Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries.

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.

Omphalocele: clinical and epidemiological profile of patients born in a tertiary care center in Rio de Janeiro.

BACKGROUND: The objective of this paper is to describe the clinical and epidemiological profile and the early outcomes of patients with omphalocele born in a fetal medicine, pediatric surgery, and genetics reference hospital in Rio de Janeiro - Brazil. To determine its prevalence, describe the presence of genetic syndromes, and congenital malformations, emphasizing the characteristics of congenital heart diseases and their most common types. METHODS: Using Latin-American Collaborative Study of Congenital Malformations (ECLAMC) database and records review, a retrospective cross-sectional study was performed, including all patients born with omphalocele between January 1st, 2016, and December 31st, 2019. RESULTS: During the period of the study, our unity registered 4,260 births, 4,064 were live births and 196 stillbirths. There were 737 diagnoses of any congenital malformation, among them 38 cases of omphalocele, 27 were live born, but one was excluded for missing data. 62.2% were male, 62.2% of the women were multiparous and 51.3% of the babies were preterm. There was an associated malformation in 89.1% of the cases. Heart disease was the most common (45.9%) of which tetralogy of Fallot was the most frequent (23.5%). Mortality rate was 61.5%. CONCLUSIONS: Our data showed a good correspondence with the existing literature. Most patients with omphalocele had other malformations, especially congenital heart disease. No pregnancy was interrupted. The presence of concurrent defects showed a huge impact on prognosis, since, even if most survived birth, few remained alive and received hospital discharge. Based on these data, fetal medicine and neonatal teams must be able to adjust parents counseling about fetal and neonatal risks, especially when other congenital diseases are present.

Cognitive impairment and markers of optical neurodegeneration in early multiple sclerosis.

INTRODUCTION: Cognitive impairment and retinal atrophy have been proposed as two potential markers of neurodegeneration in multiple sclerosis (MS). We aimed at assessing the relation between peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) atrophy and cognitive performance in early MS. METHODS: This is a multicenter cross-sectional study on patients with early MS (clinically isolated syndrome and relapsing-remitting MS), with an EDSS score ≤ 3.0. Patients with previous optic neuritis, other ocular diseases, psychiatric illness, or recent relapse were excluded. All patients underwent standardized optical coherence tomography (OCT) and neuropsychological evaluation with validated tests for MS patients. Cognitive impairment was defined as having two cognitive tasks below age- and education-adjusted norms. RESULTS: We recruited 52 patients with early MS, with an average age of 37 years (SD = 10.5), an average disease duration of 3.69 years (SD = 2.3), and a median EDSS of 1.0 (IQR = 0.5). In this sample, 15/52 patients presented cognitive impairment. Regarding OCT measurements, 7/52 patients had an average pRNFL below the 5th percentile and 2/52 had an average mGCL below the 5th percentile. The average pRNFL thickness was comparable in cognitively impaired and cognitively preserved patients (100.3 µm vs 103.1 µm, p = 0.52); the average mGCL thickness had also similar values between groups (50.5 µm vs 53 µm, p = 0.38). CONCLUSIONS: Cognitive impairment was frequent in our sample of early MS. However, no association with reduced pRNFL or mGCL thickness was found. When compared to OCT, cognitive assessment could provide an earlier marker of neurodegeneration in MS.

Endovascular treatment of bilateral isolated aneurysm of the internal iliac artery.

Isolated aneurysms of the iliac arteries comprise less than 2% of abdominal aneurysms. The internal iliac artery is involved in 10-30% of cases. In most cases patients are asymptomatic, unless rupture occurs. They can be diagnosed by Doppler ultrasonography, magnetic resonance imaging or, preferably, angiotomography. Significant expansion, diameter of 3 cm or greater, and symptomatic cases are indications for surgery. We present the case of a patient with an incidental ultrasonographic finding of bilateral aneurysm of the internal iliac arteries, both with indications for surgery. The patient was successfully treated with endovascular techniques, first repairing the right internal iliac with a branched iliac stent graft, preserving patency, then embolizing the left internal iliac artery. Knowledge of the various different techniques and devices and their limitations is fundamental to adequate planning of endovascular treatment, even in rare cases.

