Kynurenine pathway in type 2 diabetes: Role of metformin.

The Kynurenine pathway (KP) which is involved in the synthesis of nicotinamide adenine dinucleotide (NAD) from tryptophan (Trp) is intricate in the development of insulin resistance (IR) and type 2 diabetes (T2D). Inflammatory reactions in response to cardiometabolic disorders can induce the development of IR through the augmentation of KP. However, kynurenine (KYN), a precursor of kynurenic acid (KA) is increased following physical exercise and involved in the reduction of IR. Consequently, KP metabolites KA and KYN have anti-diabetogenic effects while other metabolites have diabetogenic effects. KP modulators, either inhibitors or activators, affect glucose homeostasis and insulin sensitivity in T2D in a bidirectional way, either protective or detrimental, that is not related to the KP effect. However, metformin through inhibition of inflammatory signaling pathways can reduce the activation of KP in T2D. These findings indicated a strong controversy regarding the role of KP in T2D. Therefore, the objectives of this mini review were to clarify how KP induces the development of IR and T2D. In addition, this review aimed to find the mechanistic role of antidiabetic drug metformin on the KP, and how KP modulators affect the pathogenesis of T2D.

Intensive Care Unit Nurses' Experiences in Caring for End-of-Life Patients in Saudi Arabia: A Qualitative Study.

Background: Although extensive research on appropriate treatments has been conducted, how nurses provide care to patients at the end-of-life (EOL) is unclear, particularly among intensive care unit (ICU) nurses in Saudi Arabia. Purpose: To explore intensive care unit nurses' experiences in providing end-of-life care in Saudi Arabia. Methods: This study utilized an exploratory, descriptive, qualitative approach. A purposive sampling technique was used to recruit ICU nurses (n = 10) working in ICUs at a tertiary teaching hospital in Riyadh, Saudi Arabia. Using a semi-structured interview guide, ten individual interviews were conducted. Data were analyzed using thematic analysis. The trustworthiness of this study was ensured by following Lincoln and Guba's (1985) criteria. Findings: Four major themes related to ICU nurses' experiences of providing EOL care emerged, including: "feeling challenged but driven", "holistic caring", "collaborative working ethics", and "caring for the undying and dying". Conclusions: This study adds to the body of knowledge about the experience of ICU nurses caring for EOL patients. It offers valuable insights into challenges, coping strategies, holistic caring, collaboration, and the management of critical or dying patients at EOL in the ICUs.

Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment and cognitive dysfunctions. It has been shown that hypoglycemia can adversely affect AD neuropathology. It is well-known that chronic hyperglycemia in type 2 diabetes (T2D) is regarded as a potential risk factor for the development and progression of AD. However, the effect of recurrent hypoglycemia on the pathogenesis of AD was not deeply discussed, and how recurrent hypoglycemia affects AD at cellular and molecular levels was not intensely interpreted by the previous studies. The underlying mechanisms for hypoglycaemia-induced AD are diverse such as endothelial dysfunction, thrombosis, and neuronal injury that causing tau protein hyperphosphorylation and the accumulation of amyloid beta (Aß) in the brain neurons. Of note, the glucagon hormone, which controls blood glucose, can also regulate the cognitive functions. Glucagon increases blood glucose by antagonizing the metabolic effect of insulin. Therefore, glucagon, through attenuation of hypoglycemia, may prevent AD neuropathology. Glucagon/GLP-1 has been shown to promote synaptogenesis, hippocampal synaptic plasticity, and learning and memory, while attenuating amyloid and tau pathologies. Therefore, activation of glucagon receptors in the brain may reduce AD neuropathology. A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology.

The potential role of brain renin-angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?

Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin-angiotensin system (RAS) is intricate in the PD neuropathology through modulation of oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, modulation of brain RAS by angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may be effective in reducing the risk and PD neuropathology. It has been shown that all components including the peptides and enzymes of the RAS are present in the different brain areas. Brain RAS plays a critical role in the regulation of memory and cognitive function, and in the controlling of central blood pressure. However, exaggerated brain RAS is implicated in the pathogenesis of different neurodegenerative diseases including PD. Two well-known pathways of brain RAS are recognized including; the classical pathway which is mainly mediated by AngII/AT1R has detrimental effects. Conversely, the non-classical pathway which is mostly mediated by ACE2/Ang1-7/MASR and AngII/AT2R has beneficial effects against PD neuropathology. Exaggerated brain RAS affects the viability of dopaminergic neurons. However, the fundamental mechanism of brain RAS in PD neuropathology was not fully elucidated. Consequently, the purpose of this review is to disclose the mechanistic role of RAS in in the pathogenesis of PD. In addition, we try to revise how the ACEIs and ARBs can be developed for therapeutics in PD.

