease. This review aims to summarize both the current SA infections known in athletes and the diagnostic methods employed for recognition, pointing to possible preventive strategies and the factors that can act as a springboard for the appearance of SA and subsequent transmission between athletes.
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http://dx.doi.org/10.3390/antibiotics9060332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345113PMC
June 2020

HNP-1 and HBD-1 as Biomarkers for the Immune Systems of Elite Basketball Athletes.

Antibiotics (Basel) 2020 Jun 7;9(6). Epub 2020 Jun 7.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Acute or strenuous exercise is sometimes related to upper respiratory tract infections in athletes. Practicing intense and regular exercise can lead to incorrect activation of the immune system, causing athletes to be excluded from training programs and competitions. Defensins are small antimicrobial peptides that are part of the innate immune system and dynamically involved in several biological activities. In this study, we highlight the role of human defensins in competitive basketball athletes. In particular, we consider the behavior of alpha- and beta-defensins together with white blood cells in a cohort of players. Moreover, we focus our attention on cortisol, a physiological indicator of stress, and testosterone, both of which are human hormones involved in muscle metabolism. The free-testosterone/cortisol ratio is considered to be an indicator of overtraining among athletes. This paper provides an up-to-date information of the role of human defensins as self-defense molecules during a continuous stressor such as long-term exercise, and it recognizes them as potential markers of infection.
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http://dx.doi.org/10.3390/antibiotics9060306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345027PMC
June 2020

Human Defensins: A Novel Approach in the Fight against Skin Colonizing a.

Antibiotics (Basel) 2020 04 21;9(4). Epub 2020 Apr 21.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

is a microorganism capable of causing numerous diseases of the human skin. The incidence of skin infections reflects the conflict between the host skin's immune defenses and the virulence elements. Antimicrobial peptides (AMPs) are small protein molecules involved in numerous biological activities, playing a very important role in the innate immunity. They constitute the defense of the host's skin, which prevents harmful microorganisms from entering the epithelial barrier, including However, uses ambiguous mechanisms against host defenses by promoting colonization and skin infections. Our review aims to provide a reference collection on host-pathogen interactions in skin disorders, including infections and its resistance to methicillin (MRSA). In addition to these, we discuss the involvement of defensins and other innate immunity mediators (i.e., toll receptors, interleukin-1, and interleukin-17), involved in the defense of the host against the skin disorders caused by , and then focus on the evasion mechanisms developed by the pathogenic microorganism under analysis. This review provides the "state of the art" on molecular mechanisms underlying skin infection and the pharmacological potential of AMPs as a new therapeutic strategy, in order to define alternative directions in the fight against cutaneous disease.
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http://dx.doi.org/10.3390/antibiotics9040198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235756PMC
April 2020

Melancholia: does this ancient concept have contemporary utility?

Int Rev Psychiatry 2020 Aug - Sep;32(5-6):466-470. Epub 2020 Mar 16.

Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

Many efforts have been made to develop coherent and clinically useful categories of depressive illness, especially to facilitate prediction of morbidity and guide treatment-response. They include proposals to resurrect the ancient concept of , as a form of severe depression with particular symptomatic and proposed psychobiological characteristics. However, modern research is inconsistent in supporting differences between melancholic and nonmelancholic depression. In our recent study of over 3200 patient-subjects with DSM-5 major depressive episodes with/without melancholic characteristics, and matched for illness severity, prevalence of melancholic features was 35.2% with remarkably few clinical and demographic differences between melancholic and nonmelancholic subjects. Also, our systematic review of trials comparing melancholic and nonmelancholic subjects found little difference in responses to antidepressant treatments. These findings indicate that the concept of melancholia may have limited value for clinical prediction and treatment-selection. Overlap of symptoms in melancholic and nonmelancholic depression, based on DSM criteria, may limit distinction of melancholia; alternative definitions can be sought, and psychomotor retardation is a particularly strong differentiating feature. For now, however, melancholia seems best considered a state-dependent depression-type strongly associated with greater symptomatic severity, rather than a distinct syndrome. Its DSM-5 current status as a depression-type specifier seems appropriate, and it may be a logical target for genetic and other biomedical studies.
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http://dx.doi.org/10.1080/09540261.2019.1708708DOI Listing
November 2021

Setup of Quantitative PCR for Oral spp. Evaluation in Celiac Disease Diagnosis.