Amorphous multimetal based catalyst for oxygen evolution reaction.

The development of efficient, low-cost water splitting electrocatalysts is needed to store energy by generating sustainable hydrogen from low power clean but intermittent energy sources such as solar and wind. Here, we report a highly sustained low overpotential for oxygen evolution reached by the unique combination of three metals (NiCoV) prepared from a simple low temperature auto-combustion process. The amorphous multimetal oxygen evolving catalyst could be stably coated on a stainless-steel support using a tribochemical particle blasting method to create an oxygen evolution reaction (OER) electrode with a low overpotential of 230 mV at 10 mA cm-2 and a low Tafel slope of 40 mV dec-1. In addition to their low overpotential, this oxygen evolving electrocatalyst preserved performance demonstrating a stability after 10 h at the technologically relevant current density and without any surface morphology alteration. Given the importance of sustainable hydrogen production, the development of this new OER catalyst points the way to removing a key technical bottleneck for the water splitting reaction and could offer a route to cost reduction and lowering hurdles to more widespread adaptation of electrolyser technologies for hydrogen production. Supplementary Information: The online version contains supplementary material available at 10.1007/s43939-024-00087-5.

Neuropsychological Assessment in the Distinction Between Biomarker Defined Frontal-Variant of Alzheimer's Disease and Behavioral-Variant of Frontotemporal Dementia.

BACKGROUND: Frontal-variant of Alzheimer's disease (fvAD) was purposed for patients with AD pathology that, despite the typical amnestic presentation, show early and progressive deterioration of behavior and executive functions, closely resembling the behavioral-variant of frontotemporal dementia (bvFTD). This leads to a challenging differential diagnosis where neuropsychological evaluation and in vivo pathological evidence are essential. OBJECTIVE: To evaluate the contribution of a comprehensive neuropsychological assessment (NP) battery in distinguishing between fvAD-dementia and bvFTD supported by cerebrospinal fluid (CSF) biomarkers. METHODS: We included 40 patients with a baseline NP profile with prominent early executive and/or behavioral dysfunction, who meet both diagnosis of bvFTD and fvAD-dementia, according to international criteria. All patients underwent comprehensive NP assessment and CSF-AD biomarker evaluation. Neuropsychological domains as well as clinical and sociodemographic features, and APOE genotype were compared between groups. RESULTS: 21 patients (52.5%) met the biological criteria for AD (decreased Aß42 together with increased T-tau or P-tau in CSF) and were therefore classified as fvAD (mean age was 64.57, with 47.6% female). There were no differences between groups regarding age/age-at-onset, gender, or educational level. Regarding neuropsychological profile, performances in language and memory functions were equivalent in both groups. Significant differences were found in visuo-constructional abilities (p = 0.004), Trail Making Test A (p < 0.001), and Raven's Colored Progressive Matrices (p = 0.019), with fvAD patients showing worst performances. CONCLUSION: In patients with an early prominent frontal profile, a higher impairment in attention and visuo-spatial functions, signaling additional right hemisphere fronto-parietal dysfunction, point towards a diagnosis of fvAD-dementia and may be useful in clinical practice.

Zincon-Modified CNTs Electrochemical Tool for Salivary and Urinary Zinc Detection.

Recently, the abnormal level of zinc emerged as a powerful indicator or risk factor for metabolic, endocrine, neurodegenerative and cardiovascular diseases, including cancer. Electrochemical detection has been explored to quantify zinc in a precise, rapid, and non-expensive way; however, most of the current electrochemical systems lack in specificity. In this work we studied a highly selective and sensitive electrochemical method to detect quickly and reliably free zinc ions (Zn2+). The surface of the working electrode was modified with zincon electropolymerized on carbon nanotube (CNT) to enable the binding of zinc in complex body fluids. After being physicochemically characterized, the performances of the zincon-CNT complex was electrochemically assessed. Square Wave Voltammetry (SWV) was used to determine the calibration curve and the linear range of zinc quantification in artificial saliva and urine. This zincon- CNT system could specifically quantify mobile Zn2+ in salivary and urinary matrices with a sensitivity of ~100 ng·mL-1 and a limit of detection (LOD) of ~20 ng·mL-1. Zincon-modified CNT presented as a desirable candidate for the detection and quantification of free zinc in easily body fluids that potentially can become a diagnostic non-invasive testing platform.

