Antimicrobial Susceptibility Profiles of Klebsiella pneumoniae Strains Collected from Clinical Samples in a Hospital in Southern Italy.

Infections caused by antibiotic-resistant bacteria represent a serious threat to global public health. Recently, due to its increased resistance to carbapenems and ß-lactams, Klebsiella pneumoniae has become one of the main causes of septicemia, pneumonia, and urinary tract infections. It is crucial to take immediate action and implement effective measures to prevent further spread of this issue. This study aims to report the prevalence and antibiotic resistance rates of K. pneumoniae strains isolated from clinical specimens from 2015 to 2020 at the University Hospital of Salerno, Italy. More than 3,800 isolates were collected from urine cultures, blood cultures, respiratory samples, and others. K. pneumoniae isolates showed broad resistance to penicillin and cephalosporins, and increased susceptibility to fosfomycin and gentamicin. Extended spectrum beta-lactamase (ESBL) isolates accounted for 20-22%. A high percentage of strains tested were resistant to carbapenems, with an average of 40% to meropenem and 44% to ertapenem. The production of ESBLs and resistance to carbapenems is one of the major public health problems. Constant monitoring of drug-resistant isolates is crucial for developing practical approaches in implementing antimicrobial therapy and reducing the spread of K. pneumoniae in nosocomial environments.

SARS-CoV-2 Lysate Stimulation Impairs the Release of Platelet-like Particles and Megakaryopoiesis in the MEG-01 Cell Line.

SARS-CoV-2 infection causes a considerable inflammatory response coupled with impaired platelet reactivity, which can lead to platelet disorders recognized as negative prognostic factors in COVID-19 patients. The virus may cause thrombocytopenia or thrombocytosis during the different disease stages by destroying or activating platelets and influencing platelet production. While it is known that several viruses can impair megakaryopoiesis by generating an improper production and activation of platelets, the potential involvement of SARS-CoV-2 in affecting megakaryopoiesis is poorly understood. To this purpose, we explored, in vitro, the impact of SARS-CoV-2 stimulation in the MEG-01 cell line, a human megakaryoblastic leukemia cell line, considering its spontaneous capacity of releasing platelet-like particles (PLPs). We interrogated the effect of heat-inactivated SARS-CoV-2 lysate in the release of PLPs and activation from MEG-01, the signaling pathway influenced by SARS-CoV-2, and the functional effect on macrophagic skewing. The results highlight the potential influence of SARS-CoV-2 in the early stages of megakaryopoiesis by enhancing the production and activation of platelets, very likely due to the impairment of STATs signaling and AMPK activity. Overall, these findings provide new insight into the role of SARS-CoV-2 in affecting megakaryocyte-platelet compartment, possibly unlocking another avenue by which SARS-CoV-2 moves.

BAG3 induces α-SMA expression in human fibroblasts and its over-expression correlates with poorer survival in fibrotic cancer patients.

Hypoxia and angiogenesis in solid tumors are often strictly linked to the development of fibrotic tissues, a detrimental event that compromises the antitumor immunity. As a consequence, tumor aggressiveness and poor patient prognosis relate to higher incidence of tissue fibrosis and stromal stiffness. The molecular pathways through which normal fibroblasts are converted in cancer-associated fibroblasts (CAFs) have a central role in the onset of fibrosis in tumor stroma, thus emerging as a strategic target of novel therapeutic approaches for cancer disease. Several studies addressed the role of BAG3 in sustaining growth and survival of cancer cell and also shed light on the different mechanisms in which the intracellular protein is involved. More recently, new pieces of evidence revealed a pivotal role of extracellular BAG3 in pro-tumor cell signaling in the tumor microenvironment, as well as its involvement in the development of fibrosis in tumor tissues. Here we report further data showing the presence of the BAG3 receptor (Interferon-induced transmembrane protein [IFITM]-2) on the plasma membrane of normal dermal fibroblasts and the activity of BAG3 as a factor able to induce the expression of α-smooth muscle actin and the phosphorylation of AKT and focal adhesion kinase, that sustain CAF functions in tumor microenvironment. Furthermore, in agreement with these findings, bag3 gene expression has been analyzed by high throughput RNA sequencing databases from patients-derived xenografts. A strong correlation between bag3 gene expression and patients' survival was found in several types of fibrotic tumors. The results obtained provide encouraging data that identify BAG3 as a promising therapeutic target to counteract fibrosis in tumors.

