Antigenic drift in influenza strains allows viruses to avoid being fully suppressed by seasonal vaccines. As a result, public interest has led to increased scrutiny and reevaluation of anti-influenza antiviral drugs as possible solutions. Unfortunately, many anti-influenza drugs developed around the globe suffer from a lack of sufficient clinical trials, as well as a lack of toxicity data. This is especially true of Arbidol, a popularly used drug for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, which were developed in the United States, also fall victim to inconclusive clinical trials and adverse effects. Adamantanes, while proven to be effective in treating influenza A, are encountering rapid, widespread cross-resistance. Baloxavir marboxil, a newer anti-influenza medication, shows promise in treating acute uncomplicated influenza, and may avoid the development of resistance when coadministered with other antiviral drugs. This review explores the antivirals available for influenzas treatment at this time.

More than 15,000 prescriptions and over the counter drugs are available according to the US Food and Drug Administration website. Moreover, several herbal medicines and dietary supplements are readily available to add to the list of possible drugs, which can potentially cause adverse drug interactions. These are a pressing concern for all as they can interfere with many dental procedures. Additionally, the number of geriatric patients seen in routine dental practice has increased over time. This implies that there are more patients with multiple diseases and health conditions like hypertension, diabetes, problems associated with the cardiovascular, renal and gastrointestinal systems, arthritis, osteoporosis, etc. All these require patients to be on certain medications. Furthermore, advancement in the dental field has led to more complex dental procedures (implants, grafts) being carried out in a general dental practice. These advanced and slightly more invasive treatments require the use of certain drugs before, during and after the treatment like local anesthetics, vasoconstrictors, anxiolytics, analgesics and antibiotics. All of these can possibly interact with medications a patient is already taking and can also interfere with the current dental treatment and create complications. This article aims to provide necessary information about commonly encountered systemic diseases and associated treating medications, their mechanism of action, possible complications and their management. The classes of drugs discussed include anti-platelet agents, vitamin K antagonists, novel oral anticoagulants, bisphosphonates, disease-modifying anti-rheumatic drugs and oral contraceptives.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

Introduction: Periodontitis is a severe oral infection that can contribute to systemic inflammation. A large body of evidence suggests a role for systemic inflammation in the initiation of neurodegenerative disease. This systematic review synthesized data from observational studies to investigate the association between periodontitis and neuroinflammation in adults. Methods and materials: A systematic literature search of PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed for studies published from the date of inception up to September 2021. Search terms for the exposure “oral disease” and outcome “dementia”, “neuroinflammation” and “cognitive decline” were used. Study selection and data extraction were independently undertaken by two reviewers. The final eligible articles were included only if the exposure is periodontitis and the outcome is cognitive impairment or dementia or a topic related to this condition, and if the study was conducted in an adult population. The quality and risk of bias were assessed by Newcastle Ottawa Scale (NOS). Qualitative synthesis was used to narratively synthesize the results. Six cohort studies, three cross-sectional studies, and two case-control studies met the inclusion criteria. These eleven studies were only narratively synthesized. Meta-analysis was not performed due to the methodological heterogeneity of the studies. Results: All the included studies show evidence of an association between periodontitis and cognitive im-pairment or dementia and Alzheimer’s disease pathology. Conclusion: Nonetheless, the mechanisms responsible for the association between periodontitis and dementia are still unclear.

Multiple biological pathways manifest and latent, meant for human survival, become a liability in cancer cure. With an increasing understanding of innumerable complex paths, cancer progression and development of resistance is no surprise. For the three “vasculature-immune-phenotypic” fundamental changes, hypoxia is the maestro orchestrating the whole gamut of changes (through the master manipulator - HIF-1 α), simultaneously transactivating hundreds of pro-angiogenic genes. Such a complex molecular bio-network begs the question, “Is our cancer research caught in such a tangled web that we have lost sight of the Spider?”. Hypoxia is this Spider weaving compensatory webs with every intervention/ obstruction. Anti-angiogenic (AAG) research has been conducted mainly in silos – exploring independent paths. This review conceptualizes a convergence of a multitude of research worldwide to a single theme of normalizing vasculature as a primary baseline for overcoming resistance to AAGs or their combinations.

There is now considerable evidence that several infectious agents (viruses, bacteria, or parasites) may play a contributing role in the development of Alzheimer’s disease (AD). The six primary suspects are herpes viruses, spirochetal bacteria, Chlamydia pneumoniae, Porphyromonas gingivalis, mycobacteria, and toxoplasma parasites. Also, some of the antimicrobial and antiviral agents that are used to treat them have shown promise for AD interventions. I describe this evidence and assert it is now time to accelerate clinical trials of these existing drugs, already federally approved, to determine if such treatments can delay, halt, or reverse AD.

Currently, the use of medications during pregnancy in Latin America is common; studies with Latin American samples find that nearly 90% of pregnant women use some medication at least once during pregnancy. Furthermore, approximately 21% of the respondents self-medicated. Worldwide, the prevalence of this disease is 32%. The most common medications are nonsteroidal anti-inflammatory drugs and analgesics. Many of these drugs are available over the counter without a prescription. For this reason, a systematic review of the literature on the adverse effects on the woman and the fetus was performed. Objective: To determine the adverse effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on pregnant women and fetuses during pregnancy. Methods: Systematic literature review. The following search strategy was used for the databases: Science Direct, PubMed, Scopus and Web of Science, through September 3, 2022. The population of pregnant women without previous comorbidities was defined. The intervention of interest was the use of NSAIDs during pregnancy. The outcomes of interest were adverse effects for the mother or fetus (weight of the newborn, congenital malformations present in the fetus, systemic effects in the pregnant woman during her gestation period). The types of studies included clinical trials, cohort studies and case‒control studies. Results: 1 study included 2,985 pregnant women without previous comorbidities. The use of aspirin more frequently during pregnancy stands out. The adverse effects on the fetus were preterm birth <37 weeks, low birth weight < 2500 g and increased admission to the neonatal intensive care unit. No adverse effects were found for the mother. Conclusions: There are not enough data indicating that the use of NSAIDs during pregnancy is safe. Some studies show that the use of NSAIDs during pregnancy could be related to problems in the development and growth of the fetus and health effects for the mother during pregnancy, so it is advisable to use these drugs under medical prescription and for the shortest possible time. in the gestation stage.

SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

At a time when the world faces an emotional breakdown, crushing our dreams if not taking our lives, we realize that together we must fight the war against the COVID-19 outbreak even if almost the majority of the scientific community finds itself confined to home. Every day, like everyone else, we, scientists, listen to the latest news with its promises and announcements. Across the world, a surge of clinical trials trying to cure or slow down the coronavirus pandemic has been launched to bring hope instead of fear and despair. One first proposed clinical trial has drawn worldwide hype to the benefit of chloroquine (CQ), a well-known and broadly used anti-malarial drug, in the treatment of patients infected by the recently emerged deadly coronavirus (SARS-CoV-2). We should consider this information in the light of the long-standing anti-inflammatory and anti-viral properties of CQ-related drugs. Yet, none of the articles promoting the use of CQ in the current pandemic evoked a possible molecular or cellular mechanism of action that could account for any efficacy. Here, given the interaction of viruses with macroautophagy (hereafter referred to as autophagy), a CQ-sensitive anti-viral safeguard pathway, we would like to discuss the pros, but also the cons concerning the current therapeutic options targeting this process.

Preterm infants often experience frequent intermittent hypoxia (IH) episodes which is associated with neuroinflammation. We tested the hypotheses that early caffeine and/or non-steroidal in-flammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH-induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hy-peroxia (50% O2) from birth (P0) to P14. For early treatment, the pups were administered: 1) dai-ly caffeine citrate (Cafcit, 20 mg/kg IP loading on P0, followed by 5 mg/kg from P1-P14); 2) ke-torolac topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) caffeine+ketorolac co-treatment; 5) caffeine+ibuprofen co-treatment; or 6) equivalent volume saline. On P14, animals were placed in room air (RA) with no further treatment. For late treatment, pups received similar treatments from P15-P21 (caffeine and/or ketorolac), or P15-P17 (ibuprofen). RA control were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, mye-lination, and biomarkers of inflammation. IH caused significant inflammation, reduced mye-lination, and apoptosis in preterm rat brains, an effect that was improved predominantly with combined caffeine/NSAID early treatment. Early caffeine/NSAID co-treatment confers syner-gistic neuroprotection against IH-induced damage.

The improvement of health and social care needs the introduction of shared solution at transnational level. The SI4CARE (Social Innovation for Integrated Health Care) project is a transnational initiative within the Adriatic-Ionian regions aiming to develop strategies to improve the current status of health and social care. The Municipality of Miglierina, a small rural town in Calabria, which is a member the project, is developing a pilot action related to the use of wearable device for monitoring people affected by dementia with the project partner Ra.Gi.. Ra.Gi. is a non-profit organization dedicated to assisting people with dementia in day care centers and so-called dementia-friendly communities. The pilot is based on the use of smart wearable devices to monitor these patients during their daily lifetime. This paper focuses on the design and implementation of the system discussing the proposed application, the strengths and weaknesses. Finally, the possibility of extending the experiment to the other Adriatic-Ionian region is presented.

α-synuclein is a constituent of Lewy bodies and mutations of its gene cause familial PD. A previous study showed that a variant of α-synuclein gene (SNCA), namely the 263bp allele of Rep1 was associated to faster motor progression in PD. On the contrary, a recent report failed to detect a detrimental effect of Rep1 263 on both motor and cognitive outcomes in PD. Aim of this study was to evaluate the influence of the Rep1 variants on disease progression in Parkinson’s Disease (PD) patients. We recruited and genotyped for SNCA-Rep1 426 PD patients with age at onset ≥40 years and disease duration ≥4 years. We then analyzed frequency and time of occurrence of wearing-off, dyskinesia, freezing of gait, visual hallucinations and dementia. SNCA Rep1 263 carriers showed increased risk of both dementia (HR=3.03) and visual hallucinations (HR=2.69) compared to 263 non-carriers. In conclusion, SNCA Rep 1 263 allele is associated to a worst cognitive outcome in PD.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from the patients’ bodies. A potential strategy called “lock-in apoptosis” targeting the budding phase of life cycle of virus leading to susceptibility to apoptosis of HIV-1 infected cells for elimination of HIV-1 reservoirs and ultimately for a complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA) approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases. The limited availability of effective antibiotics has encouraged the development of innovative strategies such as combinatory therapy to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory and the antimicrobial combinatory effect of celecoxib with oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs were determined for standard strains and clinical isolates of S. aureus strains, counting methicillin-resistant strains (MRSA), by the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated by the checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all the tested strains (MIC ranging from 32 to 64 mg/mL), followed by diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/mL). Several synergistic effects were observed for tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was obtained against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/mL with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/mL). This is the first report on the antistaphylococcal combinatory effect of celecoxib with oxacillin. Our findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. Thus, this study presents novel findings that celecoxib could, in some cases, resensitise MRSA strains to become susceptible to certain β-lactams (e.g., oxacillin) not previously tested.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

Dementia is a public health priority, in which memory impairments are prevalent and affects an individual’s daily activities. Research has tried to find ways to support memory problems of individuals with dementia. Self reference effect (SRE) has been shown to benefit memory in healthy, non-dementia group. The study aimed to investigate if SRE will improve memory performance of individuals with dementia. We used ecologically valid Ownership Procedure and the Remember/Know Paradigm to examine the Self-Reference Effect (SRE) on memory. It was hypothesised that participants living with dementia will perform differently in the recall of items that were self-referentially encoded compared to items other-referentially encoded and that the memory will be different in control participants than in those that live with dementia. The research found that self-referential processes did not have effect on memory in individuals with dementia. We suggest that impaired self-awareness may have contributed to the lack of this effect. However, we had a small sample size and these findings should be treated with caution.

