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A Fourier transform spectrometer (FTS) that incorporates a closed-loop controlled, electrothermally actuated microelectromechanical systems (MEMS) micromirror is proposed and experimentally verified. The scan range and the tilting angle of the mirror plate are the two critical parameters for MEMS-based FTS. In this work, the MEMS mirror with a footprint of 4.3 mm × 3.1 mm is based on a modified lateral-shift-free (LSF) bimorph actuator design with large piston and reduced tilting. Combined with a position-sensitive device (PSD) for tilt angle sensing, the feedback controlled MEMS mirror generates a 430 µm stable linear piston scan with the mirror plate tilting angle less than ±0.002°. The usable piston scan range is increased to 78% of the MEMS mirror’s full scan capability, and a spectral resolution of 0.55 nm at 531.9 nm wavelength, has been achieved. It is a significant improvement compared to the prior work.

Background: In the past decade, the incidence of thyroid cancer (TC) has shown a stable increase, for both sexes, in many parts of the world at a rate faster than for any other type of malignancy. The aim of our study was to analyze and report changes in TC incidence in Serbia, as well as to evaluate potential reasons for these changes. So far, the incidence of TC in Serbia has not been reported. Material and Methods: This is a retrospective descriptive epidemiological study of TC data from the Cancer Register for Serbia for a ten year period, from 1999 to 2008. Crude rates (CR), age-specific rates (ASR), age-adjusted rates (AAR), linear trends and average annual percentage changes (AAPC) were calculated and analyzed. Results: TC incidence increased substantially for both genders with the highest increase in 2007 for the age group 50- 59 (females 14.2, males 10.3). TC was three times more common in females (CR 4.7:1.5). The AAR for females ranged 1.9-4.8 (3.3, 95% CI 2.6-4.0), for males 1.0-2.6 (1.0, 95% CI 0.8-1.2) and for both sexes combined 1.4-3.2 (2.2, 95% CI 1.7-2.6). The incidence trend for males showed an increase (y =0.05x + 0.70, p =0.058). It was highly statistically significant for females (y =0.31x + 1.61, p <0.001) and both genders combined (y =0.18x + 1.18, p <0.001). AAPC was highest for ages 20-29 and 30-39, for females (+25.2%) and males (+17.3%), respectively. Conclusions:We found a substantial increase in TC incidence in Serbia for both genders. The highest increase in TC incidence was found in females aged 20 to 29 years while the highest incidence was found in the age group 50 to 59. [ABSTRACT FROM AUTHOR]

Substantial evidence from previous clinical studies, randomized trials, and patient registries confirms the existence of significant differences in cardiac morphology, pathophysiology, prevalence of specific coronary artery disease (CAD), and clinical course of myocardial infarction (MI) between men and women. The aim of this review is to investigate the impact of sex or gender on the development and clinical course of MI, the mechanisms and features of left ventricular (LV) remodeling, and heart failure (HF). The main sex-related difference in post-MI LV remodeling is adverse LV dilatation in males versus concentric LV remodeling or concentric LV hypertrophy in females. In addition, women have a higher incidence of microvascular dysfunction, which manifests as impaired coronary flow reserve, distal embolism, and a higher prevalence of the no-reflow phenomenon. Consequently, impaired myocardial perfusion after MI is more common in women than in men. Regardless of age or other comorbidities, the incidence of reinfarction, hospitalization for HF, and mortality is significantly higher in females. There is therefore a "sex paradox": despite the lower prevalence of obstructive CAD and HF with reduced ejection fraction (HFrEF), women have a higher mortality rate after MI. Different characteristics of the coronary network, such as plaque formation, microvascular dysfunction, and endothelial inflammation, as well as the prolonged time to optimal coronary flow restoration, secondary mitral regurgitation, and pulmonary vascular dysfunction, lead to a worse outcome in females. A better understanding of the mechanisms responsible for MI occurrence, LV remodeling, and HF in men and women would contribute to optimized patient therapy that would benefit both sexes.

