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When dysbiosis meets dystrophy: an unwanted gut-muscle connection
No full textDuchenne muscular dystrophy (DMD) is a devastating neuromuscular degenerative disease with no known cure to date. In recent years, the hypothesis of a "gut-muscle axis" has emerged suggesting that bidirectional communication between the gut microbiota and the muscular system regulates the muscular function and may be perturbed in several muscular disorders. In addition, the excessive consumption of sugar and of lipid-rich processed food products are factors that further aggravate the phenotype for such diseases and accelerate biological aging. However, these unhealthy microbiota profiles can be reversed by individualized dietary changes to not only alter the microbiota composition but also to reset the production of microbial metabolites known to trigger beneficial effects typically associated with prolonged health span. Two recent studies (in this issue of EMBO Mol Med) highlight the interesting potential of microbiota-informed next-generation dietary intervention programs to be considered in genetically linked muscle disorders like DMD
Hide-and-sniff: can anti-trafficking dogs detect obfuscated wildlife parts?
No full textWildlife detection dog (WDD) programs are increasingly being developed to combat illegal wildlife trafficking. However, there is little scientific research available on how sniffer dogs perform when wildlife parts are hidden during the smuggling process, which hampers the effectiveness of WDD programs. Here, we investigate the ability of WDDs to detect wildlife parts that are hidden in legally traded goods. We employed a smell test using the two most smuggled wildlife parts worldwide: elephant ivory and pangolin scales, in combination with two obfuscation items of plant and animal origin commonly employed by smugglers. We then established the sensitivity of the dogs to the target substances. Our results showed that there was a large variation between the two dogs in their sensitivity to ivory and pangolin scales. However, both dogs were generally less sensitive to ivory compared to pangolin scales, and stronger-smelling obfuscation items could potentially lower the sensitivity of the dogs to the wildlife parts. Our study highlights the potential of dogs to detect hidden wildlife parts, but their effectiveness may depend on other aspects such as training, personality, the health of the dog, the type of wildlife substance, and the obfuscation item used. Given the variability of our findings, WDD programs need to invest in research to optimize the number and type of dogs with the right balance of traits to successfully detect wildlife parts that could potentially be obfuscated during smuggling
Meta-Analysis and Systematic Review of HLA DQ2/DQ8 in Adults with Celiac Disease
Get PDFAlthough people with human leukocyte antigens (HLA) DQ2 and/or DQ8 are more likely to develop celiac disease (CD), the condition cannot be fully explained by this genetic predisposition alone. Multiple, as yet unidentified, factors contribute to the genesis of CD, including genetics, the environment, and the immune system. In order to provide insight into a prospective possibility and an expanded screening technique, we aim to undertake a comprehensive and meta-analytical study of the assessment and distribution of HLA class II (HLA-DQ2/DQ8) in adult CD patients. A systematic review was conducted using an electronic search of databases (PubMed, Google Scholar, Embase, and Direct Science) from January 2004 to February 2022. DQ2/DQ2 homozygotes have the highest risk of developing CD. DQ2/DQ8 typing is an effective test to exclude CD from the differential diagnosis of a patient with CD symptoms. Although other non-HLA genes have been associated with CD, they are rarely considered at diagnosis because they account for only a small proportion of the heritability of CD. This finding, together with the information gathered previously, may be useful in considering widely available and economically feasible screening options for celiac disease in young people
Virtual Screening, Synthesis, and Biological Evaluation of Some Carbohydrazide Derivatives as Potential DPP-IV Inhibitors
Get PDFDipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a–5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber’s guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents
Ecological Grief in Filipino Youth