Alzheimer's disease is characterized by a progressive decline of cognitive functions. The class of drugs used for the treatment are acetylcholinesterase inhibitors. Essential oils have contributed to folk medicine and discovery of new drugs for a long time. The purpose of the study was to investigate the in vitro and in silico the anti-acetylcholinesterase activity, as well as acute toxicity of the essential oil of Lippia origanoides. EOLO was obtained by hydrostelting and analyzed by gas chromatography-mass spectrometry. The inhibition assay of acetylcholinesterase enzyme activity was evaluated in vitro, as well as in silico by docking. The effects of EOLO on hematological, biochemical and behavioral parameters were analyzed in mices. We expose that EOLO shows good anti-acetylcholinesterase activity and low toxicity, possibly resulting from the action of the majority compounds thymol, carvacrol and p-cymene. The anti-acetylcholinesterase potential in vitro demonstrating a 70% inhibition. The docking results elucidated the participation of the major phenolics in AChE inhibition by interacting with the catalytic cavity of AchE. The acute oral toxicity test classified as low toxicity. These results contribute to expand the knowledge about essential oil of Lippia origanoides. Therefore, appears to be promising for herbal medicine production with anti-acetylcholinesterase and antioxidant activity.

Herbal cosmetics are cosmetics derived from plants. One example is bakuchiol. Bakuchiol is a meroterpene phenol from the seeds of the Psoralea corylifolia plant. Bakuchiol can be derived from Psoralea grandulosa, Pimelea drupaceae, Ulmus davidiana, Otholobium pubescens, and Piper longum. Bakuchiol has antioxidant, anti-inflammatory, and anti-aging activities such as retinol. Bakuchiol will replace retinol with much better safety. Bakuchiol and retinoids share similar cellular pathways, such as the regulation of retinoic acid, the expression of collagen, and extracellular matrix synthesis enzymes. Bakuchiol has many benefits for the skin, so cosmetics and skin therapy can use bakuchiol. This review aims to provide information about the activity of bakuchiol, which has benefits for facial skin, so that this review can be a reference in making cosmetics containing bakuchiol. Bakuchiol has many benefits for skincare such as anti-aging, anti-hyperpigmentation, anti-oxidant, anti-inflammatory, anti-acne, and anti-melanogenesis. Products containing bakuchiol on the market are cleansers, serum, nanoemulsion, and cream.

Young dementia carers (YDCs) rarely receive appropriate training and support. Their visibility and identification remain dangerously low and as a consequence, support initiatives being developed are failing to reach them. This study explored the success (or failure) of YDCs identification pathways as well as the barriers and enablers to their implementation. An explorative qualitative approach was followed drawing on the experiences of parents of YDCs, dementia researchers, professionals in the field of dementia/young carers and young adult carers. Data collection involved semi-structured interviews (n=17) and a participatory 2-hour workshop to discuss and critique preliminary themes as well as explore strategies to increase the visibility and identification of YDCs. Five themes were identified: A ‘whole family approach’ (as a pathway to identification); ‘Not a carer’ (self/family identification); A postcode lottery (high variability of support services); Tailored support that is ‘fit for purpose’ and the ‘power’ of peer support. Recommendations on potential initiatives and actions that can help raise awareness and increase identification success of YDCs are proposed. Our findings support the need for a broad and holistic approach to the identification of YDCs that runs alongside the development of support initiatives that are accessible and relatable. The support itself will play a role in improving subsequent identification or hindering it if not ‘fit for purpose’.

Ageing of the world population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioural and psychological syndromes known as neuropsychiatric or behavioural and psychological symptoms of dementia remarkably reduce the quality of life of patients. Rising evidence is unraveling the pathophysiology of these symptoms in which all the neurotransmitter systems in the Central Nervous System (CNS) are implicated, with a pivotal role of alterations of the glutamatergic neurotransmission. Pharmacological agents for the treatment of these disorders endowed with efficacy and safety are not available yet; aromatherapy provides the best evidence in the control of agitation, the most resistant symptom. Basic research effort demonstrates that the essential oil of bergamot induces anxyolitic-like effects, devoid of sedation, typical of benzodiazepines, with noteworthy advantage for demented patients. People suffering from dementia often cannot verbalize pain, thus resulting unrelieved and contributing to agitation. Bergamot essential oil provides extensive evidence of analgesic properties independent from the route of administration. Among other mechanisms, modulation of autophagy, a process involved in neuropathic pain, seems to be implicated in the analgesic activity of bergamot essential oil. These data, together with the reported safety profile form the rational basis for bergamot as a neurotherapeutic to be trialed for the control of behavioural and psychological symptoms of dementia.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

Hospitalizations for patients with diabetes and dementia take a significant health and economic toll on older adults in the United States. The present study sought to examine the differences in hospitalization characteristics and outcomes associated with diabetes and dementia separately and together using discharge record data of Los Angeles County residents aged 50+ from the California Department of Health Care Access and Information for the period 2019-2021. Results from multiple linear regression analyses indicated that when compared to those with no diabetes or dementia, patients with diabetes alone exhibited the highest total charges, while those with comorbid diabetes and dementia exhibited lower charges (p≤.05). Results of a multinomial logistic regression found that patients with comorbid diabetes and dementia had the highest odds of having a length of stay of 7+ days (AOR=1.49; 95% CI=1.44-1.53). A matched-case control analysis found that comorbid diabetes and dementia was associated with significantly lower odds of hypertensive disease than diabetes alone (MOR=0.81; 95% CI=0.67-0.97). These results highlight the complexity of factors affecting variation in hospitalization outcomes across these distinct disease profiles. Findings suggest a need to carefully consider this complexity when developing health policies or strategies to improve hospitalization outcomes involving these disease conditions.

Background. Amyotrophic Lateral Sclerosis (ALS) is a devastating disease involving motor neuron degeneration. The few drugs approved for treatment have at most a marginal benefit, and death usually occurs 2-5 years after diagnosis. Methods. A thorough manual examination of the relevant literature, covering over 35,000 papers. Results. Two major phenomena that are generally not known to clinicians were found. First, insulin signaling is impaired in ALS even in patients not diagnosed with diabetes (DB). Almost all studies that have explicitly tested insulin function in non-DB ALS patients using glucose tolerance tests (18 out of 20, 1964-2022, different groups) have found it to be impaired. Second, there is strong evidence for excessive insulin-independent glucose uptake (IIGU) in ALS. In addition, (i) early/late diabetes are associated with increased/decreased risk, respectively; (ii) insulin-based diabetes drugs are protective in ALS in large retrospective human studies; and (iii) strong animal and human evidence shows that insulin opposes all of the major pathological processes in ALS. Conclusion. Most ALS patients have insulin impairment, yet this is commonly not diagnosed, likely because excessive IIGU normalizes glucose levels. The impairment promotes disease progression. Late diabetes is associated with decreased risk because high glucose levels indicate non-excessive IIGU, and because diabetes drugs are protective. Insulin-based treatment (e.g., GLP1 agonists, insulin) is beneficial and can be disease-modifying in ALS and in frontotemporal dementia variants comorbid with ALS. ALS patients should be routinely tested for insulin function and treated if test results are positive.

Background: The psychomotor agitation of the behavioural and psychological symptoms of dementia (BPSD) is one of the common issues in aged care facilities, leading to the poor functional and medical consequences. Psychotropic interventions are the preferred choice of treatment, but which medication should be the prescribers first preference? This review aims to compare pharmacological interventions for psychomotor agitation, judging them according to their effectuality and justifiability profiles. This is to be achieved by retrieving information from Randomised Control Trials (RCTs) and systematic reviews. Objectives: This review evaluates evidence from RCTs, systematic reviews, and meta-analyses of BPSD patients who have taken agitation treatments. Assessing the efficacy of selective serotonin reuptake inhibitors (SSRI) and antipsychotic treatments when compared to each other for the purpose of improving agitation outcomes. Methods: This review includes RCT that compared one or more active ingredient medications with another medication or with a placebo, along with systematic reviews comparing citalopram (SSRI) with antipsychotics such as quetiapine, olanzapine, and risperidone. Studies were extracted by searching and accessing databases, such as PubMed, OVID, and Cochrane with restrictions of date from 2000 to 2021 and English language. Conclusion: There is still limited studies of SSRIs for the treatment of agitation in BPSD. SSRIs such as citalopram were associated with a reduction in symptoms of agitation, and lower risk of adverse effects compared to antipsychotics. Future studies are required to assess the long-term safety and efficacy of SSRI treatments for agitation in BPSD.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Context: A clinical video telehealth (CVT) program was implemented improve access and quality of dementia care to patients and their caregivers in rural areas. The program was offered as part of an established dementia clinic/geriatric primary care clinic in collaboration with five community-based outpatient clinics (CBOC’s) affiliated with the Tennessee Valley Healthcare System (TVHS) in middle Tennessee. Telehealth support was provided by a physician – social worker team visit. Methods: Telehealth training and equipment were provided to clinic personnel, functioning part-time with other collateral clinical duties. Patients and caregivers were referred by primary care providers and had an average of 1 to 2 CVT encounters originating at their local CBOC lasting 20 to 30 minutes. Clinical characteristics and outcomes of patients and caregivers receiving CVT support were collected by retrospective electronic medical record (EMR) review. Results: Over a 3-year period 45 CVT encounters were performed on patient-caregiver pairs, followed for a mean of 15 (1-36) months. Some 80% patients had dementia confirmed and 89% of these had serious medical comorbidities, took an average of 8 medications, and resided at a distance of 103 (76-148) miles from the medical center. Dementia patients included 33% with late stage dementia, 25% received additional care from a mental health provider, 23% took antipsychotic medications, 19% transitioned to a higher level of care, and 19% expired an average of 10.2 months following consultation. Caregiver distress was present in 47% of family members. Consult recommendations included 64% community-based long-term care services and supports (LTSS), 36% medications, and 22% further diagnostic testing. Acceptance of the CVT encounter was 98%, with 8770 travel miles saved. Conclusion: CVT is well received and may be helpful in providing dementia care and supporting dementia caregivers to obtain LTSS for high-need older adults in rural areas.

