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This paper presents a method for selecting pilot points used in secondary voltage control of active distribution networks. A unique formulation for pilot point selection is presented as a multi-objective stochastic optimization problem solved using differential evolution. The pilot point selection method considers multiple operating cases with different combinations of solar photovoltaic generation, loads, and electric vehicle uncertainties. The proposed methodology is applied to the IEEE 33 bus test system and a large Australian distribution feeder while observability, controllability, and robustness metrics are used to compare the proposed method against existing methods. Compared with the existing pilot point selection approaches, it is found that the proposed method obtains the most observable, controllable, and robust set of pilot points, making the method effective for the optimal selection of pilot points used in secondary voltage control of active distribution networks.

Abstract Background Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. Methods The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. Conclusions The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Abstract In finance, portfolio optimization aims at finding optimal investments maximizing a trade-off between return and risks, given some constraints. Classical formulations of this quadratic optimization problem have exact or heuristic solutions, but the complexity scales up as the market dimension increases. Recently, researchers are evaluating the possibility of facing the complexity scaling issue by employing quantum computing. In this paper, the problem is solved using the Variational Quantum Eigensolver (VQE), which in principle is very efficient. The main outcome of this work consists of the definition of the best hyperparameters to set, in order to perform Portfolio Optimization by VQE on real quantum computers. In particular, a quite general formulation of the constrained quadratic problem is considered, which is translated into Quadratic Unconstrained Binary Optimization by the binary encoding of variables and by including constraints in the objective function. This is converted into a set of quantum operators (Ising Hamiltonian), whose minimum eigenvalue is found by VQE and corresponds to the optimal solution. In this work, different hyperparameters of the procedure are analyzed, including different ansatzes and optimization methods by means of experiments on both simulators and real quantum computers. Experiments show that there is a strong dependence of solutions quality on the sufficiently sized quantum computer and correct hyperparameters, and with the best choices, the quantum algorithm run on real quantum devices reaches solutions very close to the exact one, with a strong convergence rate towards the classical solution, even without error-mitigation techniques. Moreover, results obtained on different real quantum devices, for a small-sized example, show the relation between the quality of the solution and the dimension of the quantum processor. Evidences allow concluding which are the best ways to solve real Portfolio Optimization problems by VQE on quantum devices, and confirm the possibility to solve them with higher efficiency, with respect to existing methods, as soon as the size of quantum hardware will be sufficiently high.

Abstract Background Malnutrition and muscle wasting are common in ICU patients and predict adverse patient-centered outcomes. The Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) conducted a nationwide survey to identify the nutritional practices in the Italian ICUs and to plan future, training interventions to improve the national clinical practice. Methods Nationwide online survey, involving Italian ICUs, developed by experts affiliated with SIAARTI. Invitations to participate were distributed through emails and social networks. Data were collected over a period of three months (October 1 to December 31, 2022) during 2022. Results One hundred full responses from participating ICUs were collected. The number of beds is 20 in 11 ICUs. Most ICUs (87%) are mixed, cardiac (5%), neurosurgical (4%), or pediatric ICUs (1%). Although the nutritional program is widely prescribed based on the patients’ general evaluation, 52 ICUs (52%) do not perform nutritional risk evaluation at admission in case of > 24-h stay. Daily caloric intake is mainly based on the 25 kcal/kg equation; otherwise, the Harris-Benedict formula is mostly used, whereas indirect calorimetry is less used. Most clinicians apply a personalized nutritional approach to organ failure. Most ICUs have a nutritional management protocol, and enteral nutrition (EN) is frequently started within 2 days from admission, while supplemental parenteral nutrition is used when EN is insufficient by most clinicians. The EN administered seems to correspond to that prescribed, but it is stopped if the gastric residual gastric is > 300–500 ml in most ICUs. Conclusion Prescription, route, and mode of administration of nutritional support seem to be in line with international recommendations, while suggestions on the tools for assessing the nutritional risk and monitoring efficacy and complications seem far less followed. Future national clinical studies are necessary to investigate the optimal nutritional and metabolic management of critically ill patients and the correspondence with the results of this survey on actual practices.

Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases where benzodiazepines are not adequate in controlling persistent autonomic hyperactivity or anxiety, dexmedetomidine could be utilized. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the ICUs, with the potential reduction in healthcare costs. The purpose of this systematic review and meta-analysis (PROSPERO CRD42018084370) is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care for the treatment of AWS. We retrieved literature from PubMed, EMBASE, and CENTRAL until 10 January 2024. Eligible studies were both randomized trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was tracheal intubation; secondary outcomes were (i) bradycardia and (ii) hypotension. A total of 3585 papers were retrieved: 2635 from EMBASE, 930 from Medline, and 20 from CENTRAL. After eliminating duplicates, 2960 papers were screened by title and abstract; 75 out of the 2960 papers were read in full text. The qualitative synthesis included nine of all manuscripts read in full text. The quantitative synthesis included eight studies for the primary outcome (tracheal intubation), seven for the secondary outcome bradycardia, and six for the secondary outcome hypotension. The meta-analysis showed that Dexmedetomidine, as adjunctive therapy, is not more effective than standard therapy in reducing the risk of tracheal intubation in AWS [RR: 0.57, 95% CI: 0.25–1.3, p = 0.15]. It also appears to be less safe than sedative therapy as it significantly increases the risk of bradycardia [RR: 2.68, 95% CI: 1.79–4.16, p = 0.0016]. Hypotension was not significantly different in patients who received dexmedetomidine [RR: 1.5, 95% CI: 0.69–3.49, p = 0.21].

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New β-lactam/β-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection (n = 234), complicated intra-abdominal infections (n = 220), hospital-acquired pneumonia (n = 276), and ventilator-associated pneumonia (n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms.

Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2–5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease’s stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients’ satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.

