Subjective Cognitive Complaints Given in Questionnaire: Relationship With Brain Structure,Cognitive Performance and Self-Reported Depressive Symptoms in a 25-Year Retrospective Cohort Study

BackgroundSubjective cognitive complaints are common but it is unclear whether they indicate an underlying pathological process or reflect affective symptoms.Method800 community-dwelling older adults were drawn from the Whitehall II cohort. Subjective cognitive complaint inquiry for memory and concentration, a range of neuropsychological tests and multimodal MRI were performed in 2012–2016. Subjective complaints were again elicited after 1 year. Group differences in grey and white matter, between those with and without subjective complaints, were assessed using voxel-based morphometry and tract-based spatial statistics, respectively. Mixed effects models assessed whether cognitive decline or depressive symptoms (over a 25-year period) were associated with later subjective complaints. Analyses were controlled for potential confounders and multiple comparisons.ResultsMean age of the sample at scanning was 69.8 years (±5.1, range: 60.3–84.6). Subjective memory complaints were common (41%) and predicted further similar complaints later (mean 1.4 ± 1.4 years). There were no group differences in grey matter density or white matter integrity. Subjective complaints were not cross-sectionally or longitudinally associated with objectively assessed cognition. However, those with subjective complaints reported higher depressive symptoms (“poor concentration”: odds ratio = 1.12, 95% CI 1.07–1.18; “poor memory”: odds ratio = 1.18, 1.12–1.24).ConclusionsIn our sample subjective complaints were consistent over time and reflected depressive symptoms but not markers of neurodegenerative brain damage or concurrent or future objective cognitive impairment. Clinicians assessing patients presenting with memory complaints should be vigilant for affective disorders. These results question the rationale for including subjective complaints in a spectrum with Mild Cognitive Impairment diagnostic criteria.     

Analysis of Kinematic Differences in Hand Motion between Novice and Experienced Operators in IR: A Pilot Study

PurposeTo prospectively validate electromagnetic hand motion tracking in interventional radiology to detect differences in operator experience using simulation.MethodsSheath task: Six attending interventional radiologists (experts) and 6 radiology trainees (trainees) placed a wire through a sheath and performed a “pin-pull” maneuver, while an electromagnetic motion detection system recorded the hand motion. Radial task: Eight experts and 12 trainees performed palpatory radial artery access task on a radial access simulator. The trainees repeated the task with the nondominant hand. The experts were classified by their most frequent radial artery access technique as having either palpatory, ultrasound, or overall limited experience. The time, path length, and number of movements were calculated. Mann-Whitney U tests were used to compare the groups, and P < .05 was considered significant.ResultsSheath task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (11.7 seconds ± 3.3 vs 19.7 seconds ± 6.5, P < .01; 1.1 m ± 0.3 vs 1.4 m ± 0.4, P < .01; and 19.5 movements ± 8.5 vs 31.0 movements ± 8.0, P < .01, respectively). Radial task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (24.2 seconds ± 10.6 vs 33.1 seconds ± 16.9, P < .01; 2.0 m ± 0.5 vs 3.0 m ± 1.9, P < .001; and 36.5 movements ± 15.0 vs 54.5 movements ± 28.0, P < .001, respectively). The trainees had a shorter path length for their dominant hand than their nondominant hand (3.0 m ± 1.9 vs 3.5 m ± 1.9, P < .05). The expert palpatory group had a shorter path length than the ultrasound and limited experience groups (1.8 m ± 0.4 vs 2.0 m ± 0.4 and 2.3 m ± 1.2, respectively, P < .05).ConclusionsElectromagnetic hand motion tracking can differentiate between the expert and trainee operators for simulated interventional tasks.     

The glia doctrine: Addressing the role of glial cells in healthy brain ageing

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction.     

Evaluation of non-targeting,C- or N-pH (low) insertion peptide modified superparamagnetic iron oxide nanoclusters for selective MRI of liver tumors and their potential toxicity in cirrhosis

