Garlic and onion are either cooked like a vegetable because of their green leaves or are also used as a condiment. Many scientific studies affirm the positives of both for their anti-inflammatory, antioxidant, and antimicrobial potential. Moreover, garlic and onion are regularly employed to treat cardiovascular illnesses, strokes, atherosclerosis, hypertension, hyperlipidemias, and thrombosis, and are also proved effective against Alzheimer's, diabetes, and cancers. Here we have compiled a piece of information regarding the compounds present in garlic and onion along with their pharmacological properties. Although much more studies are required to refine the utilization and enhance garlic and medicine's effectiveness. We hope this work will provide helpful information regarding their pharmacological aspects.

Medicinal mushrooms have got much attention from biologists in the last decades. Leucocalocybe mongolica Imai remains one of the famous clinical and edible mushrooms used in traditional Chinese medicine and Mongolian medicine to treat various diseases. It also commonly consumes in Chinese and Mongolian daily dishes. Numerous biochemical components exist in L. mongolica, especially in the fruiting bodies include; polysaccharides, sterol, lectins, laccase, amino acids, terpenes, volatile compounds, and so on. These biomedical components possess a lot of medicinal properties and provide diverse therapeutical effects for human health, such as anti-tumor activity, antiproliferative activity, anti-diabetes properties, hypotensive effect, hepatoprotective effect, antioxidant activity, cardioprotective effect, and so on. However, this review's main objectives are to illustrate some basics about the bioactive components in L. mongolica and its pharmacological effects on the human body. In addition to giving forward some suggestions for future research on this medicinal mushroom.

The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. The use of small molecules, called pharmacological chaperones (PCs), that can restore the folding, trafficking and biological activity of mutated enzymes has been extensively explored in LSDs as a therapeutic alternative. PCs have the advantage of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules, mainly based in molecules mimicking the enzyme substrates, have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of the identified PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

In the clinical electrophysiologic practice, the reading and comparing electroencephalographic (EEG) recordings some times is insufficient and take to much time. That is why in the last years it has begun to introduce new methods of EEG analysis, that give a better and faster understanding of the EEG dynamics and allow a rapid intervention in the patient's treatment. Tools coming from the information theory or nonlinear system as an entropy and complexity have been shown to be a very good alternative to address this problem. In this work we introduce a novel method -the permutation Lempel-ziv complexity vs permutation entropy map. This method was applied to EEG of two patients with specific diagnosed pathologies during respective follow up processes of pharmacological changes in order to detect changes that are not evident with the usual inspection method. Our results show that the proposed method are useful for observing an evolutionary retrospective clinical effects of pharmacological interventions in both patients, and from these, to follow the clinical response to the proposed treatment.

Ehretia laevis Roxb. (Boraginaceae) has been extensively used as a traditional remedy for the treatment of a diverse range of ailments related to the respiratory system, the gastrointestinal tract, the reproductive system, and against several infections. This review critically assesses and documents, for the first time, the fragmented information on E. laevis, including its botanical description, folklore uses, bioactive phytometabolites and pharmacological activities. The goal is to explore this plant therapeutically. Ethnomedicinal surveys reveal that E. laevis has been used by tribal communities in Asian countries for the treatment of various disorders. Quantitative and qualitative phytochemical investigations of E. laevis showed the presence of important phytoconstituents such as pentacyclic triterpenoids, phenolic acids, flavonoids, fatty acids, steroids, alkaloids, aliphatic alcohols, hydrocarbons, amino acids, carbohydrates, vitamins and minerals. Fresh plant parts, crude extracts, fractions and isolated compounds have been reported to exhibit broad spectrum of therapeutic activities viz., antioxidant, antiarthritic, antidiabetic, anti-inflammatory, antiulcer, antidiarrheal, antidysenteric, wound healing and anti-infective activities. E. laevis is shown to be an excellent potential source of drugs for the mitigation of jaundice, asthma, dysentery, ulcers, diarrhea, ringworm, eczema, diabetes, fissure, syphilis, cuts and wounds, inflammation, liver problems, venereal and infectious disorders. Although few investigations authenticated its traditional uses but employed uncharacterized crude extracts of the plant, the major concerns raised are reproducibility of therapeutic efficacy and safety of plant material. The outcomes of limited pharmacological screening and reported bioactive compounds of E. laevis suggest that there is an urgent need for in-depth pharmacological investigations of the plant.