Abstract Renal replacement therapies (RRT) are essential to support critically ill patients with severe acute kidney injury (AKI), providing control of solutes, fluid balance and acid–base status. To maintain the patency of the extracorporeal circuit, minimizing downtime periods and blood losses due to filter clotting, an effective anticoagulation strategy is required. Regional citrate anticoagulation (RCA) has been introduced in clinical practice for continuous RRT (CRRT) in the early 1990s and has had a progressively wider acceptance in parallel to the development of simplified systems and safe protocols. Main guidelines on AKI support the use of RCA as the first line anticoagulation strategy during CRRT in patients without contraindications to citrate and regardless of the patient’s bleeding risk. Experts from the SIAARTI-SIN joint commission have prepared this position statement which discusses the use of RCA in different RRT modalities also in combination with other extracorporeal organ support systems. Furthermore, advise is provided on potential limitations to the use of RCA in high-risk patients with particular attention to the need for a rigorous monitoring in complex clinical settings. Finally, the main findings about the prospective of optimization of RRT solutions aimed at preventing electrolyte derangements during RCA are discussed in detail.

This paper introduces an energy management algorithm for a hybrid solar and biogas-based electric vehicle charging station (EVCS) that considers techno-economic and environmental factors. The proposed algorithm is designed for a 20-kW EVCS and uses a fuzzy inference system in MATLAB SIMULINK to manage power generation, EV power demand, charging periods, and existing charging rates to optimize real-time charging costs and renewable energy utilization. The results show that the proposed algorithm reduces energy costs by 74.67% compared to existing flat rate tariffs and offers lower charging costs for weekdays and weekends. The integration of hybrid renewables also results in a significant reduction in greenhouse gas emissions, with payback periods for charging station owners being relatively short, making the project profitable.

Abstract Background Dexmedetomidine is a highly selective alpha-2 receptor agonist without any effect on the GABA receptor. It provides an excellent sedative and analgesic profile with few side effects. We report our experience with dexmedetomidine use during orthopaedic surgery under locoregional anaesthesia to ensure adequate sedation and optimal postoperative pain control. Methods In this retrospective analysis, we included 128 patients who underwent orthopaedic surgery between January 2019 and December 2021. All patients received the same local anaesthetic dose of 20 ml of ropivacaine 0.375% + mepivacaine 0.5% for axillary and supraclavicular block and 35 ml of ropivacaine 0.375% + mepivacaine 0.5% for triple nerve block (femoral, obturator and sciatic nerve). The cohort was divided into two groups based on sedation drugs used during surgery (dexmedetomidine, or group D, vs midazolam, or group M). All patients received postoperative 24-h analgesia consisting of 60 mg of ketorolac, 200 mg of tramadol and 4 mg of ondansetron. The primary outcome measured how many patients in the two groups required an analgesic rescue dose of pethidine and the time to first pethidine administration. To reduce confounding, we included patients in two groups with non-statistically different demo-anamnestic parameters and who received the same dose of intraoperative local anaesthetic and postoperative analgesia. Results The number of patients in group D who did not require a rescue dose of analgesia was significantly greater than in group M (49 vs 11, p < 0.001). Time-to-first postoperative opioid administration did not show a fundamental difference between the two groups under examination (523.75 ± 131.55 min vs 564 ± 117.84 min). Total opioid consumption was higher in the M group than in the D group (3529.8 ± 30.36 μg vs 1864.8 ± 31.59 μg, p 0.075), with a mean opioid consumption significantly higher in the M group than in the D group (26.26 ± 42.8 μg vs 69.21 ± 46.1 μg, p < 0.001): D group received 62.06% less opioid than M group. Conclusions The continuous infusion of dexmedetomidine during orthopaedic surgery performed under locoregional anaesthesia has been shown to increase the analgesic effect of local anaesthetics and reduce the consumption of major opioids in the postoperative period. Dexmedetomidine offers a unique ability to supply sedation and analgesia without respiratory depression, having a wide safety margin and an excellent sedative capacity. It does not increase the rate of postoperative complications.

Abstract Background We present a case of fungal keratitis caused by Scedosporium apiospermum, which is a rare agent. Case description A 34-year-old Caucasian male patient was admitted to our clinic with complaints of pain and blurred vision in the left eye. The patient had a history of wearing contact lenses for 3 years. According to the Snellen chart, the patient’s visual acuity was 20/20 and counting fingers at 30 cm, for right and left eyes, respectively. A 3 × 3 mm corneal abscess at the center of the cornea with hypopyon in the patient’s left eye was observed. After the patient was hospitalized, fortified gentamicin and fortified cefazolin drops were started 24 times per day. Intravenous fluconazole 1 × 800 mg loading, 1 × 400 mg maintenance dose, intravenous vancomycin 4 × 500 mg and intravenous cefoperazone + sulbactam 2 × 2 g treatments were started. We observed S. apiospermum in the corneal scraping sample, which the identification was performed by combined phenotypic characteristics and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry on the sixth day of treatment. The drops were revised as fortified vancomycin, ceftazidime, and voriconazole drops 24 times per day. Intravenous voriconazole 2 × 6 mg/kg loading and 2 × 4 mg/kg maintenance dose treatments were started. Three weeks later, left eye visual acuity increased to 20/40, and the corneal abscess regressed. On second-year follow-up, his visual acuity increased to 20/25 for the left eye and the cornea was transparent. Conclusion Scedosporium group is an opportunistic filamentous fungus that is very rarely seen and causes severe keratitis infections. In the literature, to the best of our knowledge, three cases of keratitis due to S. apiospermum after contact lenses were reported, and all were treated with penetrating keratoplasty. In this case, unlike the others, only medical treatment was applied. In cases with suspected fungal keratitis, medical treatment should be started without waiting for the culture result, the findings should be followed and penetrating keratoplasty should be performed in the case of no response to treatment.

Abstract Landslide early warning systems at regional scale are typically based on correlations between landslides that occurred in the past and rainfall monitoring data in order to identify trigger rainfall thresholds. Recently, the availability of large datasets of atmospheric measurements allows including additional variables, increasing the reliability of the models. However, conducting the analyses with traditional techniques can be quite complex and time-consuming. The purpose of this preliminary study is to demonstrate that machine learning techniques can be used to analyze monitoring data in order to select the most relevant variables for the triggering of shallow rainfall-induced landslides at regional scale. The models developed herein were tested in one of the alert zones defined by civil protection for the management of geo-hydrological risk in Campania region, Italy. Two data sources were used in the analysis. The atmospheric variables are derived from the ERA5-Land atmospheric reanalysis. The data on landslide events are retrieved from “FraneItalia”, a georeferenced catalog of landslides occurred in Italy developed by consulting online sources from 2010 onwards. The models developed were calibrated and validated in order to define combinations of rainfall variables and soil water content for the prediction of the occurrence of landslides. Finally, the performance of the models was assessed using statistical indicators derived from contingency matrices.