Diagnostics (Basel) 2019 Dec 26;10(1). Epub 2019 Dec 26.

Ceinge Biotecnologie Avanzate S. C. a R. L., 80131 Naples, Italy.

Coeliac disease (CD) is a multifactorial autoimmune disorder and gut dysbiosis contributes to its pathogenesis. We previously profiled by 16S rRNA sequencing duodenal and oropharyngeal microbiomes in active CD (a-CD), gluten-free diet (GFD) patients, and controls (CO) and found significantly higher levels of spp., with pro-inflammatory activities, in a-CD patients than in the other two groups. In this study, we developed a fast and simple qPCR-based method to evaluate the abundance of the oral spp. and the diagnostic performances of the test in CD diagnosis. The spp. abundances detected by quantitative PCR (qPCR) were: CO = 0.14, GFD = 0.15, a-CD = 2.08, showing a similar trend to those previously measured by next generation sequencing (NGS). In particular, spp. values obtained by both methods were significantly higher ( < 0.001) in a-CD than in the other two groups GFD and CO-the latter almost overlapping. We calculated by ROC curve analysis the threshold of 1.12 ng/μL of spp. to discriminate between CO+GFD and a-CD patients with 100% and 96.7% of diagnostic sensitivity and specificity, respectively. In conclusion, our data, if confirmed in other cohorts, suggest the q-PCR evaluation of oral spp. could be a fast and simple method to assess CD-associated dysbiosis for diagnostic purposes.
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http://dx.doi.org/10.3390/diagnostics10010012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168164PMC
December 2019

Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery.

J Vis Exp 2019 11 5(153). Epub 2019 Nov 5.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II; CEINGE - Advanced Biotechnology;

Neisseria meningitidis (meningococcus) is a narrow-host-range microorganism, globally recognized as the leading cause of bacterial meningitis. Meningococcus is a transient colonizer of human nasopharynx of approximately 10% of healthy subject. In particular circumstances, it acquires an invasive ability to penetrate the mucosal barrier and invades the bloodstream causing septicaemia. In the latest case, fulminating sepsis could arise even without the consequent development of meningitis. Conversely, bacteria could poorly multiply in the bloodstream, cross the blood brain barrier, reach the central nervous system, leading to fulminant meningitis. The murine models of bacterial meningitis represent a useful tool to investigate the host-pathogen interactions and to analyze the pathogenetic mechanisms responsible for this lethal disease. Although, several experimental model systems have been evaluated over the last decades, none of these were able to reproduce the characteristic pathological events of meningococcal disease. In this experimental protocol, we describe a detailed procedure for the induction of meningococcal meningitis in a mouse model based on the intracisternal inoculation of bacteria. The peculiar signs of human meningitis were recorded in the murine host through the assessment of clinical parameters (e.g., temperature, body weight), evaluation of survival rate, microbiological analysis and histological examination of brain injury. When using intracisternal (i.cist.) inoculum, meningococci complete delivery directly into cisterna magna, leading to a very efficient meningococcal replication in the brain tissue. A 1,000-fold increase of viable count of bacteria is observed in about 18 h. Moreover, meningococci are also found in the spleen, and liver of infected mice, suggesting that the liver may represent a target organ for meningococcal replication.
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http://dx.doi.org/10.3791/60047DOI Listing
November 2019

An International Society of Bipolar Disorders task force report: Precursors and prodromes of bipolar disorder.

Bipolar Disord 2019 12 18;21(8):720-740. Epub 2019 Sep 18.

Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.