Engineering surgical stitches to prevent bacterial infection.

Surgical site infections (SSIs) account for a massive economic, physiological, and psychological burden on patients and health care providers. Sutures provide a surface to which bacteria can adhere, proliferate, and promote SSIs. Current methods for fighting SSIs involve the use of sutures coated with common antibiotics (triclosan). Unfortunately, these antibiotics have been rendered ineffective due to the increasing rate of antibiotic resistance. A promising new avenue involves the use of metallic nanoparticles (MNPs). MNPs exhibit low cytotoxicity and a strong propensity for killing bacteria while evading the typical antibiotic resistance mechanisms. In this work, we developed a novel MNPs dip-coating method for PDS-II sutures and explored the capabilities of a variety of MNPs in killing bacteria while retaining the cytocompatibility. Our findings indicated that our technique provided a homogeneous coating for PDS-II sutures, maintaining the strength, structural integrity, and degradability. The MNP coatings possess strong in vitro antibacterial properties against P aeruginosa and S. aureus-varying the %of dead bacteria from ~ 40% (for MgO NPs) to ~ 90% (for Fe2O3) compared to ~ 15% for uncoated PDS-II suture, after 7 days. All sutures demonstrated minimal cytotoxicity (cell viability > 70%) reinforcing the movement towards the use MNPs as a viable antibacterial technology.

Pediatric cerebral sinus venous thrombosis: clinical characterization of a Portuguese cohort.

INTRODUCTION: Pediatric cerebral sinus venous thrombosis (CSVT) is a rare entity. Risk factors differ from the adults, and treatment is not consensual. With this work, we aimed to characterize a pediatric cohort from two Portuguese tertiary centers. METHODS: All patients under 18 years old with confirmed CSVT admitted between 2006 and 2019 were retrospectively included. Demographics, clinical presentation, workup, and follow-up were evaluated. RESULTS: Fifty-three patients were included, 29 were male (54.7%). Median age was 5 years (IQR 11.08, range 0-17 years old). Headache, seizures and impairment of consciousness were the most frequent manifestations. A risk factor was identified in 90.6% (n = 48), mostly infections (43.8%; n = 21). CNS complications were comprised of hemorrhage, venous infarction, hydrocephalus and edema. Treatment included anticoagulation in 36 patients (67.9%), and there were no recurrences on follow-up. Prognosis was favorable, with most patients presenting no or only slight disability comparing to same age and sex children, on the follow-up. DISCUSSION: In this cohort, impairment of consciousness was the most frequent clinical presentation and infections were the most frequent risk factors. The outcome was mainly favorable, with most patients presenting none or mild disability and without recurrences on follow-up. Studies are needed to define the criteria for anticoagulation and its recommended duration in children.

Alzheimer's Disease Diagnosis Based on the Amyloid, Tau, and Neurodegeneration Scheme (ATN) in a Real-Life Multicenter Cohort of General Neurological Centers.

