Medicinal cannabis improves sleep in adults with insomnia: a randomised double-blind placebo-controlled crossover study.

Insomnia or difficulty falling and or staying asleep is experienced by up to 30% of the general population. This randomised crossover double-blind placebo-controlled 6-week trial aimed to assess the tolerability and effectiveness of the Entoura-10:15 medicinal cannabis oil on sleep in adults with insomnia. A total of 29 participants with self-reported clinical insomnia completed the crossover trial. Participants were randomly allocated to receive placebo or active oil containing 10 mg/ml tetrahydrocannabinol (THC) and 15 mg/ml cannabidiol (CBD) over 2-weeks titrated 0.2-1.5 ml/day, followed by a 1-week wash-out period before crossover. Tolerability was assessed by daily diary. Effectiveness was measured by saliva midnight melatonin levels, validated questionnaires, i.e., the Insomnia Severity Index, and the Fitbit activity/sleep wrist tracker. Entoura-10:15 medicinal cannabis oil was generally well tolerated, and was effective in improving sleep, whereby 60% of participants no longer classified as clinical insomniacs at the end of the 2-week intervention period. Midnight melatonin levels significantly improved in the active group by 30% compared to a 20% decline in the placebo group (p = 0.035). Medicinal cannabis oil improved both time and quality of sleep, in particular light sleep increased by 21 min/night compared to placebo (p = 0.041). The quality of sleep improved overall by up to 80% in the active group (pPhase2  = 0.003), including higher daily functioning (p = 0.032). Observed effects were more pronounced in Phase 2 due to the period effect and loss of blinding. Entoura-10:15 medicinal cannabis oil was well tolerated and effective in improving sleep in adults with insomnia.

The effects of cardiovascular and orthopaedic surgery on vitamin concentrations: a narrative review of the literature and mechanisms of action.

Given the rise in worldwide chronic diseases, supplemented by an aging population, the volume of global major surgeries, encompassing cardiac and orthopedic procedures is anticipated to surge significantly. Surgical trauma can be accompanied by numerous postoperative complications and metabolic changes. The present review summarized the results from studies assessing the effects of orthopedic and cardiovascular surgery on vitamin concentrations, in addition to exploring the possible mechanisms associated with changes in concentrations. Studies have revealed a potentially severe depletion in plasma/serum concentrations of numerous vitamins following these surgeries acutely. Vitamins C, D and B1 appear particularly vulnerable to significant depletions, with vitamin C and D depletions consistently transpiring into inadequate and deficient concentrations, respectively. The possible multifactorial mechanisms impacting postoperative vitamin concentrations include changes in hemodilution and vitamin utilization, redistribution, circulatory transport and absorption. For a majority of vitamins, there has been a lack of investigation into the effects of both, cardiac and orthopedic surgery. Additionally, studies were predominantly restricted to short-term postoperative investigations, primarily performed within the first postoperative week of surgery. Overall, results indicated that further examination is necessary to determine the severity and clinical significance of the possible depletions in vitamin concentrations that ensue cardiovascular and orthopedic surgery.

The effects of surgery on plasma vitamin C concentrations and cognitive function: a protocol for a prospective, observational study.

BACKGROUND: Post-operative cognitive function has recently become an area of focus for researchers. The most commonly reported perioperative neurocognitive disorders include delirium and longer-lasting post-operative cognitive dysfunctions. The contributing pathophysiology to these complications remains unclear. A number of studies have systematically revealed a significant post-operative plasma vitamin C depletion. Recent insights have also exhibited a link between plasma vitamin C and numerous biological roles in brain function, with deficiencies potentially compromising cognitive function. AIM: The present prospective, observational study will investigate whether there is a possible link between post-operative plasma vitamin C depletion and cognitive dysfunction. METHODS: The cohort will consist of surgical patients, between the ages of 65 and 85 years, undergoing hip replacement surgery or a control group not exposed to surgical trauma. Participants will have their plasma vitamin C concentrations tested alongside a battery of computer-based cognitive assessments and paper and pen based cognitive tests. Further assessments will include dietary nutritional intake, serum vitamin B12 concentrations, cardiovascular biomarkers, wound healing, sleep quality, pain, mood and inflammatory cytokines. Participants will be tested at baseline (1-2 weeks prior to surgery) and subsequent testing sessions will be performed within 1 week, 4-6 weeks, 3 months and 6 months following surgery. CONCLUSIONS: Findings from this observational study will provide insight into whether there is a concomitant depletion in post-operative plasma vitamin C concentrations and cognition function. Extrapolated results may prompt future, extensive randomized controlled trials to assess whether vitamin C supplementation can alleviate or even prevent post-operative cognitive complications.

