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Anaerobic digestion (AD) has the potential to catalyse the shift from a linear to a circular economy. However, effective treatment and management of both solid (DSF) and liquid (DLF) digestate fraction treatment and management require adopting sustainable technologies to recover valuable by-products like energy, biofuels, biochar, and nutrients. This study reviews state-of-the-art advanced technologies for DSF and DLF treatment and valorisation, using life cycle assessment (LCA) and techno-economic analysis (TEA) in integrated digestate management (IDM). Key findings highlight these technologies' potential in mitigating environmental impacts from digestate management, but there's a need to improve process efficiency, especially at larger scales. Future research should prioritize cost-effective and eco-friendly IDM technologies. This review emphasizes how LCA and TEA can guide decision-making and promote sustainable agricultural practices. Ultimately, sustainable IDM technologies can boost resource recovery and advance circular economy principles, enhancing the environmental and economic sustainability of AD processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cardiovascular disease is a significant cause of morbidity and mortality among non-communicable diseases worldwide. Evidence shows that a healthy dietary pattern positively influences many risk factors of cardiometabolic health, stroke, and heart disease, supported by the effectiveness of healthy diet and lifestyles for the prevention of CVD. High quality and safety of foods are prerequisites to ensuring food security and beneficial effects. Contaminants can be present in foods mainly because of contamination from environmental sources (water, air, or soil pollution), or artificially introduced by the human. Moreover, the cross-contamination or formation during food processing, food packaging, presence or contamination by natural toxins, or use of unapproved food additives and adulterants. Numerous studies reported the association between food contaminants and cardiovascular risk by demonstrating that (1) the cross-contamination or artificial sweeteners, additives, and adulterants in food processing can be the cause of the risk for major adverse cardiovascular events and (2) environmental factors, such as heavy metals and chemical products can be also significant contributors to food contamination with a negative impact on cardiovascular systems. Furthermore, oxidative stress can be a common mechanism that mediates food contamination-associated CVDs as substantiated by studies showing impaired oxidative stress biomarkers after exposure to food contaminants.This narrative review summarizes the data suggesting how food contaminants may elicit artery injury and proposing oxidative stress as a mediator of cardiovascular damage., (© 2024. The Author(s).)

Neurofibromatosis type 1 (NF-1) microdeletion syndrome accounts for 5 to 11% of individuals with NF-1. The aim of our study was to characterize a large cohort of individuals with NF-1 microdeletion syndrome and expand its natural history. We conducted a retrospective chart review from 1994 to 2024 of individuals with NF-1 microdeletion syndrome followed at two large Neurofibromatosis Clinics. This cohort consists of 57 individuals with NF-1 microdeletion syndrome (28 type-1, 4 type-2, 2 type-3, 9 atypical deletions, and 14 indeterminate). We note 38/56 (67.9%) with describable facial features, 25/57 (43.8%) with plexiform neurofibromas, and 3/57 (5.2%) with malignant peripheral nerve sheath tumors within the observed period. The most reported neurodevelopmental manifestations from school-age or older individuals included 39/49 (79.6%) with developmental delays, 35/49 (71.4%) with expressive and/or receptive speech delays, 33/41 (80.5%) with learning difficulties, and 23/42 (54.8%) with attention-deficit/hyperactivity disorder. Full-scale IQ testing data was available for 22 individuals (range: 50-96). Of the 21 adults in this cohort, 14/21 (66.7%) graduated from high school, and 4/21 (19.0%) had some college experience. Many individuals received academic support (i.e., special education, individual education plan). In this cohort, neurocognitive outcomes in adults varied more than typically reported in the literature., (© 2024 The Author(s). American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)

Candida auris has been identified by the World Health Organization (WHO) as a critical priority pathogen on its latest list of fungi. C. auris infections are reported in the bloodstream and less commonly in the cerebrospinal fluid and abdomen, with mortality rates that range between 30% and 72%. However, no large-scale epidemiology studies have been reported until now. The diagnosis of C. auris infections can be challenging, particularly when employing conventional techniques. This can impede the early detection of outbreaks and the implementation of appropriate control measures. The yeast can easily spread between patients and in healthcare settings through contaminated environments or equipment, where it can survive for extended periods. Therefore, it would be desirable to screen patients for C. auris colonisation. This would allow facilities to identify patients with the disease and take appropriate prevention and control measures. It is frequently unsusceptible to drugs, with varying patterns of resistance observed among clades and geographical regions. This review provides updates on C. auris , including epidemiology, clinical characteristics, genomic analysis, evolution, colonisation, infection, identification, resistance profiles, therapeutic options, prevention, and control.

