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Background: ATTR-CM is becoming more prevalent, and disease-modifying therapy has been investigated in recent years with promising results. Diflunisal has shown TTR-stabilizing properties assessed by biomarkers and echocardiography, but there are no trials addressing the evolution of morphological changes with CMR. Methods and Results: AMILCA-DIFLU is an exploratory pilot study prospective, single-center, non-randomized, open-label clinical trial. Patients diagnosed with ATTR-CM underwent clinical, functional, biochemical and imaging assessment before and one year after diflunisal therapy initiation. Of the twelve ATTR-CM patients included, only nine patients completed treatment and study protocol in 12 months. To increase the sample size, we included seven real-world patients with one year of diflunisal treatment. Among the group of patients who completed treatment, diflunisal therapy did not show improvement in cardiac disease status as assessed by many cardiac and inflammatory biomarkers, 6MWT and CMR parameters after one year of treatment. However, a non-significant trend towards stabilization of CMR parameters such as LVEF, ECV and T2 at one year was found. When comparing the group of patients who completed diflunisal therapy and those who did not, a significant decrease in the distance performed in the 6MWT was found in the group of patients who completed treatment at one year (-14 ± 81.8 vs. -173 ± 122.2; p = 0.032). Diflunisal was overall well tolerated, showing only a statistically significant worsening in renal function in the group of diflunisal-treatment patients with no clinical relevance or need for treatment discontinuation. Conclusions: In patients with ATTR-CM, treatment with diflunisal was overall well tolerated and tended to stabilize or slow down amyloid cardiac disease progression assessed by CMR parameters, cardiac and inflammatory biomarkers and functional capacity.

Advancements in psychotropic therapy for pregnant women are pivotal for addressing maternal mental health during the perinatal period. Screening for mood and anxiety symptoms during pregnancy is recommended to enable early intervention. Psychotropic medications, including antidepressants, benzodiazepines, antipsychotics, and mood stabilizers, are commonly used, but challenges remain regarding their safety and efficacy during pregnancy. Pregnancy induces significant changes in pharmacokinetics, necessitating personalized dosing strategies and careful monitoring. Real-time monitoring technologies, such as smartphone-integrated platforms and home-based monitoring, enhance accessibility and accuracy. Prospective studies and collaboration among healthcare providers are essential for evidence-based guidelines and optimal treatment strategies. Reducing stigma around mental health during pregnancy is crucial to ensure women seek help and discuss treatment options, promoting understanding and acceptance within the community.

Addressing the complexities of managing viral infections during pregnancy is essential for informed medical decision-making. This comprehensive review delves into the management of key viral infections impacting pregnant women, namely Human Immunodeficiency Virus (HIV), Hepatitis B Virus/Hepatitis C Virus (HBV/HCV), Influenza, Cytomegalovirus (CMV), and SARS-CoV-2 (COVID-19). We evaluate the safety and efficacy profiles of antiviral treatments for each infection, while also exploring innovative avenues such as gene vaccines and their potential in mitigating viral threats during pregnancy. Additionally, the review examines strategies to overcome challenges, encompassing prophylactic and therapeutic vaccine research, regulatory considerations, and safety protocols. Utilizing advanced methodologies, including PBPK modeling, machine learning, artificial intelligence, and causal inference, we can amplify our comprehension and decision-making capabilities in this intricate domain. This narrative review aims to shed light on diverse approaches and ongoing advancements, this review aims to foster progress in antiviral therapy for pregnant women, improving maternal and fetal health outcomes.