Mulberry (Morus) cultivated worldwide in diverse agro-ecological conditions recognized as the fodder of silkworms (Bombyx mori). In India, ranging from high altitude Himalayan region to coastal region, the farmers generally cultivate these four species of mulberry (Morus alba, M. indica, M. serrata, and M. laevigata). Mulberry fruit is used in traditional medicine for several years in China and also consumed as food material in different countries of Asia and Africa. Mulberry fruit, along with high nutritious value, contains many bioactive phytochemicals that are30 of health benefits and can fight against many diseases. Many researchers attracted to this property of mulberry fruit, and they isolated bioactive polysaccharides, anthocyanins, flavonols, flavonols, phenolic acids, alkaloids, and melatonins. These compounds have antioxidant property and due to this, either in synergistically or in the pure form, these components have direct or indirect curative activity on diabetes, inflammation, tumor, hepatic diseases, immunomodulation, hyperlipidemia, neural damage, and chronic diseases. This tremendous bioactivity of mulberry fruit extract may open up a new dimension in the food and medicine industry. The present review provides recent findings of the phytochemical foundation and their bioactivities, which may encourage many researchers to explore the molecular mechanism of the biological activities which can be used for human welfare.

Picrasma javanica Blume or also known as Picrasma nepalensis or Picrasma philippinensis is a plant belongs to the Simaroubaceae family, which is known for its secondary metabolites namely quassinoids with various pharmacological properties including antitumor, antimalarial and antiviral. The plant traditionally used as medicine for different diseases in Myanmar, Thailand and Indonesia. The purpose of this study is to discern the phytochemical constituents and pharmacological activities of Picrasma javanica. The background, phytochemical constituents and pharmacological benefits of Picrasma javanica were reviewed and supported from previous studies, including in vivo and in vitro studies. The literature used in the review comprises of published books, journals, reviews and articles published from the year of 1969 to 2018, which are available in ScienceDirect, PubMed, Scopus and GoogleScholar. Chemical structures presented in this paper are either drawn with ACD/ChemSketch. Picrasma javanica possesses several phytochemical constituents, including quassinoids, alkaloids and triterpenoids. Compounds of the plant were isolated and studied for their pharmacological activities such as antimalarial, antiproliferative, antiviral, antimicrobial and membrane stabilising activity. Most importantly, these studies showed that the key players for the pharmacological benefits are quassinoids and alkaloids present in the plant.Picrasma javanica indeed has therapeutic potentials which may be beneficial for people. However, further extensive studies must be done on the plant as the detailed information on its pharmacological activities are still lacking.

In 1789, the Annonaceae family was cataloged by de Jussieu. It encompasses tropical and subtropical plants which are widespread in distribution across various continents such as Asia, South and Central America, Australia and Africa. The genus of Annona is one of the 120 genera of the Annonaceae family and contains more than 119 species of trees and shrubs. The majority of these species are found in tropical America with more than 105 species (26 of them are endemic). Due to its edible fruits and medicinal properties, Annona is the most important genus of Annonaceae family. Despite Annona having many species, only limited species of this family are economically important such as A. squamosa L. (sugar apple), A. cherimola Mill. (Cherimoya), A. muricata L. (guanabana or soursop), A. atemoya Mabb. (atemoya), a hybrid between A. cherimola and A. squamosa, A. reticulata L. (custard apple), A. glabra L. (pond-apple) and A. macroprophyllata Donn. Sm. (ilama). Phytochemically, several classes of secondary metabolites such as acetogenins, essential oils, alkaloids, terpenoids and flavonoids have been described in this genus. A variety of pharmacological activities have been reported from various parts of Annona species specially leaves and seeds including applications against antibacterial, anticancer, antidiabetic and anti-inflammatory.