The impact of climate change on water availability and quality has affected agricultural irrigation. The use of treated wastewater can alleviate water in agriculture. Nevertheless, it is imperative to ensure proper treatment of wastewater before reuse, in compliance with current regulations of this practice. In decentralized agricultural scenarios, the lack of adequate treatment facilities poses a challenge in providing treated wastewater for irrigation. Hence, there is a critical need to develop and implement innovative, feasible, and sustainable treatment solutions to secure the use of this alternative water source. This study proposes the integration of intensive treatment solutions and natural treatment systems, specifically, the combination of up-flow anaerobic sludge blanket reactor (UASB), anaerobic membrane bioreactor (AnMBR), constructed wetlands (CWs), and ultraviolet (UV) disinfection. For this purpose, a novel demo-scale plant was designed, constructed and implemented to test wastewater treatment and evaluate the capability of the proposed system to provide an effluent with a quality in compliance with the current European wastewater reuse regulatory framework. In addition, carbon-sequestration and energy analyses were conducted to assess the sustainability of the proposed treatment approach. This research confirmed that UASB rector can be employed for biogas production (2.5 L h -1 ) and energy recovery from organic matter degradation, but its effluent requires further treatment steps to be reused in agricultural irrigation. The AnMBR effluent complied with class A standards for E. coli, boasting a concentration of 0 CFU 100 mL -1 , and nearly negligible TSS levels. However, further reduction of BOD 5 (35 mg L -1 ) is required to reach water quality class A. CWs efficiently produced effluent with BOD 5 below 10 mg L -1 and TSS close to 0 mg L -1 , making it suitable for water reuse and meeting class A standards. Furthermore, CWs demonstrated significantly higher energy efficiency compared to intensive treatment systems. Nonetheless, the inclusion of a UV disinfection unit after CWs was required to attain water class B standards., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The study investigated the dissipation ability of a vegetated free water surface (FWS) constructed wetland (CW) in treating pesticides-contaminated agricultural runoff/drainage water in a rural area belonging to Bologna province (Italy). The experiment simulated a 0.1% pesticide agricultural water runoff/drainage event from a 12.5-ha farm by dissolving acetamiprid, metalaxyl, S-metolachlor, and terbuthylazine in 1000 L of water and pumping it into the CW. Water and sediment samples from the CW were collected for 4 months at different time intervals to determine pesticide concentrations by multiresidue extraction and chromatography-mass spectrometry analyses. In parallel, no active compounds were detected in the CW sediments during the experimental period. Pesticides dissipation in the wetland water compartment was modeled according to best data practices by fitting the data to Single First Order (SFO), First Order Multi-Compartment (FOMC) and Double First Order in Parallel (DFOP) kinetic models. SFO (except for metalaxyl), FOMC and DFOP kinetic models adequately predicted the dissipation for the four investigated molecules, with the DFOP kinetic model that better fitted the observed data. The modeled distribution of each pesticide between biomass and water in the CW highly correlated with environmental indexes as K ow and bioconcentration factor. Computed DT50 by DFOP model were 2.169, 8.019, 1.551 and 2.047 days for acetamiprid, metalaxyl, S-metolachlor, and terbuthylazine, respectively. Although the exact degradation mechanisms of each pesticide require further study, the FWS CW was found to be effective in treating pesticides-contaminated agricultural runoff/drainage water within an acceptable time. Therefore, this technology proved to be a valuable tool for mitigating pesticides runoff occurring after intense rain events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Human immunodeficiency virus (HIV) infection has historically been related to the development of specific cancers, some of which are so closely linked to the infection, such as Kaposi's Sarcoma (KS), that they have earned the name Acquired Immuno-Deficiency Syndrome (AIDS)-defining cancers (ADCs). While the development of antiretroviral therapy (ART) has decreased the incidence of AIDS-defining cancers, the resulting aging of people living with HIV (PLWH) highlighted an increased occurrence of other forms of cancer. At the "Gaetano Martino" hospital in Messina, we developed a multidisciplinary approach by creating a bridge between the Oncology Unit and the Infectious Diseases Unit to carry out screening and a more rapid diagnostic and therapeutic journey for cancers in PLWH. The goal is to improve the diagnosis of various types of cancer by involving other professionals, such as gastroenterologists and gynecologists, to ensure faster access to treatment and, therefore, a greater chance of survival. In addition, our multidisciplinary approach has also included vaccine screening, offered by the "Gaetano Martino" hospital and useful for preventing the development of specific forms of cancer in the entire population and particularly in PLWH.

