Randomized controlled trials of non-pharmacological interventions for healthy seniors: Effects on cognitive decline, brain plasticity and activities of daily living-A 23-year scoping review.

Little is known about the simultaneous effects of non-pharmacological interventions (NPI) on healthy older adults' behavior and brain plasticity, as measured by psychometric instruments and magnetic resonance imaging (MRI). The purpose of this scoping review was to compile an extensive list of randomized controlled trials published from January 1, 2000, to August 31, 2023, of NPI for mitigating and countervailing age-related physical and cognitive decline and associated cerebral degeneration in healthy elderly populations with a mean age of 55 and over. After inventorying the NPI that met our criteria, we divided them into six classes: single-domain cognitive, multi-domain cognitive, physical aerobic, physical non-aerobic, combined cognitive and physical aerobic, and combined cognitive and physical non-aerobic. The ultimate purpose of these NPI was to enhance individual autonomy and well-being by bolstering functional capacity that might transfer to activities of daily living. The insights from this study can be a starting point for new research and inform social, public health, and economic policies. The PRISMA extension for scoping reviews (PRISMA-ScR) checklist served as the framework for this scoping review, which includes 70 studies. Results indicate that medium- and long-term interventions combining non-aerobic physical exercise and multi-domain cognitive interventions best stimulate neuroplasticity and protect against age-related decline and that outcomes may transfer to activities of daily living.

Cognitive enrichment through art: a randomized controlled trial on the effect of music or visual arts group practice on cognitive and brain development of young children.

BACKGROUND: The optimal stimulation for brain development in the early academic years remains unclear. Current research suggests that musical training has a more profound impact on children's executive functions (EF) compared to other art forms. What is crucially lacking is a large-scale, long-term genuine randomized controlled trial (RCT) in cognitive neuroscience, comparing musical instrumental training (MIP) to another art form, and a control group (CG). This study aims to fill this gap by using machine learning to develop a multivariate model that tracks the interconnected brain and EF development during the academic years, with or without music or other art training. METHODS: The study plans to enroll 150 children aged 6-8 years and randomly assign them to three groups: Orchestra in Class (OC), Visual Arts (VA), and a control group (CG). Anticipating a 30% attrition rate, each group aims to retain at least 35 participants. The research consists of three analytical stages: 1) baseline analysis correlating EF, brain data, age, gender, and socioeconomic status, 2) comparison between groups and over time of EF brain and behavioral development and their interactions, including hypothesis testing, and 3) exploratory analysis combining behavioral and brain data. The intervention includes intensive art classes once a week, and incremental home training over two years, with the CG receiving six annual cultural outings. DISCUSSION: This study examines the potential benefits of intensive group arts education, especially contrasting music with visual arts, on EF development in children. It will investigate how artistic enrichment potentially influences the presumed typical transition from a more unified to a more multifaceted EF structure around age eight, comparing these findings against a minimally enriched active control group. This research could significantly influence the incorporation of intensive art interventions in standard curricula. TRIAL REGISTRATION: The project was accepted after peer-review by the Swiss National Science Foundation (SNSF no. 100014_214977) on March 29, 2023. The study protocol received approval from the Cantonal Commission for Ethics in Human Research of Geneva (CCER, BASEC-ID 2023-01016), which is part of Swiss ethics, on October 25, 2023. The study is registered at clinicaltrials.gov (NCT05912270).

Musical and psychomotor interventions for cognitive, sensorimotor, and cerebral decline in patients with Mild Cognitive Impairment (COPE): a study protocol for a multicentric randomized controlled study.

BACKGROUND: Regular cognitive training can boost or maintain cognitive and brain functions known to decline with age. Most studies administered such cognitive training on a computer and in a lab setting. However, everyday life activities, like musical practice or physical exercise that are complex and variable, might be more successful at inducing transfer effects to different cognitive domains and maintaining motivation. "Body-mind exercises", like Tai Chi or psychomotor exercise, may also positively affect cognitive functioning in the elderly. We will compare the influence of active music practice and psychomotor training over 6 months in Mild Cognitive Impairment patients from university hospital memory clinics on cognitive and sensorimotor performance and brain plasticity. The acronym of the study is COPE (Countervail cOgnitive imPairmEnt), illustrating the aim of the study: learning to better "cope" with cognitive decline. METHODS: We aim to conduct a randomized controlled multicenter intervention study on 32 Mild Cognitive Impairment (MCI) patients (60-80 years), divided over 2 experimental groups: 1) Music practice; 2) Psychomotor treatment. Controls will consist of a passive test-retest group of 16 age, gender and education level matched healthy volunteers. The training regimens take place twice a week for 45 min over 6 months in small groups, provided by professionals, and patients should exercise daily at home. Data collection takes place at baseline (before the interventions), 3, and 6 months after training onset, on cognitive and sensorimotor capacities, subjective well-being, daily living activities, and via functional and structural neuroimaging. Considering the current constraints of the COVID-19 pandemic, recruitment and data collection takes place in 3 waves. DISCUSSION: We will investigate whether musical practice contrasted to psychomotor exercise in small groups can improve cognitive, sensorimotor and brain functioning in MCI patients, and therefore provoke specific benefits for their daily life functioning and well-being. TRIAL REGISTRATION: The full protocol was approved by the Commission cantonale d'éthique de la recherche sur l'être humain de Genève (CCER, no. 2020-00510) on 04.05.2020, and an amendment by the CCER and the Commission cantonale d'éthique de la recherche sur l'être humain de Vaud (CER-VD) on 03.08.2021. The protocol was registered at clinicaltrials.gov (20.09.2020, no. NCT04546451).