The COVID-19 pandemic, besides stimulating new integrated assistance systems 1, has altered the clinical approach in I.C.U., the management of medical information, and the methods of communication between doctors and family members. The transmission of news between the hospital and the family was ensured via a multimedia network, replacing the understanding between doctor and family established with de visu meetings. The pandemic emergency has forced healthcare professionals to adopt this new method of communication, exposing the doctor to a series of critical issues related to the transmission of sensitive data. A review of the scientific literature underlines that not many articles deal with regulations and issues related to the processing of health data in the COVID period; however, there are many challenges such as security risks, privacy, ethical and process standardization issues. We believe that this topic should be the subject of an urgent debate, deepening the matter with a specific medico-legal background.

IntroductionThere is a need to index important clinical characteristics in pediatric cardiac surgery that can be obtained early in the postoperative period and accurately predict postoperative outcomes.MethodologyA prospective cohort study was conducted in the pediatric cardiac ICU and ward on all children aged

Recently, many approaches were proposed to support human resource management in finding the best human resources for available jobs. However, existing solutions do not effectively evaluate employees’ skills, or they do only partially, neither provide mechanisms to describe subjects’ skills and desiderata. To face this issue, this paper proposes a decision model for assisting human resource management in effectively evaluating the degree of mutual satisfaction in job-employee assignments. In particular, the decision model has been devised with the following core characteristics: i) employees’ skills are modeled by combining hard skills (e.g.: academic training and competencies) and soft skills (e.g.: socio-relational experiences); ii) employees’ soft skills are self-evaluated, giving importance not so much to experiences possessed but rather how such skills have been applied over time; iii) employees and managers can self-evaluate their preferences to enable the achievement of the optimal allocation by maximizing the global mutual satisfaction iv) partial matches between characteristics and desires of both employees and jobs are measured through a set of tailored fuzzy metrics. The proposed decision model has been validated in a real case to support the allocation of newly hired employees among open job positions in a Public Administration. Results showed an adequate ability of the proposed model both to support the description of employees, skills, jobs and preferences, and to suggest the best allocation maximizing the global mutual satisfaction. Summarizing, a decision model for human resource management with innovative characteristics is proposed and used to support decisions for a real allocation problem.

Background: There is significant underutilisation of allocated health service resources when a scheduled flexible cystoscopy (FC) is cancelled because a pre-cystoscopy urinalysis (PCU) suggests “infection”, despite patients being asymptomatic for urinary tract infection (UTI). Objective: To evaluate the risk of UTI or urinary sepsis when FC is performed in asymptomatic patients with a PCU positive for leucocyte esterase and/or nitrites. Design, setting, and participants: A prospective cohort study was conducted in a high-volume UK centre recruiting all patients undergoing outpatient FC. Intervention: A protocol was developed to guide response to PCU performed prior to FC, which was performed regardless of the result, unless patients were symptomatic for UTI. All patients completed a questionnaire to identify risk factors and were followed up via a telephone survey and a review of electronic clinical records. Outcome measurements and statistical analysis: Post-FC UTI was defined as hospital admission with UTI/urinary sepsis or if patients were symptomatic for UTI with receipt of antibiotics or with positive urine culture and sensitivity. An analysis of the association was performed. Results and limitations: An initial pilot study confirmed the safety and feasibility of our protocol. Of 1996 patients, 136 (6.8%) developed a UTI by our definition, with 51 (2.6%) having a culture-proven infection. The risk was higher in patients with a positive PCU (odds ratio [OR] 1.61, 95% confidence interval [CI] = 1.07–2.40, p = 0.02), history of UTI (OR 1.72, 95% CI = 1.09–2.73, p = 0.02), or a bladder tumour on FC (OR 2.22, 95% CI = 1.27–3.90, p = 0.005). No patient with a positive PCU developed urinary sepsis. The main limitation of this study was the lack of pre-protocol control. Conclusions: We observed a clinically low and acceptable risk of UTI, with no incidence of sepsis, when FC was performed in asymptomatic patients with a PCU suggesting “infection”. Routine cancellation of these patients is unnecessary and may worsen the burden on health service resources. Patient summary: We evaluated the safety of performing flexible cystoscopy when the urine dipstick on the day suggested presence of an “infection” but the patient had no symptoms of urinary tract infection (UTI). Our study in over 2000 patients demonstrated a low incidence of UTI, and none of these patients developed sepsis. We therefore recommend that flexible cystoscopy should not be cancelled automatically on the basis of the dipstick result alone, as it might delay a time-sensitive crucial diagnosis.

Battery Energy Storage Systems (BESS) are essential for increasing distribution network performance. Appropriate location, size, and operation of BESS can improve overall network performance. The appropriately scaled and installed BESS helps meet peak energy demand, improve the advantages of integrating renewable and distributed energy sources, improve power quality control, and lower the cost of expanding or re-configuring the distribution networks. This paper investigates the feasibility of BESS for providing short-term and long-term ancillary services in power distribution grids by reviewing the developments and limitations in the last decade (2010–2022). The short-term ancillary services are reviewed for voltage support, frequency regulation, and black start. The long-term ancillary services are reviewed for peak shaving, congestion relief, and power smoothing. Reviewing short-term ancillary services provides renewable energy operators and researchers with a vast range of recent BESS-based methodologies for fast response services to distribution grids. Long-term ancillary services will provide the distributed network system operators and researchers with current BESS-based bulk-energy methods to improve network reliability and power quality and maximize revenue from renewable energy generation. The review presents a list of energy storage policies and BESS projects worldwide with a cost-benefit analysis. The challenges for deploying BESS in distribution grids recommended solutions for the implementation challenges, and future research directions are also presented.