The compelling role of allopurinol in hyperuricemia-induced epilepsy: Unrecognized like tears in rain.

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy.

Parkinson's disease (PD) is a neurodegenerative disorder of the brain and is manifested by motor and non-motor symptoms because of degenerative changes in dopaminergic neurons of the substantia nigra. PD neuropathology is associated with mitochondrial dysfunction, oxidative damage and apoptosis. Thus, the modulation of mitochondrial dysfunction, oxidative damage and apoptosis by growth factors could be a novel boulevard in the management of PD. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase type B (TrkB) are chiefly involved in PD neuropathology. BDNF promotes the survival of dopaminergic neurons in the substantia nigra and enhances the functional activity of striatal neurons. Deficiency of the TrkB receptor triggers degeneration of dopaminergic neurons and accumulation of α-Syn in the substantia nigra. As well, BDNF/TrkB signalling is reduced in the early phase of PD neuropathology. Targeting of BDNF/TrkB signalling by specific activators may attenuate PD neuropathology. Thus, this review aimed to discuss the potential role of BDNF/TrkB activators against PD. In conclusion, BDNF/TrkB signalling is decreased in PD and linked with disease severity and long-term complications. Activation of BDNF/TrkB by specific activators may attenuate PD neuropathology.

Gastrointestinal basidiobolomycosis: a rare manifestation of Basidiobolus ranarum in a non-endemic region.

Gastrointestinal basidiobolomycosis (GIB) is a rare fungal infection caused by the Basidiobolus ranarum, and it possesses a significant challenge to diagnose it as it presents with non-specific symptoms that often mimic cancer. Herein, we report a case of GIB in a 51-year-old male from the central region of Saudi Arabia, a non-endemic region of GIB, which was initially misdiagnosed as colon cancer. A 51-year-old man presented with abdominal pain for two-months, non-bloody diarrhea, loss of appetite, and weight loss. Abdominal examination revealed a large mass measuring ~10x15cm. Radiological findings prompted the diagnosis of a colon mass, and the patient was surgically treated under that impression. Hemicolectomy and end colostomy with mucous fistula from distal sigmoid stump were done. Histopathology was consistent with GIB. The diagnosis of GIB presents a serious challenge and requires a high index of clinical suspicion.

A Mutual Nexus Between Epilepsy and α-Synuclein: A Puzzle Pathway.

Alpha-synuclein (α-Syn) is a specific neuronal protein that regulates neurotransmitter release and trafficking of synaptic vesicles. Exosome-associated α-Syn which is specific to the central nervous system (CNS) is involved in the pathogenesis of epilepsy. Therefore, this review aimed to elucidate the possible link between α-Syn and epilepsy, and how it affects the pathophysiology of epilepsy. A neurodegenerative protein such as α-Syn is implicated in the pathogenesis of epilepsy. Evidence from preclinical and clinical studies revealed that upregulation of α-Syn induces progressive neuronal dysfunctions through induction of oxidative stress, neuroinflammation, and inhibition of autophagy in a vicious cycle with subsequent development of severe epilepsy. In addition, accumulation of α-Syn in epilepsy could be secondary to the different cellular alterations including oxidative stress, neuroinflammation, reduction of brain-derived neurotrophic factor (BDNF) and progranulin (PGN), and failure of the autophagy pathway. However, the mechanism of α-Syn-induced-epileptogenesis is not well elucidated. Therefore, α-Syn could be a secondary consequence of epilepsy. Preclinical and clinical studies are warranted to confirm this causal relationship.