This study investigated co-constructed research poetry as a way to understand the lived experiences of people affected by rarer dementia and as a means to use poetry to convey those experiences to healthcare professionals. Using mixed-methods, 71 people living with rarer dementia and care-partners (stakeholders) contributed to co-constructing 27 poems with professional poets; stakeholders’ verbatim words were analysed with descriptive qualitative analysis. Stakeholders were also surveyed and interviewed about their participation. Healthcare professionals (n = 93) were surveyed to elicit their responses to learning through poetry and its acceptability as a learning tool. Poems conveyed a shared narrative of different aspects of lived experience, often owing to atypical symptoms, misunderstandings by professionals, lack of support pathways, and a continuous struggle to adapt. Stakeholder surveys indicated it was a valuable experience to both co-create and respond to the poems, whilst group interviews revealed people’s experiences of the research poetry were characterised by reflection on lived experience, curiosity and exploration. Healthcare professionals’ responses reinforced the poetry’s capacity to stimulate cognitive and affective learning specific to rare dementia support and prompt both empathy and critical thinking in practice. As the largest poetry-based study that we are aware of, this novel accessible approach of creating group poems yielded substantial information about the experiences and needs of those affected by rarer dementia and how poetry can contribute to healthcare education and training.

Sensory processing is a crucial function of the nervous system that significantly affects a large portion of the population, particularly older individuals who may be dealing with different forms of dementia. The global population of people aged 65 or older has reached a substantial count of around 703 million, representing approximately 9% of the total global population. Within this demographic, an estimated 5-8% of those aged 60, highlighting the growing need to address sensory modulation challenges for healthy aging. Sensory diet, derived from sensory integration theory, provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain. Recent neuroimaging studies have revealed intricate structural and functional alterations in the brain associated with the implementation of sensory diets. Furthermore, the integration of the Metaverse, augmented reality, and virtual reality has opened up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. This article offers a comprehensive exploration of the effectiveness of sensory diets in enhancing attentional control, self-regulation, and alleviating sensory-related distress among the healthy aging and dementia population. By employing precise quantitative evaluations such as sensory processing scales and advanced neuroimaging methodologies, it presents solid evidence of the tangible impact of these interventions. Emphasizing the importance of interdisciplinary cooperation and leveraging technological advancements, the article underscores the crucial need for customized sensory diets to optimize sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia.

Schizophrenia is a spectrum of neuropsychiatric deformities, characterized by hallucination, delusion, mood disorders, speech pathology, and neurocognitive deficits. Among various clinical manifestations, hallucination has been recognized as a core psychotic symptom that occurs more frequently in schizophrenia. A significant number of subjects with neurocognitive disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and other neurological diseases like stroke and epileptic seizure also experience hallucinations. While aberrant neurotransmission has been linked to the neuropathogenic events of schizophrenia, the specific cellular mechanism contributing to hallucinations remains ambiguous. Neurodegeneration in the hippocampus of the brain has been identified as a predominant pathogenic determinant of dementia. While the scientific proof for the neurodegeneration in schizophrenia is limited, the occurrence of dementia in schizophrenia has become increasingly evident. To note, both neurodegenerative, neurodevelopmental, and neuropsychiatric disorders display impaired neurogenesis in the brain. Impaired neurogenesis in the hippocampus has been linked to dementia and mood disorders. Notably, the early phase of many neurodegenerative disorders has been characterized by reactive neuroblostosis and aberrant cell cycle activation in mature neurons leading to the fluctuation in neurogenic processes leading to abnormal synaptogenesis and neurotransmission in the brain. Thus, this article emphasizes a hypothesis that aberrant neurogenic processes could be an underlying mechanism of hallucination in schizophrenia and other neurological diseases.

Background: Demonstrate a theoretical and empirical justification for including potentially protective factors in Sporadic Creutzfeldt-Jakob case-controlled studies alongside the almost exclusively studied risk-enhancing factors. Methods: Synthesize existing sCJD and Alzheimer's disease (AD) research to suggest the plausibility of shared neuroprotective factors. A fixed effects longitudinal analysis of 26 countries across 10 time periods examines whether factors identified to protect against AD are associated with population-level sCJD incidence rates. Results: Increased consumption of beans and nuts, both of which are thought to protect against AD risk, is associated with lower population level sCJD incidence. Conclusion: This study suggests that factors that protect against other neurodegenerative diseases might offer protection from sCJD. The low marginal burden of including protective factors in sCJD questionnaires offers a chance to better understand sCJD at little additional cost.

Introduction:Few robust studies have analyzed association between cognitive tests and the marital status of Mild Cognitive Impairment (MCI) group with ADNI dataset. To test the hypothesis that Rey Auditory Verbal Learning test (RAVLT) cognition performance with marital status is associated with greater odds of MCI group than either RAVLT independently, we used TADPOLE data to evaluate cross-sectional associations between RAVLT performance in immediate response, learning, forgetting, and perception of forgetting with marital status and MCI. Methods: Subjects with MCI and Normal Cognition were included. Logistic regression models indicate associations between four RAVLT subgroups (low and high performance of immediate response, immediate response with learning, performance of immediate response with learning and forgetting, performance of immediate response with learning, forgetting and perception of forgetting) and MCI group. Models adjust for age, sex, race, marital status, ethnicity, education, APOE4 genotype, hippocampus, whole-brain, ventricles and ICV. Results: The sample (n=6560) had a mean age of 77 / 67 years, 44% were female, 58% in MCI group. Only all RAVLT subgroups test with age 61 to 70(OR 0.26, 95% CI 0.15-0.45), age 71 or older(OR 0.07, 95% CI,0.04-0.12), race:black/african american(OR 0.13, 95% CI 0.03-0.52)race:more than one(OR 0.05, 95% CI 0.01-0.24), marital status:never married(OR 0.2, 95% CI 0.12-0.34). Conclusion: Studies are needed to evaluate other cognitive test with missing data within TADPOLE dataset as modifiable risk factor for MCI.

According to the World Health Organization (WHO), dementia is the seventh leading reason of death among all illnesses and one of the leading causes of disability among the world’s elderly people. Day by day the number of Alzheimer’s patients is raising. Considering the increasing rate and the dangers, Alzheimer’s disease should be diagnosed carefully. Machine learning is a potential technique for Alzheimer’s diagnosis but general users do not trust machine learning models due to the black-box nature. Even, some of those models do not provide the best performance because of using only neuroimaging data. To solve these issues, this paper proposes a novel explainable Alzheimer’s disease prediction model using a multimodal dataset. This approach performs a data-level fusion using clinical data, Freesurfer MRI segmentation data, and psychological data. For Alzheimer’s disease vs cognitively normal prediction, the random forest classifier provides 100% accuracy. Furthermore, Alzheimer’s disease and non-Alzheimer’s dementia should be classified properly because their symptoms are similar. To the best of our knowledge, we are the first to present a three-class classification on Alzheimer’s disease vs cognitively normal vs non-Alzheimer’s dementia and achieved 99.86% accuracy using an ensemble model. Besides, a novel Alzheimer’s patient management architecture is also proposed in this work..

Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5–2 cases per million per year). Genetic (10-15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram) and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests such as RT-QuIC is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain among others) to try to universalize access to early diagnosis in the case of prion diseases.

As a result of an increasing population of aged people in sub-Saharan Africa, dementia is predicted to surge up to 90% by 2030. This review is set to assess the prevalence of dementia, for 65+ aged population in sub-Saharan states and particularly in Tanzania. Subsequently, the review will identify the possible risks factors – age, gender, level of education, cardiovascular problems, diabetes and mild cognitive impairment – and will lay out the challenges of reducing the dementia burden in Tanzania. Additionally, the review explores the current approaches in solving dementia disorders, including a general view of the public understanding of dementia. Also, the review recognises the gaps in government funding to mental health, a barrier to service access and the need for further research on Alzheimer’s and other dementias. Lastly, the review links the sustainable development goals (SDGs) addressed and appreciate the impact of the coronavirus pandemic on the fight against dementia.

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases of reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that the chronic waterborne exposure of DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.

Canadians overwhelmingly do not want to live in long-term-care (LTC) facilities when they age; yet many end up there for lack of homecare, because family caregivers burn out, or because they and their professional advisors are unaware of alternatives to institutions. Not only is institutional dementia care problem-driven, it segregates disabled people, thereby abrogating human rights. Because systemic ageism and ableism cloud elder care, institutions remain the default option for Canadians with dementia. Yet, decades of deinstitutionalization enabled younger disabled Canadians to live in the community with supports. Why not elders? We describe a plethora of noninstitutional dementia-care alternatives. We then present a roadmap for considering all relevant care options in service plans, one that incorporates supported decision-making by people with dementia. We propose a paradigm shift in how Canada serves its elder citizens—not just the current generation, but those to come, including ourselves.

The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2] (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), are studied as potential scaffolds for future anti-cancer drug development. Their cytotoxicity and cell migration inhibitory activity are analyzed, and an untargeted metabolomics approach is em-ployed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2] was particularly cy-totoxic against the B16 cell line. While [Co(κ3-TpmOH)2] significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] is associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2] is associated with dysregulation of cell adhesion and membrane structural pathways, suggesting its antiproliferative and anti-migration properties can be due to changes in the overall cellular adhesion mechanisms.

Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process.

Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.