Ginger-Mechanism of action in chemotherapy-induced nausea and vomiting: A review.

Despite advances in antiemetic therapy, chemotherapy-induced nausea and vomiting (CINV) still poses a significant burden to patients undergoing chemotherapy. Nausea, in particular, is still highly prevalent in this population. Ginger has been traditionally used as a folk remedy for gastrointestinal complaints and has been suggested as a viable adjuvant treatment for nausea and vomiting in the cancer context. Substantial research has revealed ginger to possess properties that could exert multiple beneficial effects on chemotherapy patients who experience nausea and vomiting. Bioactive compounds within the rhizome of ginger, particularly the gingerol and shogaol class of compounds, interact with several pathways that are directly implicated in CINV in addition to pathways that could play secondary roles by exacerbating symptoms. These properties include 5-HT3, substance P, and acetylcholine receptor antagonism; antiinflammatory properties; and modulation of cellular redox signaling, vasopressin release, gastrointestinal motility, and gastric emptying rate. This review outlines these proposed mechanisms by discussing the results of clinical, in vitro, and animal studies both within the chemotherapy context and in other relevant fields. The evidence presented in this review indicates that ginger possesses multiple properties that could be beneficial in reducing CINV.

The effects of long-chain omega-3 fish oils and multivitamins on cognitive and cardiovascular function: a randomized, controlled clinical trial.

OBJECTIVE: Fish oils and multivitamins are two of the most commonly used dietary supplements. Fish oil use may reduce vascular risk factors associated with cognitive decline, thus providing benefits to both heart and brain health. Multivitamins may also have direct effects on brain function. The present study investigated the effects of fish oil, with and without the addition of a multivitamin, on cognitive and cardiovascular function. METHODS: In a randomized, placebo-controlled, double-blind fashion, 160 healthy adults aged 50-70 years were randomized to receive either 3 g of fish oil (240 mg eicosapentaenoic acid [EPA] + 240 mg docosahexaenoic acid [DHA]) with a multivitamin, 6 g of fish oil (480 mg EPA + 480 mg DHA) with a multivitamin, or 6 g of fish oil without a multivitamin or a placebo. Cognitive performance, brachial blood pressure, and aortic (central) blood pressure were measured at baseline, 6 weeks, and 16 weeks. RESULTS: Treatment allocation had no effect on the primary cognitive outcomes at endpoint. Absolute increases in the red blood cell omega-3/6 ratio were associated with improvements in spatial working memory. The group receiving 6 g fish oil without the multivitamin displayed a significant decrease in aortic pulse pressure and aortic augmentation pressure, two measures of aortic blood pressure and aortic stiffness. CONCLUSIONS: Fish oil decreased aortic pulse pressure and augmentation pressure. Reductions in aortic blood pressure were not accompanied by consistent improvements in cognition.

Effects of multivitamin, mineral and herbal supplement on cognition in younger adults and the contribution of B group vitamins.

OBJECTIVE: Cognitive benefits of multivitamins have been observed in the elderly, but fewer trials have investigated younger, healthy cohorts. This randomised, double-blind, placebo-controlled study investigated the cognitive effects of 16-week multivitamin supplementation in adults aged 20-49 years. METHOD: A total of 138 participants aged 20-50 years were randomised and 116 completed the trial. The participants completed a computerised battery of cognitive tasks before and after 16-week supplementation with a multivitamin containing minerals and herbs or placebo. Blood measures of homocysteine, vitamin B6, B12 and folate were collected at both time points. RESULTS: In men, there was a strong trend (p = 0.01; which did not reach significance when adjusted for multiple comparisons) for the multivitamin to improve performance on the incongruent stroop task, a measure of selective attention and response inhibition. There were no cognitive benefits of multivitamin supplements in women. Multivitamin supplementation substantially increased blood levels of vitamin B6, B12 and folate in both genders and decreased homocysteine in men. In men who received the multivitamin, improved stroop congruent performance was associated with increased vitamin B6 levels. CONCLUSION: Multivitamin supplementation may be useful for maintaining levels of B vitamins. The effects of multivitamins on speeded attention such as the stroop task in young adults warrant further investigation.

