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Abstract Host-directed therapies aiming to strengthen the body’s immune system, represent an underexplored opportunity to improve treatment of tuberculosis (TB). We have previously shown in Mycobacterium tuberculosis (Mtb)-infection models and clinical trials that treatment with the histone deacetylase (HDAC) inhibitor, phenylbutyrate (PBA), can restore Mtb-induced impairment of antimicrobial responses and improve clinical outcomes in pulmonary TB. In this study, we evaluated the efficacy of different groups of HDAC inhibitors to reduce Mtb growth in human immune cells. A panel of 21 selected HDAC inhibitors with different specificities that are known to modulate infection or inflammation was tested using high-content live-cell imaging and analysis. Monocyte-derived macrophages or bulk peripheral blood cells (PBMCs) were infected with the green fluorescent protein (GFP)-expressing Mtb strains H37Ra or H37Rv and treated with HDAC inhibitors in the micromolar range in parallel with a combination of the first-line antibiotics, rifampicin, and isoniazid. Host cell viability in HDAC inhibitor treated cell cultures was monitored with Cytotox-red. Seven HDAC inhibitors were identified that reduced Mtb growth in macrophages > 45–75% compared to average 40% for PBA. The most effective compounds were inhibitors of the class III HDAC proteins, the sirtuins. While these compounds may exhibit their effects by improving macrophage function, one of the sirtuin inhibitors, tenovin, was also highly effective in extracellular killing of Mtb bacilli. Antimicrobial synergy testing using checkerboard assays revealed additive effects between selected sirtuin inhibitors and subinhibitory concentrations of rifampicin or isoniazid. A customized macrophage RNA array including 23 genes associated with cytokines, chemokines and inflammation, suggested that Mtb-infected macrophages are differentially modulated by the sirtuin inhibitors as compared to PBA. Altogether, these results demonstrated that sirtuin inhibitors may be further explored as promising host-directed compounds to support immune functions and reduce intracellular growth of Mtb in human cells.

Nature is increasingly recognized for its potential to address societal challenges in cities, through the delivery of ecosystem services (ES). However, large-scale assessments quantifying this potential are rare. In this study, we modelled five ES (local temperature regulation, flood control, global climate regulation, habitat maintenance, and human interaction with nature) across 708 European urban areas. Using a supply-demand approach, we assessed ES delivery: the extent to which ES supply was sufficient to meet the corresponding societal demands. We found that ES delivery varied both spatially and between ES. On average, nearly 50% of the demand was fulfilled, with the highest values for habitat maintenance (81 ± 15%; mean ± SD), flood control (65 ± 13%), and human interaction with nature (59 ± 15%) and much lower values for local temperature regulation (23 ± 28%) and global climate regulation (16 ± 28%). We further found positive pairwise correlations between all ES (Spearman’s ρ from 0.15 to 0.65), with the strongest correlation between habitat maintenance and global climate regulation. Variation in ES delivery across the urban areas was mainly related to differences in the share of green space and the size of the urban areas, whereby ES delivery was positively related to both. Our broad-scale comparative assessment can serve as a starting point for more sophisticated model-based assessments quantifying the full potential of urban nature to meet societal demands across large areas, for example by including a broader set of ES and accounting for city-specific demands.

SUMMARY: Introduction: Scarless latissimus dorsi (LD) flap is a breast reconstruction technique, which allow to cover the lower pole of implant with a large portion of the LD muscle without skin paddle; it represents a surgical solution that transpose vascularized tissue avoiding the failure of breast reconstruction, following necrosis of mastectomy skin flaps. Material and Method: A retrospective review of patients undergoing immediate or delayed breast reconstruction using scarless LD flap reconstructions was performed. Clinical data obtained from follow-up visits were recorded. To evaluate breast shape contentment and patient satisfaction, the patients were requested to answer the Breast-Q, version 2.0 reduction module postoperative scales questionnaire at the 12-month follow-up. Results: We performed 19 scarless LD flap reconstructions between September 2019 and June 2022. The surgical time in average (considering minutes ± SD) was 130 (±15) minutes. The aesthetic assessment was good/excellent in 83% of patients. This was statistically significant (P=0.0). Conclusions: The scarless LD flap reconstruction is a valid and reliable solution, which has the advantage to reduce the risk of exposed prosthesis if native skin necrosis occurs.

Abstract The use of tobacco cigarettes produces locomotor muscle weakness and fatigue intolerance. Also, smokers and chronic obstructive pulmonary disease patients have a greater incidence of muscle injury and a deficient myogenic response. However, the effects of smoke exposure on the recovery from eccentric exercise‐induced muscle injuries are unknown. Mice were exposed daily to cigarette smoke (CS) or room air (Air) for 4 months; the anterior crural muscles from one limb were injured by a lengthening contractions protocol (LCP) and recovered for 7 days. Lung compliance was greater, and body weights were lower, in CS‐exposed than in the Air group. In LCP‐subjected limbs, CS exposure lowered tibialis anterior myofiber cross‐sectional area, decreased the size of centrally nucleated myofibers, and decreased extensor digitorum longus (EDL) mass, but did not affect EDL force from both limbs. CS exposure upregulated the mRNA levels of several myogenic (Pax7, Myf5, nNOS) genes in the EDL. The combination of CS exposure and LCP decreased Myf5 and nNOS mRNA levels and exacerbated pro‐inflammatory mRNA levels. These data suggest that smoke exposure leads to an excessive pro‐inflammatory response in regenerating muscle that is associated with a lower muscle mass recovery from a type of injury that often occurs during strenuous exercise.

