Ageing and dementia in low and middle income countries–Using research to engage with public and policy makers

While two thirds of the 24 million people with dementia worldwide live in low and middle income countries, very little research has been conducted to support policy making in these regions. Among the non-communicable diseases, dementia (in common with other chronic NCDs linked more to long-term disability than to mortality) has been relatively under-prioritized. International agreements, plans and policy guidelines have called for an end to ageist discrimination and a focus upon reducing disadvantage arising from poverty and the consequences of ill health. Social protection, access to good quality age-appropriate healthcare and addressing the problem of disability are all key issues. However, as yet, little progress has been made in addressing these concerns. In this review we outline the current international policy agenda for older individuals, and its specific relevance to those with dementia and other disabling non-communicable diseases. We consider the potential for epidemiological research to raise awareness, refine the policy agenda, and promote action, using the example of the dissemination strategy developed by the 10/66 Dementia Research Group.     

Correction to: Effect of a Focused Social and Communication Intervention on Preterm Children with ASD: A Pilot Study

Journal of Autism and Developmental Disorders - A correction to this paper has been published: https://doi.org/10.1007/s10803-021-05109-2     

Prolonged distal motor latency of median nerve does not improve diagnostic accuracy for CIDP

Journal of Neurology - Compression of the median nerve at the carpal tunnel can give demyelinating features and result in distal motor latency (DML) prolongation fulfilling the EFNS/PNS...     

Estimation of optical properties of neuroendocrine pancreas tumor with double-integrating-sphere system and inverse Monte Carlo model

The investigation of laser-tissue interaction is crucial for diagnostics and therapeutics. In particular, the estimation of tissue optical properties allows developing predictive models for defining organ-specific treatment planning tool. With regard to laser ablation (LA), optical properties are among the main responsible for the therapy efficacy, as they globally affect the heating process of the tissue, due to its capability to absorb and scatter laser energy. The recent introduction of LA for pancreatic tumor treatment in clinical studies has fostered the need to assess the laser-pancreas interaction and hence to find its optical properties in the wavelength of interest. This work aims at estimating optical properties (i.e., absorption, μ _a , scattering, μ _s , anisotropy, g, coefficients) of neuroendocrine pancreas tumor at 1064 nm. Experiments were performed using two popular sample storage methods; the optical properties of frozen and paraffin-embedded neuroendocrine tumor of the pancreas are estimated by employing a double-integrating-sphere system and inverse Monte Carlo algorithm. Results show that paraffin-embedded tissue is characterized by absorption and scattering coefficients significantly higher than frozen samples (μ _a of 56 cm^?1 vs 0.9 cm^?1, μ _s of 539 cm^?1 vs 130 cm^?1, respectively). Simulations show that such different optical features strongly influence the pancreas temperature distribution during LA. This result may affect the prediction of therapeutic outcome. Therefore, the choice of the appropriate preparation technique of samples for optical property estimation is crucial for the performances of the mathematical models which predict LA thermal outcome on the tissue and lead the selection of optimal LA settings.     

Selective induction of apoptosis in MCF7 cancer-cell by targeted liposomes functionalised with mannose-6-phosphate

Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells.     

Ultrasound-mediated transdermal transport of insulin in vitro through human skin using novel transducer designs

Recent studies have shown that ultrasound (US)-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to improve low-frequency (20 kHz) US methods for enhancing the transport of insulin in vitro across human skin. The feasibility of using US produced by small, lightweight novel transducers was explored for enhancing the transport of insulin across skin. Previous investigators have used US devices such as large, heavy sonicators or commercially obtained transducers for this type of research. The experiments carried out in this study used two low-profile novel US transducer arrays, the stack and standard array, for improved transport of insulin. The stack array generated a spatial peak temporal peak intensity (I(SPTP)) of 15.4 +/- 0.6 mW/cm(2) and the standard array had an I(SPTP) of 173.7 +/- 1.2 mW/cm(2). Spectrophotometeric absorption techniques were used for determining insulin transport in vitro across human skin. Compared with passive transmission (4.1 +/- 0.5 U) over an exposure period of 1 h, the standard array facilitated over a sevenfold increase in the noninvasive transdermal transport of Humulin R insulin (45.9 +/- 12.9 U). Using Humalog insulin with the standard array, there was a fourfold increase in the US-facilitated transmission over that in the control. These promising results indicate that low-frequency US can be used in a practical device for enhanced transport across the stratum corneum.     

Migrainous Infarction in a Patient With Sporadic Hemiplegic Migraine and Cystic Fibrosis: A 99mTc-HMPAO Brain SPECT Study

Genetic mutations of sporadic hemiplegic migraine (SHM) are mostly unknown. SHM pathophysiology relies on cortical spreading depression (CSD), which might be responsible for ischemic brain infarction. Cystic fibrosis (CF) is caused by a monogenic mutation of the chlorine transmembrane conductance regulator (CFTR), possibly altering brain excitability. We describe the case of a patient with CF, who had a migrainous stroke during an SHM attack. A 32-year-old Caucasian male was diagnosed with CF, with heterozygotic delta F508/unknown CFTR mutation. The patient experiences bouts of coughing sometimes triggering SHM attacks with visual phosphenes, aphasia, right-sided paresthesia, and hemiparesis. He had a 48-hour hemiparesis triggered by a bout of coughing with hemoptysis, loss of consciousness, and severe hypoxia-hypercapnia. MRI demonstrated transient diffusion hyperintensity in the left frontal-parietal-occipital regions resulting in a permanent infarction in the primary motor area. Later, a brain perfusion SPECT showed persistent diffuse hypoperfusion in the territories involved in diffusion-weighted imaging alteration. Migrainous infarction, depending on the co-occurrence of 2 strictly related phenomena, CSD and hypoxia, appears to be the most plausible explanation. Brain SPECT hypoperfusion suggests a more extensive permanent neuronal loss in territories affected by aura. CF may be then a risk factor for hemiplegic migraine and stroke since bouts of coughing can facilitate brain hypoxia, triggering auras.