Over the years there has been an increase in the development of assistive technologies (AT’s). The implementation and scaling of AT’s at care organizations remains challenging. Moreover, to date, it has been underexplored during which stages of dementia these technologies can be best implemented. Previous work has developed an infographic providing guidance on when best to introduce AT’s for people with dementia. Although this infographic is relevant, it was based solely on the experience of the authors during various national and international projects. However, over the years a wide spread of studies has been conducted in the field of dementia on the use and implementation of technology for PwD. Therefore, in this paper we will revise the current infographic based on the insight gained from existing literature and complement these by interviews with expert on the implementation of care technology

Cognitive impairment in patients with Parkinson’s disease (PD), which may occur in various severities, represents one of the commonest and most disabling non-motor manifestations during the course of the disease, causing a negative impact on patients’ quality of life. Eventually, it becomes a burden for the family members and/or the caregivers of patients, as it progresses to PD dementia. Current pharmacological treatments for cognitive impairment in PD exhibit partial efficacy, while novel effective therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline, and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, improvement of mitochondrial function, regulation of synaptic plasticity, impact on gut-brain axis, modulation of neuroinflammation, upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this overview, we aim to cover the clinical aspects of PD associated cognitive impairment, highlighting recent evidence on emerging treatment approaches that are currently under investigation at a preclinical and clinical level.

Dementia is a rising public health concern. Feeding and nutritional problems increase as the disease progresses, affecting clinical course and caregiver burden. While some guidelines advise against percutaneous endoscopic gastrostomy (PEG) and tube feeding in advanced dementia, conflicting evidence exists. This study aims evaluating nutritional status and the influence of PEG-feeding on outcome and evolution of nutritional/progonosis markers of patients with severe dementia (PWSD) who underwent gastrostomy for nutritional support. We conducted a 16-year rectrospective study on 100 PEG-fed PWSD with strong familiar support. We evaluated survival PEG-feeding period, safety, and objective nutritional/progonosis data at the gastrostomy day and after 3 months: Body Mass Index (BMI), Mid Upper Arm Circumference, Tricipital Skinfold, Mid-Arm Muscle Circumference, albumin, transferrin, total cholesterol and hemoglobin. Most patients presented low values in these nutritional/progonosis parameters. No major life-threatening PEG complications were reported. The mean survival time after gastrostomy was 27.9 months (median of 17 months). Female sex, BMI recovery at 3 months, and higher baseline hemoglobin levels were associated with a reduced risk of death and increased survival time. The study concluded that, in carefully selected PWSD with strong familiar support, PEG feeding can improve nutritional status and have a positive impact on survival.

Background: Assessment and management of pain in elderly people with cognitive impairment is particularly challenging. Physiological changes due to aging as well as comorbidities and polypharmacy are responsible for a complex clinical approach. Concomitantly, in cognitive impairment, including advanced dementia, changes in central nervous system along with changes in the peripheral nervous system due to aging have a significant impact in pain perception. Often clinicians decide to prescribe opioids in order to relief pain, also without a clear indication. Aim: This review aims to investigate the effect of opioids in elderly patients with cognitive impairment. Methods: A literature search of PubMed/Medline, Scopus, and Cochrane databases was conducted using keyword searches to generate lists of articles which were screened for relevance by title and abstract to give a final list of articles for full-text review. Further articles were identified by snowballing from the reference lists of the full-text articles. Results: This review discuss the complex physiological and pharmacological changes in elderly as well as the neurological changes that affect pain perception in this population. Additionally, it focuses on cognitive impairment and pain in Alzheimer’s disease and other dementias, the pain assessment in the elderly with cognitive impairment as well as the safety of opioid use in elderly. Information regarding opioid prescription in nursing homes as well as recorded indications for opioids use, type and dosing of opioid and compliance of treatment in advanced dementia are also provided. Conclusions: Opioid prescription in elderly population with cognitive impairment is particularly complex. All healthcare professionals involved in the care of such patients, need to be aware of the challenges and strive to ensure analgesic use is guided by appropriate and accurate pain assessment.

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) or hypoxic (1% oxygen) condition without or with NL (100 or 300 µg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.

Background and Aims: Screening and assessment of cognitive changes in adults with Intellectual Disabilities, mainly Down Syndrome (DS), is crucial to offer appropriate services to their needs. We present a systematic review of the existing instruments assessing dementia, aiming to support researchers and clinicians’ best practice. Methods: Searches were carried out in the databases Web of Science; PubMed; PsycINFO in March 2019 and updated in May 2020. Studies were selected and examined if they: (1) focused on assessing age-related cognitive changes in person with ID; (2) included adults and/or older adults; (3) included scales and batteries for cognitive assessment. Results: Forty-eight cross-sectional studies and twenty-six longitudinal studies were selected representing a total sample of 5,851 participants (4,089 DS and 1,801 with other ID). In those studies, we found 38 scales, questionnaires, and inventories, and 14 batteries for assessing cognitive and behavioural changes in adults with DS and other ID. Conclusion: The most used instrument completed by an informant or carer was the Dementia Questionnaire for Learning Disabilities (DLD), and its previous versions. We discuss the strengths and limitations of the instruments and outline recommendations for future use.

Subjective Cognitive Decline (SCD) is a possible earliest detectable sign of dementia, but we do not know what mental processes lead to elevated concern. We summarize the previous literature on the biomarkers and functional neuroanatomy of SCD. To extend the current most-popular theory of SCD, compensatory hyperactivition, we introduce a new model: breakdown of homeostasis in the prediction error minimization system. A cognitive prediction error is a discrepancy between an implicit cognitive predictions and the corresponding outcome. Experiencing frequent prediction errors may be a primary source of elevated subjective concern. Our homeostasis breakdown model explains the progression both from normal cognition to SCD and from SCD to advanced dementia stages.

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

This systematic review provides a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It explores cognitive impairments in memory, attention, and executive function, and the relation between brain abnormalities and these deficits. The paper emphasizes the use of neuropsychological tests in diagnosis and early psychosis management, while also discussing interventions, the impact of dementia on psychosis, and the neurobiological patterns associated with these conditions. Additionally, it underlines the importance of childhood trauma in the development of psychosis and examines the effects of substance abuse and brain injury. Neuropsychological evaluations and targeted therapies are highlighted as crucial for the understanding, diagnosis, and treatment of psychotic disorders. The research further includes evidence of neurocognitive dysfunction in individuals with a high risk of psychosis and emphasizes the advanced brain aging in schizophrenia and bipolar disorder. The necessity of comprehensive clinical evaluations and targeted therapies for cognitive impairments is underscored throughout the research. The potential effects of dementia on individuals with psychosis, neurobiological patterns, the role of childhood trauma, the impact of psychosis in dementia patients, and proposed treatments are also explored in depth. Overall, the paper underscores the integral role neuropsychological knowledge plays in understanding, diagnosing, managing, and treating psychotic spectrum disorders.

One of the major obstacles confronting the formulation of a mechanistic understanding for Alzheimer’s disease (AD) is its immense complexity – a complexity that traverses the full structural and phenomenological spectrum, including molecular, macromolecular, cellular, neurological and behavioural processes. This complexity is reflected by the equally complex diversity of risk factors associated with AD. However, more than merely mirroring disease complexity, risk factors also provide fundamental insights into the aetiology and pathogenesis of AD as a neurodegenerative disorder since they are central to disease initiation and subsequent propagation. Based on a systematic literature assessment, this review has identified 30 risk factors for AD and then extended the analysis to further identify neuroinflammation as a unifying mechanism present in all 30 risk factors. Although other mechanisms (e.g. vasculopathy) were present in multiple risk factors, dysfunction of the neuroimmune-neuroinflammation axis was uniquely central to all 30 identified risk factors. Though the nature of the neuroinflammatory involvement varied, activation of microglia and the release of pro-inflammatory cytokines was a common pathway shared by all risk factors. This observation provides further evidence for the importance of immunopathic mechanisms in the aetiopathogenesis of AD.

In advanced Parkinson’s disease (PD), and especially in PD related dementia (PDD), psychotic symptoms are common. One of the manifestations of psychosis in PD is delusional misidentification syndrome, a phenomenon in which the patient believes the identity of a person, object or location has been duplicated or altered. Our patient, a 75-year-old female, was diagnosed with idiopathic Parkinson’s disease at the age of 68. Recently, her cognition deteriorated and she developed the believe that she lived in a replica of her real home. The delusion resolved completely with rivastigmine patches. Also visual hallucinations improved on treatment. This suggests that the dysfunctional connections were likely to be cholinergic.

Frontotemporal dementia (FTD) is the second most common form of presenile dementia; however, its diagnosis has been poorly investigated. Previous attempts to diagnose FTD using quantitative electroencephalography (qEEG) have yielded inconsistent results in both spectral and functional connectivity analyses. This study aimed to introduce an accurate qEEG marker that could be used to diagnose FTD and other neurological abnormalities. We used open-access electroencephalography data from OpenNeuro to investigate the power ratio between the frontal and temporal lobes in the resting state of 23 patients with FTD and 29 healthy controls. Spectral data were extracted using a Fast Fourier Transform in the delta (1–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–32 Hz), and gamma (32–45 Hz) bands. We found that the spectral power ratio between the frontal and temporal lobes is a promising qEEG marker of FTD. Frontal/temporal (F/T) theta/alpha, alpha/theta, al-pha/gamma, and gamma/alpha showed a consistently high discrimination score for the diagnosis of FTD for different parameters and referencing methods. The study findings can serve as reference for future research focused on diagnosing FTD and other neurological anomalies.

Background: No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims: To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods: In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results: Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD.Conclusions: Petersen’s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.

Background: The Apolipoprotein E4 (ApoE4) genotype is strongly associated with Alzheimer’s disease (AD), although the presence of the ApoE4 allele alone is not sufficient to explain AD. The pathophysiology of amnestic mild cognitive impairment (aMCI) remains unclear. This study aims to examine associations between peripheral blood biomarkers coupled with ApoE4 and episodic and semantic memory. Methods: The CERAD battery was completed and various biomarkers were assayed in 60 subjects with aMCI, 60 with AD and 62 healthy controls. Results: Deficits in semantic and episodic memory were significantly predicted by anion gap and bicarbonate, albumin and glucose coupled with Apo E4. Furthermore, these peripheral biomarkers interacted with ApoE to predict greater memory impairments. Conclusions: Peripheral blood biomarkers may interact with pathways related to ApoE4 to predict greater semantic and episodic memory impairments, thus contributing to the pathophysiology of aMCI and AD. Our data suggest that the transition from aMCI to AD could at least in some cases be associated with significant interactions between ApoE4 and those peripheral blood biomarkers.