Objectives: Post-stroke fatigue (PSF) is an experience characterized by an early feeling of exhaustion with fatigue, a lack of energy, and difficulty in exertion, both motor and cognitive. To counteract fatigue and limit its effects on activities of daily living, the use of vitamins and minerals is known in addition to the pharmacological approach. However, few studies have evaluated the effect of vitamin and mineral supplementation on fatigue management. SiderAL® Med is a food for special medical purposes with a complete formulation containing vitamins, sucrosomal minerals, copper and algal calcium. The aim of the study is to evaluate whether nutritional supplementation with SiderAL® Med improves the symptom of fatigue and motor and cognitive function in stroke patients. Design: This is a pilot, randomized study with a control group. Setting: Post-Acute Rehabilitation Unit of the Fondazione Policlinico “A. Gemelli” IRCCS. Participants: Twenty-four patients with stroke outcomes, admitted to rehabilitation, were recruited and randomized into the experimental group (Sid-G) and the control group (CG). Intervention: The Sid-G patients, in association with the pharmacological and rehabilitation therapy foreseen during hospitalization, took SiderAL® Med, one sachet per day for 8 weeks, while the CG patients underwent only the pharmacological and rehabilitation therapy foreseen in the daily routine. Measurements: All patients were assessed at baseline (T0), after 4 weeks (T1), after 8 weeks (T2) and after 12 weeks (T3) for motor and cognitive fatigue, balance, walking, functional capacity, cognitive performance, autonomy, quality of life and body composition. Results: Both Sid-G and CG patients showed significant improvement on most rating scales between T0-T1-T2-T3 (p = 0.0001). When comparing the two groups, a statistically significant difference emerged in favor of Sid-G with regard to motor fatigue (p = 0.007), cognitive fatigue (p = 0.009) and total fatigue (p = 0.034); balance (p < 0.001), functional capacity (p < 0.001); cognitive performance (p = 0.004); bone mineral content (p = 0.005), lean mass (p = 0.005), total mass (p < 0.001) and percentage of fat mass (p = 0.039). Conclusion: Nutritional supplementation with SiderAL® Med, in concert with intensive rehabilitation treatment, appears to be effective in managing fatigue and improving motor and cognitive performance and body composition, representing a valuable tool to associate with rehabilitation treatment in stroke patients.

ABSTRACT: Background: An increasing number of patients are using online information regarding medical issues; however, the Internet is not subject to content ratings or filters. Unreliable information found on the web can heavily influence patients to the extent that it can lead to wrong decisions in the choice of treatment. In our daily experience we meet more informed patients and given the increasing use of polyurethane-coated implants in breast reconstruction in Europe, we wondered about the level of information available online. Our study aims to assess the quality of information available online on breast reconstruction with polyurethane-coated implants. Materials and Methods: Assuming that the most used search engines are Google and Yahoo, we used a search strategy to identify online information regarding prepectoral breast reconstruction with polyurethane-coated implants. The selected websites were divided into 5 groups (practitioners, hospitals, healthcare portals, professional societies, and encyclopedias), and the quality of information was assessed by using an expanded version of the Ensuring Quality Information for Patients (EQIP) tool, which is a checklist applicable to all existing types of information. Results: Fifty-six websites were selected and were categorized into 5 groups: 17 practitioners, 9 hospitals, 13 healthcare portals, 7 professional societies, 10 encyclopedias. The average score was 17 points (range: 12 – 25). We found 13 reliable websites with a score higher than 20 using the expanded version of the EQIP tool, whereas 43 were deemed unreliable, as they scored lower. Conclusion: Proper communication between surgeon and patient is crucial in the therapeutic choice, as the available online information presently is scarce and can lead to wrong decisions if not properly verified.

Nanofiltration (NF) has been used as the default sulfate removal process in platforms to treat seawater for water flooding. Seawater is generally pretreated by chlorination and cartridge filters to reduce fouling of the membranes; however, this pretreatment is insufficient to provide water quality high enough to maintain the productivity of the NF membranes. In this study, the performances of two different pretreatment routes were evaluated. Microfiltration (MF) was evaluated as a replacement for cartridge filters, and the advanced oxidation process UV/H2O2 was evaluated as an additional stage of pretreatment upstream of the cartridge filters. The permeability of the NF membranes after 12 h of seawater sulfate removal in a bench system was 4.4 L·h−1·m−2·bar−1 when the UV/H2O2 process was adopted as the pretreatment and 2.9 L·h−1·m−2·bar−1 when the MF process was adopted, compared to 1.6 L·h−1·m−2·bar−1 achieved for the pretreatment with the cartridge filter alone. These results indicate that NF membrane fouling was significantly higher when seawater was pretreated only by the cartridge filter in comparison to both proposed pretreatments. An economic analysis showed that both systems are economically viable and can potentially reduce the operational costs of the NF sulfate removal process on platforms. HIGHLIGHTS Comprehensive analysis of cartridge filters, microfiltration, and advanced oxidation process UV/H2O2 pretreatments for seawater desalination by nanofiltration, the last which has not been well stated in the literature.; UV/H2O2 impact on reducing seawater fouling in membranes.; Economic analysis showing the impact on operational costs of the pretreatments on the nanofiltration sulfate removal process in offshore platforms.;