Introduction Recent evidence from relatively small randomized controlled trials would seem to support a useful role of ranolazine for the prevention and treatment of atrial fibrillation (AF). The present study is aimed at providing information about the possible beneficial anti-arrhythmic properties of ranolazine. In particular, the meta-analysis carried out in this study focuses on the application of ranolazine to prophylaxis and treatment of atrial fibrillation.Methods Both randomized controlled trials (RCTs) and non randomized observational studies concerning the effects of ranolazine on AF were included in the meta-analysis. In each of the considered studies, a comparison was made between a group of patients taking ranolazine and a second group treated instead with another antiarrhythmic therapy , or assigned to placebo. Efficacy outcomes were the risk of new- onset AF, the probability of conversion to sinus rhythm of patients with recent occurrence(≤ 48 h)of AF and the time to conversion to sinus rhythm. Safety endpoints were death, adverse events, QTc prolongation and hypotension.Results Ten studies ( 8 RCTs and 2 nonrandomized observational studies) were gathered on the whole. Ranolazine was effective in preventing the occurrence of AF when compared to controls (RR= 0.60; 95% CI: 0.43–0.83; p = 0.002). Subgroup analysis showed a more pronounced preventive effect of ranolazine against AF in the postoperative setting of coronary artery bypass grafting(CABG) surgery (RR= 0.39; 95% CI: 0.18-0.83; p=0.02) when compared to non- postoperative AF (RR= 0.76; 95% CI: 0.63-0.92; p=0.04). Ranolazine enhanced the chances of successful cardioversion when added to intravenous amiodarone compared to amiodarone alone (RR 1.18; 95% CI: 1.05–1.33; p = 0.004) and significantly decreased the time to cardioversion(SMD= −10.35 h; 95% CI: −18.13 hours to − 2.57 hours; p < 0.001). Overall risks of death, adverse events, and QTc prolongation were shown to be similar in the comparison between patients treated with ranolazine and controls. Conclusions Ranolazine given orally at appropriate doses showed the property to significantly quicken the conversion of AF to sinus rhythm when combined with the iv amiodarone, compared to iv amiodarone alone . Furthermore, in patients in sinus rhythm, ranolazine proved to reduce the frequency of new onset AF as well as of its recurrences, especially in patients undergone CABG surgery, known to be at high risk of developing postoperative AF. In addition, ranolazine use seems to be safe and associated with relatively few adverse events.

Plant secondary metabolites are organic compounds (alkaloids, flavonoids, phenolics, tannins, anthraquinones, saponins, steroids, lignins, terpenes) produced by plant for self-defense during growth and development in order to protect them from harmful agents. As population is increasing and quality of life is reducing couple with outbreak of some diseases that are posing threat on the economy, a lot of medicinal plants have attracted interest of researchers because of the usefulness of these metabolites in pharmaceuticals, food and cosmetic industries. In this review, the pharmacological activities of some medicinal plants that are rich in secondary metabolites were studied, means of identifying and quantifying using spectrophotometry and chromatography techniques were also discussed. However, this will assist to reduce the uses and dependent on the synthetic drug and the onset of the age related diseases.

Low back pain (LBP) is a leading cause of disability. It significantly impacts the patient’s quality of life, limits their daily living activities, and reduces work productivity. To reduce the burden of LBP, several pharmacological and non-pharmacological treatment options are available. This review summarizes the role of heat therapy in the management of LBP. First, we outline the common causes of LBP, then discuss the general mechanisms of heat therapy on (LB)P, and finally review the published evidence regarding the impact of heat therapy in patients with acute or chronic non-specific LBP. This review demonstrates that continuous, low-level heat therapy provides pain relief, improves muscular strength, and increases flexibility. Therefore, this effective, safe, easy-to-use, and cost-effective non-pharmacological pain relief option is still relevant in modern clinical practice.

Nowadays, an analysis of virtual media to predict society’s reaction to any events or processes is a task of great relevance. Especially it concerns meaningful information on healthcare problems. Internet sources contain a large amount of pharmacologically meaningful information useful for pharmacovigilance purposes and repurposing drug use. An analysis of such a scale of information demands developing the methods that require the creation of a corpus with labeled relations among entities. Before, there have been no such Russian language datasets. This paper considers the first Russian language dataset where labeled entity pairs are divided into multiple contexts within a single text (by used drugs, by different users, by the cases of use, etc.), and a method based on the XLM-RoBERTa language model, previously trained on medical texts to evaluate the state-of-the-art accuracy for the task of indication of the four types of relationships among entities: ADR–Drugname, Drugname–Diseasename, Drugname–SourceInfoDrug, Diseasename–Indication. As shown based on the presented dataset from the Russian Drug Review Corpus, the developed method achieves the F1-score of 81.2% (obtained using cross-validation and averaged for the four types of relationships), which is 7.8% higher than the basic classifiers.

Solidago virgaurea L. (European goldenrod, Woundwort), Asteraceae, is a familiar medicinal plant in Europe and other parts of the world, widely used and among the most researched species from its genus. The aerial parts of European goldenrod have long been used for urinary tract conditions and as an anti-inflammatory agent in the traditional medicine of different peoples. Its main chemical constituents are flavonoids (mainly derived from quercetin and kaempferol), C6-C1 and C6-C3 compounds, terpenes (mostly from the essential oil), and a large number of saponin molecules (mainly virgaureasaponins and solidagosaponins). Published research on its potential activities is critically reviewed here: antioxidant, antiinflammatory, analgesic, spasmolitic, antihypertensive, diuretic, antibacterial, antifungal, antiparasite, cytotoxic and antitumor, antimutagenic, antiadipogenic, antidiabetic, cardioprotective, and antisenescence. The evidence concerning its potential benefits is mainly derived from non-clinical studies, some effects are rather modest, whereas others are more promising, but need more confirmation in both non-clinical models and clinical trials.