Inotodiol, a lanostane-type triterpenoid, and many phytochemicals from Chaga mushroom have been investigated for various allergic diseases. However, antiaging and anti-inflammatory activities of inotodiol under different types of oxidative stress and impact of inotodiol on collagen and hyaluronan synthesis are not sufficiently studied. Lanostane triterpenoids-rich concentrate, which contained 10% inotodiol as major (the inotodiol concentrate), was prepared from Chaga and compared with pure inotodiol in terms of anti-inflammatory activities on a human keratinocyte cell line, HaCaT cells, under various stimulation such as stimulation with ultraviolet (UV) B or tumor necrosis factor (TNF)-α. In stimulation with TNF-α, interleukin (IL)-1β, IL-6, and IL-8 genes were significantly repressed by 0.44~4.0 μg/mL of pure inotodiol. UVB irradiation induced overexpressions of pro-inflammatory cytokines, but those genes were significantly suppressed by pure inotodiol or inotodiol concentrate. Moreover, pure inotodiol/inotodiol concentrate could also modulate synthesis of collagen and hyaluronic acid by controlling COL1A2 and HAS2/3 expression, which implies a crucial role of pure inotodiol/inotodiol concentrate in prevention of skin aging. These results enlighten anti-inflammatory and anti-aging effect of pure inotodiol/inotodiol concentrate, and it is highly conceivable that pure inotodiol and inotodiol concentrate could be promising natural bioactive substances to be incorporated in therapeutic and beautifying applications.

Antibiotic failure is one of the most worrying health problems worldwide. Nowadays we are facing an international crisis where several issues are involved: new antibiotics are not being discovered any longer, resistance mechanisms become spread in nearly every clinical isolate of bacteria and the appearance of recurrent infections caused by persistent bacteria complicates the overcoming of infections. In this context, it has been explored new anti-infectious strategies against MDR and persistent bacteria as well as the rescue of FDA-approved compounds (drug repurposing). Among the highlighted new anti-infectious strategies we find anti-microbial peptides, anti-virulence compounds, phage therapy and new molecules. On the other hand, as drugs of repurposing that have been described, we have anti-inflammatory compounds, anti-psychotics, anti-helmintic drugs, anti-cancerous and statins.

Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.

Eating and drinking difficulties are common in dementia, but little is known about the experiences of ethnic minority groups managing these difficulties at home. We undertook qualitative semi-structured interviews, exploring the meaning of food, the impact of dementia on eating and drinking and carers’ experiences of support. Interviews were audio-recorded and transcribed verbatim. We interviewed 17 carers and people with dementia from ethnic minority backgrounds, using reflexive thematic analysis to analyse data. Food/drink had strong links to identity, culture and emotions. Providing culturally familiar foods, celebrating traditional festivals and supporting previous food-related roles promoted reminiscence, which encouraged people with dementia to eat and drink, as did social interactions. However, these strategies sometimes led to distress in those with more advanced dementia. Food choices were also influenced by carer strain, generational differences and the impact of health conditions. Despite a strong sense of duty to care for relatives at home, there was low awareness of community support services. Carers expressed a need for culturally tailored support for managing dementia-related eating and drinking difficulties at home. Healthcare professionals must provide contextually relevant advice to carers, being mindful of how cultural backgrounds can affect dietary choices.

Background: The psychomotor agitation of the BPSD is one of the common issues in aged care facilities, leading to the poor functional and medical consequences. Psychotropic interventions are the preferable choice of treatment. But which medication should be the prescribers first preference? This review aims to compare pharmacological interventions for psychomotor agitation, judging them according to their effectuality and justifiability profiles. This is to be achieved by retrieving information from RCTs and systematic reviews. Objectives: This review evaluates evidence from RCTs, systematic reviews, and meta-analyses of BPSD patients who had taken agitation treatments. Assessing the efficacy of antidepressants and antipsychotic treatments when compared to each other for the purpose of improving agitation outcomes. Methods: This narrative review includes RCTs and retrospective studies that were comparing one or more active ingredient medications with another or with a placebo, along with sys-tematic reviews comparing antidepressants with antipsychotics such as quetiapine, olanzapine, and risperidone. Studies extracted by searching accessing databases, such as PubMed, OVID, and Cochrane with restrictions of date from 2000 to 2021 and English language. Quality of evidence: The quality of systematic reviews was judged against AMSTAR score, and RCTs were judged according to CONSORT checklist for RCT protocols. Conclusion: There are still few studies of serotonin targeting treatment of agitation in BPSD. The SSRIs such as citalopram were associated with a reduction in symptoms of agitation, and lower risk of adverse effects compared to antipsychotics. This review also illustrates brexpiprazole as a target of multimodal neurotransmitters such as dopamine, serotonin, and norepinephrine; and dextromethorphan, OR dextromethorphan associated with bupropion or quinidine as a blockade of NMDA receptors. The outcome of this review suggests that further studies involving more dementia/Alzheimer’s participants should be conducted. Future studies are required also to assess the long-term safety and efficacy of SSRI, brexpiprazole, dextromethorphan treatments for agitation in BPSD.

Aim: This research is aimed at examining the cost-effectiveness of olanzapine versus risperidone in dementia patients with behavioural and psychological symptoms in Thailand. Methods: An existing Markov model based on a critical review through the comprehensive literature search and a justification for the most appropriate model for a Thai setting was adapted to simulate the disease progression of patients with dementia with behavioural disturbances until their need for full-time care (FTC). The time to the FTC state was estimated by a predictive equation developed by Rive et al. (2010). The model was conducted to assess the expected costs and outcomes associated with olanzapine compared with risperidone for Thai patients with BPSD aged 60 years and above. This model performed over a five-year time horizon with a one-month cycle length based on a societal perspective. The incremental cost-effectiveness ratio was used as the estimated outcome. Sensitivity analyses were also conducted to demonstrate the robustness of the results. Results: Over 5 years, olanzapine was found to be a cost-effective therapeutic option for the treatment of behaviourally disturbed patients with dementia compared with risperidone, in Thailand from a societal perspective (ICER < THB 160,000). The model underwent extensive sensitivity analyses, which also confirmed that olanzapine was the dominant strategy following the base-case findings. Conclusions: By comparison with risperidone, the model suggests that olanzapine can be regarded as a cost-effective therapeutic strategy for the management of patients with behavioural and psychological symptoms in Thailand.

Amnestic mild cognitive impairment (aMCI) is a condition characterized by mild deficits in episodic and semantic memory and learning. The conversion rate of aMCI to Alzheimer disease (AD) is significantly higher in aMCI than in the general population. The aim of this study is to examine whether aMCI is a valid diagnostic category or whether aMCI comprises different subgroups based on cognitive functions. We recruited 60 aMCI patients, 60 with AD and 61 healthy controls who completed neuropsychological tests of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-NP) and biomarkers including serum anion gap (AGAP). Principal component analysis, support vector machine and Soft Independent Modeling of Class Analogy (SIMCA) showed that AD patients and controls were highly significantly discrimanted from each other, while patients with aMCI overlap considerably with normal controls. SIMCA showed that 68.3% of the aMCI patients were assigned to the control class (named: aMCI-HC), 15% to AD (aMCI-AD), while 16.6% did not belong to either class (aMCI-strangers). aMCI-HC subjects showed sings of very mild cognitive decline and impaired recall. aMCI-strangers showed signs of mild cognitive impairment with impaired fluency and naming. aMCI-AD cases showed a cognitive profile reminiscent of AD an increased AGAP levels. In conclusion, our SIMCA model may classify subjects afforded a clinical diagnosis of aMCI according to Petersen’s criteria into three clinically relevant subgroups and help in the early detection of AD by identifying aMCI patients at risk to develop AD and those that have an AD prodrome.

Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.

This article proposes the use of intranasal rifampin as a means to improve protein homeostasis and disaggregate misfolded proteins in the age-related neurodegenerative proteinopathies. Alzheimer’s disease, Parkinson’s disease, multi-system atrophy, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis and Huntington’s disease are all, at the core, proteinopathies. Although these diseases varying greatly in the specific disease-associated proteins, anatomic sites of the abnormal protein deposition and clinical presentations, what they have in common is disruption of normal “housekeeping” functions related to protein homeostasis, proteostasis. The prospect of pharmacologically augmenting autophagic capacity with a known drug repurposed to improve proteostasis is attractive; to accomplish these ends with an inexpensive drug with relative ease of delivery adds to the attractiveness. Rifampin can be delivered to the brain via the intranasal route. Rifampin has been used for decades primarily against mycobacterial infection; it has been given with intravenous, oral, intrathecal and topical routes including as eyedrops and nasal spray. Rifampin disaggregates toxic oligomers in vitro; given intranasally, rifampin improves memory and clears pathologic proteins in animal models of the proteinopathies. Rifampin acts as both a gatekeeper and a housekeeper against the abnormal proteins of these diseases. This article suggests the merit of a clinical trial with intranasal rifampin to boost protein homeostasis in the most common age-related neurodegenerative proteinopathy, Alzheimer’s disease. The primary outcome of such a trial is change in risk of Alzheimer’s pathology as measured by plasma-based amyloid peptide 42/40 testing pretreatment and follow-up testing after 6 months of intranasal rifampin.

Immune-mediated necrotizing myopathy (IMNM) is a rare and severe disease that corresponds to a specific entity of idiopathic inflammatory myopathy. Patients with IMNM suffer from proximal muscle weakness, and present high levels of creatine kinase and necrotic myofibers. Anti-Signal Recognition Particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies (HMGCR) have recently been identified in two thirds of patients with IMNM and are used as a hallmark of the disease. In this review, we provide a detailed description of these antibodies and the tests used to detect them in the serum of patients. Based on in vitro studies and mouse models of IMNM, we will discuss the role of autoantibodies in the pathogenesis of the disease. Finally, in the light of the latest knowledge, we will conclude with a review of recent therapeutic approaches.

Three new polyketides (penidihydrocitrinins A–C, 1–3) and 14 known compounds (4–17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1–17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on microglial activation in LPS-stimulated BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Moreover, compounds 6, 7, and 8 not only suppressed osteoclastogenesis, but also promoted osteoblast mineralization.

