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Introduction: Neuropathic pain is defined as pain induced by a lesion or disease of the somatosensory nervous system. Pharmacological and non-pharmacological treatments are frequently employed. In the current clinical investigation, we assessed the effects of sex on the safety and effectiveness of medications used to treat neuropathic pain. Methods: We conducted a prospective analysis between 1 February 2021 and 20 April 2024, involving patients with neuropathic pain referred to the Ambulatory of Pain Medicine of "Renato Dulbecco" University Hospital in Catanzaro (Calabria, Italy). Patients over 18 years old with signs of neuropathic pain (Douleur Neuropathique en 4 questionnaire ≥ 4) were included. Exclusion criteria comprised patients with Alzheimer's disease; patients with nociplastic or nociceptive pain; and patients with neoplasms. Patients with fewer than two accesses to ambulatory care were excluded, as were those who did not sign the informed consent. Clinical data were collected from each enrolled patient and subsequently analyzed, considering clinical outcomes. Sex and gender differences in efficacy were estimated using multivariate linear modeling and propensity-score matching. Results: During the study, 531 patients were screened, and 174 were enrolled (33.5%, mean age 61.5 ± 13.1; 64 males and 110 females, mean age 60.6 ± 13.4 and 61.96 ± 13.0) in accordance with the inclusion and exclusion criteria. Only minor differences in treatment prescription were observed based on age, body mass index, and comorbidities. Smoking, sex, educational level, and body mass index did not induce a significant change in pain perception. Males required slightly higher, though not significantly, doses of drugs for pain control than females. The treatment was not significantly more effective for females than for males. Females did not exhibit a significantly lower number of adverse drug reactions compared to males. Conclusions: The current study found that there are no appreciable differences between the sexes when it comes to the treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

Escin, extracted from horse chestnut (Aesculus hippocastanum) has anti-edema and anti-inflammatory effects. It is used to treat several clinical conditions, including venous insufficiency, pain, inflammation, and edema. Considering escin's pharmacodynamic, the inhibition of the bradykinin pathway represents a particular effect, decreasing the local edema and conferring an advantage in comparison to other compounds. In this narrative review, we described the effects of escin considering its effects on bradykinin pathway. [ABSTRACT FROM AUTHOR]

Liver transplant patients are frail subjects due to lifelong therapy with immunosuppressants. In these patients, comorbidity and polytherapy increase the risk of adverse drug reactions. In this study, we report the development of hyponatremia, probably related to pantoprazole in a liver transplant patient. Sertraline dismission and treatment with sodium chloride did not improve clinical symptoms and laboratory levels. Pantoprazole dismission induced an improvement in clinical symptoms and the normalization of sodium levels. A five-month follow-up revealed the absence of clinical symptoms and normal serum sodium levels. [ABSTRACT FROM AUTHOR]

Introduction: Drug treatment can be related to the development of adverse drug reactions (ADRs). Aim: In this paper, we evaluated ADRs in patients admitted to the Ambulatory of Pain Medicine of the University Hospital Renato Dulbecco in Catanzaro. Methods: We conducted a prospective analysis between 1 February 2021 and 20 July 2023 on patients with neuropathic pain referred to the Ambulatory of Pain Medicine of "Renato Dulbecco" University Hospital in Catanzaro (Calabria, Italy). Patients aged >18 years with clinical signs of neurologic pain and a score upon completing the Douleur Neuropathique en 4 Questions (DN4) questionnaire of ≥4 were included. The association between drugs and ADR or between drugs and drug–drug-interactions (DDIs) was evaluated using Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. Results: During the study period, we analyzed 2370 patients referred to the ambulatory of pain medicine. After the evaluation of inclusion and exclusion criteria, 33.5% of patients were enrolled. All patients presented at least one comorbidity and daily used a mean of five drugs (range 3–11). Using the Naranjo score, the development of ADRs was documented in 112 patients (score 6). Using parametric and non-parametric statistical analysis, we failed to report an association between ADR and dosage or ADR and patient characteristics. Conclusion: Our results show the development of ADRs in 18% of patients with neuropathic pain. This low percentage of drug interaction could be a limitation in real life because it is probably due to the site of the study and the appropriate prescription of drugs. Therefore, it shows that it is necessary to motivate healthcare to pay attention to the prescription of drugs in poly-treated patients to reduce the risk of ADRs. [ABSTRACT FROM AUTHOR]