Assessment of chronic rhinosinusitis with nasal polyps: Development of the Nasal Polyp Patient Assessment Scoring Sheet tool.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with a wide range of validated subjective and objective assessment tools to assess disease severity. However, a comprehensive and easy-to-use tool that integrates these measures for determining disease severity and response to treatment is still obscure. The objective of this study was to develop a standardized assessment tool that facilitates diagnosis, uniform patient monitoring, and comparison of treatment outcomes between different centers both in routine clinical practice and in research. Methods: To develop this tool, published literature on assessment tools was searched on various databases. A panel of 12 steering committee members conducted an advisory board meeting to review the findings. Specific outcome measures to be included in a comprehensive assessment tool and follow-up sheet were then collated following consensus approval from the panel. The tool was further validated for content and revised with expert recommendations to arrive at the finalized Nasal Polyp Patient Assessment Scoring Sheet (N-PASS) tool. Results: The N-PASS tool was developed by integrating the subjective and objective measures for CRS assessment. Based on expert opinions, N-PASS was revised to be used as an easy-to-use guidance tool that captures patient-reported and physician-assessed components for comprehensively assessing disease status and response to treatment. Conclusion: The N-PASS tool can be used to aid in the diagnosis and management of CRS cases with nasal polyps. The tool would also aid in improved monitoring of patients and pave the way for an international disease registry. Level of evidence: Oxford Level 3.

Actual Scope of Nursing Practice in Saudi Ministry of Health Hospitals.

BACKGROUND: Articulating a clear scope of practice for all nursing categories is essential for improving patient safety, quality of care, and nurse retention. However, this is not the case in many countries, including Saudi Arabia. This study aimed to analyze the actual scope of practice for nursing staff in Saudi Ministry of Health hospitals. METHODS: The study used a cross-sectional exploratory design. The sampling method used in the study was the quota sampling technique. The scale utilized in this study was the Actual Scope of Practice (ASCOP) scale. Data were collected in March 2021 through an electronic form questionnaire completed by 286 nurses in two hospitals in Al-Hasa province in Saudi Arabia. RESULTS: The overall mean score for ASCOP was 4.64 out of 6. When participants were grouped according to select characteristics (various nursing staff categories, educational levels, years of experience, nationality, gender, and type of work setting), the results revealed no statistically significant differences in overall ASCOP mean scores, except for gender and nationality. CONCLUSIONS: The overall mean scores of nursing activities performed in practice do not significantly differ across nurses with different professional categories (health assistant, nursing technician, nursing specialist, and senior nursing specialist), indicating no clear scope of practice for each nursing category, in turn leading to role overlap among them in practice. The current study's findings can guide decision-makers to develop a clear scope of practice for nurses. The findings should also urge the decision-makers to reevaluate the usefulness of having multiple professional categories of nurses who are allowed to carry out almost the same job duties.

Prevalence of co-infection of human immunodeficiency virus in diagnosed tuberculosis cases: Meta-analysis.

Objective: The objective of the study was to find pooled prevalence and risk factors of co-infection of human immunodeficiency virus (HIV) in diagnosed tuberculosis (TB) cases. Methods: Search engines including PubMed and Google Scholar were used to find literature using search terms such as "co-infection," "HIV," "Acquired Immunodeficiency Syndrome," TB and "Prevalence" among others. All original studies conducted on the prevalence of HIV co-infection among diagnosed TB patients that were freely available in full length had a clear methodology and relevant results were included in the study. Result: From 1021 initial studies, a total of 18 studies were selected for analysis. A total of 18 studies were included with a total sample size of 44943. The minimum prevalence of HIV-TB was reported in a study from Pakistan as 0.29% and the maximum prevalence of HIV-TB was found in Nigeria, that is, 44.20%. The pooled prevalence of HIV/TB co-infection was 16.291% (95%; 9.57-24.38) using the random effect method. As per Begg's test, there was no publication bias. As I2 is 99.74% so, there is high heterogeneity among studies; hence, random effect model is preferred. Conclusion: The study concludes that the pooled prevalence of HIV/TB co-infection was found to be 16.291% (95%; 9.57-24.38). The risk of mortality will be substantially raised by the co-existence of HIV-TB co-infection, so early screening and emphasizing the urgent need for integrated health-care interventions can cope with the situation.

Predictors of Leadership Competencies Among Nurse Executives in the Kingdom of Saudi Arabia.