An emerging role for BAG3 in gynaecological malignancies.

BAG3, a member of the BAG family of co-chaperones, is a multidomain protein with a role in several cellular processes, including the control of apoptosis, autophagy and cytoskeletal dynamics. The expression of bag3 is negligible in most cells but can be induced by stress stimuli or malignant transformation. In some tumours, BAG3 has been reported to promote cell survival and resistance to therapy. The expression of BAG3 has been documented in ovarian, endometrial and cervical cancers, and studies have revealed biochemical and functional connections of BAG3 with proteins involved in the survival, invasion and resistance to therapy of these malignancies. BAG3 expression has also been shown to correlate with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix. Some aspects of BAG3 activity, such as its biochemical and functional interaction with the human papillomavirus proteins, could help in our understanding of the mechanisms of oncogenesis induced by the virus. This review aims to highlight the potential value of BAG3 studies in the field of gynaecological tumours.

Role of BAG3 in cancer progression: A therapeutic opportunity.

BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility. A secreted form of BAG3 has been identified in studies on pancreatic ductal adenocarcinoma (PDAC). Secreted BAG3 can bind to a specific receptor, IFITM2, expressed on macrophages, and induce the release of factors that sustain tumour growth and the metastatic process. BAG3 neutralisation therefore appears to constitute a novel potential strategy in the therapy of PDAC and, possibly, other tumours.

Development and Improvement of an Effective Method for Air and Surfaces Disinfection with Ozone Gas as a Decontaminating Agent.

Background and objectives: Ozone has been one of the most investigated and discussed sanitization methods. This paper reports a procedure to sanitize air hospital environments, in particular chirurgical surgery rooms that require high levels of disinfection. The purpose of this work was the development and implementation of a cleansing and sanitizing procedure for critical clinical settings with ozone, to prevent hospital infections by the elimination of all toxic and harmful microorganisms in the air, and ensure safe use for operators and patients. Materials and Methods: The protocol for the study involved a structured selection of a representative environment of healthcare structures such as high, medium, and low-risk settings in air and examples of hospital furniture. Results: The concentration of ozone was measured during sanitization treatment and the estimation of the total microbial count in the air and on different surfaces before and after the sanitization operations was performed. The results demonstrated a significant reduction in the microbial count that always fell below the threshold value. Conclusions: Currently, there are no air treatment strategies available for inactivating airborne organisms during hospital outbreaks, which is most probably due to the lack of approved protocols.

The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NFκB and STAT3 pathways in cystic fibrosis cells.

OBJECTIVE: N6-isopentenyladenosine (iPA) is an intermediate of the mevalonate pathway that exhibits various anti-cancer effects. However, studies on its anti-inflammatory activity are scarce and underlying molecular mechanisms are unknown. Therefore, we aimed to investigate the ability of iPA to exert anti-inflammatory effects in the human cystic fibrosis (CF) cell model of exacerbated inflammation. MATERIALS AND METHODS: TNFα-stimulated CF cells CuFi-1 and its normal counterpart NuLi-1 were pre-treated with increasing concentrations of iPA and cell viability and proliferation were assessed by MTT and BrdU assays. The effect of iPA on IL-8 and RANTES secretion was determined by ELISA, and the activation and expression of signaling molecules and selenoproteins were studied by Western blot. To assess the direct effect of iPA on NFκB activity, luciferase assay was performed on TNFα-stimulated HEK293/T cells transfected with a NFκB reporter plasmid. RESULTS: We demonstrated for the first time that iPA prevents IL-8 and RANTES release in TNFα-stimulated CF cells and this effect is mediated by increasing the expression of the direct NFκB inhibitor IκBα and decreasing the levels of STAT3. Consistent with this, we showed that iPA inhibited TNFα-mediated NFκB activation in HEK/293T cells. Finally, we also found that iPA improved the levels of glutathione peroxidase 1 and thioredoxin reductase 1 only in CF cells suggesting its ability to maintain sufficient expression of these anti-oxidant selenoproteins. CONCLUSIONS: Our findings indicate that iPA can exert anti-inflammatory activity especially in the cases of excessive inflammatory response as in CF.

The Main Determinants of Diabetes Mellitus Vascular Complications: Endothelial Dysfunction and Platelet Hyperaggregation.

