One Size Does Not Fit All: Choosing Practical Cognitive Screening Tools for Your Practice

Every year, millions of patients worldwide undergo cognitive testing. Unfortunately, new barriers to the use of free open access cognitive screening tools have arisen over time, making accessibility of tools unstable. This article is in follow-up to an editorial discussing alternative cognitive screening tools for those who cannot afford the costs of the Mini-Mental State Examination and Montreal Cognitive Assessment (see www.dementiascreen.ca ). The current article outlines an emerging disruptive “free-to-fee” cycle where free open access cognitive screening tools are integrated into clinical practice and guidelines, where fees are then levied for the use of the tools, resulting in clinicians moving on to other tools. This article provides recommendations on means to break this cycle, including the development of tool kits of valid cognitive screening tools that authors have contracted not to charge for (i.e., have agreed to keep free open access). The PRACTICAL.1 Criteria ( PRACTI cing C linician A ccessibility and L ogistical Criteria Version 1 ) are introduced to help clinicians select from validated cognitive screening tools, considering barriers and facilitators, such as whether the cognitive screening tools are easy to score and free of cost. It is suggested that future systematic reviews embed the PRACTICAL.1 criteria, or refined future versions, as part of the standard of review. Methodological issues, the need for open access training to insure proper use of cognitive screening tools, and the need to anticipate growing ethnolinguistic diversity by developing tools that are less sensitive to educational, cultural, and linguistic bias are discussed in this opinion piece. J Am Geriatr Soc 68:2207–2213, 2020.     

Respiratory cycle entrainment of septal neurons mediates the fast coupling of sniffing rate and hippocampal theta rhythm

Memory for odour information may result from temporal coupling between the olfactory and hippocampal systems. Respiration defines the frequency of olfactory perception, but how the respiratory rate affects hippocampal oscillations remains poorly understood. The afferent connectivity of the medial septum/diagonal band of Broca complex (MS/DB) proposes this region as a crossroads between respiratory and limbic pathways. Here we investigate if the firing rates of septal neurons integrate respiratory rate signals. We demonstrate that approximately 50% of MS/DB neurons are temporally correlated with sniffing frequency. Moreover, a group of slow‐spiking septal neurons are phase‐locked to the sniffing cycle. We show that inter‐burst intervals of MS/DB theta cells relate to the sniff rate. Intranasal odour infusion evokes sniff phase preference for the activity of fast‐spiking MS/DB neurons. Concurrently, the infusion augments the correlation between sniffing and limbic theta oscillations. During periods of sniffing–theta correlation, CA1 place cells fired preferentially during the inhalation phase, suggesting the theta cycle as a coherent time frame for central olfactory processing. Furthermore, injection of the GABAergic agonist muscimol into medial septum induces a parallel decrease of sniffing and theta frequencies. Our findings provide experimental evidence that MS/DB does not merely generate theta rhythm, but actively integrates sensorimotor stimuli that reflect sniffing rate. Such integration may provide temporal oscillatory synchronisation of MS/DB‐innervated limbic structures with the sniffing cycle.     

Collapsin response‐mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition

The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth.     

Gender differences among homeless people in Tehran,Iran

Aim

Gender differences among homeless people may affect the frequency of their risky behaviours. This study was conducted to evaluate the behaviour patterns of homeless men and women in Tehran and compare the probable differences.

Subject and methods

In this study, 593 homeless people were recruited from five centres that house homeless people in Tehran, the capital city of Iran. A researcher-designed questionnaire was used to study behavioural patterns.

Results

In this study, homeless people (513 males and 80 females, all Iranian nationals) were enrolled in the study from June to August 2012. Mean age and mean duration of homelessness among women (35.46 and 12.68 months) were lower than those among men (42.74 and 56.85 months) (p?=?0.001). Although lifetime history of incarceration in men was higher than in women (p?=?0.002), mean duration of imprisonment in the last 10 years in men (21.25 months) and women (17.76 months) was not statistically different (p?=?0.07). Accommodation locality in the past 6 months varied between men and women. Women were current drug users more often than men were (61.53 % versus 45.26 %) (p?=?0.02). The type of drug consumption in women (methamphetamine) differed from that of men (opium and heroin). More men had a history of injecting drugs than did women (30.02 % versus 12.30 %) (p?=?0.003). Condom use at the last sexual encounter was reported to be higher in women compared to men (74.60 % versus 26.62 %) (p?=?0.001).