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

Acemella oleracea is known as toothache plant belongs to the family of Asteraceae. It is treated as a medicinal remedy like tuberculosis, illness, cough, rheumatism, and illness. This study was concentrated on the antioxidant, cytotoxic, antimicrobial & thrombolytic activities of methanol extract of Acmella oleracea leaves using in vitro model. The antioxidant activity was estimated as trolox equivalent antioxidant capacity utilizing the DPPH and reducing power tests. The plant extract was tested for its cytotoxic action using a brine shrimp lethality bioassay, thrombolytic activity using clot disruption, and antibacterial activity using a disc diffusion assay technique against four distinct gram-positive and gram-negative bacteria. IC₅₀ value of standard ascorbic acid for DPPH was 7.8µg/ml and the IC50 of the methanol extract of Acmella oleracea leaves was 198.34µg/ml that was moderate effect at all compare with ascorbic acid. Thrombolytic assay of Streptokinase as a positive control showed 88.49% where the extract shows 18.69% lytic activity shows the assay. In this study, the sample of LC₅₀ results of cytotoxicity assay was 1.431 µg/mL which can be treated as less activity. Moreover, the extracts showed low to moderate antibacterial activity against both gram-negative and gram-positive bacterial stains (zone of inhibition-10-26 mm). Vibrio Mimicus bacteria stains exhibited the highest level of activity, with a range of 23 for the diameter of the growth inhibition zone. The current review shows leaf extracts of Acmella oleracea may be used as a source of antioxidant and thrombolytic activity, as well as a significant source of antibacterial and anticancer substances. Further research is required to evaluate in-vivo the pharmacological activity of Acmella oleracea leaves in order to identify the essential metabolites and potential mechanisms.

Methotrexate (MTX) is a potent drug for the treatment of various diseases globally amidst being a chemotherapeutic and immunosuppressant agent. However, hepatotoxicity induced by MTX could be life-threatening if left untreated. Folate supplementation is concurrently applied to reduce the adverse effects of MTX, albeit efficacy compromise. Therefore, there is the need to understand the process for the prevention and treatment strategies for MTX induced hepatotoxicity (MIH). In recent times, preliminary preclinical and clinical findings indicate the potential of natural phytobioactive compounds for MIH prevention and treatment. This mini review therefore summarizes proposed mechanisms of MIH and recent advances in the prevention and treatment prospects of natural phytobioactive compounds on MIH.

The use of plant extracts in the synthesis of metal nanoparticles is a very attractive approach in the field of green synthesis. To benefit from the potential synergy between the biological activities of the Moringa oleifera leaves extract and metallic bismuth, our study aimed at synthesizing bismuth nanoparticles using a hydroalcoholic extract of M. oleifera leaves as a means of green synthesis that yields nontoxic products and reduces the production of wasteful material. To this end, the M. oleifera leaves extract was treated with a bismuth nitrate pentahydrate solution. A color change from light brown to dark brown indicates the synthesis of bismuth nanoparticles. The total phenolic content in the M. oleifera leaves extract used was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. Antioxidant property of MO synthesised bismuth Nanoparticles was evaluated and in line with the extract used in the synthesis of NPs. The physical properties of the synthesized bismuth nanoparticles were characterized using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized bismuth nanoparticles have a size in the range of 40.4-57.8 nm with amorphous morphology. Using DPPH and phosphomolybdate assays, our findings revealed that the M. oleifera leaves extract and the synthesized bismuth nanoparticles possess antioxidant properties. Using resazurin microtiter assay, we also demonstrate that the M. oleifera leaves extract and the synthesized bismuth nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis, similarly to the inhibition exerted by Moringa extract, especially against Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 µg/mL; MIC values for the bismuth nanoparticles: 500, 500, 500, and 250 µg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized bismuth nanoparticles display relatively stronger anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 µg/mL; MIC values for the bismuth nanoparticles: 250, 250, 62.5, and 62.5 µg/mL, respectively). Thus, the hydroalcoholic extract of M. oleifera leaves was successfully used in the synthesis of bismuth nanoparticles, showing a positive antioxidant, anti-bacterial, and anti-fungal activity. Therefore, the synthesized bismuth nanoparticles can potentially be employed in the alleviation of symptoms associated with oxidative stress and in the topic treatment of Candida infections.

The synthesis of metal nanoparticles using plant extracts is a very promising method in green synthesis. The medicinal value of Moringa oleifera leaves and the anti-microbial activity of metallic copper were combined in the present study to synthesize copper nanoparticles having a desirable added-value inorganic material. The use of a hydroalcoholic extract of M. oleifera leaves for the green synthesis of copper nanoparticles is an attractive method as it leads to the production of harmless chemicals and reduces waste. The total phenolic content in the M. oleifera leaves extract was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The M. oleifera leaves extract was treated with a copper sulphate solution. A color change from brown to black indicates the formation of copper nanoparticles. Characterization of the synthesized copper nanoparticles was performed using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized copper nanoparticles have an amorphous nature and particle size of 35.8-49.2 nm. We demonstrate that the M. oleifera leaves extract and the synthesized copper nanoparticles display considerable antioxidant activity. Moreover, the M. oleifera leaves extract and the synthesized copper nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 μg/mL; MIC values for the cooper nanoparticles: 500, 500, 500, and 250 μg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized copper nanoparticles exert relatively more potent anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 μg/mL; MIC values for the cooper nanoparticles: 125, 125, 62.5, and 31.2 μg/mL, respectively). Our study reveals that the green synthesis of copper nanoparticles using a hydroalcoholic extract of M. oleifera leaves was successful. In addition, the synthesized copper nanoparticles can be potentially employed in the treatment of various microbial infections due to their potent antioxidant, anti-bacterial, and anti-fungal activities.

The anti-money laundering (AML) process has failed both in identifying suspicious cases in due time as in assisting the AML analysts in decision making. Starting from a new generic anti-fraud approach, this article presents the main aspects related to the development of a multi-agent system that goes beyond the capture of suspicious transactions, seeking to assist the human expert in the analysis of suspicious behaviour. First, a transactional behavioural profile of clients is obtained in a data mining process. A set of rules, obtained through data mining over a real database, in conjunction with specific rules based on legal aspects and in the expertise of the AML analysts make up the agents' knowledge base. The cases for which the system was unable to suggest a decision are flagged as requiring more detailed analysis. The system analysed 6 months of real transactions and indicated several suspicious profiles, a set of these suspects was investigated by the AML analysts who proved the suspicion of several cases, including some that had not been identified by the systems in execution.

Several vaccines against COVID -19 have been developed and licenced to enhance the immune response against SARS-CoV-2. Similarly, infection with SARS-CoV-2 before vaccination has been shown to provide significant protection against severe infection and hospitalisation. The aim of this study was to investigate the effect of three doses of Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies and interferon γ. Our results showed that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while endocrinological diseases decreased the level of neutralizing antibodies and anti-N-IgG antibodies, suggesting that these diseases alter the effect of vaccine immunity. In addition, there was a significant decrease in anti-S1 IgG levels 6 months and in anti-N IgG levels 18 months post-infection, while neutralizing antibody and interferon γ levels were constant at 3, 6 and 18 months post-infection. Therefore, our results confirm the importance of hybrid immunity as the strongest and most durable compared to exclusively natural or vaccine-induced immunity. Significant positive correlations were found between humoral and cellular immunity markers: neutralizing antibodies, anti-S1 IgG, anti-N IgG and interferon γ, indicating a unique coordinated response specific to COVID-19.

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. The role of dysfunctional mitochondria in psychopathology is well-established, however, the association of these organelles with sleep physiology is novel. Indeed, reducing neuronal oxidative stress by importing mitochondria from astrocytes, may be the purpose of human slumber. This model may explain mitochondrial dysfunction during anesthesia as well as in the rare genetic disease, fatal familial insomnia. In this narrative review, we focus on the salience network of the brain, a common denominator for insomnia, neuropsychiatric and neurodegenerative disorders. We also discuss mitochondria-protecting strategies, including membrane lipid replacement, natural and synthetic phenazine and phenothiazine derivatives.

This study uses explainable artificial intelligence to analyze major predictors of poor self-rated health, dementia and their comorbidity, which include various aspects of social support. Data came from the Korean Longitudinal Study of Ageing (2016-2018), with 5527 participants aged 56 or more. The dependent variables were: (1) poor self-rated health (SRH) with 5 categories (very good, good, middle, poor, very poor); (2) dementia (no, yes); and (3) their comorbidity with 4 categories (SRH very good, good or middle, dementia no; SRH very good, good or middle, dementia yes; SRH poor or very poor, dementia no; SRH poor or very poor, dementia yes). The 49 demographic, socioeconomic and health-related predictors were included. The accuracy and area under the receiver operating characteristic curve (AUC) were compared for logistic regression and the random forest. Logistic regression and the random forest registered similar AUCs with the range of 0.80-0.87. Based on random forest variable importance, 18 out of top-20 predictors were identical for SRH, dementia and their comorbidity: previous SRH, life satisfaction - health, age, body mass index, income, chronic diseases, life satisfaction - economic, life satisfaction - overall, grandchildren alive, friendship meeting, brothers/sisters alive, class identity, children alive, social activity - friendship, education, children in weekly contact, religion and drinker. However, some variations were found among the three dependent variables, i.e., previous SRH for comorbidity (1st) and SRH (1st) compared to dementia (11th), grandchildren alive for SRH (6th) and dementia (4th) compared to comorbidity (9th), chronic diseases for comorbidity (6th) compared to SRH (10th) and dementia (10th). In terms of Shapley Additive Explanation (SHAP) values, the probability of dementia is expected to decrease by 5.57% in case a predictor grandchildren alive is included to the model. This study highlights the importance of social support for the prediction of poor self-rated health, dementia and their comorbidity. Specifically, the promotion of family support and friendship activity for elders would be vital for the prevention and management of their self-rated health and dementia.

Background: dementia is a significant health issue worldwide. Mild cognitive impairment (MCI) can transform into dementia over time. General practitioners may be the first to notice the cognitive deficit, so they may need a screening test in the event of suspicion, which they must be able to use under great time pressure. We examined the usability of the Hungarian Test Your Memory (TYM-Hun) self-administered dementia test in general practice, and with the results of the received tests, we tried to draw conclusions regarding the population. Methods: In the four Hungarian cities with medical universities, general practitioners filled out 368 questionnaires with their clients over 50 years of age. Results: the total scores of the test showed a significant correlation with education and the type of occupation, while a significant negative correlation with age. We found the clock drawing test and recall indicates cognitive decline the earliest. Based on the TYM-Hun results, the prevalence levels for MCI and dementia are slightly higher in Hungary than globally. Conclusion: the test can sensitively indicate MCI and early-stage dementia as a screening test, and two of its subtests can raise the possibility of cognitive impairment at an earlier age than the others.