(1) Background: Osteoarthritis (OA) is a debilitating joint disease. The are several therapies available for OA. According to current knowledge, the combination of Platelet-Rich Plasma (PRP) and Pulsed Radiofrequency (PRF) can be applied in the treatment of pain of nociceptive origin due to peripheral tissue damage. (2) Methods: We performed a narrative review identifying the articles by searching electronic databases. A retrospective analysis of patients with OA treated with PRF and PRP in “Vito Fazzi” Hospital (Lecce, Italy) was performed. (3) Results: A total of four publications on the use of PRP and PRF in degenerative joint arthritis were included in our review. In our experience, two patients with OA were treated with PRP and PRF after unsuccessful conservative treatment. Patient pain score, daily activity ability, active range of activity, and muscle strength improved after treatment. Patients reported a higher level of satisfaction. No major adverse events were reported. (4) Conclusions: The goal of the combined application of the two treatments is to make full use of the analgesic effect of PRF and the repairing effect of PRP. At present, the therapeutic potential of PRP and PRF in OA remains unmet.

Cardiomyopathies are mostly determined by genetic mutations affecting either cardiac muscle cell structure or function. Nevertheless, cardiomyopathies may also be part of complex clinical phenotypes in the spectrum of neuromuscular (NMD) or mitochondrial diseases (MD). The aim of this study is to describe the clinical, molecular, and histological characteristics of a consecutive cohort of patients with cardiomyopathy associated with NMDs or MDs referred to a tertiary cardiomyopathy clinic. Consecutive patients with a definitive diagnosis of NMDs and MDs presenting with a cardiomyopathy phenotype were described. Seven patients were identified: two patients with ACAD9 deficiency (Patient 1 carried the c.1240C>T (p.Arg414Cys) homozygous variant in ACAD9; Patient 2 carried the c.1240C>T (p.Arg414Cys) and the c.1646G>A (p.Ar549Gln) variants in ACAD9); two patients with MYH7-related myopathy (Patient 3 carried the c.1325G>A (p.Arg442His) variant in MYH7; Patient 4 carried the c.1357C>T (p.Arg453Cys) variant in MYH7); one patient with desminopathy (Patient 5 carried the c.46C>T (p.Arg16Cys) variant in DES); two patients with mitochondrial myopathy (Patient 6 carried the m.3243A>G variant in MT-TL1; Patient 7 carried the c.253G>A (p.Gly85Arg) and the c.1055C>T (p.Thr352Met) variants in MTO1). All patients underwent a comprehensive cardiovascular and neuromuscular evaluation, including muscle biopsy and genetic testing. This study described the clinical phenotype of rare NMDs and MDs presenting as cardiomyopathies. A multidisciplinary evaluation, combined with genetic testing, plays a main role in the diagnosis of these rare diseases, and provides information about clinical expectations, and guides management.

Abstract The main focus of this paper is to present the current prospects, potentials, research activities, future concerns, and applications of solar photovoltaic (PV) systems in Bangladesh. Despite the existence of several articles in the literature on solar energy prospects in Bangladesh, the diffusion of several solar PV applications throughout the country, their rapid progress analysis, and existing feasibility study outcome analysis are still unrevealed. Therefore, an endeavour has been made for the first time to condense the government and non‐government contributions to disseminating solar energy throughout the country. Twenty‐one feasibility studies at different locations of Bangladesh are reviewed and analysed, in terms of financial viability, sensitivity analysis, and greenhouse gas emissions, to foresee the prospects of solar energy in Bangladesh. Sensitivity analyses are performed, with six sensitivity variables, which reveal that the total net present cost of the solar project implementation may be increased by 20% (maximum) in the lowest solar potential area than the highest one with an average payback period of 13 years. This paper also identifies the policy gaps, classifies the barriers into eight categories, and discusses the conceivable approaches to defeat those barriers, followed by recommendations in six different aspects.

Abstract Some systems, in spite of having multiple outputs, have only one control input, which makes their control a challenge. Two novel controllers are proposed that utilise an adaptive finite‐time sliding mode control (AFSMC) scheme for a class of single‐input multiple‐output (SIMO) nonlinear systems in the presence of unknown mismatched uncertainties. To alleviate the inherent chattering phenomenon of sliding mode control, new forms of the two designed controllers are suggested by using new sliding surfaces. Not only can the proposed AFSMC scheme stabilise the system in a finite time, but also it can provide estimated data of the uncertainty upper bound in the controller. Lyapunov stability theory is used to obtain finite‐time stability analysis of the closed‐loop system. Finally, simulation results are carried out in Simulink/MATLAB for a four‐dimensional autonomous hyper‐chaotic system with mismatched uncertainties as an example of SIMO uncertain nonlinear systems to reveal the effectiveness of the proposed controllers.

BackgroundBlinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Despite its efficacy, it has also been associated with the development of potentially serious adverse events such as the cytokine release syndrome (CRS) and neurologic events. The present meta-analysis aimed to assess the safety profile of blinatumomab in terms of serious adverse events, CRS, and neurologic events (such as seizure and encephalopathy) in pediatric patients with B-cell ALL.Methods and findingsA systematic review was conducted in Pubmed up to December 10, 2021 to retain pediatric clinical trials on blinatumomab. A random effect meta-analysis approach was used. This study followed the PRISMA statement. Four out of the 255 initial references were selected, of which 2 were phase 1/2 clinical trials and 2 phase 3 clinical trials. Blinatumomab was associated with a lower risk of serious adverse events (Risk ratio RR, 0.56; 95% CI, 0.32–0.99), febrile neutropenia (RR, 0.13; 95% CI, 0.06–0.26), infection (RR, 0.40; 95% CI, 0.29–0.56), and grade ≥ 3 adverse events (RR, 0.79; 95% CI, 0.67–0.93) compared to chemotherapy. No difference in the risk of CRS (RR, 8.37; 95% CI, 0.27–260.97) and seizure (RR, 6.43; 95% CI, 0.79–53.08) was observed between groups, while for encephalopathy a higher risk was associated with blinatumomab compared to chemotherapy (RR, 8.90; 95% CI, 1.08–73.29).ConclusionOur data support the good safety profile of bliantumomab in treating pediatric patients with B-ALL.