Most world countries are experiencing a remarkable aging process. Meanwhile, 50 million people are affected by Alzheimer's disease (AD) and related dementia and there is an increasing trend in the incidence of these major health problems. In order to address these, the increasing evidence suggesting the protective effect of dietary interventions against cognitive decline during aging may suggest a response to this challenge. There are nutrients with a neuroprotective effect. However, Western diets are poor in healthy n-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic acid (DHA), iodine (I), and other nutrients that may protect against cognitive aging. Given DHA richness in chub mackerel ( Scomber colias ), high vitamin B9 levels in quinoa ( Chenopodium quinoa ), and I abundance in the seaweed Saccorhiza polyschides , a functional hamburger rich in these nutrients by using these ingredients was developed and its formulation was optimized in preliminary testing. The effects of culinary treatment (steaming, roasting, and grilling vs. raw) and digestion on bioaccessibility were evaluated. The hamburgers had high levels of n-3 PUFAs in the range of 42.0-46.4% and low levels of n-6 PUFAs (6.6-6.9%), resulting in high n-3/n-6 ratios (>6). Bioaccessibility studies showed that the hamburgers could provide the daily requirements of eicosapentaenoic acid (EPA) + DHA with 19.6 g raw, 18.6 g steamed, 18.9 g roasted, or 15.1 g grilled hamburgers. Polyphenol enrichment by the seaweed and antioxidant activity were limited. The hamburgers contained high levels of Se and I at 48-61 μg/100 g ww and 221-255 μg/100 g ww, respectively. Selenium (Se) and I bioaccessibility levels were 70-85% and 57-70%, respectively, which can be considered high levels. Nonetheless, for reaching dietary requirements, considering the influence of culinary treatment and bioaccessibility, 152.2-184.2 g would be necessary to ensure daily Se requirements and 92.0-118.1 g for I needs.

The progression from prediabetes to type-2 diabetes depends on multiple pathophysiological, clinical, and epidemiological factors that generally overlap. Both insulin resistance and decreased insulin secretion are considered to be the main causes. The diagnosis and approach to the prediabetic patient are heterogeneous. There is no agreement on the diagnostic criteria to identify prediabetic subjects or the approach to those with insufficient responses to treatment, with respect to regression to normal glycemic values or the prevention of complications. The stratification of prediabetic patients, considering the indicators of impaired fasting glucose, impaired glucose tolerance, or HbA1c, can help to identify the sub-phenotypes of subjects at risk for T2DM. However, considering other associated risk factors, such as impaired lipid profiles, or risk scores, such as the Finnish Diabetes Risk Score, may improve classification. Nevertheless, we still do not have enough information regarding cardiovascular risk reduction. The sub-phenotyping of subjects with prediabetes may provide an opportunity to improve the screening and management of cardiometabolic risk in subjects with prediabetes.

Background: the diagnosis of infertility and its related treatment can be traumatic, leading to profound psychological distress and a variety of psychopathological symptoms. The primary objective of this study is to contrast the linguistic features of narratives from women undergoing Assisted Reproductive Treatment with those of women not undergoing any fertility treatment. This study examines the speech of both groups of individuals as an indicator of their capacity to cope with current and past distressing experiences., Method: 44 women (mean age 36.05; SD = 4.66) enrolled in a fertility medical center in Rome, and 43 control women (mean age 36.07; SD = 3.47) completed a socio-demographic questionnaire and a semi-structured interview designed to collect their memories of a neutral, a positive, and a negative event. This interview also aimed to investigate: (a) (for women with fertility difficulties) how they realized they and their partner had fertility problems and a description of an event when they talked about these difficulties with their partner; and (b) (for control group participants) the most difficult moment of their pregnancy and an event when they talked about it with their partner. The interviews were audio recorded and transcribed, and the text was analyzed using the referential process (RP) linguistic measures software., Results: Mann-Whitney non-parametric U tests for the independent samples showed several significant differences regarding the linguistic measures applied to the narratives of neutral, positive, negative, and difficult experiences in the form of a linguistic style, with more intellectualization and defenses in all the narratives associated with the women with fertility problems compared to the women in the control group., Conclusions: the traumatic and painful experience of infertility and ART seems to characterize the whole mode of narrating life experiences. Present findings sustain the importance of helping women to elaborate on their experience and to understand and recognize the difficult feelings that are activated in relation to the difficulties of having a child.