BACKGROUND: The ATN scheme was proposed as an unbiased biological characterization of the Alzheimer's disease (AD) spectrum, grouping biomarkers into three categories: brain Amyloidosis-A, Tauopathy-T, Neurodegeneration-N. Although this scheme was mainly recommended for research, it is relevant for diagnosis. OBJECTIVE: To evaluate the ATN scheme performance in real-life cohorts reflecting the inflow of patients with cognitive complaints and different underlying disorders in general neurological centers. METHODS: We included patients (n = 1,128) from six centers with their core cerebrospinal fluid-AD biomarkers analyzed centrally. A was assessed through Aß42/Aß40, T through pTau-181, and N through tTau. Association between demographic features, clinical diagnosis at baseline/follow-up and ATN profiles was assessed. RESULTS: The prevalence of ATN categories was: A-T-N-: 28.3%; AD continuum (A + T-/+N-/+): 47.8%; non-AD (A- plus T or/and N+): 23.9%. ATN profiles prevalence was strongly influenced by age, showing differences according to gender, APOE genotype, and cognitive status. At baseline, 74.6% of patients classified as AD fell in the AD continuum, decreasing to 47.4% in mild cognitive impairment and 42.3% in other neurodegenerative conditions. At follow-up, 41% of patients changed diagnosis, and 92% of patients that changed to AD were classified within the AD continuum. A + was the best individual marker for predicting a final AD diagnosis, and the combinations A + T+ (irrespective of N) and A + T+N+ had the highest overall accuracy (83%). CONCLUSION: The ATN scheme is useful to guide AD diagnosis in real-life neurological centers settings. However, it shows a lack of accuracy for patients with other types of dementia. In such cases, the inclusion of other markers specific for non-AD proteinopathies could be an important aid to the differential diagnosis.

Quality of life experienced by adolescents and young adults with congenital heart disease.

This study aimed to assess the quality of life (QOL) experienced by adolescents and young adults with congenital heart disease (CHD) and to determine which factors negatively affect adjustment and which factors increase resilience. The participants in the study were 74 patients with CHD (41 males and 33 females) ranging in age from 12 to 26 years (mean age, 18.76 ± 3.86 years). Demographic information and a complete clinical history were obtained. The participants were interviewed regarding topics such as social support, family educational style, self-image, and physical limitations. They responded to questions in a standardized psychiatric interview (SADS-L) and completed a self-report questionnaire (WHOQOL-BREF) for assessment of QOL. Compared with the Portuguese population as a whole, the study patients had better QOL, especially with regard to the environmental dimension (t = 3.754; P = 0.000) and social relationships (t = 2.333; P = 0.022). Patients who had undergone surgery experienced poorer QOL in the physical dimension (t = -1.989; P = 0.050), in social relationships (t = -2.012; P = 0.048) and overall (Mann-Whitney U = 563.000; P = 0.037). Social support played a positive role in the QOL of the patients, both in the physical dimension (t = 3.287; P = 0.002) and in social relationships (t = 3.669; P = 0.000). A higher school achievement also was associated with higher levels of QOL overall (Mann-Whitney U = 457.000; P = 0.046) as well as in the physical (t = 2.045; P = 0.045) and environmental (t = 2.413; P = 0.018) dimensions. Physical limitations had a detrimental impact on general QOL (Mann-Whitney U = 947.500; P = 0.001) and on the physical (t = -2.910; p = 0.005) and psychological (t = -2,046; P = 0.044) dimensions. Patients with CHD tended to perceive QOL as better when their social networks were supportive.

Quality of life of patients with congenital heart diseases.

OBJECTIVES: To assess the perception of the quality of life of adolescents and young adults with congenital heart disease and to examine the variables that have a negative impact on it and that add a resilience effect. METHODS: A total of 22 male and 18 female patients, aged 12-26 years, of whom 27 were admitted to surgery and 13 were not, participated in this study. All patients had complete medical records and were interviewed once; demographic and clinical data were collected, and patients filled a questionnaire on quality of life, the WHOQOL-BREF, and underwent an interview on social support, educational style, self-image, functional limitations, and emotional adjustment. RESULTS/CONCLUSIONS: Our patients showed a better perception of quality of life than did the general population, on the basis of psychological, social relationship and environment scales. Older patients hold a better perception of quality of life on the psychological scale. Cyanosis did not show any significant impact over perception of quality of life decay; however, the number of surgical procedures and the persistence of moderate-to-severe residual injuries had considerable detrimental effect. Social support had an impact on increasing resilience, promoting adjustment to illness. Several factors may play a role in adjustment to congenital heart disease, either improving the perception of quality of life or worsening it. We may conclude that some buffer variables on congenital heart disease may play roles in increasing the perception of quality of life of patients during their lifetime, social support probably explaining why the perception of quality of life is better than in the normal population. The number of surgeries and the moderate-to-severe residual injuries, however, reverted that effect.