Klippel–Trenanauy syndrome (KTS) is a rare genetic disease determined by overexpression of the phosphatidylinositol-4-5-bisphosphate 3 kinase catalytic subunit (PIK3CA) gene. The clinical presentation is characterized by venous and capillary malformations and lymphatic malformation. To date, no definitive treatment has been suggested in order to improve the clinical symptoms related to the developments of a skin wound. In this case, we describe a young man with KTS that developed a severe skin wound in the lower right limb unresponsive to the common treatment but responsive to a treatment with oxygen-ozone therapy, pulsed magnetic fields (diamagnetic treatment), and topical fixed association of cocum caprylate, oleic acid, quercetin, and 18-β glycyrrhetinic acid. This is the first case that supports a multistep approach to treat a rare and severe disease, and we hope that other studies can support our data. [ABSTRACT FROM AUTHOR]

Accidental soft tissue injuries are a frequent injury. Platelet-rich plasma (PRP) is an interesting therapeutic option for wounds and skin damage. In this case report, we describe a 37-year-old man that presented to our ward of pain medicine for an accidental severe leg injury associated with skin and soft tissue loss, with severe pain and poor sensation. History revealed the use of recreational drugs without viral infections or systemic diseases. Wound debridement, wound dressings, systemic antibiotics (amoxicillin 1000 mg tid and azithromycin 500 mg od), and non-steroidal anti-inflammatory drugs (ibuprofen 600 mg bid) reduced pain but did not improve the skin and soft tissue. A fibrin membrane with concentrated growth factors was applied, yielding an improvement in the injury in 16 months without the need for skin grafting. [ABSTRACT FROM AUTHOR]

Pathogens and pests constantly challenge food security and safety worldwide. The use of plant protection products to manage them raises concerns related to human health, the environment, and economic costs. Basic substances are active, non-toxic compounds that are not predominantly used as plant protection products but hold potential in crop protection. Basic substances' attention is rising due to their safety and cost-effectiveness. However, data on their protection levels in crop protection strategies are lacking. In this review, we critically analyzed the literature concerning the field application of known and potential basic substances for managing diseases and pests, investigating their efficacy and potential integration into plant protection programs. Case studies related to grapevine, potato, and fruit protection from pre- and post-harvest diseases and pests were considered. In specific cases, basic substances and chitosan in particular, could complement or even substitute plant protection products, either chemicals or biologicals, but their efficacy varied greatly according to various factors, including the origin of the substance, the crop, the pathogen or pest, and the timing and method of application. Therefore, a careful evaluation of the field application is needed to promote the successful use of basic substances in sustainable pest management strategies in specific contexts. [ABSTRACT FROM AUTHOR]

This study is aimed to set severe constraints on a whole class of non-commutative space-times scenarios as a class of universality for several quantum gravity models. To this end, slight violations of the Pauli exclusion principle—predicted by these models—are investigated by searching for Pauli forbidden K α and K β transitions in lead. The selection of a high atomic number target material allows to test the energy scale of the space-time non-commutativity emergence at high atomic transition energies. As a consequence, the measurement is very sensitive to high orders in the power series expansion of the Pauli violation probability, which allows to set the first constraint to the "triply special relativity" model proposed by Kowalski-Glikman and Smolin. The characteristic energy scale of the model is bound to Λ > 5.6 · 10 − 9 Planck scales. [ABSTRACT FROM AUTHOR]

In agreement with the International Association for the Study of Pain, chronic pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. To date, there are several types of pain: nociceptive, neuropathic, and nociplastic. In the present narrative review, we evaluated the characteristics of the drugs used for each type of pain, according to guidelines, and their effects in people with comorbidity to reduce the development of severe adverse events. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes associated with extracellular matrix protein turnover and tissue degradation. They participate to many different physiological reactions but are also hyperactivated in several diseases. Various literature studies have documented that MMPs play a role in the modulation of neuropathic and nociceptive pain. The heterogeneity of clinical and pre-clinical data is an important issue in this experimental context. Despite the presence of a good number of studies on MMP inhibitors, these drugs showed scarce efficacy and relevant side effects. In the present manuscript, we reviewed studies in the literature that define a possible role of MMPs in pain and the effects of their modulation. [ABSTRACT FROM AUTHOR]

Oomycetes-borne diseases represent a serious problem for agriculture sustainability due to the high use of chemical products employed for their control. In recent years, increasing concerns on side effects associated with fungicide utilization have led to the reduction of the permissible modes of action, with the remaining ones continuously threatened by the increase of resistant strains in the pathogen populations. In this context, it is mandatory to develop new generation fungicides characterized by high specificity towards the target species and low environmental impact to guarantee the sustainability, productivity, and quality of food production. Fungicide discovery is a lengthy and costly process, and despite these urgent needs, poor description and formalization of high-throughput methodologies for screening the efficacy of active compounds are commonly reported for these kinds of organisms. In this study, a comprehensive picture of two high-throughput practices for efficient fungicide screening against plant-pathogenic oomycetes has been provided. Different protocols using multiwell plates were validated on approved crop protection products using Phytophthora infestans and Pythium ultimum as the model species. In addition, detailed statistical inputs useful for the analysis of data related to the efficacy of screenings are included. [ABSTRACT FROM AUTHOR]

