Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Self-assembled multilayer formation of an aromatic bifunctional molecule via selective ionic interaction

The formation of self-assembled multilayers of an aromatic bifunctional molecule, 4-carboxythiophenol, in a non-centrosymmetric structure via selective ion incorporation of cadmium ions is demonstrated. It is found from quartz crystal microgravimetry and ellipsometry studies that reasonably compact films of up to 7 monolayers may be deposited by self-assembly after which the film quality deteriorates. Films such as those obtained in this study containing highly polarizable molecules in a non-centrosymmetric structure may have important application in areas such as non-linear optics

Long-term stability of self-assembled monolayers of an aromatic bifunctional molecule during adsorption of silver colloidal particles

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An optical absorption investigation of cross-linking of gold colloidal particles with a small dithiol molecule

The controlled aggregation of colloidal metal particles is a problem of technological importance in the generation of, for example, quantum wires. In this communication, we present results of an optical absorption spectroscopy investigation of the flocculation of gold colloidal particles capped with a small bifunctional molecule (1,3-propanedithiol). The self-assembly of the dithiol molecule on the gold surface leads to thiol surface functionalization of the colloidal particles, which may thereafter be used to chemically cross-link the gold clusters. Optical absorption measurements performed immediately after capping the gold colloidal particle surface with the dithiol molecules clearly show the growth of a long-wavelength component, indicating that the clusters aggregate in open string-like structures. Increasing the surface coverage of the dithiol molecules on the clusters leads to a greater flocculation rate, but prevents the formation of large gold clusters in direct contact, as indicated by X-ray diffraction measurements of the aggregates. This approach of controlled cross-linking of colloidal particles may have important applications in the generation of metal cluster networks

Facile surface modification of colloidal particles using bilayer surfactant assemblies: a new strategy for electrostatic complexation in Langmuir-Blodgett films

Preliminary investigations have recently indicated that interdigitated bilayer assemblies of fatty acid molecules form spontaneously on colloidal silver particle surfaces while such bilayer structures are not observed on planar silver films. In this paper, this problem is probed further through contact angle and quartz crystal microgravimetry measurements of monolayer formation of lauric acid molecules on well-defined hydrophobic monolayers (formed from octadecanethiol chemisorbed on gold films) as a function of solution pH. The repulsive interaction between the ionized carboxylic acid groups in the lauric acid molecules prevents the formation of bilayer assemblies on planar surfaces. However, nanoscale surface curvature of colloidal particles permits interdigitation of the hydrocarbon chains in the bilayers, thereby maximizing the hydrophobic interaction as well as considerably reducing the electrostatic repulsive interactions of the headgroups, leading to stable bilayer assemblies. The strategy based on bilayer formation on colloidal particles is flexible and is used to derivatize colloidal silver particles with carboxylic acid and amine functional groups and thereafter electrostatically immobilize them at the air-hydrosol interface using the conjugate Langmuir monolayer. Good quality multilayer colloidal particle films can be deposited by the Langmuir-Blodgett technique, indicating that the bilayer assemblies on the colloidal particles are quite robust. This novel approach considerably extends the scope for the generation of nanoscale architectures using self-assembly of surface-modified colloidal particles

Selective binding of divalent cations at the surface of self-assembled monolayers of an aromatic bifunctional molecule studied on a quartz crystal microbalance

Self-assembled monolayers (SAMs) of a small aromatic bifunctional molecule, 4-carboxythiophenol, formed on gold films have been used to selectively bind Cd<SUP>2+</SUP> and Pb<SUP>2+</SUP> ions at the surface of the SAMs. SAMs formed with this molecule on Au have a surface rich in carboxylic acid functionality which can be used to bind the above-mentioned cations through an ion-exchange process. The kinetics of ion exchange, as well as the pH dependence of the binding of Cd<SUP>2+</SUP> and Pb<SUP>2+</SUP> ions on the SAM surface, have been followed using quartz crystal microbalance measurements. It is found that, at low pH where the carboxylic acid groups are expected to be unionized, significant mass increase is observed. At high pH, the percentage of ion exchange is found to be twice that expected from charge neutrality constraints (0.5 Cd<SUP>2+</SUP>/Pb<SUP>2+</SUP> ion per carboxylic acid group). This is tentatively explained as being due to incorporation of Cd(OH)<SUP>+</SUP> and Pb(OH)<SUP>+</SUP> ions. The titration curve obtained yields an equilibrium binding constant of ~5.3 for both ions, which is close to that obtained for these ions in Langmuir monolayers and Langmuir-Blodgett multilayer films