Objectives: To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years.

Methods: We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies.

Results: Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention.

Conclusions: The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.
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http://dx.doi.org/10.1111/bdi.12831DOI Listing
December 2019

Celiac disease-associated Neisseria flavescens decreases mitochondrial respiration in CaCo-2 epithelial cells: Impact of Lactobacillus paracasei CBA L74 on bacterial-induced cellular imbalance.

Cell Microbiol 2019 08 20;21(8):e13035. Epub 2019 May 20.

CEINGE-Biotecnologie Avanzate SCarl, Naples, Italy.

We previously identified a Neisseria flavescens strain in the duodenum of celiac disease (CD) patients that induced immune inflammation in ex vivo duodenal mucosal explants and in CaCo-2 cells. We also found that vesicular trafficking was delayed after the CD-immunogenic P31-43 gliadin peptide-entered CaCo-2 cells and that Lactobacillus paracasei CBA L74 (L. paracasei-CBA) supernatant reduced peptide entry. In this study, we evaluated if metabolism and trafficking was altered in CD-N. flavescens-infected CaCo-2 cells and if any alteration could be mitigated by pretreating cells with L. paracasei-CBA supernatant, despite the presence of P31-43. We measured CaCo-2 bioenergetics by an extracellular flux analyser, N. flavescens and P31-43 intracellular trafficking by immunofluorescence, cellular stress by TBARS assay, and ATP by bioluminescence. We found that CD-N. flavescens colocalised more than control N. flavescens with early endocytic vesicles and more escaped autophagy thereby surviving longer in infected cells. P31-43 increased colocalisation of N. flavescens with early vesicles. Mitochondrial respiration was lower (P < .05) in CD-N. flavescens-infected cells versus not-treated CaCo-2 cells, whereas pretreatment with L. paracasei-CBA reduced CD-N. flavescens viability and improved cell bioenergetics and trafficking. In conclusion, CD-N. flavescens induces metabolic imbalance in CaCo-2 cells, and the L. paracasei-CBA probiotic could be used to correct CD-associated dysbiosis.
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http://dx.doi.org/10.1111/cmi.13035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618323PMC
August 2019

Virulence Traits of a Serogroup C Meningococcus and Isogenic Mutant, Defective in Surface-Exposed Sialic Acid, in a Murine Model of Meningitis.

Infect Immun 2019 04 25;87(4). Epub 2019 Mar 25.

Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy

In serogroup C , the () gene codes for an UDP--acetylglucosamine 2-epimerase that catalyzes the conversion of UDP--acetyl-α-d-glucosamine into -acetyl-d-mannosamine and UDP in the first step in sialic acid biosynthesis. This enzyme is required for the biosynthesis of the (α2→9)-linked polysialic acid capsule and for lipooligosaccharide (LOS) sialylation. In this study, we have used a reference serogroup C meningococcal strain and an isogenic knockout mutant to investigate the pathogenetic role of surface-exposed sialic acids in a model of meningitis based on intracisternal inoculation of BALB/c mice. Results confirmed the key role of surface-exposed sialic acids in meningococcal pathogenesis. The 50% lethal dose (LD) of the wild-type strain 93/4286 was about four orders of magnitude lower than that of the mutant. Compared to the wild-type strain, the ability of this mutant to replicate in brain and spread systemically was severely impaired. Evaluation of brain damage evidenced a significant reduction in cerebral hemorrhages in mice infected with the mutant in comparison with the levels in those challenged with the wild-type strain. Histological analysis showed the typical features of bacterial meningitis, including inflammatory cells in the subarachnoid, perivascular, and ventricular spaces especially in animals infected with the wild type. Noticeably, 80% of mice infected with the wild-type strain presented with massive bacterial localization and accompanying inflammatory infiltrate in the , indicating high tropism of meningococci exposing sialic acids toward this brain structure and a specific involvement of the in the mouse model of meningococcal meningitis.
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http://dx.doi.org/10.1128/IAI.00688-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434112PMC
April 2019

Aggression among 216 patients with a first-psychotic episode of bipolar I disorder.