Background: A growing number of clinical practice guidelines (CPGs) with regards to non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistency of recommendations, it remains uncertain how best to design and implement such non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: Clinical practice guidelines which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using the Appraisal of Guidelines for REsearch and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions that were recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: Fourteen CPGs were identified and analysed. Of the 14 CPGs appraised, only five were rated as high quality. The domain with the highest standardised percentage was “scope and purpose” (84.61%), while the “applicability” domain had the lowest standardised percentage (51.04%). Five guidelines were assessed as “recommended”, seven were rated as “recommended with modifications”, and the remaining two were considered “not recommended”. Regarding the content analysis, physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage, and acupressure were the common self-managed non-pharmacological interventions recommended by the 14 CPGs. Physical activity/exercise was the only self-managed non-pharmacological intervention that was mostly recommended for psychological and physical symptom management by the included CPGs. However, there were significant disparities in terms of level of evidence and grade of recommendation in the included CPGs. Conclusion: The recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs in order to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements on the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Also, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline was able to accelerate recovery of consciousness and to improve the outcome of this kind of patients, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI.

Non-pharmacological interventions in the fight against COVID 19 include: a) suppression, which facilitates its extinction; and b) mitigation, which reduces its speed of spread. Left unmitigated, the intensive care unit bed capacity (ICU) is exceeded over its maximum supply, resulting in increased deaths. Suppression has shown in simulation models the potential for decreasing ICU occupation below its surge limit, effectively decreasing mortality. However, for avoiding a rebound in transmission, suppression must be maintained intermittently until a vaccine is available (which may take up to 2 years). The objective of this paper was to describe the mortality patterns observed in Spain, Italy and South Korea for discussing a hypothetical combined public health policy and socioeconomic model that could potentially reduce mortality while reducing the economic impact of this pandemic in Spain. The plan is based on a progressive-voluntary reinstatement to work of the population exposed to the lowest risks (healthy non-immune family units <50 y/o and immune population) and it depends on having sufficiently available ICU beds for providing adequate support. This model, if proven correct for Spain, could eventually be followed by other countries facing a similar impact of the present pandemic.

Abstract The aim of this research is to conduct a systematic review analysing the role of the physiotherapy interventions in palliative care. PRISMA as a critical appraisal tool was utilised for the selection of the research articles. The inclusion criteria were based on the year of publication, ease of availability, language, geographical location, and study type. To ensure the credibility, databases such as Elsevier, Proquest, and EBSCO Host were used to filter the grey content. Data published in the past ten years (2009-onwards) was only included to ensure the selection of the most recent interventions used by the physiotherapists. A total of 11 articles were selected which determined that physiotherapy interventions involving breathing exercises, aerobic exercises, manual therapies, and educational awareness were critical to promoting the functional capability and empower the patients.

G protein-coupled receptors (GPCRs) play a key role in many cellular signaling mechanisms, and must select among multiple coupling possibilities in a ligand-specific manner in order to carry out a myriad of functions in diverse cellular contexts. Much has been learned about the molecular mechanisms of ligand-GPCR complexes from Molecular Dynamics (MD) simulations. However, to explore ligand-specific differences in the response of a GPCR to diverse ligands, as is required to understand ligand bias and functional selectivity, necessitates creating very large amounts of data from the needed large-scale simulations. This becomes a Big Data problem for the high dimensionality analysis of the accumulated trajectories. Here we describe a new machine learning (ML) approach to the problem that is based on transforming the analysis of GPCR function-related, ligand-specific differences encoded in the MD simulation trajectories into a representation recognizable by state-of-the-art deep learning object recognition technology. We illustrate this method by applying it to recognize the pharmacological classification of ligands bound to the 5-HT2A and D2 subtypes of class A GPCRs from the serotonin and dopamine families. The ML-based approach is shown to perform the classification task with high accuracy, and we identify the molecular determinants of the classifications in the context of GPCR structure and function. This study builds a framework for the efficient computational analysis of MD Big Data collected for the purpose of understanding ligand-specific GPCR activity.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Gymnema sylvestre is a pharmacological plant which has a rich source of bioactive compounds specifically gymnemic acid (GA) and phenolic compounds (PC) that used for pharmaceutical industries. Sources for naturally occurring bioactive compounds are limited, due to geographical and seasonal variations; on the other hand, it is commercially in demand. Biosynthesis of G. sylvestre phytochemicals through in vitro culture often enhanced by elicitation. The use of cell suspension cultures (CSC) has interested serious attention on the production of essential phytochemicals. The current study is aimed at improving the contents of GA and PC in G. sylvestre CSC using the copper oxide nanoparticles (CuO NPs). Callus was obtained on MS medium with 2.0 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), 0.1 mg/L kinetin (KIN), phytoagar (8.0 g/L), and sucrose (30 g/L). The above medium devoid of agar was used for the initiation of CSC. The CSC was treated with three levels of CuO NPs (1, 3 or 5 mg/L) to enhance the production of GA and PC. The greatest amount of GA (89.25 mg/g dry cell mass, DCM), total phenolic (245.10 mg/g), and flavonoid (4.57 mg/g) in CSC were achieved when G. sylvestre cells were treated for 48 h with 3 mg/L CuO NPs. Also, the biomedical potential (antioxidant, antidiabetic, anti-inflammatory, antibacterial, antifungal and anticancer activities) were also high in the CuO NPs (3 mg/L) treated CSC extracts of G. sylvestre. CuO NPs elicitation of CSC significantly increased production of GA (9-fold), and PC than non-elicited CSC in G. sylvestre.