In the present work, a simple two-step method is proposed for mixed oxide synthesis aimed at the achievement of antibacterial nanomaterials. In particular, Cu, Zn and Co have been selected to achieve single-, double- and triple-cation oxides. The synthesized samples are characterized by XRD, IR, SEM and EDX, indicating the formation of either crystalline or amorphous hydrocarbonate precursors. The oxides present one or two crystalline phases, depending on their composition; the triple-cation oxides form a solid solution of tenorite. Also, the morphology of the samples varies with the composition, yielding nanoparticles, filaments and hydrangea-like microaggregates. The antibacterial assays are conducted against E. coli and indicate an enhanced efficacy, especially displayed by the oxide containing 3% Co and 9% Zn incorporated into the CuO lattice. The oxides with the highest antibacterial properties are tested for their cytotoxicity, indicating a low toxicity impact, in line with literature data.

Sodium-glucose cotransporter inhibitors (SGLT2i) have demonstrated a reduction in cardiovascular events in diabetes and heart failure (HF). The mechanisms underlying this benefit are not well known and data are contradictory. The purpose of this study is to analyse the effect of dapagliflozin on cardiac structure and function in patients with normal ejection fraction. Between October 2020 and October 2021, we consecutively included 31 diabetic patients without prior history of SGLT2i use. In all of them, dapagliflozin treatment was started. At inclusion and during six months of follow-up, different clinical, ECG, analytical, and echocardiographic (standard, 3D, and speckle tracking) variables were recorded. After a follow-up period of 6.6 months, an average reduction of 18 g ( p = 0.028) in 3D-estimated left ventricle mass was observed. An increase in absolute left ventricle global longitudinal strain (LV-GLS) of 0.3 ( p = 0.036) was observed, as well as an increase in isovolumetric relaxation time (IVRT) of 10.5 ms ( p = 0.05). Moreover, dapagliflozin decreased the levels of plasma creatin-kinase (CK-MB) and atrial natriuretic peptide (ANP). In conclusion, our data show that the use of SGLT2i is associated with both structural (myocardial mass) and functional (IVRT, LV-GLS) cardiac improvements in a population of diabetic patients with normal ejection fraction.

The renin angiotensin system (RAS) has several components including signaling peptides, enzymes, and membrane receptors. The effort in characterizing this system in the periphery has led to the approval of a class of antihypertensives. Much less is known about RAS in the central nervous system. The production of RAS peptides and the expression of several RAS enzymes and receptors in dopaminergic neurons of the substantia nigra has raised expectations in the therapy of Parkinson's disease, a neurodegenerative condition characterized by lack of dopamine in the striatum, the motor control region of the mammalian brain. On the one hand, dopamine production requires reducing power. On the other hand, reducing power is required by mechanisms involved in REDOX homeostasis. This review focuses on the potential role of RAS in the regulation of neuronal/glial expression of glucose-6-phosphate dehydrogenase, which produces the NADPH required for dopamine synthesis and for reactive oxygen species (ROS) detoxification. It is known that transgenic expression of the gene coding for glucose-6-phosphate dehydrogenase prevents the death of dopaminergic nigral neurons. Signaling via angiotensin II G protein-coupled receptors, AT 1 or AT 2 , leads to the activation of protein kinase A and/or protein kinase C that in turn can regulate glucose-6- phosphate dehydrogenase activity, by Ser/Thr phosphorylation/dephosphorylation events. Long-term effects of AT 1 or AT 2 receptor activation may also impact on the concentration of the enzyme via activation of transcription factors that participate in the regulation of gene expression in neurons (or glia). Future research is needed to determine how the system can be pharmacologically manipulated to increase the availability of NADPH to neurons degenerating in Parkinson's disease and to neuroprotective glia.