Diabetes mellitus is a common disease that affects 3⁻5% of the general population in Italy. In some countries of northern Europe or in North America, it can even affect 6⁻8% of the population. Of great concern is that the number of cases of diabetes is constantly increasing, probably due to the increase in obesity and the sedentary nature of the population. According to the World Health Organization, in the year 2030 there will be 360 million people with diabetes, compared to 170 million in 2000. This has important repercussions on the lives of patients and their families, and on health systems that offer assistance to patients. In this review, we try to describe in an organized way the pathophysiological continuity between diabetes mellitus, endothelial dysfunction, and platelet hyperaggregation, highlighting the main molecular mechanisms involved and the interconnections.

The Impact of Aging on Cardio and Cerebrovascular Diseases.

A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms. Although improvements in treatment of cardiovascular diseases in the elderly population have increased the survival rate, several studies are needed to understand the best management option to improve therapeutic outcomes. The aim of this review is to give a 360° panorama on what goes on in the fragile ecosystem of elderly, why it happens and what we can do, right now, with the tools at our disposal to slow down aging, until new discoveries on aging, cardio and cerebrovascular diseases are at hand.

The Effect of Light Exposure at Night (LAN) on Carcinogenesis via Decreased Nocturnal Melatonin Synthesis.

In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that can influence the activity of the clock's genes and be involved in the inhibition of cancer development. On the other hand, in the literature, some papers highlight that artificial light exposure at night (LAN)-induced circadian disruptions promote cancer. In the present review, we summarize the potential mechanisms by which LAN-evoked disruption of the nocturnal increase in melatonin synthesis counteracts its preventive action on human cancer development and progression. In detail, we discuss: (i) the Warburg effect related to tumor metabolism modification; (ii) genomic instability associated with L1 activity; and (iii) regulation of immunity, including regulatory T cell (Treg) regulation and activity. A better understanding of these processes could significantly contribute to new treatment and prevention strategies against hormone-related cancer types.

BAG3 is involved in neuronal differentiation and migration.

Bcl2-associated athanogene 3 (BAG3) protein belongs to the family of co-chaperones interacting with several heat shock proteins. It plays a key role in protein quality control and mediates the clearance of misfolded proteins. Little is known about the expression and cellular localization of BAG3 during nervous system development and differentiation. Therefore, we analyze the subcellular distribution and expression of BAG3 in nerve-growth-factor-induced neurite outgrowth in PC12 cells and in developing and adult cortex of mouse brain. In differentiated PC12 cells, BAG3 was localized mainly in the neuritic domain rather than the cell body, whereas in control cells, it appeared to be confined to the cytoplasm near the nuclear membrane. Interestingly, the change of BAG3 localization during neuronal differentiation was associated only with a slight increase in total BAG3 expression. These data were coroborated by transmission electron microscopy showing that BAG3 was confined mainly within large dense-core vesicles of the axon in differentiated PC12 cells. In mouse developing cortex, BAG3 appeared to be intensely expressed in cellular processes of migrating cells, whereas in adult brain, a diffuse expression of low to medium intensity was detected in neuronal cell bodies. These findings suggest that BAG3 expression is required for neuronal differentiation and migration and that its role is linked to a change in its distribution pattern rather than to an increase in its protein expression levels.

Understanding the relationship between Sentinel Events and Sources of Work Related Stress for prevention programmes. An Italian survey.

OBJECTIVES: According to Legislative Decree n. 81/08 and Ministerial Circular of 18/11/2010, this paper proposes to verify the relationship between the sources of risk of stress, sentinel events and gender. METHODS: Sentinel events and their variations are mapped for three years. Successively, a self-reported OPRA (Organizational and Psychosocial Risk Assessment) questionnaire was administered. The sample was not probabilistic and balanced for two categories: Inside Sentinel Event and Outside Sentinel Event. 249 subjects were extracted from a population of 770 subjects of a debt collection firm. A two-way ANOVA was applied. RESULTS: The results show that sentinel events and Gender have no relationship with the inventory of sources of risk. CONCLUSIONS: Future research should consider the relationship between stressors and their exposure time, considering the working environment dynamics. In this way, the relationship between stressors and sentinel events can be studied and tested in greater detail, showing empirical evidence that may be useful for health prevention programmes.

A Narrative Review Exploring the Similarities between Cilento and the Already Defined "Blue Zones" in Terms of Environment, Nutrition, and Lifestyle: Can Cilento Be Considered an Undefined "Blue Zone"?