Abstract Nowadays, transformer‐less Photovoltaic‐based grid‐connected inverters are more popular in renewable energy application due to their reduced size, cost, and high efficiency. However, the absence of galvanic isolation leads to the flow of leakage current in such system hindering personal safety, and deteriorating power quality. Therefore, this paper presents a five‐level transformer‐less inverter topology for PV applications with less component count and reduced complexity. The proposed inverter topology completely eliminates the common mode leakage current. Besides, the proposed topology has an inherent capability to boost the voltage without using any magnetic component or boosting circuit, and is based on the principle of switched/auxiliary capacitor. The proposed topology do not have any limitation of modulation index since the auxiliary capacitors are naturally balanced, hence less complex or no dedicated control scheme is required for balancing/regulating the auxiliary capacitor voltages. In order to verify the performance of the proposed inverter topology, a laboratory prototype is developed which confirms the operation, and feasibility of the proposed inverter. Results depicting the output voltage, load current, and voltage across the auxiliary capacitor are presented for various operating conditions. Further, simulation results depicting the leakage current in the proposed, H5, and H6 topologies are included. Finally, a quantitative comparison study is done, highlighting the benefits of the proposed inverter topology regarding boosted voltage, elimination of leakage current, and reduced component count.

Abstract Background Gram-negative bacteria are an uncommon etiology of spontaneous community-acquired adult meningitis and meningoencephalitis. Escherichia coli is a Gram-negative bacterium that is normally present in the intestinal microbial pool. Some Escherichia coli strains can cause diseases in humans and animals, with both intestinal and extraintestinal manifestations (extraintestinal pathogenic Escherichia coli) such as urinary tract infections, bacteremia with sepsis, and, more rarely, meningitis. Meningitis continues to be an important cause of mortality throughout the world, despite progress in antimicrobial chemotherapy and supportive therapy. The mortality rate fluctuates between 15% and 40%, and about 50% of the survivors report neurological sequelae. The majority of Escherichia coli meningitis cases develop as a result of hematogenous spread, with higher degrees of bacteremia also being related to worse prognosis. Cases presenting with impaired consciousness (that is, coma) are also reported to have poorer outcomes. Case presentation We describe the case of a 48-year-old caucasian woman with meningoencephalitis, with a marked alteration of consciousness on admission, and septic shock secondary to pyelonephritis caused by Escherichia coli, treated with targeted antimicrobial therapy and immunoglobulin-M-enriched immunoglobulin (Pentaglobin) preparation as adjuvant therapy. Conclusion Despite the dramatic presentation of the patient on admission, the conflicting data on the use of immunoglobulins in septic shock, and the lack of evidence regarding their use in adult Escherichia coli meningoencephalitis, we obtained a remarkable improvement of her clinical condition, accompanied by partial resolution of her neurological deficits.

Abstract This paper examines a multilevel transformer‐less grid‐tied inverter topology is proposed for PV applications. Nowadays, transformer‐less inverters are more desirous due to their small filter size, cheaper and higher efficiency. However, the removal of transformer results in the existence of leakage current due to absence of galvanic isolation. The flow of leakage current is the cause of personal safety and deteriorating power quality. A transformer‐less inverter topology is proposed which is able to solve the leakage current issue. Besides, it has the ability to generate the boosted voltage without the need of magnetic component or boosting circuit. It works on the principle of flying/switched capacitor which are able to naturally balance the voltage. Hence, it does not have the limitation of modulation index and no need of complex control scheme to balance or regulate the voltage across an auxiliary capacitor. The performance of the proposed topology is verified by implementing a laboratory prototype which validates the operation and performance of the proposed topology. Results depicting the output voltage, load current and voltage across the auxiliary capacitor are presented for various operating conditions. Moreover, a comprehensive comparison is done, in terms of component count, level and boosting ability of output voltage with leakage current condition.

Microbial colonization of surfaces is a sanitary and industrial issue for many applications, leading to product contamination and human infections. When microorganisms closely interact with a surface, they start to produce an exo-polysaccaridic matrix to adhere to and protect themselves from adverse environmental conditions. This type of structure is called a biofilm. The aim of our work is to investigate novel technologies able to prevent biofilm formation by surface coatings. We coated glass surfaces with melanin-ZnO2, melanin-TiO2, and TiO2 hybrid nanoparticles. The functionalization was performed using cold plasma to activate glass-substrate-coated surfaces, that were characterized by performing water and soybean oil wetting tests. A quantitative characterization of the antibiofilm properties was done using Pseudomonas fluorescens AR 11 as a model organism. Biofilm morphologies were observed using confocal laser scanning microscopy and image analysis techniques were used to obtain quantitative morphological parameters. The results highlight the efficacy of the proposed surface coating to prevent biofilm formation. Melanin-TiO2 proved to be the most efficient among the particles investigated. Our results can be a valuable support for future implementation of the technique proposed here in an extended range of applications that may include further testing on other strains and other support materials.

Duchenne Muscular Dystrophy (DMD) is a very severe X-linked dystrophinopathy. It is due to a mutation in the DMD gene and causes muscular degeneration in conjunction with several secondary co-morbidities, such cardiomyopathy and respiratory failure. DMD is characterized by a chronic inflammatory state, and corticosteroids represent the main therapy for these patients. To contradict drug-related side effects, there is need for novel and more safe therapeutic strategies. Macrophages are immune cells stringently involved in both physiological and pathological inflammatory processes. They express the CB2 receptor, one of the main elements of the endocannabinoid system, and have been proposed as an anti-inflammatory target in several inflammatory and immune diseases. We observed a lower expression of the CB2 receptor in DMD-associated macrophages, hypothesizing its involvement in the pathogenesis of this pathology. Therefore, we analyzed the effect of JWH-133, a CB2 receptor selective agonist, on DMD-associated primary macrophages. Our study describes the beneficial effect of JWH-133 in counteracting inflammation by inhibiting pro-inflammatory cytokines release and by directing macrophages’ phenotype toward the M2 anti-inflammatory one.