Int J Bipolar Disord 2018 Aug 11;6(1):18. Epub 2018 Aug 11.

International Consortium for Bipolar & Psychotic Disorders Research, Psychotic Disorders Division, McLean Hospital, Belmont, MA, 02478, USA.

Background: Aggression by patients with bipolar I disorder (BD-I) is not uncommon. Identifying potential risk factors early in the illness-course should inform clinical management and reduce risk.

Methods: In a study sample of 216 initially hospitalized, first-psychotic episode subjects diagnosed with DSM-IV-TR BD-I, we identified recent (within 1 month before hospitalization) aggression by ratings on the Brief Psychiatric Rating Scale-Expanded and review of detailed clinical research records. We compared subjects with versus without aggressive behavior for associations with selected demographic and clinical factors.

Results: Aggression was identified in 23/216 subjects (10.6%). It was associated significantly with recent suicide attempt (OR = 4.86), alcohol abuse (OR = 3.63), learning disability (OR = 3.14), and initial manic episode (OR = 2.59), but not with age, sex, onset-type, personality disorder, time to recovery, or functional status.

Conclusions: Among first-major episode BD-I patients with psychotic features, recent serious aggression towards others was identified in 10.6%. The odds of aggression increased by 4.9-times in association with a recent suicide attempt, more than 3-times with alcohol-abuse or learning disability, and by 2.6-times if the episode polarity was manic. The findings encourage closer management of alcohol misuse, suicide risk, and manic symptoms, and early detection of learning problems in BD-I patients.
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http://dx.doi.org/10.1186/s40345-018-0126-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161985PMC
August 2018

Oropharyngeal microbiome evaluation highlights Neisseria abundance in active celiac patients.

Sci Rep 2018 07 23;8(1):11047. Epub 2018 Jul 23.

Ceinge Biotecnologie Avanzate scarl, Naples, Italy.

We previously profiled duodenal microbiome in active (a-), gluten-free diet (GFD) celiac disease (CD) patients and controls finding higher levels of the Proteobacterium Neisseria flavescens in a-CD patients than in the other two groups. Here, we investigate the oropharyngeal microbiome in CD patients and controls to evaluate whether this niche share microbial composition with the duodenum. We characterized by 16S rRNA gene sequencing the oropharyngeal microbiome in 14 a-CD, 22 GFD patients and 20 controls. Bacteroidetes, Proteobacteria and Firmicutes differed significantly between the three groups. In particular, Proteobacteria abounded in a-CD and Neisseria species mostly accounted for this abundance (p < 0.001), whereas Bacteroidetes were more present in control and GFD microbiomes. Culture-based oropharyngeal microbiota analysis confirmed the greater abundance of Proteobacteria and of Neisseria species in a-CD. Microbial functions prediction indicated a greater metabolic potential for degradation of aminoacids, lipids and ketone bodies in a-CD microbiome than in control and GFD microbiomes, in which polysaccharide metabolism predominated. Our results suggest a continuum of a-CD microbial composition from mouth to duodenum. We may speculate that microbiome characterization in the oropharynx, which is a less invasive sampling than the duodenum, could contribute to investigate the role of dysbiosis in CD pathogenesis.
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http://dx.doi.org/10.1038/s41598-018-29443-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056421PMC
July 2018

Demographic and clinical characteristics associated with a history of bizarre delusions in a cross-diagnostic sample of individuals with psychotic disorders.

Asian J Psychiatr 2018 Jan 9;31:82-85. Epub 2018 Feb 9.

McLean Hospital, Belmont, MA, 02478, United States; Harvard Medical School, Boston, MA, 02112, United States.