No full textEcological grief is an emotional and psychological response to losses in the natural world (e.g., deforestation, wildlife loss, climate change-related loss), which is characterized by an intense feeling of longing and mourning due to ecological damages and decline (Cunsolo & Ellis, 2018). Humans’ natural affiliation with nature explains why ecological losses can have detrimental effects on our mental health and wellbeing (Aruta, 2021). In the psychology literature, however, grief is often understood as a response to a loss of loved ones and rarely extends to the losses that people encounter in the natural environment. Although emerging research began to recognize that ecological grief is a valid experience (Cunsolo & Ellis, 2018), such a grief often does not receive public acknowledgement and very little research and policy efforts are exerted to fully understand and address the source of this emotional experience
Neuroprotective Effects of Lactoferrin in Alzheimer's and Parkinson's Diseases: A Narrative Review
No full textRecent advancements in lactoferrin research have uncovered that lactoferrin does function not only as an antimicrobial protein but also as an immunomodulatory, anticancer, and neuroprotective agent. Focusing on neuroprotection, this literature review delineates how lactoferrin interacts in the brain, specifically its neuroprotective effects and mechanisms against Alzheimer’s and Parkinson’s diseases (AD and PD), the two most common neurodegenerative diseases. The neuroprotective pathways involving surface receptors (heparan sulfate proteoglycan (HSPG) and lactoferrin receptor (LfR)), signaling pathways (extracellular regulated protein kinase-cAMP response element-binding protein (ERK-CREB) and phosphoinositide 3-kinase/Akt (PI3K/Akt)), and effector proteins (A disintegrin and metalloprotease10 (ADAM10) and hypoxia-inducible factor 1α (HIF-1α)) in cortical/hippocampal and dopaminergic neurons are described. These cellular effects of lactoferrin are likely responsible for attenuating cognitive and motor deficits, amyloid-β and α-synuclein accumulation, and neurodegeneration in animal and cellular models of AD and PD. This review also discusses the inconsistent findings related to the neuroprotective effects of lactoferrin against AD. Overall, this review contributes to the existing literature by clarifying the potential neuroprotective effects and mechanisms of lactoferrin in the context of AD and PD neuropathology
Prevalence of a fall or rise in blood pressure from a sitting to a standing position in treated hypertensive patients
No full textObjective:
It is known that blood pressure (BP) fluctuates with positioning of an individual. Usually BP falls when changing from lying to standing position which can cause orthostatic/postural hypotension.
However, studies have also shown that BP rises in certain individuals from lying to standing position.
Studies have also shown that rises are associated with increasing age, obesity and presence of diabetes.
While the prevalence of orthostatic/postural hypotension is known, prevalence of rise in BP upon standing is not well documented.
It is important to identify falls or rise in BP upon standing as orthostatic/postural hypotension is associated with increased risk of falls while a rise in BP is associated with increased risk of cardiovascular events (CV).
The aim of our study is to examine the proportion of patients whose BP rises or falls upon standing amongst hypertensive patients. We also examined the association of age, diabetic status, obesity and CV with rises of BP upon standing.
Materials and Methods:
This is a cross sectional study of hypertensive patients in a primary care clinic. Demographic data was collected with weight and height measured. Sitting BP was taken twice after 5 minutes rest, standing BP was taken after 5 minutes of standing. Any fall or rise in BP from sitting to standing was categorized as fallers and risers respectively.
Results:
1736 patients were recruited into this study,734 were invited to have their standing BP done. Mean age was 66.0 ± 9.9years, mean sitting systolic blood pressure (SBP) was 144.4 ± 19.1mmHg, mean sitting diastolic blood pressure (DBP) was 82.4 ± 10.9mmHg, mean sitting heart rate (HR) was 71.4 ± 12.6 min−1. Mean standing SBP was 146.0 ± 19.7mmHg, mean standing HR was 74.1 ± 13.3mins−1.
Mean BMI was 27.1 ± 5.5 kg/m2, of which 69.5% (n = 437) were female, 51.6% (n = 379) were diabetic, and 25.3% (n = 378) were obese. Percentage of patients 65 years and older was 58.5% (n = 428). 22.5% (n = 164) of the patients also had prior CV events.
The proportion of risers and fallers upon standing was 44.5% and 52.8% respectively.
There was no significant difference between the proportion of risers and fallers with increasing age(p = 0.312) or diabetic status (p = 0.406).
However, it was statistically significant associated with obesity (BMI of 30 kg/m2 or more)(p = 0.038).
Conclusion:
Although BP usually drops upon standing, our study showed more than half of treated hypertensives had a rise in their standing BP. There was association of risers/fallers with obesity but not with age or diabetes
Determination of Chemical Composition and Investigation of Biological Activities of Ocimum basilicum L.