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial.

BACKGROUND: Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. METHODS/DESIGN: In a double-blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. DISCUSSION: Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this trial will address the significant limitations within the current literature and in doing so, will investigate the effect of ginger supplementation as an adjuvant treatment in modulating nausea and vomiting symptoms. TRIAL REGISTRATION: ANZCTR.org.au Identifier: ACTRN12613000120774.

Inflammatory Bowel Diseases and the Efficacy of Probiotics as Functional Foods.

Adverse intestinal microbiome profiles described as a dysbiotic gut are a complicit etiological operative factor that can progress and maintain inflammatory sequelae in the intestines. The disruption of the gut microbiome that ensues with intestinal dysbiosis is, for example, posited by decreases in the alpha-diversity of the gut microbiome, which is characterized by significant reductions in the abundance of bacterial members from the Bacteroidetes and Firmicutes phyla. Proteobacteria have often been recognized as gut microbial signatures of disease. For example, this happens with observed increases in abundance of the phyla Proteobacteria and Gammaproteobacteria, such as the adherent-invasive Escherichia coli strain, which has been significantly linked with maintaining inflammatory bowel diseases. Research on the administration of probiotics, often identified as gut-functional foods, has demonstrated safety, tolerability, and efficacy issues in treating inflammatory bowel diseases (IBDs). In this narrative review, we explore the efficacy of probiotics in treating IBDs with bacterial strain- and dose-specific characteristics and the association with multi-strain administration.

Effects of a multivitamin, mineral and herbal supplement on cognition and blood biomarkers in older men: a randomised, placebo-controlled trial.

OBJECTIVE: Nutritional and vitamin status may be related to cognitive function and decline in older adults. The aim of this study was to investigate the effects of nutritional supplementation on cognition in older men. METHOD: The current study was an 8-week, placebo-controlled, double-blind investigation into the effects of a multivitamin, mineral and herbal supplement (Swisse Men's Ultivite®, Swisse Vitamins Pty Ltd, Melbourne, Australia) on cognitive performance in older men. Participants were 51 male individuals aged between 50 and 74 years, with a sedentary lifestyle. Cognitive performance was assessed at baseline and post-treatment using a computerised battery of cognitive tasks, enabling the measurement of a range of attentional and memory processes. Blood measures of vitamin B(12) , folate and homocysteine were collected prior to and after supplementation. RESULTS: The results of this study revealed that contextual recognition memory performance was significantly improved following multivitamin supplementation (p < 0.05). Performance on other cognitive tasks did not change. Levels of vitamin B(12) and folate were significantly increased with a concomitant decrease in homocysteine, indicating that relatively short-term supplementation with a multivitamin can benefit these risk factors for cognitive decline. CONCLUSION: Findings from this study indicate that daily multivitamin supplementation may improve episodic memory in older men at risk of cognitive decline.

Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial.

BACKGROUND: While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. METHODS: Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant's experiences were categorised as "positive" or "negative" and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately. RESULTS: Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022) and enhanced mood (p=.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor digestive complaints. CONCLUSION: This represents the first documented qualitative investigation of participants' experience of chronic administration of a multivitamin. Results uncovered a range of subjective beneficial effects that are consistent with quantitative data from previously published randomised controlled trials examining the effects of multivitamins and B vitamin complexes on mood and well-being. TRIAL REGISTRATION: Prior to commencement this trial was registered with the Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au) ACTRN12611000092998.

Effects of a Probiotic Formulation on Seasonal Allergic Rhinitis in Adults-A Randomized Double-Blind Placebo-Controlled Trial: The Probiotics for Hay Fever Trial.