Background: Substantial inequalities in the overall prevalence and patterns of multimorbidity have been widely reported, but the causal mechanisms are complex and not well understood. This study aimed to identify common patterns of multimorbidity in Serbia and assess their relationship with air pollutant concentrations and water quality indicators., Methods: This ecological study was conducted on a nationally representative sample of the Serbian population. Data were obtained from the European Health Interview (EHIS) Survey, a periodic study designed to assess population health using widely recognized standardized instruments. The study included 13,069 participants aged 15 and older, randomly selected through a multistage stratified sampling design. Multimorbidity was defined as having two or more self-reported diagnoses of chronic non-communicable diseases. Latent class analysis (LCA) was performed to identify clusters of multimorbidity. Concentrations of particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3), as well as water quality indicators, were obtained from the Serbian Environmental Protection Agency., Results: The overall prevalence of multimorbidity was 33.4% [32.6%-34.2%]. Six latent classes of multimorbidity were identified: Healthy, Multicondition, Cardiovascular, Metabolic syndrome, Respiratory, and Musculoskeletal. Annual increases in PM10 and SO2 concentrations, as well as daily increases in O3 concentrations, significantly raised the odds of having multimorbidity (OR = 1.02, 95% CI 1.02-1.03; OR = 1.01, 95% CI 1.00-1.02 and OR = 1.03, 95% CI 1.02-1.03, respectively). A pattern of increased risk was observed with rising levels of water contamination. Exposure to physico-chemical, microbiological and combined contamination was associated with a 3.92%, 5.17% and 5.54% higher probability, respectively, of having multiple chronic conditions. There was strong evidence that air pollutants, as well as chemical and microbial water contamination, were significantly associated with higher odds of the most common clusters of multimorbidity identified by LCA., Conclusion: There is compelling evidence of an association between multimorbidity and environmental pollution, suggesting that exposure to air pollutants and water contaminants may contribute to disease accumulation and help explain geographically and socioeconomically patterned inequalities. These findings underscore the need for extensive studies that simultaneously measure both multimorbidity and pollution to explore their complex interrelationships., Competing Interests: Declarations Ethics approval and consent to participate This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Institute of Public Health of Serbia (date: 10.06.2021; n˚ 3607/1). Informed consent was obtained from all individual participants included in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Abstract: X-linked myopathy with excessive autophagy is a rare disorder caused by a mutation in the vacuolar ATPase assembly factor gene which causes slowly progressive early onset proximal weakness and loss of ambulation by the age of 50-70 years. Electrodiagnostic (EDx) testing usually shows widespread complex repetitive and myotonic discharges, even in muscles unaffected clinically. We report a 65-year-old man who presented with progressive proximal weakness since his teenage years. Extensive workup over 30 years revealed inconclusive EDx and muscle histopathology findings. The diagnosis was finally made with genetic testing. Subsequent neuromuscular ultrasound was more informative of disease severity than repeat EDx and directed a muscle biopsy that showed an autophagic vacuolar myopathy and the novel identification of vacuoles in capillary endothelial cells. Although genetic testing is required for confirmation, in milder cases of X-linked myopathy with excessive autophagy, neuromuscular ultrasound may aid in diagnosis even when EDx findings are inconclusive., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to develop a computational environment for the accurate simulation of human cancer cell irradiation using Geant4-DNA. New cell geometrical models were developed and irradiated by alpha particle beams to induce DNA damage. The proposed approach may help further investigation of the benefits of external alpha irradiation therapy., Methods: The Geant4-DNA Monte Carlo (MC) toolkit allows the simulation of cancer cell geometries that can be combined with accurate modelling of physical, physicochemical and chemical stages of liquid water irradiation, including radiolytic processes. Geant4-DNA is used to calculate direct and non-direct DNA damage yields, such as single and double strand breaks, produced by the deposition of energy or by the interaction of DNA with free radicals., Results: In this study, the "molecularDNA" example application of Geant4-DNA was used to quantify early DNA damage in human cancer cells upon irradiation with alpha particle beams, as a function of linear energy transfer (LET). The MC simulation results are compared to experimental data, as well as previously published simulation data. The simulation results agree well with the experimental data on DSB yields in the lower LET range, while the experimental data on DSB yields are lower than the results obtained with the "molecularDNA" example in the higher LET range., Conclusion: This study explored and demonstrated the possibilities of the Geant4-DNA toolkit together with the "molecularDNA" example to simulate the helium beam irradiation of cancer cell lines, to quantify the early DNA damage, or even the following DNA damage response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since the establishment of the "lipid hypothesis", according to which, cholesterol level is directly correlated to the risk of CVD, many different lipid-lowering agents have been introduced in clinical practice. A majority of these drugs, in addition to their lipid-lowering properties, may also exhibit some anti-inflammatory and immunomodulatory activities. This hypothesis was based on the observation that a decrease in lipid levels occurs along with a decrease in inflammation. Insufficient reduction in the inflammation during treatment with lipid-lowering drugs could be one of the explanations for treatment failure and recurrent CVD events. Thus, the aim of this narrative review was to evaluate the anti-inflammatory properties of currently available lipid-lowering medications including statins, ezetimibe, bile acid sequestrants (BAS), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fibrates, omega-3 fatty acids, and niacin, as well as dietary supplements and novel drugs used in modern times.