Longevity is rightly considered one of the greatest achievements of modern society, not only as a function of lifespan, but, more importantly, as a function of healthspan. There are Longevity Blue Zones (LBZs), regions around the world, such as in Okinawa, Japan; the Nicoya Peninsula, Costa Rica; Loma Linda, California; Icaria, Greece; and Ogliastra, Sardinia, that are characterized by a significant percentage of residents who live exceptionally long lives, often avoiding age-related disability to a significantly higher degree than in the Western way of life. Longevity is not a universal phenomenon, so if there are places in the world with characteristics similar to the LBZs, it is important to identify them in order to better understand what other factors, in addition to the known ones, might contribute to a long and healthy life. This narrative review aims to identify common factors between Cilento and the five LBZs, taking into account environmental, nutritional, and lifestyle factors. Articles from 2004 to the present, limited to studies published in English, German, and Italian, were searched in PubMed/Medline, Scopus, and Google Scholar. The co-authors agreed on 18 final reference texts. In order to evaluate the similarities between Cilento and the LBZs, a descriptive comparative approach was used. Cilento and the LBZs share several common factors, including a hilly altitude ranging from 355 to 600 m; a mild climate throughout the year, with temperatures between 17.4 and 23.5 degrees Celsius; traditional professions, such as agriculture and animal husbandry; and a predominantly Mediterranean or plant-based diet, with typical recipes based on legumes, tubers, vegetables, and extra virgin olive oil. Additionally, maintenance of strong intergenerational family relationships, religious devotion, and social relationships within the community are also prevalent. Given the similarities to Cilento, one might wonder if this is an LBZ waiting to be discovered. The lessons learned from this discovery could be applied to the general population to protect them from non-communicable chronic diseases and help slow the aging process.

An epidemiological qualitative/quantitative SWOT-AHP analysis in order to highlight the positive or critical aspects of dental implants: A pilot study.

OBJECTIVES: In recent years, dental implants are increasing in popularity due to their high success rate, demonstrated functionality, and aesthetic treatment results. Scientific research is very active in proposing improvements in the quality and survival of implants, taking into consideration various aspects. The objective of this study was to provide a holistic epidemiologic view of the state of dental implants, using a systematic approach based on a multimethod SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis and AHP (analytical hierarchical process) qualitative-quantitative analysis to identify the characteristics that can determine their success or failure. MATERIALS AND METHODS: The study used the hybrid method of SWOT-AHP. RESULTS: Analysis of the results showed that among strengths, the skill of the dentist was considered the most important factor, followed by the success of dental implants in the old people; among weaknesses, bruxism and chronic diseases were highlighted; for opportunities, biomechanical behavior, in terms of good mechanical strength and good tribological resistance to chemical and physical agents in the oral cavity, were considered the most important factors; finally, among threats, medical liability and biomechanical problems had equal weight. CONCLUSIONS: This study applied a multimethod SWOT-AHP approach to bring out favorable or critical evidence on the topic of dental implants. In accordance with the result of the strategic vector identified in the Twisting zone Adjustment type section, showed that implant surgery is a widespread technique but always needs improvement to increase the likelihood of success and reduce the complications that can lead to implant failure.

Current Epidemiological Status and Antibiotic Resistance Profile of Serratia marcescens.

The spread of antibiotic resistance represents a serious worldwide public health issue, underscoring the importance of epidemiology research in determining antimicrobial strategies. The purpose of this research was to investigate antibiotic resistance in Serratia marcescens isolates from clinical samples over seven years at the University Hospital "San Giovanni di Dio e Ruggi d'Aragona" in Salerno, Italy. S. marcescens is an important opportunistic pathogen associated with a wide spectrum of clinical diseases, including pneumonia, keratitis, meningitis, and urinary tract and wound infections. Outbreaks of nosocomial infections by S. marcescens strains have been documented in high-risk settings, mainly affecting immunocompromised patients and newborns. The primary objective of this study is to assess the rates of antibiotic resistance over the years to deal with a future emergency which includes the failure of various therapies due to antibiotic resistance. During the investigation, a total of 396 species of S. marcescens were isolated from various clinical samples, mainly from broncho-aspirates and sputum (31.6%) and blood cultures (21.5%). Antibiotics that showed the greatest susceptibility included ceftazidime/avibactam, amikacin, trimethoprim/sulfamethoxazole, and selected members of the cephalosporin class. However, a disconcerting trend of increasing rates of carbapenem resistance was outlined over the observation period. The absence of effective countermeasures, combined with growing antibiotic resistance that negates the effectiveness of multiple antibiotics, highlights the potential for S. marcescens infections to trigger serious clinical complications and increased mortality rates. The surveillance of Serratia marcescens infections constitutes a pivotal element in refining empiric therapy to mitigate the dissemination of antimicrobial resistance.