Schistosomiasis is a neglected tropical disease that is prevalent in low- and middle-income countries. There are five human pathogenic species, of which Schistosoma haematobium, Schistosoma mansoni and Schistosoma japonicum are the most prevalent worldwide and cause the greatest burden of disease in terms of mortality and morbidity. In addition, hybrid schistosomes have been identified through molecular analysis. Human infection occurs when cercariae, the larval form of the parasite, penetrate the skin of people while bathing in contaminated waters such as lakes and rivers. Schistosomiasis can cause both urogenital and intestinal symptoms. Urogenital symptoms include haematuria, bladder fibrosis, kidney damage, and an increased risk of bladder cancer. Intestinal symptoms may include abdominal pain, sometimes accompanied by diarrhoea and blood in the stool. Schistosomiasis affects more than 250 million people and causes approximately 70 million Disability-Adjusted Life Years (DALYs), mainly in Africa, South America, and Asia. To control infection, it is essential to establish sensitive and specific diagnostic tests for epidemiological surveillance and morbidity reduction. This review provides an overview of schistosomiasis, with a focus on available diagnostic tools for Schistosoma spp. Current molecular detection methods and progress in the development of new diagnostics for schistosomiasis infection are also discussed.

Urinary tract infections (UTIs) are prevalent bacterial infections in both community and healthcare settings. They account for approximately 40% of all bacterial infections and require around 15% of all antibiotic prescriptions. Although antibiotics have traditionally been used to treat UTIs for several decades, the significant increase in antibiotic resistance in recent years has made many previously effective treatments ineffective. Biofilm on medical equipment in healthcare settings creates a reservoir of pathogens that can easily be transmitted to patients. Urinary catheter infections are frequently observed in hospitals and are caused by microbes that form a biofilm after a catheter is inserted into the bladder. Managing infections caused by biofilms is challenging due to the emergence of antibiotic resistance. Biofilms enable pathogens to evade the host's innate immune defences, resulting in long-term persistence. The incidence of sepsis caused by UTIs that have spread to the bloodstream is increasing, and drug-resistant infections may be even more prevalent. While the availability of upcoming tests to identify the bacterial cause of infection and its resistance spectrum is critical, it alone will not solve the problem; innovative treatment approaches are also needed. This review analyses the main characteristics of biofilm formation and drug resistance in recurrent uropathogen-induced UTIs. The importance of innovative and alternative therapies for combatting biofilm-caused UTI is emphasised.

Climate change poses challenges to agricultural water resources, both in terms of quantity and quality. As an adaptation measure, the new European Regulation (EU) 2020/741 establishes different water quality classes for the use of reclaimed water in agricultural irrigation. Italy is also working on the definition of a new regulation on reclaimed water reuse for agricultural irrigation (in substitution of the current one) that will also include the specific requirements imposed by the European one. Nature-based Solutions (NBS) can be a cost-effective and environmentally friendly way to facilitate water reclamation and reuse. The present study reports the outcomes of a long-term monitoring campaign of two NBS (e.g., a constructed wetland (CW) and a lagoon system (LS)) comparing influent and effluent concentrations of different contaminants (e.g., E. coli, BOD 5 , TSS, TN and TP) with the threshold values imposed by the new regulations. The results showed that in both the case studies, E. coli (about 100 CFU 100 mL -1 ) and BOD 5 (lower than 25 mg L -1 ) mean effluent concentration need to be further reduced in reclaimed water to be suitable for unlimited reuse. As a negative aspect, in both the monitored NBS, an increase in TSS mean concentration in the effluent was observed, up to 40 mg L -1 in the case of the LS, making reclaimed water unsuitable for agricultural reuse. The CW has proven to be more effective in nitrogen removal (the effluent mean concentration was 3.4 mg L -1 ), whereas the LS was better at phosphorus removal (with an effluent mean concentration of 0.4 mg L -1 ). Based on the results, recommendations were made to further improve the performance of both systems in order to have adequate water quality, even for class A. Furthermore, the capacity of reclaimed water to meet crop water and nutrient needs was analyzed, and total nitrogen removal rate coefficients were calculated for the design of future LSs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