Background: Awareness and development of nurse executives' leadership competencies has been considered a key strategy for the success of healthcare organizations. However, only a few studies about nurse executives' leadership competencies are available in the literature, and no study has been conducted about the topic within Saudi Arabian context. The aim of this study was to assess the leadership competencies of nurse executives and the predictors of these competencies. Methods: This quantitative study used a descriptive, cross-sectional, and correlational design. The study recruited a total convenience sample of 136 nurse executives who voluntarily consented to participate. The respondents self-rated the online survey, "Leadership Competency Assessment Tool: Self-Assessment." Data collection was conducted between September 2022 and November 2022. Test of correlation and multiple regression analyses were conducted. Results: The overall mean score of nurse executives' leadership competencies was 3.38 out of 5.0, which was below the level of having excellent leadership competencies. Four dimensions had mean scores below the level of having excellent leadership competencies, namely, communication and relationship building (3.48), knowledge of the healthcare environment (3.29), leadership (3.45), and business skills (3.15), while nurse executives had excellent leadership competencies only in the professionalism dimension (3.51). Age (p=0.04), highest educational attainment (p=0.01), current role (p<0.01) and length of experience (p=0.02) as nurse executive, monthly salary (p=0.03), nationality (p=0.04), and having seminars/trainings in leadership and management (p=0.01) were considered predictors of the leadership competencies of nurse executives. Conclusion: Nurse executives reported a low level of leadership competencies, thus implying necessary actions for improvement. There were personal factors that influenced the level of nurse executives' leadership competencies. To achieve quality outcomes and maintain a high level of nursing care in hospital organizations, these findings must be considered in planning strategies related to the improvement of the leadership competencies of nurse executives.

Exploring Nurse perceptions of structural empowerment in midwifery practice in Saudi Arabia: A qualitative study.

Perceptions and experiences of midwives regarding structural empowerment during practice in Saudi Arabia were explored using a qualitative, constructive, descriptive design. Data was gathered using individual semi-structured interviews with ten midwives employed in delivery rooms, and prenatal and postnatal units of governmental hospitals in Saudi Arabia's eastern province. Data was analyzed with assistance of NVivo software, Version 12. Five themes emerged from our study: the meaning of structural empowerment, ambiguous hospital policies, the insufficient numbers of midwives, midwife-physician dynamics, and continuing education and training. Structural empowerment of midwives in maternity units may be useful in improving midwifery services in Saudi Arabia and worldwide.

What is the further research?Further studies on this topic should expand the current study's sample and include participants from more regions of Saudi Arabia. In addition, research on the psychological empowerment of midwives is needed.What is known on the subject?Midwives are educated to care for women during pregnancy, birth, and postnatal, and midwives must be empowered to fulfill this professional role. The evidence showed the importance of structural empowerment for midwives to perform their professional function and provide quality care for women during pregnancy, birth, and postnatal.What does this paper add to existing knowledge?In Saudi Arabia, there is little research evidence on how to explore the perceptions and experiences of structural empowerment among midwives. Our study provided valuable recommendations for identifying environmental practices, positive workplace characteristics, and promoting higher-quality midwifery in the workplace.What are the implications for practice?Midwife workplace empowerment is correlated with the quality of care, job satisfaction, staff effectiveness, and the positivity of the work environment. The results of this study suggest that every healthcare organization must work to bring about structural empowerment for midwives to facilitate successful practice.

High-Grade Sinonasal Small Cell Neuroendocrine Carcinoma in a Patient With Xeroderma Pigmentosum: A Case Report.

Neuroendocrine tumors are rare and highly heterogeneous neoplasms with a wide spectrum of histological differentiation, functional, and biological features. Small cell neuroendocrine carcinomas (SNECs) of the sinonasal tract are particularly rare. Pathological features of SNECs of the nasal cavity and paranasal sinuses, which are aggressive tumors, are similar to those of anaplastic small cell carcinomas of the lung. We present a case of high-grade sinonasal SNECs in a patient with Xeroderma pigmentosum complementation group C (XPC) gene-positive xeroderma, which, to our knowledge, is the first case reported worldwide.

Constituents of Stachys plants as potential dual inhibitors of AChE and NMDAR for the treatment of Alzheimer's disease: a molecular docking and dynamic simulation study.

Alzheimer's disease (AD) is a chronic neurodegenerative condition characterized by progressive cognitive impairment. While the formation of ß-amyloid plaques and neurofibrillary tangles are the hallmarks features of AD, the downstream consequence of these byproducts is the disruption of the cholinergic and glutamatergic neural systems. Growing evidence for the existence of interplay between AChE and NMDARs has opened up new venues for the discovery of novel ligands endowed with anticholinesterase and NMDAR-blocking activity. Plants belonging to the stachys genus have been extensively explored for having a broad range of therapeutic applications and have been used traditionally for millennia, to treat various CNS-related disorders, which makes them the ideal source of novel therapeutics. The present study was designed to identify natural dual-target inhibitors for AChE and NMDAR deriving from stachys genus for their potential use in AD. Using molecular docking, drug-likeness-profiling, MD simulation and MMGBSA calculations, an in-house database of biomolecules pertaining to the stachys genus was shortlisted based on their binding affinity, overall stability and critical ADMET parameters. Pre- and post-MD analysis revealed that Isoorientin effectively binds to AChE and NMDAR with various vital interactions, exhibits a stable behavior with minor fluctuations relative to two clinical drugs used as positive control, and displays strong and consistent interactions that lasted for the majority of the simulation. Findings from this study have elucidated the rationale behind the traditional use of Stachys plants for the treatment of AD and could provide new impetus for the development of novel dual-target therapeutics for AD treatment.Communicated by Ramaswamy H. Sarma.