Anti-Herpes Zoster Vaccination of Fragile Patients in Hospital Setting: A Nudge Intervention in Italy.

BACKGROUND: A nudge intervention against Herpes Zoster, created and implemented in Italy, is presented in order to administer the Shingrix vaccine on a sample of frail patients, as required by the National Prevention Plan. Individual and contextual factors associated with vaccine adherence were investigated. METHOD: 300 frail adult subjects underwent a full vaccine cycle with recombinant-Shingrix vaccine (RZV vaccine). Hospital Presidia of the Salerno University Hospital Authority, a Hospital Presidium of the Salerno Local Health Authority, and the Public Health Laboratory of the University of Salerno (Campania) participated in the intervention. An ad hoc questionnaire was administered with the following scales: EQ-5D, PSS-10, MSPSS, and representations of HZ and its consequences. RESULTS: Some variables, such as peer support, doctor-patient relationship, level of education, and perception of health, are important in vaccine adherence and information processing. The following factors emerged from the factor analysis: Trust in collective knowledge and collective responsibility (F1); beliefs about virus risk and vaccine function (F2); information about virus and symptomatology (F3); and vaccine distrust (F4). Factor 4 correlates negatively with social support indices (R = -0.363; p < 0.001). There is a significant relationship between factor 3 and satisfaction with national information campaigns (F = 3.376; gdl = 5; p-value = 0.006). CONCLUSIONS: Future vaccination campaigns should be built with the aim of personalizing information and developing contextualized strategies, starting from understanding the stakeholders involved, cultural contexts, and organizational settings.

Network analysis of drug prescriptions.

PURPOSE: Networks exist in many different aspects of the world, at social, economical, biological, and molecular levels. Network science studies their parameters, or quantitative indicators; its instruments make it possible to draw and analyze networks from a mathematical perspective. The present study is an attempt to apply network science techniques to the drug prescription process, a typical subject of Epidemiology for Public Health studies. METHODS: A drug prescription network was created using the set of drug prescriptions written during a 6-month period by a group of 99 general practitioners (GPs) operating in Italy. In this network, named co-prescription network, each drug represented a node, and different drugs prescribed to the same patient at the same moment were considered linked together. Drug prescription data for a total of 42 965 patients and 631 232 drug packages were studied. A number of co-prescription networks were obtained and analyzed on the basis of different subsets of patients by age and gender. The network parameters were measured and compared for the various subsets. RESULTS: All the drug prescription networks studied showed scale invariance behavior. The age- and gender-related co-prescription networks showed different patterns, with different levels of complexity. CONCLUSIONS: The present study shows that the drug prescription process has specific network aspects and dynamics and, more generally, that it is possible to apply instruments of network science to study public health phenomena from a new, different perspective. Further studies should be encouraged and performed.

Old, Nonagenarians, and Centenarians in Cilento, Italy and the Association of Lifespan with the Level of Some Physicochemical Elements in Tap Drinking Water.

Longevity, as a complex life-history trait, shares an ontogenetic relationship with other quantitative traits, such as epigenetic and environmental factors. Therefore, it is important to identify environmental factors that may modify the epigenome to establish healthy aging. This study explored the association between tap drinking water and longevity in Cilento, Italy, to understand whether trace elements in local drinking water may have an influence on old, nonagenarian, and centenarian people and promote their health and longevity. Data on population and water sources were collected through the National Demographic Statistics, the Cilento Municipal Archives, and the Cilento Integrated Water Service. Ordinary least squares (OLS) regression and a geographically weight regression (GWR) model were used to study the spatial relationship between the explanatory and outcome variables of longevity. The results of the study showed that the prevalence of longevity is concentrated in the central, northern and southeastern areas of the territory and that some trace elements present in tap water may contribute to local longevity in Cilento. Specifically, all Cilento municipalities had alkaline tap water, and the municipalities with the highest longevity concentrations had higher alkalinity levels than the other municipalities, soft to medium-hard water hardness, an amount of total dissolved solids equivalent to the level of excellent water, lower amounts of sodium, adequate iron concentration, and adequate dietary intake of manganese per day.