Modern physics lays its foundations on the pillars of Quantum Mechanics (QM), which has been proven successful to describe the microscopic world of atoms and particles, leading to the construction of the Standard Model. Despite the big success, the old open questions at its very heart, such as the measurement problem and the wave function collapse, are still open. Various theories consider scenarios which could encompass a departure from the predictions of the standard QM, such as extra-dimensions or deformations of the Lorentz/Poincaré symmetries. At the Italian National Gran Sasso underground Laboratory LNGS, we search for evidence of new physics proceeding from models beyond standard QM, using radiation detectors. Collapse models addressing the foundations of QM, such as the gravity-related Diósi–Penrose (DP) and Continuous Spontaneous Localization (CSL) models, predict the emission of spontaneous radiation, which allows experimental tests. Using a high-purity Germanium detector, we could exclude the natural parameterless version of the DP model and put strict bounds on the CSL one. In addition, forbidden atomic transitions could prove a possible violation of the Pauli Exclusion Principle (PEP) in open and closed systems. The VIP-2 experiment is currently in operation, aiming at detecting PEP-violating signals in Copper with electrons; the VIP-3 experiment upgrade is foreseen to become operative in the next few years. We discuss the VIP-Lead experiment on closed systems, and the strong bounds it sets on classes of non-commutative quantum gravity theories, such as the θ –Poincaré theory. [ABSTRACT FROM AUTHOR]

Downy mildew, caused by the obligate parasite Plasmopara viticola, is one of the most important threats to viticulture. The exploitation of resistant and susceptibility traits of grapevine is one of the most promising ways to increase the sustainability of disease management. Nitrogen (N) fertilization is known for influencing disease severity in the open field, but no information is available on its effect on plant-pathogen interaction. A previous RNAseq study showed that several genes of N metabolism are differentially regulated in grapevine upon P. viticola inoculation, and could be involved in susceptibility or resistance to the pathogen. The aim of this study was to evaluate if N fertilization influences: (i) the foliar leaf content and photosynthetic activity of the plant, (ii) P. viticola infectivity, and (iii) the expression of the candidate susceptibility/resistance genes. Results showed that N level positively correlated with P. viticola infectivity, confirming that particular attention should be taken in vineyard to the fertilization, but did not influence the expression of the candidate genes. Therefore, these genes are manipulated by the pathogen and can be exploited for developing new, environmentally friendly disease management tools, such as dsRNAs, to silence the susceptibility genes or breeding for resistance. [ABSTRACT FROM AUTHOR]

This prospective, open-label clinical study was carried out to evaluate both the efficacy and safety of intramuscular paravertebral injections of an oxygen–ozone (O2–O3) mixture in patients with cervicobrachial pain. We enrolled 540 subjects affected by cervicobrachial pain referred to the Ozone Therapy Ambulatory at the Mater Domini Hospital of Catanzaro (Italy) and to the Center of Pain in Taurianova (Reggio Calabria, Italy). All the subjects (n = 540) completed the treatment and the follow-up visits. The subjects received a mean of 11 cervical intramuscular treatments with an O2–O3 mixture (5 mL) with an O3 concentration of 10 μg/mL bis a week. The improvement of pain was measured by a change in the mean of the Visual Analog Scale (VAS) score from baseline to the end of treatment and during follow-ups. Patient satisfaction was assessed at the end of treatment using the SF-36 Questionnaire. The development of adverse drug reactions was recorded. The mean (±standard deviation) VAS pain score at baseline, at the end of treatment, and during follow-ups showed a significant reduction in pain over time (p < 0.001). All the patients who were enrolled (n: 540) were pain-free after one year. According to the pain distribution, all subjects showed a significant reduction in pain over time in each group (p < 0.05). No significant differences were observed with respect to sex or age. No adverse events were observed during the study. In conclusion, we documented that the intramuscular injection of an O2–O3 mixture is an effective and safe treatment option for patients with cervicobrachial pain. [ABSTRACT FROM AUTHOR]