This study was conducted to examine the effect of lending rates, net performance loans, interest income on return on asset (ROA). The population in this study is a finance company listed on the Stock Exchange in 2015-2019. The sample was determined by a porposive sampling method – 65 samples. The data used are secondary data obtained from the IDX gallery. The hypothesis in this study was tested using path analysis to determine the direct and indirect effects of the independent variables used on the dependent variable. The results of this study indicate that partially lending rates have a significant influence on interest income, while credit risk which is proxied by Net Performance Loan (NPL) has no significant effect on Interest Income. Credit Interest Rates do not have an effect on Return On Assets (ROA), while Credit Risk which is proxied by Net Performance Loan (NPL) has a significant negative effect on Return On Assets (ROA) and Interest Income has a significant positive effect on Return On Asset (ROA). The indirect relationship between lending rates and credit risk with Return On Assets (ROA) by using interest income as an intervening get significant results.

Most of the architectural and urban considerations conceived during and after the COVID pandemic seem to allude to the invention of new development paradigms, alternative to the idea of global city and metropolis. Is this answer really possible or, once again, a gap between architecture and reality that is difficult to bridge is being generated? In the following article, we try to tackle the theme of the post-COVID city starting from the existing one. In particular, starting from the suburbs; neighbourhoods built on the idea of standards that arises from the architecture-health relationship. The design of both housing and public spaces in these areas has often generated abstract places that make social networks difficult to being realized.

Background and AimThe novel coronavirus disease 2019 remains challenging. A large number of hospitalized patients are at a high risk of developing AKI. For this reason, we conducted a nationwide survey to assess the incidence and management of AKI in critically ill patients affected by the SARS-CoV-2 infection.MethodsThis is a multicenter, observational, nationwide online survey, involving the Italian Society of Nephrology and the critical care units in Italy, developed in partnership between the scientific societies such as SIN and SIAARTI. Invitations to participate were distributed through emails and social networks. Data were collected for a period of 1 week during the COVID-19 pandemic.ResultsA total of 141 responses were collected in the SIN–SIAARTI survey: 54.6% from intensivists and 44.6% from nephrologists. About 19,000 cases of COVID-19 infection have been recorded in hospitalized patients; among these cases, 7.3% had a confirmed acute kidney injury (AKI), of which 82.2% were managed in ICUs. Only 43% of clinicians routinely used the international KDIGO criteria. Renal replacement therapy (RRT) was performed in 628 patients with continuous techniques used most frequently, and oliguria was the most common indication (74.05%). Early initiation was preferred, and RRT was contraindicated in the case of therapeutic withdrawal or in the presence of severe comorbidities or hemodynamic instability. Regional anticoagulation with citrate was the most common choice. About 41.04% of the interviewed physicians never used extracorporeal blood purification therapies (EBPTs) for inflammatory cytokine or endotoxin removal. Moreover, 4.33% of interviewed clinicians used these techniques only in the presence of AKI, whereas 24.63% adopted them even in the absence of AKI. Nephrologists made more use of EBPT, especially in the presence of AKI. HVHF was never used in 58.54% of respondents, but HCO membranes and adsorbents were used in more than 50% of cases.ConclusionThis joint SIN–SIAARTI survey at the Italian Society of Nephrology and the critical care units in Italy showed that, during the COVID-19 pandemic, there was an underestimation of AKI based on the “non-use” of common diagnostic criteria, especially by intensivists. Similarly, the use of specific types of RRT and, in particular, blood purification therapies for immune modulation and organ support strongly differed between centers, suggesting the need for the development of standardized clinical guidelines.

This paper presents the results of PhD research aimed at identifying alternative models for designing collective housing, capable of moving the principles on which the house is built closer to the unstable and changing phenomena of society and the complex and contradictory characters of reality, reviewing both the themes and the methods for designing, building and managing architectural artefacts. In this perspective, computational design and digital fabrication tools are seen as possible means to manage complexity from a programmatic point of view rather than a formal one, evaluating the hypothesis that the residential building can be configured as a changing system that has adaptive and evolutionary properties.

Abstract Introduction Low back pain (LBP) is a common problem, and facet joint pain is responsible for 15–45% of cases. Treatment is multidisciplinary, and when conservative measures are not sufficient, radiofrequency (RF) is often used. It allows the interruption of nociceptive input, producing a heat lesion in a continuous or pulsed mode. Methods Medical records of 60 patients who underwent pulsed RF denervation were examined. The standard procedure provided follow-up of pain intensity. Numerical rating scale (NRS) and Douleur Neuropathique en 4 Questions (DN4) were recorded before treatment, and 15 and 40 days, and 6 months after treatment. Oswestry Disability Index (ODI) and patient satisfaction were also recorded. Successful treatment was defined as more than a 50% reduction in the NRS scores at 6 months compared with pretreatment scores. Results Scores on the NRS and DN4 were statistically different over time (p

Abstract Objective The purpose of this review is to evaluate the use and effectiveness of the local administration of tramadol in reducing post-operative pain during surgical interventions. Methods The PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases will be searched for this review. This systematic review will include studies evaluating the clinical efficacy of the local infiltration of tramadol, with no study design restrictions. Only studies that present clear descriptions of local tramadol administration are published in peer-reviewed journals in the English, Italian, Spanish, French, Portuguese or German language and are published in full will be taken into consideration. A meta-analysis will be performed when there is sufficient clinical homogeneity among the retrieved studies, and only randomized controlled studies and quasi-randomized controlled studies will be included. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess the certainty in the evidence. If a quantitative analysis cannot be conducted, a qualitative description of the results of the retrieved studies will be provided. Results A high-quality synthesis of the current evidence on the local administration of tramadol for managing post-surgical pain will be illustrated using subjective reports and objective measures of performance. The primary outcomes will include the magnitude of post-operative pain intensity improvement, with improvement being as defined by a reduction by at least 2 points in the visual analogue scale (VAS) score or numerical rating scale (NRS) score. The secondary outcomes will be the magnitude of reduction in tramadol rescue doses and in other analgesic drug doses. Conclusion This protocol will present evidence on the efficacy of tramadol in relieving post-surgical pain. Systemic review registration PROSPERO CRD42018087381