Conclusion

This study showed notable differences in behaviour patterns between homeless men and women and also indicated that homeless people in Tehran exhibit many risky behaviours.     

Carbon nanotube-based substrates for modulation of human pluripotent stem cell fate

We investigated the biological response of human pluripotent stem cells (hPSCs) cultured on a carbon nanotube (CNT) array-based substrate with the long term goal to direct hPSC germ layer specification for a wide variety of tissue engineering applications. CNT arrays were fabricated using a chemical vapor deposition system allowing for control over surface roughness and mechanical stiffness. Our results demonstrated that hPSCs readily attach to hydrophilized and extracellular matrix coated CNT arrays. hPSCs cultured as colonies in conditions supporting self-renewal demonstrated the morphology and marker expression of undifferentiated hPSCs. Conditions inducing spontaneous differentiation lead to hPSC commitment to all three embryonic germ layers as assessed by immunostaining and RT-PCR analysis. Strikingly, the physical characteristics of CNT arrays favored mesodermal specification of hPSCs. This is contradictory to the behavior of hPSCs on traditional tissue culture plastic which promotes the development of ectoderm. Altogether, these results demonstrate the potential of CNT arrays to be used in the generation of new platforms that allow for precise control of hPSC differentiation by tuning the characteristics of their physical microenvironment.     

Anatomy-based 3D skeleton extraction from femur model

Using 3D models of bones can highly improve accuracy and reliability of orthopaedic evaluation. However, it may impose excessive computational load. This article proposes a fully automatic method for extracting a compact model of the femur from its 3D model. The proposed method works by extracting a 3D skeleton based on the clinical parameters of the femur. Therefore, in addition to summarizing a 3D model of the bone, the extracted skeleton would preserve important clinical and anatomical information. The proposed method has been applied on 3D models of 10 femurs and the results have been evaluated for different resolutions of data.     

The effect of ubiquinone on functional recovery and morphometric indices of sciatic nerve regeneration

A common cause of peripheral nerve injury is trauma. The positive effect of antioxidants on the improvement of nerve regeneration has currently become a focus of attention. In this experiment, the effect of intraperitoneal administration of ubiquinone (CoQ₁₀) on an acute experimentally sciatic nerve crush was studied in a rat model. Forty-five male Wistar rats, weighing between 160-180 g were used. The rats were randomly divided into two experimental groups (n=20). Each group was further subdivided into four subgroups of five animals each. Functional studies confirmed the faster recovery of regenerated axons in the treatment group compared to the un-treated group (P<0.05). Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in the treatment group than the un-treated group (P<0.05). Intraperitoneal administration of CoQ₁₀ (10 mg/kg/day) in the early inflammatory stage of sciatic nerve crush was found to improve nerve regeneration.Key Words: Ubiquinone (coenzyme Q₁₀), Peripheral nerve regeneration, Crush     

Synthesis and characterization of osteoinductive visible light‐activated adhesive composites with antimicrobial properties

Orthopedic surgical procedures based on the use of conventional biological graft tissues are often associated with serious post‐operative complications such as immune rejection, bacterial infection, and poor osseointegration. Bioresorbable bone graft substitutes have emerged as attractive alternatives to conventional strategies because they can mimic the composition and mechanical properties of the native bone. Among these, bioactive glasses (BGs) hold great potential to be used as biomaterials for bone tissue engineering owing to their biomimetic composition and high biocompatibility and osteoinductivity. Here, we report the development of a novel composite biomaterial for bone tissue engineering based on the incorporation of a modified strontium‐ and lithium‐doped 58S BG (i.e., BG‐5/5) into gelatin methacryloyl (GelMA) hydrogels. We characterized the physicochemical properties of the BG formulation via different analytical techniques. Composite hydrogels were then prepared by directly adding BG‐5/5 to the GelMA hydrogel precursor, followed by photocrosslinking of the polymeric network via visible light. We characterized the physical, mechanical, and adhesive properties of GelMA/BG‐5/5 composites, as well as their in vitro cytocompatibility and osteoinductivity. In addition, we evaluated the antimicrobial properties of these composites in vitro, using a strain of methicillin‐resistant Staphylococcus Aureus. GelMA/BG‐5/5 composites combined the functional characteristics of the inorganic BG component, with the biocompatibility, biodegradability, and biomimetic composition of the hydrogel network. This novel biomaterial could be used for developing osteoinductive scaffolds or implant surface coatings with intrinsic antimicrobial properties and higher therapeutic efficacy.