Background: Seasonal-allergic-rhinitis (hay fever) affects approximately 4.6 million (20%) Australians each year. Hay fever manifests as runny/blocked nose and often itchy/sore/swollen eyes, with symptoms greatly impacting the quality of life. Rescue medications such as antihistamines are often needed to restore function, but they may trigger some other unwanted side effects. Probiotics have shown promise to reduce hay fever symptoms. Objective: In this randomized double-blind placebo-controlled 12-week trial, we aimed to assess the tolerability and efficacy of the probiotic formula "NC-Seasonal-Biotic" on symptoms, quality-of-life, and immunological and microbial factors. Methods: Adults, who had previously suffered from hay fever symptoms, were screened for eligibility and randomly allocated to probiotic or placebo trial powder. Treatment effectiveness was assessed by questionnaires, daily total-nasal-symptom-score, and weekly rhinoconjunctivitis quality-of-life questionnaire. Secondary outcome measures included immunological parameters such as T-cell immunity (Th1/Th2 ratio) and the stool-microbiome analysis. Tolerability was assessed weekly by the gastrointestinal symptom scale. Results: Recruitment and follow-up were challenging around the 2020/2021 hay fever season in Melbourne, Australia, due to the harsh COVID-19 restrictions and extended lockdowns. Out of the 82 adults enrolled in this study, 75% participated (n = 60), and half (n = 40) completed the 10-12-week intervention period. In the intention-to-treat analysis, no significant differences in hay fever symptoms were apparent between the groups, while quality-of-life trended toward greater improvement in the active group. Intention-to-treat analysis was confounded due to a third of all participants not completing the full 10-12-week-intervention period. Subgroup analyses of the participants (n = 40) completing the full 10-12-week study period revealed a significantly greater reduction in symptoms in the active group compared with the placebo group, including runny nose (p = 0.04) and itchy eyes (p = 0.01). Furthermore, the active group reported significant improvements in the quality-of-life, including more functionality during the day (p = 0.05), better sleep (p = 0.005), less fatigue (p = 0.04), less thirst (p = 0.007), and less irritability (p = 0.007). Immunological parameters, measured by T-helper cell ratio (Th1/Th2), improved significantly in the active group compared with the placebo group. Most microbial changes were not statistically different between the groups. The trial powder was generally well tolerated. Conclusion: Our study suggests the probiotic formula "NC-Seasonal-Biotic," taken for 10-12 weeks, as effective in reducing hay fever symptoms, such as runny nose and itchy eyes, and improved the quality-of-life and immunological parameters while being well tolerated. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ACTRN126200 01078943].

Integrative Approaches to the Treatment of Cancer.

A significant proportion of cancer patients use forms of complementary medicine or therapies. An integrative approach to cancer management combines conventional medicine with evidence-based complementary medicines/therapies and lifestyle interventions, for the treatment and prevention of disease and the optimisation of health. Its basis is a holistic one; to treat the whole person, not just the disease. It makes use of adjunct technologies which may assist the clinician in diagnosis of early carcinogenesis and monitoring of treatment effectiveness. Many factors contribute to the development of cancer including some which are largely modifiable by the patient and which oncologists may be in a position to advise on, such as stress, poor nutrition, lack of physical activity, poor sleep, and Vitamin D deficiency. An integrative approach to addressing these factors may contribute to better overall health of the patient and better outcomes. Evidence-based complementary medicine approaches include the use of supplements, herbal medicine, various practices that reduce stress, and physical therapies. Individualised to the patient, these can also help address the symptoms and signs associated with cancer and its orthodox treatment.

The effect of multivitamin supplementation on mood and stress in healthy older men.

OBJECTIVE: There is a demonstrated association between poor mood and deficiency in several micronutrients. Multivitamin supplements contain a wide range of nutrients, suggesting that they may be effective in improving mood; however, few studies have investigated this potential in randomized, controlled trials. This study investigates the effects of a multivitamin, mineral, and herbal supplement on mood and stress in a group of healthy, older male volunteers. METHODS: In this randomized, double-blind, placebo-controlled trial, fifty men, aged 50-69 years, supplemented for a period of 8 weeks with a multivitamin formulation that contained vitamins (at levels above recommended daily intakes), minerals, antioxidants, and herbal extracts, or a placebo. They completed a series of mood and stress questionnaires at baseline and post-supplementation. RESULTS: Compared with placebo, there was a significant reduction in the overall score on a depression anxiety and stress scale and an improvement in alertness and general daily functioning in the multivitamin group. CONCLUSIONS: Supplementation with a multivitamin, mineral and herbal formulation may be useful in improving alertness and reducing negative mood symptoms and may also improve feelings of general day-to-day well-being.

Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, and Vitamin D3 With or Without Intravenous Vitamin C: An International, Multicenter, Randomized Trial.

Background COVID-19 is a global pandemic. Treatment with hydroxychloroquine (HCQ), zinc, and azithromycin (AZM), also known as the Zelenko protocol, and treatment with intravenous (IV) vitamin C (IVC) have shown encouraging results in a large number of trials worldwide. In addition, vitamin D levels are an important indicator of the severity of symptoms in patients with COVID-19. Objectives Our multicenter, randomized, open-label study aimed to assess the effectiveness of HCQ, AZM, and zinc with or without IVC in hospitalized patients with COVID-19 in reducing symptom severity and duration and preventing death. Methods Hospitalized patients with COVID-19 in seven participating hospitals in Turkey were screened for eligibility and randomly allocated to receive either HCQ, AZM, and zinc (group 1) or HCQ, AZM, zinc plus IV vitamin C treatment (group 2) for 14 days. The patients also received nontherapeutic levels of vitamin D3. The trial is registered on the Australian and New Zealand Clinical Trial Registry ACTRN12620000557932 and has been approved by the Australian Therapeutic Goods Administration (TGA). Results A total of 237 hospitalized patients with COVID-19 aged 22-99 years (mean: 63.3 ± 15.7 years) were enrolled in the study. Almost all patients were vitamin D deficient (97%), 55% were severely vitamin D deficient (<25 nmol/L) and 42% were vitamin D deficient (<50 nmol/L); 3% had insufficient vitamin D levels (<75 nmol/L), and none had optimal vitamin D levels. Of the patients, 73% had comorbidities, including diabetes (35%), heart disease (36%), and lung disease (34%). All but one patient (99.6%; n = 236/237) treated with HCQ, AZM, and zinc with or without high-dose IV vitamin C (IVC) fully recovered. Additional IVC therapy contributed significantly to a quicker recovery (15 days versus 45 days until discharge; p = 0.0069). Side effects such as diarrhea, nausea, and vomiting, reported by 15%-27% of the patients, were mild to moderate and transient. No cardiac side effects were observed. Low vitamin D levels were significantly correlated with a higher probability of admission to the intensive care unit (ICU) and longer hospital stay. Sadly, one 70-year-old female patient with heart and lung disease died after 17 days in ICU and 22 days in the hospital. Her vitamin D level was 6 nmol/L on admission (i.e., severely deficient). Conclusions Our study suggests that the treatment protocol of HCQ, AZM, and zinc with or without vitamin C is safe and effective in the treatment of COVID-19, with high dose IV vitamin C leading to a significantly quicker recovery. Importantly, our study confirms vitamin D deficiency to be a high-risk factor of severe COVID-19 disease and hospitalization, with 97% of our study's patient cohort being vitamin D deficient, 55% of these being severely vitamin D deficient, and none had optimal levels. Future trials are warranted to evaluate the treatment with a combination of high-dose vitamin D3 in addition to HCQ, AZM, and zinc and high-dose intravenous vitamin C.

Herbal formula improves upper and lower gastrointestinal symptoms and gut health in Australian adults with digestive disorders.

Gastrointestinal (GI) problems affect half of Western populations. Symptoms can vary from frequent reflux to irritable bowel syndrome. The Nutrition Care (NC) Gut Relief Formula contains a combination of herbs and nutrients including curcumin, Aloe vera, slippery elm, guar gum, pectin, peppermint oil, and glutamine shown to benefit the GI system. The 16-week pre-post study tested the hypothesis that the NC Gut Relief Formula would be tolerable and effective in improving GI symptoms and gut health in adults with digestive disorders. A total of 43 participants completed the study. After a control phase, participants took 5 g/d and then 10 g/d of the formula for 4 weeks. GI symptoms and GI health were assessed by a series of validated questionnaires, for example, Leeds Dyspepsia Questionnaire, Bristol Stool Chart, Birmingham IBS Symptom Questionnaire, and by intestinal permeability and gut microbiota profile. The NC Gut Relief Formula significantly improved the frequency and severity of upper and lower GI symptoms by 60%-80%, including indigestion, heartburn, nausea, constipation or diarrhea, abdominal pain, and troublesome flatulence, and significantly improved physical functioning, energy levels, mood, and sleep by 60%-80%. All participants with normal stool, 90% with hard stool, and 66% with soft stool recovered from intestinal permeability, evident by normal lactulose to mannitol ratios. The NC Gut Relief Formula generally improved microbial profile, with a marked increase in Lactobacillus, Clostridium, and Faecalibacterium prausnitzii. Almost half of the participants with upper GI symptoms taking proton pump inhibitors for heartburn no longer required proton pump inhibitors at the end of the study. A third of participants were able to reintroduce food triggers, such as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols garlic, onion, and beans, or reflux-causing acidic/spicy foods, for example, citrus, tomato, and caffeine, in their diet after 3 months without symptom aggravation. The NC Gut Relief Formula significantly improved GI symptoms and associated quality of life over 3 months while reducing intestinal permeability, improving the microbial profile, reducing the need for reflux medication, and enabling the consumption of previous food triggers.