Central nervous system (CNS) disorders and trauma involving changes to the neuronal myelin sheath have long been a topic of great interest. One common pathological change in these diseases is the generation of myelin debris resulting from the breakdown of the myelin sheath. Myelin debris contains many inflammatory and neurotoxic factors that inhibit remyelination and make its clearance a prerequisite for healing in CNS disorders. Many professional and semiprofessional phagocytes participate in the clearance of myelin debris in the CNS. These cells use various mechanisms for the uptake of myelin debris, and each cell type produces its own unique set of pathologic consequences resulting from the debris uptake. Examining these cells' phagocytosis of myelin debris will contribute to a more complete understanding of CNS disease pathogenesis and help us conceptualize how the necessary clearance of myelin debris must be balanced with the detrimental consequences brought about by its clearance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Central nervous system (CNS) trauma activates a persistent repair response that leads to fibrotic scar formation within the lesion. This scarring is similar to other organ fibrosis in many ways; however, the unique features of the CNS differentiate it from other organs. In this review, we discuss fibrotic scar formation in CNS trauma, including the cellular origins of fibroblasts, the mechanism of fibrotic scar formation following an injury, as well as the implication of the fibrotic scar in CNS tissue remodeling and regeneration. While discussing the shared features of CNS fibrotic scar and fibrosis outside the CNS, we highlight their differences and discuss therapeutic targets that may enhance regeneration in the CNS.

Objective: To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barré syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS)., Methods: Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis., Results: Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this., Conclusions: Our study showed extensive variation in the clinical practice of EDx in GBS patients among IGOS centers across the regions., Significance: Besides EDx variation in GBS patients participating in IGOS, this diversity is likely to be present in other neuromuscular disorders and centers. This underlines the need for standardization of EDx in future multinational GBS studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Phagocytosis performed by a macrophage involves complex membrane trafficking and reorganization among various membranous cellular structures including phagosomes and vesicles derived from the phagosomes known as phagosome-derived vesicles. The present work reports on development of a technique that allows to specifically label the phagosome-derived vesicles in macrophages with a membrane dye. The technique is based on the use of microfabricated microparticles that are made of a thermosensitive nonbiodegradable polymer poly(N-isopropylacrylamide) (PNIPAM) or its derivative and contain a membrane dye 1,1'-dialkyl-3,3,3',3'-tetramethylindodicarbocyanine (DiI). The microparticles can be phagocytosed by RAW264.7 macrophages into their phagosomes, resulting in formation of intracellular DiI-positive vesicles derived from the phagosomes. The DiI-positive vesicles are motile and acidic; can be stained by fluorescently labelled dextran added in the culture medium; and can accumulate around new phagosomes, indicating that they possess properties of lysosomes. This technique is also applicable to another membrane dye 3,3'-dioctadecyloxacarbocyanine (DiO) and holds great potential to be useful for advancing our understanding of phagocytosis. STATEMENT OF SIGNIFICANCE: Phagocytosis performed by macrophages is a cellular process of great importance to various applications of biomaterials such as drug delivery and medical implantation. This work reports on a technique for characterizing phagocytosis based on the use of poly(N-isopropylacrylamide), which is a major biomaterial with numerous applications. This technique is the first of its kind and has generated an original finding about phagocytosis. In addition to drug delivery and medical implantation, phagocytosis plays critical roles in diseases, injuries and vaccination. This work could thus attract immediate and widespread interests in the field of biomaterials science and engineering., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Neutrophils are short-lived cells of the innate immune system and the first line of defense at the site of an infection and tissue injury. Pattern recognition receptors on neutrophils recognize pathogen-associated molecular patterns or danger-associated molecular patterns, which recruit them to the destined site. Neutrophils are professional phagocytes with efficient granular constituents that aid in the neutralization of pathogens. In addition to phagocytosis and degranulation, neutrophils are proficient in creating neutrophil extracellular traps (NETs) that immobilize pathogens to prevent their spread. Because of the cytotoxicity of the associated granular proteins within NETs, the microbes can be directly killed once immobilized by the NETs. The role of neutrophils in infection is well studied; however, there is less emphasis placed on the role of neutrophils in tissue injury, such as traumatic spinal cord injury. Upon the initial mechanical injury, the innate immune system is activated in response to the molecules produced by the resident cells of the injured spinal cord initiating the inflammatory cascade. This review provides an overview of the essential role of neutrophils and explores the contribution of neutrophils to the pathologic changes in the injured spinal cord., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zivkovic, Ayazi, Hammel and Ren.)