Superparamagnetic iron oxide nanoclusters (SPIONs) modified with pH (low) insertion peptide (pHLIP) could be advantageous for magnetic resonance imaging (MRI) diagnosis of liver tumors at the early stage due to their unique responsiveness to the tumor acidic microenvironment when tumor markers are unknown. However, many critical aspects including the effectiveness of selective MRI in liver tumors, types of delivery and the potential safety profile in cirrhosis need to be fully evaluated. In this study, we report the evaluation of non-targeting, C- or N-pHLIP modified SPIONs as the contrast agent for selective MRI of liver tumors and their potential toxicity profile in cirrhosis. It was found that N-pHLIP modified SPIONs did not result in the loss of liver tumor in the T2-weight MRI but provided additional dynamic details of tumor structures that would enhance the diagnosis of liver tumors at a small size below 8 mm. In addition, an enhanced safety profile was found for N-pHLIP modified SPIONs with almost fully recoverable impact in cirrhosis. In contrast, the poly-d-lysine assembled SPIONs and C-terminus linked pHLIP SPIONs had non-tumor specific MRI contrast enhancement and potential safety risks in cirrhosis due to the iron overload post injection. All these results implied the promising potential of N-terminus linked pHLIP SPIONs as an MRI contrast agent for the diagnosis of liver tumors.

The acid-responsive pHLIP modified SPION as an MRI contrast agent for liver cancer diagnosis requires the validation of both the tumor-specific enhancement and a safe profile in cirrhosis.     

Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation

Background

Human adipose tissue is an ideal autologous source of mesenchymal stem cells (MSCs) for various regenerative medicine and tissue engineering strategies. Aged patients are one of the primary target populations for many promising applications. It has long been known that advanced age is negatively correlated with an organism’s reparative and regenerative potential, but little and conflicting information is available about the effects of age on the quality of human adipose tissue derived MSCs (hAT-MSCs).

Methods

To study the influence of age, the expansion and in vitro differentiation potential of hAT-MSCs from young (<30 years), adult (35-50 years) and aged (>60 years) individuals were investigated. MSCs were characterized for expression of the genes p16^INK4a and p21 along with measurements of population doublings (PD), superoxide dismutase (SOD) activity, cellular senescence and differentiation potential.

Results

Aged MSCs displayed senescent features when compared with cells isolated from young donors, concomitant with reduced viability and proliferation. These features were also associated with significantly reduced differentiation potential in aged MSCs compared to young MSCs.

Conclusions

In conclusion, advancing age negatively impacts stem cell function and such age related alterations may be detrimental for successful stem cell therapies.     

Sulfamic acid promoted one-pot multicomponent reaction: a facile synthesis of 4-oxo-tetrahydroindoles under ball milling conditions

We report an efficient and facile one-pot synthesis of 4-oxo-tetrahydroindoles using sulfamic acid under ball milling conditions. The present protocol for preparation of biologically important 4-oxo-tetrahydroindoles offers several advantages such as mild reaction conditions, improved selectivity and higher isolated yields. Moreover, solvent-free reaction conditions and the use of ball milling make the present protocol environmentally friendly in nature.

We report an efficient and facile one-pot synthesis of 4-oxo-tetrahydroindoles using sulfamic acid under ball milling conditions.     

Current and future therapies for hepatitis C virus infection: from viral proteins to host targets

Hepatitis C virus (HCV) infection is the most important problem across the world. It causes acute and chronic liver infection. Different approaches are in use to inhibit HCV infection, including small organic compounds, siRNA, shRNA and peptide inhibitors. This review article summarizes the current and future therapies for HCV infection. PubMed and Google Scholar were searched for articles published in English to give an insight into the current inhibitors against this life-threatening virus. HCV NS3/4A protease inhibitors and nucleoside/nucleotide inhibitors of NS5B polymerase are presently in the most progressive stage of clinical development, but they are linked with the development of resistance and viral breakthrough. Boceprevir and telaprevir are the two most important protease inhibitors that have been approved recently for the treatment of HCV infection. These two drugs are now the part of standard-of-care treatment (SOC). There are also many other drugs in phase III of clinical development. When exploring the various host-cell-targeting compounds, the most hopeful results have been demonstrated by cyclophilin inhibitors. The current SOC treatment of HCV infection is Peg-interferon, ribavirin and protease inhibitors (boceprevir or telaprevir). The future treatment of this life-threatening disease must involve combinations of therapies hitting multiple targets of HCV and host factors. It is strongly expected that the near future, treatment of HCV infection will be a combination of direct-acting agents (DAA) without the involvement of interferon to eliminate its side effects.     

Occupational stress,bullying and resilience in old age

Our working years increasingly extend into the late 60s and may soon include the 70s for some people. Thus the question whether work stress has a cumulative effect in older age, and whether older employees are more vulnerable to certain sources of work stress, such as bullying in the work place, is becoming increasingly relevant. We review some of the mechanisms, which translate cumulative stress at work into ill health, particularly in older age, and summarise what is known about the effect of age-specific stress, taking age-related bullying as an example.