Bizarre delusions (BizD) are not specific to schizophrenia (SZ) and can be found in other psychotic disorders. However, to date, there are no studies investigating socio-demographic and clinical characteristics associated with BizD across the psychosis spectrum. In this study 819 subjects with a diagnosis of SZ (n = 250), schizoaffective disorder (SZA) (n = 228) and bipolar I disorder (BD) (n = 341) were included. Patients with history of BizD and with no BizD were compared with respect to socidemographic and clinical variables, and predictors of BizD were explored. Patients with BizD were less educated, less likely to be married, had higher Positive and Negative Syndrome Scale (PANSS) negative scores and lower Young Mania Rating Scale scores. Younger age, SZ and SZA diagnoses, higher PANSS positive scores, presence of reference delusions, tactile and olfactory hallucinations were predictors. Our results indicate that BizD are associated with higher illness severity, lower functionality and specific set of symptoms.
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http://dx.doi.org/10.1016/j.ajp.2018.02.011DOI Listing
January 2018

Antibacterial Activity of Pomegranate Juice and Peel Extracts on Cariogenic Bacteria.

Biomed Res Int 2017 25;2017:2152749. Epub 2017 Oct 25.

Department of Science and Technology, Sannio University, Via Port'arsa, No. 11, 82100 Benevento, Italy.

Aim: To evaluate the antimicrobial activity of hydroalcoholic extracts of pomegranate ( L.) peel and juice, against the microorganisms considered the main etiologic agents of dental caries.

Methods: The values of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined against Clarke ATCC® 25175™ strain and clinical isolate.

Results: Peel extracts inhibit effectively the growth and survival of ATCC 25175 strain and clinical isolate with MIC and MBC values of 10 g/l and 15 g/l, respectively. Furthermore, the pomegranate juice extract showed high inhibitory activity against ATCC 25175 strain with a MIC value of 25 g/l and a MBC value of 40 g/l, whereas, against , it has displayed a moderate inhibitory activity, with MIC and MBC values of 20 g/l and 140 g/l, respectively.

Conclusions: microbiological tests demonstrate that the hydroalcoholic extracts of pomegranate juice and peel are able to contrast the main cariogenic bacteria involved in tooth decay. Although being preliminary data, our results suggest that pomegranate polyphenolic compounds could represent a good adjuvant for the prevention and treatment of dental caries.
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http://dx.doi.org/10.1155/2017/2152749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676346PMC
July 2018

Ultrasonography-driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine-containing chemotherapy for the remission induction of acute myeloid leukemia.

Cancer Med 2017 Jul 26;6(7):1500-1511. Epub 2017 May 26.

Advanced Biomedical Sciences, Federico II University Medical School, Naples, Italy.

Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively (P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset.
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http://dx.doi.org/10.1002/cam4.1063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504336PMC
July 2017

The complete 12 Mb genome and transcriptome of Nonomuraea gerenzanensis with new insights into its duplicated "magic" RNA polymerase.

Sci Rep 2016 Dec 21;6(1):18. Epub 2016 Dec 21.

Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy.

In contrast to the widely accepted consensus of the existence of a single RNA polymerase in bacteria, several actinomycetes have been recently shown to possess two forms of RNA polymerases due the to co-existence of two rpoB paralogs in their genome. However, the biological significance of the rpoB duplication is obscure. In this study we have determined the genome sequence of the lipoglycopeptide antibiotic A40926 producer Nonomuraea gerenzanensis ATCC 39727, an actinomycete with a large genome and two rpoB genes, i.e. rpoB(S) (the wild-type gene) and rpoB(R) (the mutant-type gene). We next analyzed the transcriptional and metabolite profiles in the wild-type gene and in two derivative strains over-expressing either rpoB(R) or a mutated form of this gene to explore the physiological role and biotechnological potential of the "mutant-type" RNA polymerase. We show that rpoB(R) controls antibiotic production and a wide range of metabolic adaptive behaviors in response to environmental pH. This may give interesting perspectives also with regard to biotechnological applications.
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http://dx.doi.org/10.1038/s41598-016-0025-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431353PMC
December 2016
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