The changes deriving from the birth of a child with a congenital anomaly (CA) or cerebral palsy (CP) imply, in many cases, an increased interaction with health services. A cross-sectional descriptive study was conducted with a convenience sample of parents of children diagnosed with four groups of CA (severe heart anomalies, spina bifida, orofacial clefts, and Down syndrome) and/or CP. A semistructured online questionnaire to be answered by parents was sent by web link to focal points of five parent associations and professional institutions. Data were analyzed through thematic content analysis (open-ended questions) and descriptive analysis (closed-ended questions). The results indicate consistency of responses of parents of children diagnosed with different conditions, namely with respect to the perception of health services and professionals. Closed and open-ended responses indicated three main topics in the interaction between health services and parenthood: information, coordinated and integrated responses, and support. The less positive outcomes suggest unmet information needs, while positive aspects include confidence in the care provided and the "training" received from health professionals.

Infertility and related treatments can negatively affect a couple's wellbeing. The aim of this study was to evaluate couples starting assisted reproductive treatment, differences in alexithymia and quality of life levels between partners, and the association of these psychological dimensions within the couple's members. Data was collected in two fertility centres in Rome; 47 couples completed the Fertility Quality of Life (FertiQoL), the 20-item Toronto Alexithymia Scale (TAS-20), and a socio-demographic questionnaire. Data analysis showed a worsened quality of life in women compared with their partners, as well as higher externally oriented thinking in men compared with their spouses. Associations between alexithymia and quality of life levels between women and men emerged. According to the regression analysis, a better quality of life in women was predicted by a greater partner's capabilities in identifying and describing emotion as well as by a better partner's quality of life, whereas for men, a better quality of life was predicted by their spouse's higher levels of quality of life. This study highlights the protective role that couples can play in the perception of the negative impact that infertility can have on their partner's quality of life. Further investigations are needed for the development of specific therapeutic interventions for the promotion of the couples' wellbeing.

Infertility may have a very strong emotional impact on individuals, requiring adequate support, but few studies on patients' demands toward psychological support have been conducted. This study aims to explore the emotions related to the infertility and to the Assisted Reproductive Technology (ART) procedure for which patients consider useful a psychological support. A total of 324 women completed a sociodemographic and clinical questionnaire and an open-ended questionnaire on emotional needs for psychological support. The written texts were explored by the Linguistic Inquiry and Word Count (LIWC) programme and linguistic characteristics were related to sociodemographic and anamnestic variables. Specific linguistic features were connected to several individual characteristics. More specifically, differences in linguistic processes emerged comparing women with an age over or under 40 years, women undergoing their first attempts versus more attempts, women undergoing ART with or without gamete donation, and women undergoing ART for male or unknown causes, as well as those undergoing ART for female or both partners' problems. These differences seem to confirm that older age, more attempts, gamete donation, and ART for unknown or male causes are risk factors that may worsen women's psychological well-being. This study contributes to increase the knowledge about the emotional needs of patients undergoing an ART procedure to develop specific psychological intervention programs.

Proper nutrition in infancy and early childhood is crucial to ensuring optimal child development, growth, and better health outcomes later in life. The nutrient profile model proposed by WHO/Europe aims to assess the nutritional quality and promotional/marketing aspects of commercial baby foods aimed at children up to 36 months. We used commercial data from 191 baby foods collected between March 2021 and July 2021, from eight supermarket chains in the Lisbon Metropolitan area. According to the model specifications and the NOVA classification system, we assessed the nutritional quality and promotion aspects and the degree of processing, respectively. The presence of at least one sugar-contributing ingredient was found in 34.0% of the products; 13.9% of products listed sugars and 15.0% listed fruit juices or concentrates as an ingredient. The claim “No added sugar” was present in 69.6% of products. Only 35.1% of products comply with all the nutritional requirements of the model. Concerning processing classification, 61.8% of products were ultra-processed, and about 57.0% were indicated for children < 12 months. These findings reinforce the importance of implementing measures to ensure that commercial foods for infants are marketed appropriately and to promote foods with a lower degree of processing.