Abstract Context Pain is commonly experienced among patients after surgical procedures. Clinical pain management after surgery is far from being successful. Patients may control postoperative pain by self-administration of intravenous opioids using devices designed for this purpose (patient-controlled analgesia or PCA). PCA devices have been developed including the sufentanil sublingual tablet system (SSTS). A systematic review of the use of SSTS for postoperative pain is needed to identify an alternative method of pain management. Objectives To systematically review literature to establish the efficacy and the safety of PCA with SSTS used in the treatment of moderate-to-severe acute post-operative pain in a hospital setting. Methods Embase, MEDLINE, Google Scholar, and Cochrane Central Trials Register were systematically searched in December 2019 for studies examining SSTS for pain in adult after surgical procedures. The methodological quality of the studies and their results were appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively. Results Sixteen studies evaluating SSTS were included for a total of 2311 patients. All participants in the SSTS group reported NRS ≤ 4 within 24 h after surgery. Patient satisfaction was high, with a minimum of 70% satisfaction among patients treated with SSTS. The most common adverse events (AEs) overall for SSTS 15 and 30 mcg were nausea, vomiting, and headache. AEs observed in the studies were generally consistent with those associated with opioids and the postsurgical setting. Conclusions SSTS is an important system for the management of moderate-to-severe acute pain in a hospital setting. SSTS is well tolerated, with no unexpected adverse events (AEs) and no clinically meaningful vital sign changes. These data confirm the safety and tolerability of the SSTS. Successful pain management resulted in a high level of acceptance of the SSTS by patients with high satisfaction for the method of pain control.

Objectives: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). Methods: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. Results: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52–73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24–8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69–13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17–0.88; P = 0.024) was associated with use of colistin monotherapy. Conclusion: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Childhood cancer survivors (CCS) are predisposed to the onset of osteoporosis (OP). It is known that iron overload induces osteoclasts (OCs) overactivity and that the iron chelator Deferasirox (DFX) can counteract it. The Cannabinoid Receptor type 2 (CB2) and the transient receptor potential vanilloid type-1 (TRPV1) are potential therapeutic targets for OP. In this study we isolated OCs from peripheral blood of 20 CCS and investigated osteoclast biomarkers expression and iron metabolism evaluating iron release by OCs and the expression of several molecules involved in its regulation. Moreover, we analyzed the effects of CB2 and TRPV1 stimulation in combination with DFX on osteoclast activity and iron metabolism. We observed, for the first time, an osteoclast hyperactivation in CCS suggesting a role for iron in its development. Moreover, we confirmed the well-known role of CB2 and TRPV1 receptors in bone metabolism, suggesting the receptors as possible key biomarkers of bone damage. Moreover, we demonstrated a promising synergism between pharmacological compounds, stimulating CB2 or inhibiting/desensitizing TRPV1 and DFX, in counteracting osteoclast overactivity in CCS to improve their quality of life.

In this paper, a novel adaptive finite-time sliding mode backstepping (AFSMBS) control scheme is suggested to control a type of high-order double-integrator systems with mismatched disturbances and uncertainties. A robust sliding mode backstepping control method, adaptive control method, and finite-time stability notion are incorporated to provide a better tracking performance over applying them individually and to use their benefits simultaneously. The concept of a sliding mode is used to define a new form of a backstepping controller. The adaptive control method is utilized to adaptively estimate the upper bounds of the disturbances and uncertainties and the estimated data are used in the control low. The notion of the finite-time stability is incorporated with the suggested control scheme to ensure the system’s convergence within a finite time. The stability proof is obtained for the closed-loop system in a finite time utilizing the Lyapunov stability theorem. Simulation results are obtained for an example of a remotely operated vehicle (ROV) with three degrees of freedom (3-DOF) to demonstrate the efficacy of the suggested control approach.

Abstract Introduction Elevation in body temperature within the first 24 hours of ischemic stroke is fairly common and known to be associated with worse outcomes. Only after thoroughly ruling out infection and the noninfectious etiologies and in the appropriate clinical setting should the diagnosis of central fever be made. Acetaminophen and nonsteroidal anti-inflammatory drugs are typical therapeutic options. External cooling is frequently used when pharmacologic interventions are inadequate. However, reports have suggested that neurogenic fevers are somewhat resistant to traditional pharmacologic therapies. Case presentation We describe a case of a Caucasian patient with central fever after ischemic stroke not responsive to acetaminophen administration and external cooling. After an initial bolus of diclofenac sodium (0.2 mg/kg in 100 ml of saline solution for 30 minutes), a continuous infusion (75 mg in 50 ml of saline solution) was started. After 5 days of treatment, the patient’s body temperature was below 37.5 °C, and the diclofenac sodium infusion was stopped. Conclusions We observed that a low-dose diclofenac sodium infusion was effective in treating fever without systemic side effects. This treatment may be suggested as an alternative to conventional antipyretic drugs, but additional clinical trials are required.

The following work is part of a research aimed at investigate how to involve parametric software in the design of contemporary dwelling, in a process of urban regeneration which starts from the transformation of residential buildings of the last century in order to provide new forms of living able to accommodate different categories of users and respond directly to their needs.In particular, this paper intends to present an application, developed starting from the study of Tour Bois Le Prêtre transformation project designed by Lacaton & Vassal, which aims translating the main design choices in the parameters of an algorithm able to reproduce the logics of the intervention.The objective of the research is to focus on a set of parameters to be used for the development of a software useful for dwelling design, in which the project is direct result of the analysis of specific conditions and users needs.

Mung bean (Vigna radiata L.) sprouts are increasingly consumed and have become part of a healthy diet. The sprouts are composed of proteins, carbohydrates, and biochemical compounds. During germination, the phytochemical compounds are significantly elevated, especially under stress conditions such as salinity, drought, extreme temperature, and illumination. The present study examined the effects of light and germination time on the bioactive compounds in mung bean sprout extracts. Mung bean seeds were sprouted under different light exposure conditions, and the phytochemical composition and antioxidant activity of sprout extracts were determined compared to seeds. The results show that tryptophan sharply decreased during germination. On the contrary, melatonin, polyphenols, and total phenolic content (TPC) were elevated with increased germination time, correlated with increased antioxidant activity. Sprouts germinated in the dark presented higher levels of melatonin and TPC compared with those germinated under 12 h light exposure (3.6- and 1.5-fold, respectively). In conclusion, germination can enhance valuable phytochemicals and antioxidant activity of mung bean sprouts. Mung bean sprouts may be a good alternative functional food for promoting human health.