GATA2 deficiency is a rare disorder encompassing a broadly variable phenotype and its clinical picture is continuously evolving. Since it was first described in 2011, up to 500 patients have been reported. Here, we describe a cohort of 31 Italian patients (26 families) with molecular diagnosis of GATA2 deficiency. Patients were recruited contacting all the Italian Association of Pediatric Hematology and Oncology (AIEOP) centers, the Hematology Department in their institution and Italian societies involved in the field of vascular anomalies, otorhinolaryngology, dermatology, infectious and respiratory diseases. Median age at the time of first manifestation, molecular diagnosis and last follow-up visit was 12.5 (age-range, 2-52 years), 18 (age-range, 7-64 years) and 22 years (age-range, 3-64), respectively. Infections (39%), hematological malignancies (23%) and undefined cytopenia (16%) were the most frequent symptoms at the onset of the disease. The majority of patients (55%) underwent hematopoietic stem cell transplantation. During the follow-up rarer manifestations emerged. The clinical penetrance was highly variable, with the coexistence of severely affected pediatric patients and asymptomatic adults in the same pedigree. Two individuals remained asymptomatic at the last follow-up visit. Our study highlights new (pilonidal cyst/sacrococcygeal fistula, cholangiocarcinoma and gastric adenocarcinoma) phenotypes and show that lymphedema may be associated with null/regulatory mutations. Countrywide studies providing long prospective follow-up are essential to unveil the exact burden of rarer manifestations and the natural history in GATA2 deficiency., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antibiotics have played a crucial role in the reduction in the incidence of TB globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors, and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline in antibiotic development, and different economic and social conditions. In this review, we summarize recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasize that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throughout the community.

The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multidrug-resistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance genes, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.

Background Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID-19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. Methods and Results This study was conducted using data from the ISACS-COVID-19 (International Survey of Acute Coronavirus Syndromes-COVID-19) registry. Patients with a confirmed diagnosis of SARS-CoV-2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30-day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06-2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69-1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42-0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75-2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other ( P interaction =0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34-3.90]). Conclusions These findings suggest that azithromycin use in patients with COVID-19 and prior history of CVD is significantly associated with an increased risk of AHF and all-cause 30-day mortality. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05188612.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as healthcare-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

Type 1 diabetes (T1D) is a polygenic disease and does not follow a mendelian pattern. Inborn errors of immunity (IEIs), on the other hand, are caused by damaging germline variants, suggesting that T1D and IEIs have nothing in common. Some IEIs, resulting from mutations in genes regulating regulatory T-cell homeostasis, are associated with elevated incidence of T1D. The genetic spectrum of IEIs is gradually being unraveled; consequently, molecular pathways underlying human monogenic autoimmunity are being identified. There is an appreciable overlap between some of these pathways and the genetic variants that determine T1D susceptibility, suggesting that after all, IEI and T1D are 2 sides of the same coin. The study of monogenic IEIs with a variable incidence of T1D has the potential to provide crucial insights into the mechanisms leading to T1D. These insights contribute to the definition of T1D endotypes and explain disease heterogeneity. In this review, we discuss the interconnected pathogenic pathways of autoimmunity, β-cell function, and primary immunodeficiency. We also examine the role of environmental factors in disease penetrance as well as the circumstantial evidence of IEI drugs in preventing and curing T1D in individuals with IEIs, suggesting the repositioning of these drugs also for T1D therapy., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Aims: Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men., Methods and Results: This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71-0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90-1.42) and 0.86 (95% CI: 0.70-1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73-2.98; 3.85, 95% CI: 3.21-4.63; and 3.95, 95% CI: 3.04-5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94-1.67 vs. 0.83; 95% CI: 0.59-1.16, pinteraction = 0.04)., Conclusions: Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications., Competing Interests: Conflicts of interests: The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)