Ensuring timely access to affordable vaccines has been acknowledged as a global public health priority, as also recently testified by the debate sparked during the COVID-19 pandemic. Effective vaccine procurement strategies are essential to reach this goal. Nevertheless, this is still a neglected research topic. A narrative literature review on vaccine procurement was conducted, by retrieving articles from four academic databases (PubMed/MEDLINE, Scopus, Embase, WebOfScience), 'grey' literature reports, and institutional websites. The aim was to clarify key concepts and definitions relating to vaccine procurement, describe main vaccine procurement methods, and identify knowledge gaps and future perspectives. A theoretical conceptual framework was developed of the key factors involved in vaccine procurement, which include quality and safety of the product, forecasting and budgeting, procurement legislation, financial sustainability, and plurality of manufacture, contracting, investment in training, storage and service delivery, monitoring and evaluation. This information can be useful to support policymakers during planning, implementation, and evaluation of regional and national vaccine procurement strategies and policies.

The presence of phthalic acid esters (PAEs) in marine environments is an important issue. These chemicals are able to affect marine organisms, particularly marine turtles, and to act as endocrine disrupters. In this paper, for the first time, a simple and reproducible analytical method based on solid-phase extraction (SPE) coupled with gas chromatography-ion trap/mass spectrometry (GC-IT/MS) was developed for the extraction of phthalates from the blood of marine turtles. The extraction was obtained by using C 18 phthalates-free as the stationary phase. In order to individuate the best working conditions for the extraction, the adsorption isotherms and breakthrough curves were studied. The overall analytical methodology was validated in terms of limit of detection (LOD, 0.08-0.6 ng mL -1 ), limit of quantification (LOQ, 0.4-0.8 ng mL -1 ), and correlation coefficients (>0.9933). By using this procedure, percentage recoveries ranging from 89 to 103% were achieved. The precision parameters (intra-day and inter-day) were studied, and the obtained values were smaller than 12.5%. These data confirm the goodness of the proposed analytical methodology, which is applied to real samples.

Invasive pulmonary aspergillosis (IPA) has become a recognizable complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs). Alveolar damage in the context of acute respiratory distress syndrome (ARDS) appears to be the culprit in facilitating fungal invasion in COVID-19 patients, leading to a COVID-19-associated pulmonary aspergillosis (CAPA) phenomenon. From November 2020 to 15 February 2021, 248 COVID-19 patients were admitted to our ICUs, of whom ten patients (4% incidence) were classified as either probable (six) or possible (four) CAPA cases. Seven patients had positive cultural results: Aspergillus fumigatus sensu stricto (five), A. terreus sensu stricto (one), and A. welwitschiae (one). Five patients had positive bronchoalveolar lavage (BAL) and galactomannan (GM), and two patients had both positive cultural and GM criteria. All but two patients received voriconazole. Mortality rate was 30%. Strict interpretation of classic IPA definition would have resulted in eight overlooked CAPA cases. Broader diagnostic criteria are essential in this context, even though differentiation between Aspergillus colonization and invasive disease might be more challenging. Herein, we aim to raise awareness of CAPA in view of its potential detrimental outcome, emphasizing the relevance of a low threshold for screening and early antifungal treatment in ARDS patients.

Tribolium castaneum is one of the most common insect pests of stored products. Its presence makes cereals more susceptible to the spread of the fungi Aspergillus flavus , which may produce mycotoxins. The aim of this work was to evaluate the influence of T. castaneum adults on the development of a mycotoxigenic A. flavus strain in maize flour as well as the influence of this fungus on the insects. Maize flour was exposed to T. castaneum , spores of A. flavus or to both. The results revealed an interaction between T. castaneum and A. flavus as the flour exposed to both organisms was totally colonized by the fungus whereas almost all the insects were killed. Aflatoxin B1 (AFB1) revealed a significantly higher concentration in the flour inoculated with both organisms (18.8 µg/kg), being lower when exposed only to A. flavus , suggesting that the presence of insects may trigger fungal development and enhance mycotoxin production. The ability of these organisms to thrive under the same conditions and the chemical compounds they release makes the interaction between them a subject of great importance to maintain the safety of stored maize. This is the first work evaluating the interaction between T. castaneum and A. flavus mycotoxin production.