Bright morning light (BML) entrains the body clock, modulates circadian rhythm, and improves sleep-wake disturbances. However, its impact on the autonomic nervous system (ANS) at night remains unclear. Hence, we investigated the effects of BML exposure on activities of the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS) at night. This non-randomized controlled pilot study included participants ≥60 years, diagnosed with a type of dementia or cognitive disorder. We excluded participants with pacemakers. The treatment group received 2500 lx BML, whereas the control group received approximately 200 lx of general lighting. We measured the heart rate variability to quantify ANS activity. The treatment group displayed significantly increased high-frequency (HF) power (Roy's largest root=2.44; P<.01) and insignificantly decreased normalized low-frequency (LF%) power. The corresponding low-frequency/high-frequency ratio (LF/HF), insignificant decrease, and cognitive function were correlated with PSNS activity (Roy's largest root=3.92; P<.01), which is effective for moderate dementia. BML exposure reduced SNS activity and enhanced PSNS activity at night, which consequently affected cognitive function. Furthermore, the light washout intervention markedly increased SNS activity at night. BML therapy may be a useful clinical tool for alleviating the deterioration of cognitive function.

Psychotherapy is one of the evidence-based clinical interventions for the treatment of depression in older adults with dementia. Randomized Controlled Trials are often the first methodological choice to gain evidence, yet they are not applicable to a wide range of humanistic psychotherapies. Amongst all, the efficacy of the Gestalt therapy (GT) is under-investigated. The purpose of this paper is to present a research protocol aiming to assess the effects of a GT-based intervention on people with dementia (PWD) and the indirect influence on their family carers. The study implements the Single-Case Experimental Design with Time-Series Analysis that will be carried out in Italy and Mexico. Ten people in each country, who received a diagnosis of dementia and present depressive symptoms, will be recruited. Eight or more GT sessions will be provided whose fidelity will be assessed by the GT Fidelity Scale. Quantitative outcome measures are foreseen for monitoring participants’ depression, anxiety, quality of life, carers’ burden, and the caregiving dyad mutuality, at baseline and follow-up. The advantages and limitations of the research design are considered. If GT will result effective in the treatment of depression in PWD, it could enrich the range of evidence-based interventions provided by healthcare services.

Multicomponent training is recommended for people with dementia living in long-term care homes. Nevertheless, evidence is limited and people with severe dementia are often excluded from trials. Hence, the aim of this study was to investigate (1) the feasibility and (2) the requirements regarding a multicomponent training for people with moderate to severe dementia. The study was conducted as an uncontrolled single arm pilot study with a mixed methods approach. 15 nursing home residents with a mean age of 82 years (range: 75-90 years; female: 64%) with moderate to severe dementia received 16 weeks of multicomponent training. Feasibility and requirements of the training were assessed by a standardized observation protocol. Eleven participants regularly attended the intervention. The highest active participation was observed during gait exercises (64%), the lowest during strength exercises (33%). It was supportive if exercises were task-specific or related to everyday life. This study confirms that a multicomponent training for the target group is (1) feasible and well accepted. To enhance active participation (2) individual instructions and the implementation of exercises related to everyday life is required. The effectiveness of the adapted training should be tested in future randomized controlled trials.

Background: This study aimed to assess the dementia literacy (DL) level of community-dwelling adults in the four cities (Hong Kong, Guangzhou, Macau and Zhuhai) of the Greater Bay Area of China and to determine the preferred mass media for receiving dementia information. Methods: A multi-city cross-sectional study with 788 community-dwelling adults completed the survey. Dementia literacy was indirectly measured by two validated scales, 30-item Alzhiemer’s Disease Knowledge Scale (ADKS) and 20-item Dementia Attitudes Scale (DAS). When the ADKS total score was <15 and DAS total score was <70, it was considered as ‘inadequate dementia literacy’. Participants were also asked to indicate whether they would like to receive dementia information via digital media or traditional media. Chi-square tests and logistic regressions were undertaken. Results: About one-third of the participants had inadequate dementia literacy. Those with young age or secondary education preferred to get dementia information from social media. But people living in public housing would like to get information from government or hospital websites. Middle-aged participants inclined to learn dementia from television or radio. Conclusion: It is worthy to conduct territory-wide public education in dementia and develop strategies according to their preferences in the types of mass media.

Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).

Across different cultures around the globe, human beings have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants can be strongly attributed to the presence of secondary metabolites, particularly polyphenols. The health-promoting effects of Sorghum bicolor supplement Jobelyn® (SBSJ) —a unique supplement derived from the leaf sheaths of a West African variety of Sorghum bicolor (L.) Moench—have also been ascribed to its high levels of polyphenols. This review seeks to gather and synthesize findings from various experimental and clinical studies on the health benefits of SBSJ in arthritis, cancer, chronic viral infections, stroke, anaemia, and aging. SBSJ has been reported to contain potent bioactive polyphenolic compounds with polyvalent biological activities, including antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. Moreover, the probable benefits of SBSJ in chronic viral infections (e.g., HIV/AIDS and COVID-19) have been attributed to its potent anti-inflammatory and immunomodulatory activities. As this supplement is increasingly becoming one of the fastest-selling herbal medicines in Nigeria, there is a need for more robust studies (including clinical trials) in order to replicate and validate the prior insights gleaned from experimental studies.

Hydrogenated water has emerged as a novel approach in the field of health and wellness. It is be-lieved to have potent antioxidant properties that can neutralize harmful free radicals in the hu-man body. It has also been shown to be beneficial in mitigating oxidative stress-induced damage through its anti-inflammatory and anti-apoptotic pathways. We aim to conduct a systematic re-view to evaluate the potential benefits of hydrogenated water. The review protocol was uploaded on PROSPERO. After the initial search criteria, the articles were reviewed by two blinded inves-tigators, and a total of 25 articles were included in the systematic review. The potential benefits of hydrogenated water on various aspects of health, including exercise capacity, physical endurance, liver function, cardiovascular disease, mental health, COVID-19, oxidative stress, and anti-aging research, are a subject of growing interest and ongoing research. Although preliminary results in clinical trials and studies are encouraging, further research with larger sample sizes and rigor-ous methodologies is needed to substantiate these findings. Current research needs to fully ex-plain the mechanisms behind the potential benefits of hydrogenated water. Continued scientific exploration will provide valuable insights into the potential of hydrogenated water as an adjunc-tive therapeutic approach in the future.

A healthy cornea is a nonvascularized, transparent tissue. It is nourished by diffusion through the tear film, aqueous fluid and neurotrophins supplied by the corneal innervation. The cornea is devoid of both blood and lymphatic vessels, which makes it an immunologi-cally privileged tissue. Corneal neovascularization develops due to an imbalance between angiogenic and anti-angiogenic factors and can lead to a significant decrease in visual acui-ty. It may cause scarring, lipid keratopathy, and corneal edema. The resulting pathological vascularization of the cornea reduces its immune privilege and significantly worsens the prognosis after subsequent penetrating keratoplasty, increasing the risk of rejection of the transplanted flap. Neovascularization is favored by many disease processes, including auto-immune diseases, viral inflammations, mainly herpes and varicella-zoster, and blepharitis [1]. There are several options to treat corneal neovascularization, both pharmacological and surgical. Angiostatic treatment involves inhibiting the growth of new vessels by suppressing inflammatory responses. VEGF inhibitors, steroids, cyclosporine A, and amniotic membrane grafts secured to the cornea work this way. VEGF inhibitors are the agents with the direct and most potent angiostatic effect. Angioregressive treatment, on the other hand, results in the regression of already existing pathological vessels. This therapy is also based on VEGF inhibitors, which, however, have the most potent effect on newly formed and small vessels but are less effective in reducing large-caliber and mature vessels. A more effective method for such vessels is ablation, which involves surgical closure. The most commonly used an-gio-occlusive method is needle diathermy and argon or yellow laser therapy. In advanced corneal neovascularization, corneal transplant surgery may be necessary. It is best performed after pretreatment with anti-VEGF preparations, often continued after corneal transplanta-tion to reduce the risk of transplant rejection [2]. This paper discusses the pathogenesis of corneal neovascularization and the current and future trends in its treatment.

Quinoa, known as the "golden grain" for its high nutritional value, is a significant source of essential nutrients, including proteins, minerals, vitamins, polyphenols, phytosterols, and flavonoids. However, the biological functions of quinoa polysaccharides remain understudied. In this research, two crude quinoa polysaccharides extracts (Q-40 and Q-60) were obtained extracting by 40% and 60% alcohol. The purity of Q-40 and Q-60 was 58.29% and 62.15%, with protein contents of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47484 to 626488 Da, while Q-60 showed a range of 10025 to 47990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of Methicillin-resistant Staphylococcus aureus (MRSA) and E. coli, while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in application of quinoa in food and functional food industries.

Rhizophora mangle L. is a well-known medicinal plant found in mangroves worldwide used to treatment diabetes. This study evaluated the chemical composition of the acetonic extract from Rhizophora mangle barks (AERM), by HPLC-PDA and FIA-ESI-IT-MS/MS and the effects on high-fat diet induced obesity in mice and its mechanism of action by gene expression of inflammatory markers (Pparg, Ppara, Srebf1, Cd36, Tnf, Ccl2, Lep, Il10, Il6, Fasn, 18s). High-fat diet fed mice during 12 weeks was used as model of obesity and associated alterations. The results were very satisfactory, the extract, rich in polyphenolic compounds, flavonoids and phenolic acids, displayed intense antioxidant activity in vitro (608 µmol Trolox/g), and showed excellent activity against non-alcoholic fatty liver disease (NAFLD) and reverse insulin resistance in a model of diet-induced obesity. We can registered a modulatory effect of AERM in liver PPAR-γ mRNA expression associated to an important inhibition of CD36 mRNA expression suggesting that AERM induces the down regulation of CD36 mRNA via PPAR-gamma inhibition. These results support the traditional knowledge about the use of R. mangle for the treatment of type 2 diabetes and reveal the potential of AERM for the treatment of NAFLD and management of obesity and comorbidities.

Considering the multifaceted nature of neurodegenerative diseases like dementia and the neces-sity for interprofessional knowledge, this research extends its scope to encompass professionals with diverse levels of training and experience in dementia care. A need analysis for the project “My INdividual Digital EDucation.RUHR” (MINDED.RUHR) is conducted to develop an au-tomatized recommender system for individual learning content using AI. In this sub-study, the aim was to reveal didactic specialties, knowledge gaps and structural challenges of further edu-cation in dementia care of different health professions and to derive learning preference personae. Eight focus group interviews among nine health professions and up to six participants (n = 34) each took place to survey distinct didactic experiences and learning needs. The results reflect various learning preferences, with a propensity to multimedia, practical and interactive tasks. Health professions are used to digital education but show aversions against certain e-learning formats. The derived learning preference personae constitute profound blueprints for a us-er-centred digital education design process, aiming to establish personalized and representative further education in dementia care applicable to various individual preferences and structural workplace challenges of healthcare professions.