More than meets the eye: the changing face of histopathology.

This personal reflection on trends in histopathology over the past 50 years draws upon experience of professional training and practice in the specialty in the UK. Developments during this period often resulted from new therapies (and their adverse effects) necessitating greater precision in the histopathological classification of disease, for which morphology alone can be insufficient. Conversely, histopathology has contributed to advances in our understanding of disease, leading directly to novel and more effective treatments. New infections, some involving histopathology in their discovery, have also led to fresh diagnostic challenges. Increasingly, patients have benefited from fundamental changes in professionalism in pathology. Through audit, external quality assurance, continuing professional development, standardized reporting, and increasing specialization, the consistency and reliability of histopathological diagnoses have steadily improved. Regarding the specialty's future, some now see rivalry between the morphological and molecular approaches to diagnosis and classification, particularly for neoplastic disease. An integrated strategy led by the specialty is more likely to strengthen histopathology and ultimately to have the greatest benefit for patients.

Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis.

OBJECTIVES: Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment. METHODS: We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin). RESULTS: Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2-8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84-111.6; P=0.07). CONCLUSIONS: Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.

What constitutes a clinically important pain reduction in patients after third molar surgery?

BACKGROUND: For patients with surgical third molar removal, it is unknown what constitutes a clinically important change in patients' visual analogue scale (VAS) reports of pain intensity. OBJECTIVES: To determine what constitutes a clinically important change in pain intensity on a VAS following surgical removal of the third molar. METHODS: The study population consisted of patients participating in three randomized trials. Patients were asked to rate their pain three times per day over a period of seven days on a 100 mm VAS after surgical removal of the third molar. Global Perceived Effect was measured on day 1 and day 7 and was used as the external criterion for assessing clinically important pain reduction. Global Perceived Effect scores of 6 ('much improved') or higher were classified as clinically 'successful', and scores of 5 ('slightly improved') or below were classified as clinically 'unsuccessful'. For each trial, the mean absolute and relative changes in VAS scores were calculated for both 'successful' and 'unsuccessful' treatments. Sensitivity and specificity analyses were performed. RESULTS: The patients who reported 'successful' pain reduction showed a relative pain reduction of ≥69% and an absolute pain reduction >2.5 cm on the VAS, whereas patients who classified their pain reduction as 'unsuccessful' had a relative pain reduction of ≤18.5% and an absolute pain reduction <0.5 cm on the VAS. Furthermore, sensitivity and specificity analyses showed that a cut-off point of ≥50% relative pain reduction exhibited the best balance of sensitivity and specificity. CONCLUSION: Relative pain reduction of ≥50% and an absolute pain reduction of ≥2.5 cm on the VAS were most accurate in predicting a successful pain reduction after a given treatment.

Prognostic significance of Akt, phospho-Akt and BAD expression in primary breast cancer.

Apoptotic markers in breast cancer are reported to have prognostic significance. The aim of this study was to assess the prognostic value of Akt, phospho-Akt and BAD expression in primary tumours from breast cancer patients. Expression of phospho-Akt did not correlate with menopausal status, nodal involvement or tumour size, although there was a significant correlation between phospho-Akt and oestrogen receptor status and tumour grade. No association was found between phospho-Akt and BAD. However, a significant correlation was found between Akt and BAD. Akt and phospho-Akt expression did not correlate with either disease-free survival (DFS) or overall survival (OS). Conversely, BAD immunostaining correlated significantly with increasing tumour size and with oestrogen receptor (ER) immunostaining in both frozen and paraffin sections. Expression of BAD appeared to be nucleolar in addition to its cytoplasmic and nuclear staining. Comparison of immunohistochemical staining on frozen sections and paraffin sections showed a reasonable concordance in Akt and BAD immunoreactivity. However, the results showed for the first time that strong BAD expression is related to a favourable prognosis but is not an independent prognostic factor. In conclusion, these results could provide the basis for understanding how Akt, phospho-Akt and BAD expression contributes to the prognosis of invasive breast cancer.