Ready-to-eat cereals (RTECs) have become a popular breakfast option claiming to provide important nutrients to children's diets, despite being a source of excess sugar and, therefore, a health concern. Thus, food reformulation constitutes an important public health strategy that could benefit from inputs provided by nutrient profiling. This study aimed to assess the adequacy of the RTECs for children available in Portuguese supermarkets, applying three nutrient profile models (NPMs)-the nutrient profile model of the World Health Organization's Regional Office for Europe (WHO-EURO), the profile of the private-sector EU Pledge (EU-Pledge), and the national model developed by the Directorate-General of Health (NPM-PT)-in order to explore the potential for reformulation of the RTECs identified as not adequate and evaluate the impact of RTECs' reformulation on the nutritional quality of Portuguese children's diets. In total, 78 RTECs intended for children were assessed and two scenarios-current (not considering reformulation) and alternative (considering reformulation to accomplish the nutrient profile requirements)-were considered to assess the impact of reformulation on nutritional quality. Across all RTECs, only 5.1% could be promoted to children according to the considered NPMs. The most common nutrients requiring reformulation were sugar, saturated fatty acids (SFA), salt, and dietary fiber. The scenarios of reformulation considered could reduce the RTECs average content of total sugars, SFA, and salt by 43%, 8.7%, and 1.1%, respectively, and dietary fiber intake could be increased by 34%. Thus, these results support policies to implement reformulation strategies for developing healthier food products to be promoted to children.

Dopamine is derived from an amino acid, phenylalanine, which must be obtained through the diet. Dopamine, known primarily to be a neurotransmitter involved in almost any higher executive action, acts through five types of G-protein-coupled receptors. Dopamine has been studied extensively for its neuronal handling, synaptic actions, and in relation to Parkinson's disease. However, dopamine receptors can be found extra-synaptically and, in addition, they are not only expressed in neurons, but in many types of mammalian cells, inside and outside the central nervous system (CNS). Recent studies show a dopamine link between the gut and the CNS; the mechanisms are unknown, but they probably require cells to act as mediators and the involvement of the immune system. In fact, dopamine receptors are expressed in almost any cell of the immune system where dopamine regulates various processes, such as antigen presentation, T-cell activation, and inflammation. This likely immune cell-mediated linkage opens up a new perspective for the use of dopamine-related drugs, i.e., agonist-antagonist-allosteric modulators of dopamine receptors, in a variety of diseases.