Psychotic disorders occur as a result of pathobiochemical processes in the brain, which disrupt the central neurotransmission of molecules such as dopamine and glutamate. The dopamine hypothesis, adopted more than 2 decades ago, has repeatedly asserted its position as an etiopathogenetic substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. On the other hand, cognitive impairments in schizophrenia remain not fully understood but are thought to be present during all stages of the disease, as well as in the prodromal the interictal and residual phases. Over the last decade, functional magnetic resonance imaging has focused on research of brain networks like the Default mode network, the Salience network and Central executive network, enabling a deeper understanding of cognitive deficits, as well as other phenomena such as disorganization of thought and behavior. The study of the nodes of these networks, such as the precuneus and insula, informs about their complex significant roles as structures responsible for important cognitive domains such as concentration, attention, ability to understand and reproduce information, as well as memory functions. It is suggested that the neurotransmission of dopamine and glutamate play a key role in these processes and their successful modulation in the correct brain regions through psychopharmacological and biomedical instrumental methods may lead to a significant reversal of conventional paradigms. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide the translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.

A method is developed to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC). A structurally heterogeneous set of compounds active against MTBC was used to obtain a structural pattern model based on structural invariants. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets and was also able to select new active chemical structures in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

Cardiovascular disease (CVD) comprises a group of heart and circulatory disorders, which are regarded as a global medical issue with high prevalence and mortality rates. Currently, vascular regenerative surgery represents the most employed therapeutic option to treat ischemic disorders, even though not all the patients are amenable to surgical revascularization. Therefore, more efficient therapeutic approaches are urgently required to promote neovascularization. Therapeutic angiogenesis represents an emerging strategy that aims at reconstructing the damaged vascular network by stimulating local angiogenesis and/or promoting de novo blood vessel formation according to a process known as vasculogenesis. Circulating endothelial colony forming cells (ECFCs), in turn, represent truly endothelial precursors able to aggregate into bidimensional tube networks and to originate patent vessels. Accordingly, ECFCs provide the most rationale and promising cellular candidate for therapeutic purposes. The current review provides a brief outline on the origin and characterization of ECFCs and a summary of the progress in preclinical studies aiming at assessing their efficacy in a variety of ischemic disorders, including AMI, PAD, ischemic brain disease and retinopathy. We also describe how to enhance the vasoreparative potential of ECFCs by boosting specific pro-angiogenic signalling pathways either pharmacologically or through gene manipulation. Taken together, these observations suggest that ECFCs represent a useful strategy to treat ischemic diseases.

The epidemiological situation generated by COVID-19 has highlighted the importance of applying non-pharmacological measures. Among these, mass screening of the asymptomatic general population has been established as a priority strategy by carrying out diagnostic tests to limit the spread of the virus. In this article, we aim to evaluate the economic impact of mass COVID-19 screenings of an asymptomatic population through a Cost-Benefit Analysis based on the estimated total costs of mass screening versus health gains and associated health costs avoided. Excluding the value of monetized health, the Benefit-Cost ratio was estimated at approximately 0.45. However, if monetized health is included in the calculation, the ratio is close to 1.20. The monetization of health is the critical element that tips the scales in favour of the desirability of screening. Screenings with the highest return are those that maximize the percentage of positives detected.

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by the impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degree of mental retardation, autism, ataxia and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential use of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between the researchers and the patients.

Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor- abiraterone and androgen receptor antagonists- enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.