TAU is the main disease driver in Alzheimer’s and many other sporadic and genetic tauopathies. TAU is differently spliced, the role of individual splice-isoforms unclear. Murine Mapt-KO mice are healthy, and protected from Alzheimer’s, but no such case has been reported in humans. Using gnomad database, we here demonstrate that the only isoform expressed during fetal human brain development is intolerant to mutation, while other brain and peripheral nervous system TAU isoforms are dispensable. With TAU targeted therapies for Alzheimer’s and other tauopathies on the rise, we caution that TAU is essential human brain development.

Better understanding of the quality of life among nursing home residents with dementia is im-portant for developing interventions. The objectives of this cross-sectional study were to examine factors associated with poor health-related quality of life in older adults with dementia living in nursing homes in Hanoi, Vietnam. In-person interviews were conducted with 140 adults 60 years and older with dementia and information about their quality of life was obtained using the Quality of Life in Alzheimer’s Disease scale (QOL-AD). A number of sociodemographic and clinical factors associated with poor health-related quality of life (lowest tertile) were assessed through the results of physical tests, interviews with nursing home staff, and review of medical records. The average age of the study sample was 78.3 years, 65% were women, and their av-erage QOL-AD total score was 27.3 (SD = 4.4). Malnutrition, total dependence in activities of daily living, and urinary incontinence were associated with poor quality of life after controlling for multiple potentially confounding factors. Our findings show that Vietnamese nursing home residents with dementia have a moderate quality of life and interventions based on comprehen-sive geriatric assessment remain needed to modify risk factors associated with poor health-related quality of life.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Synaptic zinc ions (Zn2+) play an important role in the development of vascular dementia (VD) and Parkinson’s disease (PD). In this article, based on our study and many others, we review the mo-lecular pathways by which Zn2+ causes neurotoxicity. Zn2+ influences calcium homeostasis, energy production pathway, production of reactive oxygen species, endoplasmic reticulum stress pathway, and activated protein kinase/c-Jun amino terminal kinase (SAPK/JNK) pathway and consequently exerts neurotoxicity. Furthermore, we searched various crops for substances that protect neurones from neurotoxicity caused by Zn2+ and clarified that carnosine (β-alanylhistidine) may be a therapeutic drug for VD and PD. Here, we also review the molecular mechanisms underlying the role of carnosine as an endogenous protector and its protective effect against Zn2+-induced cyto-toxicity and discuss prospects for future neurodegenerative diseases therapeutic applications of this dipeptide.

Alzheimer's disease is a neurological illness that worsens gradually. It is known as the most frequent cause of dementia. Moreover, Alzheimer's disease is a general term for memory loss and other cognitive impairments severe enough to disrupt daily life. The disease often grows in middle-aged and elderly people with the gradual loss of cognitive ability. Since the diagnosis of the illness is time consuming, a novel machine learning approach is proposed in this research to diagnose Alzheimer's levels based on Magnetic Resonance Imaging (MRI). More specifically, to provide distinct information for classification we have implemented the proposed method on a native MRI scans dataset containing three MRI channels; namely T1, T2, and, T2 tirm, which are shown in red, blue and green, respectively. The five middle layers of these three types of MRI scans are combined to form five RGB layers. In addition, we use a Convolutional Neural Network to classify each composed layer, and the final disease type is predicted using majority voting. finally, the F1-Score has been used to assess method performance, indicated that 92% of predictions of the proposed model were accurate.

ackground: This study aimed to examine the effects of a woodworking program on psychosocial health in older adults who had mild cognitive impairment (MCI) or mild dementia (MD) in Korea. Setting: The study was carried out in a dementia center in Seoul in Korea. Population: A total of 61 participants who had MCI or MD were allocated into two groups: the experimental group (EG, n = 35) and the control group (CG, n = 26). Methods: This study was carried out using a nonequivalent control group pre-test–post-test design. The EG participated in the woodworking program a total of 10 times for 120 min per session twice a week for 5 weeks, and the CG did not participate in the woodworking program. Both groups completed the same survey before and after the intervention. In the survey, demographic characteristics, psychological health (life satisfaction, depression, self-efficacy, and resilience), and social health (social isolation and social support) were measured. Results: In the within-group comparison, there was no significant difference between any factors of the CG before and after the intervention. In contrast, the EG had a significant improvement before and after the woodworking program. Participants in the EG with MCI and MD significantly improved their social support (p < 0.05). Psychological factors (life satisfaction, depression, and self-efficacy) were positively changed, although not significantly. Conclusions: The woodworking program promoted psychosocial health, such as life satisfaction, resilience, and social support, among older adults with mild cognitive impairment and mild dementia.

Several recent epidemiological studies attempted to identify risk factors for Alzheimer's disease. Age, family history, genetic factors (APOE genotype, Down syndrome), physical activity, and a low level of schooling are significant risk factors. In this review, we summarize the known psychosocial risk factors for the development of Alzheimer's disease in Down syndrome patients and their association with neuroanatomical changes in the brains of people with Down syndrome. We completed a comprehensive review of the literature on PubMed, Google Scholar, and Web of Science about psychosocial risk factors for Alzheimer's disease, for Alzheimer's disease in Down syndrome, and Alzheimer's disease in Down syndrome and their association with neuroanatomical changes in the brains of people with Down syndrome. Alzheimer's disease causes early pathological changes in Down syndrome patients, especially in the hippocampus and corpus callosum. The field needs more data about the neuroanatomical changes during childhood, how they change with increasing age, and the presence or absence of psychosocial risk factors. Further neuroimaging and psychosocial assessment-focused research is needed to understand the mechanisms leading to Alzheimer's disease at an early age and create more sensitive and relevant clinical, memory, and reasoning assessments for people with Down syndrome.

The purpose of this study is to explore the effects of dual-task training, including cognitive tasks, on cognitive and bodily functioning and β-amyloid levels in Alzheimer's dementia patients. The subjects were 34 inpatients diagnosed with Alzheimer's dementia at a nursing hospital located in Gyeongsansi, South Korea. The patients were randomly divided into a dual-task group (n = 16) and a single-task group (n = 18). The dual-task group performed cognitive tasks at the same time as exercising tasks, while the single-task group performed only exercise tasks. Each group was trained for 30 minutes three times a week for eight weeks. The Mini-Mental State Examination was used to measure the patients’ cognitive function. Static and dynamic balance were measured to evaluate bodily functioning. Static balance was measured using Biorescue, while dynamic balance was measured using the Berg Balance Scale. Blood analysis was performed to measure levels of β-amyloid, which is known to cause Alzheimer's dementia. Both groups exhibited statistically significant improvements in gait function after the training (p < .05). The dual-task group exhibited statistically significant differences in cognitive function, static and dynamic balance function, and β-amyloid levels after training (p < .05). A significant difference was observed between the two groups (p < .05). Dual-task activities were found to be effective in improving cognitive and bodily functioning and reducing β-amyloid levels in Alzheimer's dementia patients. Therefore, dual-task training is thought to be an effective method of treating and preventing Alzheimer's dementia.

As the number of older adults with dementia increases, early diagnosis and intervention are crucially important. The purpose of this study was to conduct dementia screening on older adults to determine whether there are differences in daily activities of living, depression, loneliness, social support, and life satisfaction between older adults at high-risk for dementia compared with low-risk older adults. We hypothesized a negative relationship between high-risk older adults and these factors. This study also hypothesized a moderating effect for social support on the relationship between daily living activities and life satisfaction. This study used a cross-sectional design with survey data. Participants were recruited at 15 public community health centers in South Korea. A total of 609 older adults (male 208, female 401) living in the community were screened for early dementia, and 113 participants (18.9 %) were assigned to the high-risk group. As hypothesized, participants in the high-risk group showed significantly more negative results ​​in terms of activities of daily living, depression, loneliness, social support, and life satisfaction compared with participants in the low-risk group. The findings of this study provide a theoretical basis for the importance of early screening for dementia and policies for effective dementia prevention.

Purpose: This paper extends previous works to include the role of therapeutic gardens in the healing environment as an intervention for bettering the clinical outcomes of Alzheimer’s and dementia patients, the positive impact of healing gardens and the innovative application of technologies with nature, for promoting cognitive rehabilitation in this particular patient population.Methods: Using ISI Web of Science, PubMed, ProQuest Central, MEDLIN, Scopus and Google Scholar, a relevant literature search on the positive health implications of therapeutic gardens on Alzheimer’s and dementia patients’ in the healthcare milieu was conducted.Results: Health implication of therapeutic gardens on Alzheimer’s and dementia patients’ spans across physical, social, psychological and cognitive effects. Virtual reality (VR) technologies offer positive cognitive outcomes to Alzheimer's disease (AD) and dementia patients.Conclusion: Therapeutic gardens should be extended for speedier recovery of other patient populations. Future directions in the design of healthcare gardens with a focus on patient experience are inferred.

Our report presents the findings from a treatment program that involved plant-based diets (PBDs) and supplements for 1,750 elderly cardiology patients diagnosed with COVID-19 between April 2020 and June 2023. At the start of the program, there was no published data supporting the use of PBDs for COVID-19 patients. However, after 18 months, studies were released that indicated the effectiveness of PBDs in decreasing the incidence and severity of COVID-19. Our treatment protocol differed from these studies in several ways. We carefully controlled the quality, quantity, and processing method of the foods we provided, opting for raw instead of cooked vegetables. Additionally, we incorporated supplementation that complemented the nutrients lacking in a PBD and enhanced the anti-viral, anti-inflammatory, antioxidant, antithrombotic, and immunomodulatory properties of a PBD. Our patients recovered faster (12±1.4 days vs. 20.9±4.3 days), with lower severity (2% vs. 10-20%), hospitalizations (0 vs. 5-10%), and deaths (0 vs. 15-17%) compared to the general population. These favorable outcomes are particularly noteworthy given Indonesia's high COVID-19 morbidity and mortality rates, among the highest in Asia. The findings of this report provide valuable insights for practitioners in managing high-risk elderly COVID-19 patients, particularly in avoiding severity and mortality.

The goal of this study was to develop a rapid diagnostic kit for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HC). Observer scores and absolute signal intensities from the VFA were validated by ELISA. The rapid ten minute point of care VFA test engineered demonstrated a limit of detection of 0.5 IU/ml for ANA and αDNA autoantibodies in human plasma with inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in 22 SLE and 18 HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and 84% accuracy in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease and rapid turnaround, it can also be used to assess SLE prevalence estimates.