The gallbladder and vermiform appendix influence the assemblage of intestinal microorganisms.

Surgical procedures for the symptomatic removal of the gallbladder and the vermiform appendix have been posited to adversely shift the assemblage of the intestinal microbiome increasing the risk of disease. The associated mechanisms have been linked with dysbiosis of the gut microbiota. Cholecystectomy causes changes of bile acid compositions and bile secretion patterns as bile acids interact with the intestinal microbiota in a bidirectional capacity. An appendectomy precludes the further recolonization of the proximal colon with a commensal biofilm that could maintain a stable intestinal microbiome. Epidemiological studies indicate that there is an increased risk of disease rather than causality following a cholecystectomy and appendectomy. This narrative review summarizes studies that report on the role that bile salts and the appendix, contribute to the assemblage of the intestinal microbiome in health and disease.

New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers.

The current screening-test for prostate cancer, affecting 10% of men worldwide, has a high false negative rate and a low true positive rate. A more reliable screening test is needed. Circulating-Tumor-Cells (CTC) provide a biomarker for early carcinogenesis, cancer progression and treatment effectiveness. The cytology-based ISET®-CTC Test is a clinically validated blood test with high sensitivity and specificity. This study aimed to evaluate the ISET®-CTC test combined with prostate-specific-marker staining as a screening test for the detection of prostate cancer. We selected a group of 47 men from our ongoing CTC screening study involving 2,000 patient-tests from Sep-2014 to July-2019, who also underwent standard diagnostic cancer testing before or after CTC testing. While 20 of the 47 men were diagnosed with prostate cancer before the ISET®-CTC test, 27 men underwent screening. We studied the CTC identified in 45 CTC-positive men by Immuno-Cyto-Chemistry (ICC) assays with the prostate-specific-marker PSA. CTC were ICC-PSA-marker positive in all men diagnosed with primary prostate cancer (n = 20). Secondary cancers were detected in 63% (n = 7/11) of men with mixed CTC-population (ICC-PSA-positive/ICC-PSA-negative). Of the 27 men screened, 25 had CTC, and 84% of those (n = 20) were positive for the prostate-specific-PSA-marker. Follow-up testing suggested suspected prostate cancer in 20/20 men by a positive PSMA-PET scan, and biopsies performed in 45% (n = 9/20) men confirmed the diagnosis of early prostate cancer. Kidney cancer or B-cell lymphoma were detected in two men with ICC-PSA-marker negative CTC. Our study suggests that the combination of ISET®-CTC and ICC-PSA-marker-testing has an estimated positive-predictive-value (PPV) of 99% and a negative-predictive-value (NPV) of 97%, providing a more reliable screening test for prostate cancer than the standard PSA-blood-test (PPV = 25%; NPV = 15.5%). Our findings warrant further studies to evaluate the new test's potential for prostate cancer screening on a population level.

Gender Differences in Plasma Vitamin C Concentrations and Cognitive Function: A Pilot Cross-Sectional Study in Healthy Adults.