The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer's disease: a new perspective.

Alzheimer's disease (AD) is the most common type of dementia associated with amyloid beta (Aß) deposition. Dysfunction of the neuronal clearance pathway promotes the accumulation of Aß. The plasminogen-activating system (PAS) is controlled by various enzymes like tissue plasminogen activators (tPA). Neuronal tPA enhances the conversion of plasminogen to plasmin, which cleaves Aß; this function is controlled by many inhibitors of PAS, including a plasminogen-activating inhibitor (PAI-1) and neuroserpin. Therefore, the objective of the present narrative review was to explore the potential role of tPA/neuroserpin in the pathogenesis of AD. PAI-1 activity is increased in AD, which is involved in accumulating Aß. Progressive increase of Aß level during AD neuropathology is correlated with the over-production of PAI-1 with subsequent reduction of plasmin and tPA activities. Reducing plasmin and tPA activities promote Aß by reducing Aß clearance. Neuroserpin plays a critical role in the pathogenesis of AD as it regulates the expression and accumulation of Aß. Higher expression of neuroserpin inhibits the neuroprotective tPA and the generation of plasmin with subsequent reduction in the clearance of Aß. These observations raise conflicting evidence on whether neuroserpin is neuroprotective or involved in AD progression. Thus, neuroserpin over-expression with subsequent reduction of tPA may propagate AD neuropathology.

Irisin/PGC-1α/FNDC5 pathway in Parkinson's disease: truth under the throes.

Parkinson's disease (PD) is considered one of the most common neurodegenerative brain diseases which involves the deposition of α-synuclein. Irisin hormone, a newly discovered adipokine, has a valuable role in diverse neurodegenerative diseases. Therefore, this review aims to elucidate the possible role of the irisin hormone in PD neuropathology. Irisin hormone has a neuroprotective effect against the development and progression of various neurodegenerative disorders by increasing the expression of brain-derived neurotrophic factor (BDNF). Irisin hormone has anti-inflammatory, anti-apoptotic, and anti-oxidative impacts, thereby reducing the expression of the pro-inflammatory cytokines and the progression of neuroinflammation. Irisin-induced PGC-1α could potentially prevent α-synuclein-induced dopaminergic injury, neuroinflammation, and neurotoxicity in PD. Inhibition of NF-κB by irisin improves PGC-1α and FNDC5 signaling pathway with subsequent attenuation of PD neuropathology. Therefore, the irisin/PGC-1α/FNDC5 pathway could prevent dopaminergic neuronal injury. In conclusion, the irisin hormone has a neuroprotective effect through its anti-inflammatory and antioxidant impacts with the amelioration of brain BDNF levels. Further preclinical and clinical studies are recommended in this regard.

Role of brain renin-angiotensin system in depression: A new perspective.

Depression is a mood disorder characterized by abnormal thoughts. The pathophysiology of depression is related to the deficiency of serotonin (5HT), which is derived from tryptophan (Trp). Mitochondrial dysfunction, oxidative stress, and neuroinflammation are involved in the pathogenesis of depression. Notably, the renin-angiotensin system (RAS) is involved in the pathogenesis of depression, and different findings revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may be effective in depression. However, the underlying mechanism for the role of dysregulated brain RAS-induced depression remains speculative. Therefore, this review aimed to revise the conceivable role of ACEIs and ARBs and how these agents ameliorate the pathophysiology of depression. Dysregulation of brain RAS triggers the development and progression of depression through the reduction of brain 5HT and expression of brain-derived neurotrophic factor (BDNF) and the induction of mitochondrial dysfunction, oxidative stress, and neuroinflammation. Therefore, inhibition of central classical RAS by ARBS and ACEIs and activation of non-classical RAS prevent the development of depression by regulating 5HT, BDNF, mitochondrial dysfunction, oxidative stress, and neuroinflammation.

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aß). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aß. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aß and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aß. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aß clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon-like peptide 1 (GLP-1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP-1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.