Identification of Aspergillus to species level is important since sibling species may display variable susceptibilities to multiple antifungal drugs and also because correct identification contributes to improve the knowledge of epidemiological studies. Two retrospective laboratory studies were conducted on Aspergillus surveillance at the Portuguese National Mycology Reference Laboratory. The first, covering the period 2017-2018, aimed to study the molecular epidemiology of 256 Aspergillus isolates obtained from patients with respiratory, subcutaneous, or systemic infections and from environmental samples. The second, using our entire collection of clinical and environmental A. fumigatus isolates ( N = 337), collected between 2012 and 2019, aimed to determine the frequency of azole-resistant A. fumigatus isolates. Aspergillus fumigatus sensu stricto was the most frequent species in both clinical and environmental samples. Overall, and considering all Aspergillus sections identified, a high frequency of cryptic species was detected, based on beta-tubulin or calmodulin sequencing (37% in clinical and 51% in environmental isolates). Regarding all Fumigati isolates recovered from 2012-2019, the frequency of cryptic species was 5.3% (18/337), with the identification of A. felis (complex), A. lentulus , A. udagawae , A. hiratsukae , and A. oerlinghauensis . To determine the frequency of azole resistance of A. fumigatus , isolates were screened for azole resistance using azole-agars, and 53 possible resistant isolates were tested by the CLSI microdilution reference method. Nine A. fumigatus sensu stricto and six Fumigati cryptic isolates showed high minimal inhibitory concentrations to itraconazole, voriconazole, and/or posaconazole. Real-time PCR to detect cyp51A mutations and sequencing of cyp 51A gene and its promoter were performed. The overall frequency of resistance to azoles in A. fumigatus sensu stricto was 3.0%. With this retrospective analysis, we were able to detect one azole-resistant G54R mutant A. fumigatus environmental isolate, collected in 2015. The TR 34 /L98H mutation, linked to environmental transmission route of azole resistance, was the most frequently detected mutation ( N = 4; 1.4%). Our findings underline the demand for correct identification and susceptibility testing of Aspergillus isolates.

Ginkgo biloba L. leaf extracts and herbal infusions are used worldwide due to the health benefits that are attributed to its use, including anti-neoplastic, anti-aging, neuro-protection, antioxidant and others. The aim of this study was to evaluate the effect of an aqueous Ginkgo biloba extract on HepG2 cell viability, genotoxicity and DNA protection against paraquat-induced oxidative damage. Exposure to paraquat (PQ), over 24 h incubation at 1.0 and 1.5 µM, did not significantly reduce cell viability but induced concentration and time-dependent oxidative DNA damage. Ginkgo biloba leaf extract produced dose-dependent cytotoxicity (IC 50 = 540.8 ± 40.5 µg/mL at 24 h exposure), and short incubations (1 h) produced basal and oxidative DNA damage (>750 and 1500 µg/mL, respectively). However, lower concentrations (e.g., 75 µg/mL) of Ginkgo biloba leaf extract were not cytotoxic and reduced basal DNA damage, indicating a protective effect at incubations up to 4 h. On the other hand, longer incubations (24 h) induced oxidative DNA damage. Co-incubation of HepG2 cells for 4 h, with G. biloba leaf extract (75 µg/mL) and PQ (1.0 or 1.5 µM) significantly reduced PQ-induced oxidative DNA damage. In conclusion, the consumption of Ginkgo biloba leaf extract for long periods at high doses/concentrations is potentially toxic; however, low doses protect the cells against basal oxidative damage and against environmentally derived toxicants that induce oxidative DNA damage.

Lysosomal storage diseases are a group of rare genetic disorders characterized by the accumulation of storage molecules in late endosomes/lysosomes. Most of them result from mutations in genes encoding for the catabolic enzymes that ensure intralysosomal digestion. Conventional therapeutic options include enzyme replacement therapy, an approach targeting the functional loss of the enzyme by injection of a recombinant one. Even though this is successful for some diseases, it is mostly effective for peripheral manifestations and has no impact on neuropathology. The development of alternative therapeutic approaches is, therefore, mandatory, and striking innovations including the clinical development of pharmacological chaperones and gene therapy are currently under evaluation. Most of them, however, have the same underlying rationale: an attempt to provide or enhance the activity of the missing enzyme to re-establish substrate metabolism to a level that is consistent with a lack of progression and/or return to health. Here, we will focus on the one approach which has a different underlying principle: substrate reduction therapy (SRT), whose uniqueness relies on the fact that it acts upstream of the enzymatic defect, decreasing storage by downregulating its biosynthetic pathway. Special attention will be given to the most recent advances in the field, introducing the concept of genetic SRT (gSRT), which is based on the use of RNA-degrading technologies (RNA interference and single stranded antisense oligonucleotides) to promote efficient substrate reduction by decreasing its synthesis rate.