BACKGROUND: A number of investigations have highlighted the importance of vitamin C in maintaining brain health. Biologically, vitamin C has exhibited roles in neuromodulation, neurodevelopment, vascular support, and neuroprotection. Vitamin C's contribution to cognitive function in both cognitively intact and impaired cohorts has previously been assessed, with little focus on gender variability. OBJECTIVE: The present study explored the interaction between gender and plasma vitamin C on cognitive performance, and the effect of different amounts of plasma vitamin C (adequate/inadequate) on various cognitive tasks by gender. METHODS: This retrospective analysis was conducted in healthy adults (n = 80, female = 52, male = 28, 24-96 y) with a range of blood plasma vitamin C concentrations. Cognitive assessments included the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and 2 pen-and-paper tests, the Symbol Digits Modalities Test (SDMT) and the Hopkins Verbal Learning Test-Revised (HVLT-R). Food-frequency questionnaires were used to elucidate dietary consumption. RESULTS: After adjusting for a number of potential covariates such as age, number of prescribed medications and dose of vitamin C supplementation, results indicated a significant interaction (P < 0.001) between plasma vitamin C and gender on cognitive function, on both the computerized and pen-and-paper assessments. A novel finding was that the performance of males with inadequate plasma vitamin C was poorer on tasks involving components of memory (short/delayed), inhibition, and visual perception, whereas females presenting with inadequate vitamin C were more compromised on tasks involving psychomotor performance/motor speed. Additionally, females with adequate vitamin C concentrations exhibited higher performance than males on tasks involving recall, recognition, attention, and focus. CONCLUSIONS: Further larger-scale investigations are required to establish a cause-and-effect relation and to elucidate whether differences in cognitive function between genders may be attributed to plasma vitamin C status.This trial was registered at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369440&isReview=true as ACTRN12615001140549.

The Contribution of Plasma and Brain Vitamin C on Age and Gender-Related Cognitive Differences: A Mini-Review of the Literature.

There is increasing evidence that sex differences in the brain may contribute to gender-related behavioral differences, including cognitive function. Literature has revealed gender dimorphisms in cognitive function between males and females. Additionally, several risk factors associated with cognitive decline depend on chronological age. It is well recognized that the process of aging is associated with a decline in cognitive ability and brain function. Various explanations may account for these gender-related cognitive differences and age-associated cognitive changes. Recent investigations have highlighted the importance of vitamin C in maintaining brain health and its association with cognitive function in both cognitively intact and impaired cohorts. The present review explores previous literature that has evaluated differences in plasma/brain vitamin C between genders and during aging. It then assesses whether these age and gender-related differences may affect the relationship between plasma/brain vitamin C and cognition. The purpose of this review was to examine the evidence for a link between plasma/brain vitamin C and cognition and the impact of gender and age on this relationship. Epidemiological studies have frequently shown higher vitamin C plasma concentrations in women. Similarly, aging has been systematically associated with reductions in plasma vitamin C levels. A range of animal studies has demonstrated potential gender and age-related differences in vitamin C brain distribution and utilization. The reviewed literature suggests that gender differences in plasma and brain vitamin C may potentially contribute to differences in gender-associated cognitive ability, particularly while females are pre-menopausal. Additionally, we can propose that age-associated differences in plasma and brain vitamin C may be potentially linked to age-associated cognitive differences, with older cohorts appearing more vulnerable to experience declines in plasma vitamin C concentrations alongside compromised vitamin C brain regulation. This review encourages future investigations to take into account both gender and age when assessing the link between plasma vitamin C concentrations and cognitive function. Further large scale investigations are required to assess whether differences in cognitive function between genders and age groups may be causally attributed to plasma vitamin C status and brain distribution and utilization.

The effects of knee arthroplasty on plasma vitamin C concentrations and cognitive function: a case study.

Post-operative neurocognitive disorders are becoming well-documented conditions, with their pathogenesis remaining unclear. Vitamin C is a molecule that has recently demonstrated both a potential link with cognitive function and a significant post-operative decline. Here, we present a case study of a 72-year-old male who underwent total knee replacement surgery. The patient demonstrated a substantial decline in plasma vitamin C concentrations, indicative of a severe deficiency, during the first post-operative week (post-operative Days 3 and 7). Similarly, at these time points, a number of validated paper and pen tests revealed a substantial decline in cognition on tasks relating to total recall, delayed recall, motor speed, recognition and motor speed, with no signs of delirium. These results provide the justification for larger, cohort studies to determine whether post-operative plasma vitamin C depletions could contribute to cognitive deficits post-operatively.