Background: Hospital wastewater is a major source of antimicrobial resistance (AMR) outflow into the environment. This study uses metagenomics to study how hospital clinical activity impacts antimicrobial resistance genes (ARGs) abundances in hospital wastewater.Methods: Sewage was collected over a 24-h period from multiple wastewater collection points (CPs) representing different specialties within a tertiary hospital site and simultaneously from community sewage works. High throughput shotgun sequencing was performed using Illumina HiSeq4000. ARG abundances were correlated to hospital antimicrobial usage (AMU), data on clinical activity and resistance prevalence in clinical isolates.Results: Microbiota and ARG composition varied between CPs and overall ARG abundance was higher in hospital wastewater than in community influent. ARG and microbiota compositions were correlated (Procrustes analysis, p=0.014). Total antimicrobial usage was not associated with higher ARG abundance in wastewater. However, there was a small positive association between resistance genes and antimicrobial usage matched to ARG phenotype (IRR 1.11, CI 1.06–1.16, p

This comprehensive review of the recently published literature offers an overview of a very topical and complex healthcare problem: secondary peritonitis from multidrug-resistant pathogens, especially carbapenem-resistant Enterobacterales (CRE). Spontaneous secondary peritonitis and postsurgical secondary peritonitis are among the major causes of community- and healthcare- acquired sepsis, respectively. A large number of patients enter ICUs with a diagnosis of secondary peritonitis, and a high number of them reveal infection by CRE, P. aeruginosa or A. baumannii. For this reason, we conceived the idea to create a synthetic report on this topic including updated epidemiology data, a description of CRE resistance patterns, current strategies of antimicrobial treatment, and future perspectives. From this update it is clear that antimicrobial stewardship and precision medicine are becoming essential to fight the emergence of antimicrobial resistance and that even if there are new drugs effective against CRE causing secondary peritonitis, these drugs have to be used carefully especially in empirical therapy.

(1) Background: The aim of this study was to assess the clinical and microbiological characteristics of multidrug-resistant infections in a neuromuscular semi-intensive/sub-intensive care unit; (2) Methods: Retrospective analysis on data from 18 patients with NMD with proven MDRO/XDRO colonisation/infection from August 2021 to March 2022 was carried out; (3) Results: Ten patients were males (55.6%), with a median age of 54 years, and there were fourteen patients (77.8%) with amyotrophic lateral sclerosis. All patients had at least one invasive device. Ten (55.6%) patients developed MDRO/XDRO infection (with a median time of 24 days) while six (33.3%) were colonised. The Charlson comorbidity index was >2 in both groups but higher in the infected compared with the colonised (4.5 vs. 3). Infected patients were mostly females (seven patients) with a median age of 62 years. The most common pathogens were Acinetobacter baumannii and Pseudomonas aeruginosa, infecting four (28.6%) patients each. Of eighteen infectious episodes, nine were pneumonia (hospital-acquired in seven cases). Colistin was the most commonly active antibiotic while carbapenems were largely inactive. Eradication of infection occurred in seven infectious episodes (38.9%). None of those with infection died; (4) Conclusions: MDRO/XDRO infections are common in patients with neuromuscular diseases, with carbapenem-resistant non-fermenting Gram-negative bacilli prevailing. These infections were numerically associated with the female sex, greater age, and comorbidities. Both eradication and infection-related mortality appeared low. We highlight the importance of infection prevention in this vulnerable population.

Nature mimicking implies the design of nanostructured materials, which can be assembled into a hierarchical structure, thus outperforming the features of the neat components because of their multiple length scale organization. This approach can be effectively exploited for the design of advanced photocatalysts with superior catalytic activity for energy and environment applications with considerable development in the recent six years. In this context, we propose a review on the state of the art for hierarchical photocatalyst production. Particularly, different synthesis strategies are presented, including template-free structuring, and organic, inorganic, and hybrid templating. Furthermore, emerging approaches based on hybrid and bio-waste templating are also highlighted. Finally, a critical comparison among available methods is carried out based on the envisaged application.

Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern the medical community. Molecular and cellular target therapies, together with immunotherapy, are promising strategies to overcome these concerns. Cannabinoids, enzymes involved in their metabolism, and cannabinoid receptors type 1 (CB1) and type 2 (CB2) constitute the endocannabinoid system, involved in inflammation, immune response, and cancer. CB2 receptor stimulation exerts anti-proliferative and anti-invasive effects in many tumors. In this study, we evaluated the effects of CB2 stimulation on B-ALL cell lines, SUP-B15, by RNA sequencing, Western blotting, and ELISA. We observe a lower expression of CB2 in SUP-B15 cells compared to lymphocytes from healthy subjects, hypothesizing its involvement in B-ALL pathogenesis. CB2 stimulation reduces the expression of CD9, SEC61G, TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways. Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed.

Heparin plays multiple biological roles depending on the availability of active sites strongly influenced by the conformation and the structure of polysaccharide chains. Combining different components at the molecular scale offers an extraordinary chance to easily tune the structural organization of heparin required for exploring new potential applications. In fact, the combination of different material types leads to challenges that cannot be achieved by each single component. In this study, hybrid heparin/silica nanoparticles were synthesized, and the role of silica as a templating agent for heparin supramolecular organization was investigated. The effect of synthesis parameters on particles compositions was deeply investigated by Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA). Transmission Electron Microscopy (TEM) reveals a different supramolecular organization of both components, leading to amazing organic-inorganic nanoparticles with different behavior in drug encapsulation and release. Furthermore, favorable biocompatibility for healthy human dermal fibroblasts (HDF) and tumor HS578T cells has been assessed, and a different biological behavior was observed, ascribed to different surface charge and morphology of synthesized nanoparticles.

Poikiloderma with neutropenia (PN) is a very rare genetic disorder mainly characterized by poikiloderma and congenital neutropenia, which explains the recurrence of respiratory infections and risk of developing bronchiectasis. Patients are also prone to develop hematological and skin cancers. Here, we present the case of a patient, the only child of apparently unrelated Serbian parents, affected by PN resulting from the homozygous mutation NM_024598.3:c.243G>A (p.Trp81Ter) of USB1; early onset of poikiloderma (1 year of age) was associated with cutaneous mastocytosis. We also provide a review of the literature on this uncommon condition with a focus on dermatological findings.