Get PDFThis study aimed to determine the chemical composition of the essential oils (EOs) of Ocimum basilicum L., as well as to evaluate the antibacterial, antidiabetic, dermatoprotective, and anti-inflammatory properties, and the EOs and aqueous extracts of O. basilicum. The antibacterial activity was evaluated against bacterial strains, Gram-positive and Gram-negative, using the well diffusion and microdilution methods, whereas the antidiabetic activity was assessed in vitro using two enzymes involved in carbohydrate digestion, α-amylase and α-glucosidase. On the other hand, the dermatoprotective and anti-inflammatory activities were studied by testing tyrosinase and lipoxygenase inhibition activity, respectively. The results showed that the chemical composition of O. basilicum EO (OBEO) is dominated by methyl chavicol (86%) and trans-anethol (8%). OBEO exhibited significant antibacterial effects against Gram-negative and Gram-positive strains, demonstrated by considerable diameters of the inhibition zones and lower MIC and MBC values. In addition, OBEO exhibited significant inhibition of α-amylase (IC50 = 50.51 ± 0.32 μg/mL) and α-glucosidase (IC50 = 39.84 ± 1.2 μg/mL). Concerning the anti-inflammatory activity, OBEO significantly inhibited lipoxygenase activity (IC50 = 18.28 ± 0.03 μg/mL) compared to the aqueous extract (IC50 = 24.8 ± 0.01 μg/mL). Moreover, tyrosinase was considerably inhibited by OBEO (IC50 = 68.58 ± 0.03 μg/mL) compared to the aqueous extract (IC50 = 118.37 ± 0.05 μg/mL). The toxicological investigations revealed the safety of O. basilicum in acute and chronic toxicity. The finding of in silico analysis showed that methyl chavicol and trans-anethole (main compounds of OBEO) validate the pharmacokinetics of these compounds and decipher some antibacterial targets
Grief Support and Coping Mechanism Mediate the Effect of Grief on Burnout Among Intensive Care Unit Nurses: A Structural Equation Modeling Analysis
No full textBackground: Patients' death caused the intensive care unit (ICU) nurses to grieve, which led to their burnout. Intensive care unit nurses use various coping mechanisms and need support to overcome grief.
Objective: The aim of this study was to identify the mediation effects of coping mechanisms and grief support on the impact of grief on burnout.
Method: This cross-sectional study among 660 ICU nurses from 9 hospitals used 4 self-reported instruments to collect data, apart from the sociodemographic and employment-related variables. A final model was developed through structural equation modeling after establishing the construct validities of the measures through confirmatory factor analysis.
Results: The representation of ICU nurses from each hospital was greater than 50%, with the majority being female (90.8%) with a mean age of 27.27 years. Most nurses perceived the absence of grief, low burnout, and moderate to low grief support. The nurses use various coping mechanisms. Grief support significantly mediated the relationship between grief and burnout using a bootstrapping method with a mediation strength using the variance counted for (VAF) of 34.95%. The final model fit indices with acceptable values validated the direct and indirect relationships of grief, grief support, and coping mechanisms on burnout.
Discussion: The significant influence of grief support in mediating the effect of grief on burnout is an important finding. The nursing and hospital management can use this finding to provide grief support to ICU nurses, enhance the grief support resources, and promote future studies to test the model's validity and applicability to health care professionals who frequently face patients' death
Homeobox Gene Expression Dysregulation as Potential Diagnostic and Prognostic Biomarkers in Bladder Cancer
Get PDFHomeobox genes serve as master regulatory transcription factors that regulate gene expression during embryogenesis. A homeobox gene may have either tumor-promoting or tumor-suppressive properties depending on the specific organ or cell lineage where it is expressed. The dysregulation of homeobox genes has been reported in various human cancers, including bladder cancer. The dysregulated expression of homeobox genes has been associated with bladder cancer clinical outcomes. Although bladder cancer has high risk of tumor recurrence and progression, it is highly challenging for clinicians to accurately predict the risk of tumor recurrence and progression at the initial point of diagnosis. Cystoscopy is the routine surveillance method used to detect tumor recurrence. However, the procedure causes significant discomfort and pain that results in poor surveillance follow-up amongst patients. Therefore, the development of reliable non-invasive biomarkers for the early detection and monitoring of bladder cancer is crucial. This review provides a comprehensive overview of the diagnostic and prognostic potential of homeobox gene expression dysregulation in bladder cancer