Recurrence Quantification Analysis of F-Waves and the Evaluation of Neuropathies

Electrodiagnostic (EDX) patterns of neuropathic dysfunction have been based on axonal/demyelinating criteria requiring prior assumptions. This has not produced classifications of desired sensitivity or specificity. Furthermore, standard nerve conduction studies have limited reproducibility. New methodologies in EDX seem important. Recurrent Quantification Analysis (RQA) is a nonlinear method for examining patterns of recurrence. RQA might provide a unique method for the EDX evaluation of neuropathies. RQA was used to analyze F-wave recordings from the abductor hallucis muscle in 61 patients with neuropathies. Twenty-nine of these patients had diabetes as the sole cause of their neuropathies. In the other 32 patients, the etiologies of the neuropathies were diverse. Commonly used EDX variables were also recorded. RQA data could separate the 29 patients with diabetic neuropathies from the other 32 patients (P<0.009). Statistically significant differences in two EDX variables were also present: compound muscle action potential amplitudes (P<0.007) and F-wave persistence (P<0.001). RQA analysis of F-waves seemed able to distinguish diabetic neuropathies from the other neuropathies studied, and this separation was associated with specific physiological abnormalities. This study would therefore support the idea that RQA of F-waves can distinguish between types of neuropathic dysfunction based on EDX data alone without prior assumptions

Effect of geometric constraints on the self-assembled monolayer formation of aromatic disulfides on polycrystalline gold

The self-assembled monolayer (SAM) formation tendency of two comparatively small aromatic disulfide molecules, namely naphthalene disulfide (NDS) and diphenyl disulfide (DDS), has been investigated using quartz crystal microgravimetry (QCM), cyclic voltammetric, and impedance techniques. The typical time period for monolayer formation on polycrystalline gold has been found to be about 2 h for both the molecules from the QCM data. A significant change in double-layer capacitance values (from 21 μF/cm2 for bare gold to ~14 and ~8 μF/cm2 for NDS and DDS, respectively) upon monolayer formation for both the cases has been observed, which correlates well with the QCM area per molecule values (~49 and 36 Å2 for NDS and DDS, respectively). The difference in the permeability of the two monolayers to simple ionic species was also investigated using K3Fe(CN)6 as redox probes in aqueous solution. A mixed linear/radial mode of diffusion is observed at the DDS-modified electrode in contrast to a predominant linear one at the electrode derivatized with a NDS monolayer. Impedance measurements indicate apparent surface coverages of 99.6 and 99.8% and rate constants of 9.4 × 10−5 and 4.1 × 10−5 cm/s for the Fe(CN)63−/4− couple in the case of NDS and DDS, respectively. These results strongly demonstrate the effect of geometrical constraints in controlling the microscopic structure and the packing density of the SAMs and highlight the importance of intramolecular conformational changes in controlling the monolayer packing density

Healing of peri-implant tissue following flapless implant surgery

Background: Flapless surgery for implant placement has been gaining popularity among implant surgeons. it has numerous advantages, including preservation of circulation, decreased surgical time; improved patient comfort; and accelerated recuperation. Materials and Methods: As a part of the study to evaluate crestal bone loss changes after placement of implant using the flapless technique, we placed twenty endosseous implants. Access was achieved to the crestal bone using a tissue punch. Clinical and radiographic analyses were performed second and fourth months after placement of the implant. Postoperative pain was measured by the visual analog scale at the 4th, 8th, and 24th hour. Results: The findings of the present study demonstrate that the average crestal bone loss around the implant at 4 months using the flapless technique was 0.19 mm. No implants failed to osseointegrate, and no implants exhibited bone loss greater than 0.5 mm in the first four months. This present study shows significantly less postoperative pain in the flapless technique of implant placement. Conclusion: The flapless approach is a predictable procedure when patient selection and surgical technique are appropriate