Effect of farnesol on Staphylococcus aureus biofilm formation and antimicrobial susceptibility.

Staphylococcus aureus is among the leading pathogens causing bloodstream infections able to form biofilms on host tissue and indwelling medical devices and to persist and cause disease. Infections caused by S. aureus are becoming more difficult to treat because of increasing resistance to antibiotics. In a biofilm environment particularly, microbes exhibit enhanced resistance to antimicrobial agents. Recently, farnesol was described as a quorum-sensing molecule with possible antimicrobial properties. In this study, the effect of farnesol on methicillin-resistant and -susceptible strains of S. aureus was investigated. With viability assays, biofilm formation assessment, and ethidium bromide uptake testing, farnesol was shown to inhibit biofilm formation and compromise cell membrane integrity. The ability of farnesol to sensitize S. aureus to antimicrobials was assessed by agar disk diffusion and broth microdilution methods. For both strains of staphylococci, farnesol was only able to reverse resistance at a high concentration (150 microM). However, it was very successful at enhancing the antimicrobial efficacy of all of the antibiotics to which the strains were somewhat susceptible. Therefore, synergy testing of farnesol and gentamicin was performed with static biofilms exposed to various concentrations of both agents. Plate counts of harvested biofilm cells at 0, 4, and 24 h posttreatment indicated that the combined effect of gentamicin at 2.5 times the MIC and farnesol at 100 microM (22 microg/ml) was able to reduce bacterial populations by more than 2 log units, demonstrating synergy between the two antimicrobial agents. This observed sensitization of resistant strains to antimicrobials and the observed synergistic effect with gentamicin indicate a potential application for farnesol as an adjuvant therapeutic agent for the prevention of biofilm-related infections and promotion of drug resistance reversal.

Clearance of hepatitis C virus is not associated with single nucleotide polymorphisms in the IL-1, -6, or -10 genes.

Hepatitis C virus (HCV) commonly causes a chronic infection, but a minority of patients are able to clear the virus and do not run the risk of developing HCV-induced organ damage. Genetic associations between immunoregulatory cytokines interleukin (IL)-1, -6, and -10 with clinical features of HCV, including virus clearance, have been inconsistent. We determined cytokine genotypes in 606 patients who had serologic evidence of HCV exposure, 190 (18%) of whom were consistently negative for HCV RNA, indicating successful virus clearance. There was no significant difference in genotype frequencies between HCV clearance and nonclearance groups for IL-1B (-511 and +3954), IL-1A (+4845), IL-1RN (+2018), IL-6 (-174), or IL-10 (-1082). We conclude that these single nucleotide polymorphisms are unlikely to play an important, if any, role in determining the likelihood of clearing HCV infection.

Alphastatin, a 24-amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo.

Angiogenesis, the development of new blood vessels from existing vasculature, is crucial for the development and metastasis of solid tumors. Here, we show for the first time that a 24-amino acid peptide derived from the amino terminus of the alpha chain of human fibrinogen (termed "alphastatin") has potent antiangiogenic properties, inhibiting both the migration and tubule formation of human dermal microvascular endothelial cells in response to vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) in vitro. Moreover, alphastatin markedly inhibits the growth of tumors in a syngeneic murine model. Tumors from mice receiving daily injections of alphastatin for 12 days exhibited large areas of intravascular disruption and thrombosis with substantial cellular necrosis. Importantly, alphastatin administration had no detectable effect on vessels in such normal tissues as liver, lungs, and kidney. Taken together, these data indicate that alphastatin is a potent new antiangiogenic agent in vitro and antivascular agent in vivo.

Lytic and lysogenic infection of diverse Escherichia coli and Shigella strains with a verocytotoxigenic bacteriophage.

A verocytotoxigenic bacteriophage isolated from a strain of enterohemorrhagic Escherichia coli O157, into which a kanamycin resistance gene (aph3) had been inserted to inactivate the verocytotoxin gene (vt2), was used to infect Enterobacteriaceae strains. A number of Shigella and E. coli strains were susceptible to lysogenic infection, and a smooth E. coli isolate (O107) was also susceptible to lytic infection. The lysogenized strains included different smooth E. coli serotypes of both human and animal origin, indicating that this bacteriophage has a substantial capacity to disseminate verocytotoxin genes. A novel indirect plaque assay utilizing an E. coli recA441 mutant in which phage-infected cells can enter only the lytic cycle, enabling detection of all infective phage, was developed.