Although the increased expression of members of the chondroitin sulfate proteoglycan family, such as neuron-glial antigen 2 (NG2), have been well documented after an injury to the spinal cord, a complete picture as to the cellular origins and function of this NG2 expression has yet to be made. Using a spinal cord injury (SCI) mouse model, we describe that some infiltrated bone marrow-derived macrophages (BMDMΦ) are early contributors to NG2/CSPG4 expression and secretion after SCI. We demonstrate for the first time that a lesion-related form of cellular debris generated from damaged myelin sheaths can increase NG2/CSPG4 expression in BMDMΦ, which then exhibit enhanced proliferation and decreased phagocytic capacity. These results suggest that BMDMΦ may play a much more nuanced role in secondary spinal cord injury than previously thought, including acting as early contributors to the NG2 component of the glial scar., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Hammel, Shi, Cheng, Zivkovic, Wang, Xu, He, Guo, Ren and Zuo.)

Dietary supplementation with sugar cane derivates may modulate low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The purpose of this study was to determine if dietary supplement (DS), containing Octacosanol (20 mg) and vitamin K2 (45 µg), could restore the disrupted physiologic relation between LDL-C and serum PCSK9. Double-blind, randomized, placebo-controlled, single-center study including 87 patients on chronic atorvastatin therapy was conducted. Eighty-seven patients were randomized to receive DS ( n = 42) or placebo ( n = 45), and followed for 13 weeks. Serum PCSK9 levels, lipid parameters and their relationship were the main efficacy endpoints. The absolute levels of PCSK9 and LDL-C were not significantly different from baseline to 13 weeks. However, physiologic correlation between % change of PCSK9 and % change of LDL-C levels was normalized only in the group of patients treated with DS ( r = 0.409, p = 0.012). This study shows that DS can restore statin disrupted physiologic positive correlation between PCSK9 and LDL-C. Elevated PCSK9 level is an independent risk factor so controlling its rise by statins may be important in prevention of cardiovascular events.

Background: To collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial., Methods: Twenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT)., Results: RMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (P = .039). Reductions of motor evoked potential (MEP) amplitude (P = .013) and accommodation half-time (P = .002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine., Conclusions: The relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half-time supports the reduction of cortical and axonal hyperexcitability with mexiletine., (© 2020 Wiley Periodicals LLC.)

Objective: Patients with hereditary transthyretin (TTR) amyloidosis (hATTR) often experience disease progression after orthotopic liver transplant (POLT) due in part to wild type ATTR amyloid deposition. The management strategy is not defined. We propose that TTR gene silencing with an antisense oligonucleotide or a small interfering ribonucleic acid may be a treatment for these patients., Methods: We reviewed the charts of hATTR patients POLT treated with a TTR gene silencing agent at 7 different Amyloid Clinics between 2018-2020., Results: Nine hATTR patients with POLT were treated with TTR gene silencing therapy (Inotersen). The median age was 61 years. The median time from OLT to initiation of TTR gene silencing therapy was 7.5 years. The median duration of therapy was 12 months. Neuropathy impairment score remained stable or improved in all patients. Five patients stopped treatment: 3 because of thrombocytopenia, 2 because of reversible liver rejection. Three patients who discontinued treatment subsequently experienced worsening of their neuropathy., Conclusion: TTR gene silencing therapy in hATTR patients with POLT could be a treatment option. Vigilant monitoring of renal, liver and bone marrow functions is necessary because of frequent complications. Further studies are needed to determine efficacy.

Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern-Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0-14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (n = 6,014) were retrieved from 16 population-based SEE registries (1983-2015). Poisson regression and meta-analyses on birth season were performed in nine countries with available live birth data (n = 4,987). Subanalyses by birth month, age, gender and principal histology were also conducted. Children born during winter were at a slightly increased risk of developing a CNS tumor overall [incidence rate ratio (IRR): 1.06, 95% confidence intervals (CI): 0.99-1.14], and of embryonal histology specifically (IRR: 1.13, 95% CI: 1.01-1.27). The winter peak of embryonal tumors was higher among boys (IRR: 1.24, 95% CI: 1.05-1.46), especially during the first 4 years of life (IRR: 1.33, 95% CI: 1.03-1.71). In contrast, boys <5 years born during summer seemed to be at a lower risk of embryonal tumors (IRR: 0.73, 95% CI: 0.54-0.99). A clustering of astrocytomas was also found among girls (0-14 years) born during spring (IRR: 1.23, 95% CI: 1.03-1.46). Although the present exploratory results are by no means definitive, they provide some indications for age-, gender- and histology-related seasonal variations of CNS tumors. Expansion of registration and linkage with cytogenetic reports could refine if birth seasonality is causally associated with CNS tumors and shed light into the complex pathophysiology of this lethal disease., (© 2020 UICC.)