High-intensity, low-frequency magnetic fields (MFs) have been widely used in the treatment of diseases and in drug delivery, even though they could induce structural changes in pharmacological molecules. Morphological changes in ketoprofen and KiOil were investigated through Fourier-transform infrared spectroscopy (FT-IR). Unsupervised principal component analysis was carried out for data clustering. Clinical validation on 22 patients with lower back pain was managed using diamagnetic therapy plus topical ketoprofen or KiOil. The Numerical Rating Scale (NRS) and Short-Form Health Survey 36 (SF-36) were used to evaluate clinical and functional response. Ketoprofen showed clear clustering among samples exposed to MF (4000–650 cm−1), and in the narrow frequency band (1675–1475 cm−1), results evidenced structural changes which involved other excipients than ketoprofen. KiOil has evidenced structural modifications in the subcomponents of the formulation. Clinical treatment with ketoprofen showed an average NRS of 7.77 ± 2.25 before and an average NRS of 2.45 ± 2.38 after MF treatment. There was a statistically significant reduction in NRS (p = 0.003) and in SF-36 (p < 0.005). Patients treated with KiOil showed an average NRS of 7.59 ± 2.49 before treatment and an average NRS of 1.90 ± 2.26 after treatment (p < 0.005). SF-36 showed statistical significance for all items except limitations due to emotional problems. A high-intensity pulsed magnetic field is an adjunct to topical treatment in patients with localized pain, and the effect of MF does not evidence significant effects on the molecules. [ABSTRACT FROM AUTHOR]

Durable resistance is a key objective in genetic improvement for disease resistance in grapevines, which must survive for years in the field in the presence of adaptable pathogen populations. In this study, the adaptation of 72 Northern Italian isolates of Plasmopara viticola, the downy mildew agent, has been investigated into Bianca, possessing Rpv3-1, the most frequently exploited resistance locus for genetic improvement, and Mgaloblishvili, a Vitis vinifera variety possessing the newly discovered Rpv29 locus. Infection parameters (latency period, infection frequency, and disease severity) and oospore production and viability were evaluated and compared to those of Pinot noir, the susceptible reference. The expected levels of disease control were achieved by both resistant cultivars (>90% on Bianca; >25% on Mgaloblishvili), despite the high frequency of isolates able to grow on one (28%) or both (46%) accessions. The disease incidence and severity were limited by both resistant cultivars and the strains able to grow on resistant accessions showed signatures of fitness penalties (reduced virulence, infection frequency, and oospore density). Together, these results indicate an adequate pathogen control but suitable practices must be adopted in the field to prevent the diffusion of the partially adapted P. viticola strains to protect resistance genes from erosion. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains one of the most important health challenges worldwide. Control of the TB epidemic has not yet been achieved because of the lack of an effective vaccine and rapid and sensitive diagnostic approaches, as well as the emergence of drug-resistant forms of M. tuberculosis. Cellular immunity has a pivotal role against M. tuberculosis infection, but the role of humoral immunity is still controversial. We analyzed the frequency, absolute counts, and phenotypic and functional subsets of B lymphocytes in the peripheral blood of patients with active TB and subjects with latent infection compared to healthy donors. Moreover, we analyzed serum levels of total Ig and their IgA, IgM, and IgG isotypes and the titers of preexisting antibodies against a pool of common viral pathogens. FlowCT and unsupervised clusterization analysis show that patients with active TB and LTBI subjects have modest non-significant reduction in the numbers of circulating B lymphocytes as compared to healthy donors. Moreover, LTBI subjects had high percentages of atypical B cell population and lower percentages of naive and switched memory B cells. These findings were supported by gene expression and GSEA analysis. Moreover, there were no differences between active TB patients, LTBI subjects and HD, either in serum levels of total Ig isotypes or in preexisting IgG antibody titers, to ten different antigens from eight common pathogenic viruses, clearly demonstrating that either active or latent M. tuberculosis infection preserves the antibody production capacity of long-lived plasma cells. Thus, our results agree with previous studies reporting unaltered B cell frequencies in the blood of active TB patients and LTBI individuals as compared to healthy controls. [ABSTRACT FROM AUTHOR]

The wealth of theoretical and phenomenological information about Quantum Chromodynamics at short and long distances collected so far in major collider measurements has profound implications in cosmology. We provide a brief discussion on the major implications of the strongly coupled dynamics of quarks and gluons as well as on effects due to their collective motion on the physics of the early universe and in astrophysics. [ABSTRACT FROM AUTHOR]