Perception of sweetness in simple and complex taste stimuli by adults and children.

Currently, there is little information on the ability of children to analyse complex chemosensory stimuli in terms of the presence and magnitude of the components. The present study investigates this question by comparing the ability of 95 adults and 8- to 9-year-olds to estimate the sweetness of several concentrations of sucrose in water and in three foods, namely, orange drink, custard and shortbread biscuits, using a magnitude estimation procedure. The results indicated that similar response functions were produced by adults and children for the sweetness of aqueous solutions of sucrose, custard and biscuits, but not for orange juice, where the functions produced by both female and male children were significantly flatter than those of the adults. Stimulus context may have influenced the ratings of children in the no-sucrose and highest sucrose concentration conditions with two of the foods. The absence of differences between the response functions of the female and male children with all types of stimuli indicated that gender had no influence on their responses. It is concluded that, at mid-childhood, humans are capable of estimating the sweetness of sucrose in foods, but that they have a tendency to limit the range of numbers used in their estimates of sweetness at high concentrations of sucrose in some foods.

Cultural interpretation services within a multicultural context: an exploration of the problematic and ethical issues facing social service institutions.

This paper explores the challenges for social service agencies which offer cultural interpretation services in their bid to meet the needs of service seekers and recipients from linguistic minorities. The author argues that cultural interpretation is provided by institutions that have done little more than add a service for clients from cultural minorities, while leaving intact their service structures--structures that have historically viewed language and "cultural differences" as problems. This orientation will need to change if these services are to be accessible and equitable for Canadians from linguistic and ethnic minorities. While cultural interpreters remain critical to service delivery, they need to work within institutions where service providers and administrators understand language as a cultural, social, and political instrument through which individuals articulate their identities, realities, and understandings of their cultural contexts and service needs. This paper concludes by identifying some of the ethical dilemmas and questions that attend the needed institutional changes.

A comparison of the ability of 8-9-year-old children and adults to detect taste stimuli.

Conflicting data exist in the literature regarding the maturity of the human sense of taste during childhood and if gender influences gustatory development. To investigate these 2 questions, taste detection thresholds for the 4 common tastants sucrose, sodium chloride, citric acid, and caffeine were established for 61 young adults and 68 children aged 8-9 years old, using a paired-comparison forced-choice procedure. No significant differences were found between the mean thresholds of women and men, or between those of female children and adults. In contrast, male children had significantly higher thresholds for all 4 tastants than adult females, for all tastants except caffeine than adult men, and for sucrose and sodium chloride than female children. It is concluded that the taste sensitivity of 8-9-year-old males, although well developed, has not fully matured, and that taste sensitivity is not affected by gender in young adults.

Risk management in obstetrics and gynaecology.

When medical negligence claims in the fields of obstetrics and gynaecology are retrospectively analyzed, a distinction must be drawn between the categories of claims most likely to be submitted and those categories most likely to succeed.Although some types of injury may be difficult to avoid, too many successful claims are found to relate to medical acts and omissions which with due care could have been avoided. A programme of risk management should concentrate on improved communication with patients (including the correct transmission and assimilation of data), better counselling (including the advice and information underlying informed consent), measures to ensure clinical competence (including caution in delegation to juniors and wider use of referral to senior staff) and the enforcement of well-devised rules for the maintenance of patient records.

Nausea and vomiting in early pregnancy.

To study the problem of nausea and vomiting in early pregnancy an epidemiological survey was undertaken, obtaining information from 500 consecutive antenatal patients. Seventy-six percent of women complained of symptoms during the first trimester, and in only 27% had the symptoms resolved by the twelfth week. Job efficiency was markedly impaired. Women who suffered nausea premenstrually, or on the oral contraceptive pill, were much more likely to develop symptoms, lending credence to a hormonal etiology for the condition.

The St. Thomas's Hospital maternity case notes study: a randomised controlled trial to assess the effects of giving expectant mothers their own maternity case notes.

At an antenatal clinic in St. Thomas's Hospital, London, 246 expectant mothers were randomly allocated to hold either their own maternity case notes or the standard co-operation card. Information was collected on three occasions during their care on attitudes and health behaviour. Clinical outcomes were recorded and the effects of the two systems on clinic administration were observed. More of the notes group expressed satisfaction with most aspects of their care and delivery and significantly more of the notes group felt well informed and satisfied with their companion during labour. There were no differences in clinical outcomes between the two groups except that, for no identifiable systematic reason, there were more assisted deliveries among the notes group. A number of administrative advantages resulted from mothers holding their own notes and although initial reservations were found amongst professional staff interviewed at the start of the study, the results proved persuasive and the practice of giving mothers their own notes is now to be extended throughout the department.