In this paper, we study a variational problem with nonconstant gradient constraints. Several aspects related to problems with gradient constraints have been studied in the literature and have seen new developments in recent years. In the case of constant gradient constraint, the problem is the well-known elastic–plastic torsion problem. A relevant issue in this type of problem is the existence of Lagrange multipliers. Here, we consider the equivalent Lagrange multiplier formulation of a nonconstant gradient-constrained problem, and we investigate the class of solutions having a radial symmetry. We rewrite the problem in the radial symmetry case, and we analyse the different situations that may arise. In particular, in the planar case, we derive a condition characterizing the free boundary and obtain the explicit radial solution to the problem and the L p Lagrange multiplier. Some examples support the results. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a common cause of male lower urinary tract symptoms (LUTS) that can reduce quality of life. Even if several drugs can be used in its treatment, the development of adverse drug reactions (ADRs) represents the most common cause of low adherence. In the present study, we evaluate both the efficacy and the safety of a new nutrient fixed combination of Pollen Extract plus Teupolioside, named Xipag®, in patients with LUTS. We conduct a pilot single center open label clinical study between 1 March 2020 and 30 June 2020 in patients with BPH referred to general practitioner's ambulatories. Male patients > 45 years, sexually active, with clinical symptoms of LUTS and with a diagnosis of HPB were enrolled and received one tablet/day of Xipag® (T0), for three months (T1: end of treatment). The IPSS and IIEF-5 questionnaires were carried out at T0 and T1 and represent the first end point, whereas the primary safety end point was considered the absence of ADR or of drug–drug interactions related to Xipag® administration. During the study period, 25 subjects aged 43 to 76 years (mean 62.7 ± 9) were enrolled and completed the study. The clinical evaluation in T1 documented that Xipag® induced a statistically significant improvement (p < 0.01) in symptoms, as documented by the IPSS questionnaire (range 22.7–88.9; mean 55.2 ± 23.6), without the development of ADRs. In conclusion, this is the first real-world study that showed the efficacy and the safety of Xipag® in the BPH patients with LUTS. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a betacoronavirus, which induced a severe pandemic infectious disease around the world. Even if several drugs have been suggested for its treatment, to date, the only strategy to reduce the severity of disease is represented by the use of vaccine. However, the lack of pre-marketing evidence in frail patients suggests the necessity of the real-world study of a vaccine benefit–risk profile. In this study, we evaluated the efficacy and the safety of SARS-CoV-2 vaccination in a cohort of 33 patients treated with an immunosuppressant after solid organ transplant. Both CLIA and LS/MS analysis were used to evaluate the levels of immunoglobulin (Ig)G anti SARS-CoV-2 and the therapeutic drug monitoring of immunosuppressant drugs. We documented that SARS-CoV-2 vaccination induced a dose- and gender-related serological response. In particular, in 63.6% of the enrolled patients, we documented a significant serological response at T2, and after a time related decrease, the booster dose induced a serological response in 72.7% of enrolled patients. In conclusion, the vaccine anti SARS-CoV-2 is immunogenic in patients under immunosuppression, and is not related to the development of ADRs. We also suggest that the booster dose could be used to increase the efficacy of the vaccination, particularly in women. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome (CRPS) is a neurologic chronic pain condition hard to diagnose and treat, and able to significantly impact the quality of life. Currently, the available multimodal, individualized treatments (i.e., pharmacological and non-pharmacological therapies including invasive procedures) are aimed only at symptom control. Herein, we report a 69-year-old Caucasian female who came to our attention due to a 3-year history of severe (10/10) burning pain in her right ankle, along with oedema and local changes in skin color and temperature, which occurred after the ankle sprain. Previous pharmacological attempts failed due to multiple drug intolerance. Clinical examination confirmed the CRPS type I diagnosis, and a weekly diamagnetic therapy protocol was started since the patient refused further medications and interventional procedures. After 10 weeks of treatment, a significant (p < 0.01) reduction in pain severity and absence of oedema (difference in ankles' circumference: from 3 cm to 0) were observed, with consequent improvements in quality of life and no adverse events. Although high-quality clinical evidence is still lacking, our case report suggests further investigating the potential use of diamagnetic therapy as a non-invasive and safe adjunctive treatment for CRPS, and as an alternative when patients did not benefit from drugs and/or refuse invasive procedures. [ABSTRACT FROM AUTHOR]

Tuberculous meningitis (TBM) is a severe form of tuberculosis. We report the development of fatal TBM in a 2-year-old previously healthy child, suggesting that TBM must be evaluated in children of all ages with non-specific symptoms of central nervous involvement because a diagnostic delay induces a negative prognosis. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 vaccination campaign is probably one of the most historic public hygiene measures in modern medicine. The drama of the pandemic has forced the scientific community to accelerate the development and commercialization of vaccines, thereby enhancing the phases of active surveillance. Among the adverse events following immunization (AEFI) reported, those of an audiovestibular interest, such as sudden sensorineural hearing loss (SSNHL), tinnitus, dizziness, and vertigo, constitute a very small percentage. There are many plausible etiological hypotheses, and scientific research needs to pay more attention to the correct collection of data, which up until now have often been inadequate and fragmented, on which to base future studies. SSNHL, new onset tinnitus, vertigo, and dizziness require a prompt evaluation, while the proposed treatment is the same as it is for events unrelated to vaccination. These are uncommon adverse events, and the risk rates for these diseases have not increased in conjunction with the COVID-19 vaccinations, therefore there is no justification of any hesitation towards the vaccination campaign. [ABSTRACT FROM AUTHOR]

Lung cancer is a common neoplasm, usually treated through chemotherapy, radiotherapy and/or surgery. Both clinical and experimental studies on cancer cells suggest that some drugs (e.g., statins) have the potential to improve the prognosis of cancer. In fact, statins blocking the enzyme "hydroxy-3-methylglutaryl-coenzyme A reductase" exert pleiotropic effects on different genes involved in the pathogenesis of lung cancer. In this narrative review, we presented the experimental and clinical studies that evaluated the effects of statins on lung cancer and described data on the effectiveness and safety of these compounds. We also evaluated gender differences in the treatment of lung cancer to understand the possibility of personalized therapy based on the modulation of the mevalonate pathway. In conclusion, according to the literature data, statins exert multiple effects on lung cancer cells, even if the evidence for their use in clinical practice is lacking. [ABSTRACT FROM AUTHOR]

Vertigo in children is a challenging topic. The lack of dedicated trials, guidelines and papers causes inhomogeneity in the treatment of vertigo in children. Meniere's disease, migraine equivalents, vestibular neuritis, paroxysmal positional benign vertigo (BPPV), persistent postural-perceptual dizziness (PPPD) and motion sickness may affect children with various degrees of incidence and clinical severity compared to adults. Several drugs are proposed for the management of these conditions, even if their use is subordinated to the child's age. In this review, we summarize the existing evidence related to the use of drugs for this clinical condition in children as a start point for new trials, stating the urgent need for international guidelines. [ABSTRACT FROM AUTHOR]

Lower-extremity ulcers are associated with an increasing prevalence and significant economic and social costs. To date, there is no high-quality evidence related to an optimal treatment algorithm. A multimodal approach is needed particularly in patients with comorbidity and polytherapy. Herein, we report the case of a 94-year-old Caucasian female with comorbidity and polytherapy who was admitted to our observation for a history (1 year) of chronic painful malleolar mixed ulcer. After clinical evaluation, she was treated with a twice daily pain relief therapy and with a weekly diamagnetic therapy protocol plus a local treatment. During the clinical examination, we documented a statistically significant improvement in both pain (VAS score from 8 to 2 p < 0.01) and foot ulcer (surface reduction from 6 cm × 4 cm to 2 cm × 2 cm, p < 0.01) at the sixth week of combined treatment. The ulcer completely healed at the ninth week. This is the first study to document the effect of diamagnetic therapy as an add-on therapy in the management of wound healing. In conclusion, even if high-quality evidence is still lacking, diamagnetic therapy might represent an interesting option as an add-on treatment for ulcer. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) has deeply affected the management of patients with severe asthma, treated with add-on biological therapies. Objective: In this study, severe asthmatic patients on treatment with one of three different biologics (omalizumab, mepolizumab, benralizumab) underwent a survey to evaluate the effects of COVID-19 on the management of their clinical condition, with regard to the changes caused by the limited access to health facilities during the pandemic period. Methods: In this prospective observational study, 28 severe asthmatic outpatients referring to the Respiratory Unit of Magna Graecia University Hospital, Catanzaro (Italy), were asked to answer a telephone survey from May to July 2021. This survey included the evaluation of demographic and clinical data, as well as the number of lung function tests performed, exacerbations, biologic doses administered at hospital, or at general practitioner office, or through self-administration. Adherence to biological therapies before and during the pandemic period was also assessed. Moreover, the most recent asthma control test (ACT) score and the last forced expiratory volume in the first second (FEV1) measurement, recorded during the pandemic phase, were compared to the pre-pandemic (baseline) period. Results: When comparing the pre-pandemic data with the pandemic observations, the mean ACT score and the exacerbation rate did not significantly change [ACT, 21.5 ± 2.8 to 23.0 ± 3.9 (p = 0.1); exacerbation rate, 0.3 ± 0.6 and 0.5 ± 1.5 (p = 0.3)]. When considering some variables related to disease management in the same periods, a statistically significant difference was detected with regard to the mean number of outpatient visits (5.2 ± 3.8 vs. 0.9 ± 2.5, p < 0.0001), as well as to the mean number of accesses to health facilities for the administration of biological drugs (from 7.0 ± 3.4 to 2.5 ± 3.9, p < 0.0001). None of the patients reported to have been infected with the SARS-CoV-2 virus and no adverse drug reactions (ADR) occurred during the study. Conclusions: The above results suggest that COVID-19 pandemic did not induce any significant change related to severe asthma control. Indeed, add-on treatment with biological drugs was regularly continued, despite the obvious limited access to health facilities. [ABSTRACT FROM AUTHOR]

One year on from the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine has made several steps towards increasing the therapeutic options against its treatment. Despite the lack of specific therapies, international societies have introduced new guidelines and launched several trials to test the efficacy of new protocols and drugs. Drug repurposing has been a fundamental strategy to find quick ways to fight the pathogen, even if it is new compounds that are drawing the attention of the scientific community. Tailored therapy should be considered to be a milestone in treatment in order to increase drug efficacy and to reduce drug toxicity. Therefore, both drug characteristics (i.e., pharmacokinetic, pharmacodynamic and safety) and the patient characteristics (i.e., stage of disease, comorbidity, concomitant treatments and the mutation of single nucleotides) could represent the key to achieving this objective. In the present study we performed a narrative review of the pharmacological treatment used to date in the management of coronavirus disease 2019 (COVID-19). [ABSTRACT FROM AUTHOR]

Diabetic neuropathy and Peripheral Arterial Disease (PAD) are the main etiological factors in foot ulceration. Herein, we report our experience of diabetic foot ulceration (DFU) management, with an analysis of the relationship between the rate of lower extremity amputation, in persons with infected DFU, after revascularization procedures performed to prevent major amputation. This study highlights the role of different biomarkers, showing their usefulness and potentiality in diabetic foot ulcer management, especially for the early diagnosis and therapy effectiveness monitoring. A retrospective analysis, from September 2016 to January 2021, of diabetic patients presenting diabetic foot with DFU, was performed. All patients were treated with at least one vascular procedure (endovascular, open, hybrid procedures) targeting PAD lesions. Outcomes measured were perioperative mortality and morbidity. Freedom from occlusion, primary and secondary patency, and amputation rate were registered. A total of 267 patients, with a mean age of 72.5 years, were included in the study. The major amputation rate was 6.2%, minor amputation rate was 17%. In our experience, extreme revascularization to obtain direct flow reduced the rate of amputations, with an increase in ulcer healing. [ABSTRACT FROM AUTHOR]

The goal of this investigation was to identify potential risk factors to predict the onset of medication-related osteonecrosis of the jaw (MRONJ). Through the identification of the multiple variables positively associated to MRONJ, we aim to write a paradigm for integrated MRONJ risk assessment built on the combined analysis of systemic and local risk factors. The characteristics of a cohort of cancer patients treated with zoledronic acid and/or denosumab were investigated; beyond the set of proven risk factors a new potential one, the intake of new molecules for cancer therapy, was addressed. Registered data were included in univariate and multivariate logistic regression analysis in order to individuate significant independent predictors of MRONJ; a propensity score-matching method was performed adjusting by age and sex. Univariate logistic regression analysis showed a significant effect of the parameters number of doses of zoledronic acid and/or denosumab (OR = 1.03; 95% CI = 1.01–1.05; p = 0.008) and chemotherapy (OR = 0.35; 95% CI = 0.17–0.71; p = 0.008). The multiple logistic regression model showed that breast, multiple myeloma, and prostate cancer involved a significantly higher risk compared to lung cancer; a significant effect of the combined variables number of doses of zoledronic acid and/or denosumab (OR = 1.03; 95% CI = 1.01–1.06); p-value = 0.03) and exposure to novel molecule treatment (OR = 34.74; 95% CI = 1.39–868.11; p-value = 0.03) was observed. The results suggest that a risk assessment paradigm is needed for personalized prevention strategies in the light of patient-centered care. [ABSTRACT FROM AUTHOR]

Vestibular disorders may generate complex signs and symptoms, which may alter patients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/usefulness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) pharmacodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs. [ABSTRACT FROM AUTHOR]

Any interaction between finite quantum systems in a separable joint state can be viewed as encoding classical information on an induced holographic screen. Here we show that when such an interaction is represented as a measurement, the quantum reference frames (QRFs) deployed to identify systems and pick out their pointer states induce decoherence, breaking the symmetry of the holographic encoding in an observer-relative way. Observable entanglement, contextuality, and classical memory are, in this representation, logical and temporal relations between QRFs. Sharing entanglement as a resource requires a priori shared QRFs. [ABSTRACT FROM AUTHOR]

Background: The aim of the present work was to analyze a 10-year retrospective series of surgically treated medication-related osteonecrosis of the jaws (MRONJ) cases, reporting the clinical outcome and success rate for each adopted procedure in order to draw a treatment algorithm that is able to standardize clinical decision making and maximize the success of oral surgical treatment of MRONJ. Methods: Different surgical approaches were categorized taking into consideration two variables (a) hard tissue management (defined as debridement, saucerization or marginal resective surgery of maxillary necrotic bone) and (b) soft tissue management (defined as type of flap design and related modality of wound-healing). Results: For the retrospective cohort study, 103 MRONJ patients were enrolled and a total of 128 surgical procedures were performed. The role of radical-intended surgery using local flaps in MRONJ treatment was investigated, as well as palliative treatments. All stage I–II patients completely healed when a combination of radical necrotic bone surgery associated with a first intention healing of soft tissues was obtained. In stage III, when a patient was not eligible for maxillo-facial surgery, the use of palliative surgical strategies was effective in symptom relief in order to maintain a better quality of life for the duration of the patient's life. Conclusions: Oral surgery with radical intent associated with a flap design able to ensure first intention healing might represent a valid option for the majority of MRONJ patients. The designed decision tree allows clinicians to assess individual surgical approaches for MRONJ treatment in accordance with patient-centered outcomes and surgical skills. [ABSTRACT FROM AUTHOR]

This paper focuses on social farming, a new "branch" which includes activities that make use of agricultural, rural and natural resources in order to produce food and social services. It investigates the case of Calabria, one of the least developed regions in Italy and in Europe, which suffers from several serious problems; for example, the low level of accessibility, and the presence of the Mafia organisations. We wondered whether in such a region social farming can make a significant contribution to its social and economic development. Using the data collected by means of a qualitative investigation of some of the most important Calabrian social farms, we studied their characteristics, their strategies, their social mission, and their role in the local socio-economic context. We found that most of them are successful, in both economic and social terms, and their role in the local community is positive. Moreover, they are making a valuable contribution to the cultural change required to overcome the predominance of the Mafia. [ABSTRACT FROM AUTHOR]

Aluminum alloy sheets are gaining increasing interest in the construction of some or all components of the car body in view of their lightweight properties which can allow significant fuel consumption reduction. In order to be suitable for car body application, aluminum alloy sheets should have sufficient mechanical properties both in static (e.g., structural stability and durability) and dynamic conditions (e.g., crash test). Static and dynamic mechanical tests (strain rates: ε ˙ ≈ 1 × 10−3 s−1 and ε ˙ ≈ 5 × 102 s−1 respectively) were conducted on AA6016 alloy sheet (1 mm thick), in T4 and T6 temper and for the longitudinal, transverse, and diagonal rolling directions by means of standard static tensile test and modified Hopkinson bar dynamic tests. Microstructural and fracture morphology observations are also reported. The results show that the ultimate tensile strength increases by 13−14%, and the elongation at fracture increases by 75−105%, depending on the temper, by increasing the strain rate. [ABSTRACT FROM AUTHOR]

International studies are dealing with the promotion of sustainable food systems more frequently. Additionally, places of purchase and sharing in the choice of food to be consumed have become a network system for families. The aim of this work is to analyse the preferences of Swedish consumers for local/artisanal cheeses and the purchase motivations that guide their choices. We also studied the role played by consumers' favourite shopping locations (retail store, hypermarket, city market, supply chain). On the one hand, we examined the attractiveness and the power exercised by the various stores and on the other hand, we viewed the consumer in relation to the frequency of purchase, and the confidence with the sales points. We interviewed 200 people in the city of Östersund, highlighting habits, consumption preferences and reasons for purchasing. A multiple correspondence analysis explores the reasons behind the purchase preferences of the local 'Källarlagrad getost' artisan cheese from the Slow Food brand. The representations of social network analysis are used to show the complex articulations that influence the choices of consumers in terms of type of cheese purchased/consumed and places of purchase/consumption. The results showed that Swedish consumers, in the purchase of cheeses, have a loyalty point at the point of sale, follow the advice of the seller and are attentive to the reputation of the product. Those who buy Källarlagrad getost are sensitive to safety, appreciate artisan cheeses and choose them for their versatility, have a strong connection with the territory and wish to contribute to supporting the local economy. Knowing these characteristics and preferences of Swedish consumers living in a city in the north of the country is important for marketing activities and for promoting tourism and sustainable gastronomy. [ABSTRACT FROM AUTHOR]