Neuropsychological features of progranulin-associated frontotemporal dementia: a nested case-control study.

The distinction between sporadic and genetic behavioural-variant frontotemporal dementia (bvFTD) regarding some neuropsychological (NP) features remains challenging. Specifically, progranulin (GRN)-associated bvFTD frequently presents with early episodic memory impairment and some degree of parietal dysfunction which are supporters of Alzheimer's disease (AD) diagnosis. In this context, we aimed to characterize the NP profile of GRN-bvFTD as compared to sporadic-bvFTD and AD in patients with mild dementia (Mini-Mental State Examination score ≥ 17 and Clinical Dementia Rating Scale score ≤ 1. We identified 21 patients at Centro Hospitalar e Universitário de Coimbra, Portugal with GRN mutations belonging to fifteen different families. As our focus was bvFTD variants, FTD-related aphasic forms (3 patients) were excluded. The remaining 18 GRN-bvFTD were further matched with 18 sporadic-bvFTD and 18 AD patients according to disease staging, age and education. All patients completed the Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA) and a comprehensive NP assessment battery. Results were converted into z-scores. Differences between groups in individual NP measures and NP domains were assessed through non-parametric tests (Kruskal-Wallis test analysis) and eta squared (ŋ2) was calculated as a measure of effect size. Group comparisons show that GRN patients have worse performances on verbal retrieval processes (P = 0.039, ŋ2 = 0.110) and visuoconstructive abilities (P = 0.039, ŋ2 = 0.190) than sporadic bvFTD forms. When compared to AD, GRN patients present a higher impairment in frontal (P = 0.001, ŋ2 = 0.211) and parietal (P = 0.041, ŋ2 = 0.129) measures and a better performance in memory tasks (P = 0.020, ŋ2 = 0.120). Sporadic-bvFTD forms are worse than AD in frontal measures (P = 0.032, ŋ2 = 0.200), being better in both memory (P = 0.010, ŋ2 = 0.131) and visuospatial skills (P = 0.023, ŋ2 = 0.231). Considering these results, we conclude that GRN-bvFTD patients present a NP profile that associates the typical patterns of FTD and AD deficits. This is particularly expressive in visuoconstructive abilities, which was the more discriminative feature between groups, followed by episodic verbal memory. This study was approved by the Institutional Ethics Committee of Centro Hospitalar e Universitário de Coimbra, Portugal (CE-029/2019) on June 24, 2019.

Microelectrochemical Smart Needle for Real Time Minimally Invasive Oximetry.

A variety of brain disorders such as neural injury, brain dysfunction, vascular malformation, and neurodegenerative diseases are associated with abnormal levels of oxygen. Current methods to directly monitor tissue oxygenation in the brain are expensive and invasive, suffering from a lack of accuracy. Electrochemical detection has been used as an invasiveness and cost-effectiveness method, minimizing pain, discomfort, and injury to the patient. In this work, we developed a minimally invasive needle-sensor with a high surface area to monitor O2 levels in the brain using acupuncture needles. The approach was to directly etch the iron from stainless steel acupuncture needles via a controlled pitting corrosion process, obtaining a high microporous surface area. In order to increase the conductivity and selectivity, we designed and applied for the first time a low-cost coating process using non-toxic chemicals to deposit high surface area carbon nanoparticle, catalytically active laccase, and biocompatible polypyrrole. The physicochemical properties of the materials were characterized as well as their efficacy and viability as probes for the electrochemical detection of PO2. Our modified needles exhibited efficient electrocatalysis and high selectivity toward O2, with excellent repeatability. We well engineered a small diagnostic tool to monitor PO2, minimally invasive, able to monitor real-time O2 in vivo complex environments.

Electroceutical Silk-Silver Gel to Eradicate Bacterial Infection.

With more than 50% of bacteria resistant to standard antibiotics, new strategies to treat bacterial infection and colonization are needed. Based on the concept of targeting the bacteria synergistically on various fronts, it is hypothesized that an electrical insult associated with antibacterial materials may be a highly effective means of killing bacteria. In this work, an injectable conductive gel based on silk fibroin (SF) and silver nanoparticles (Ag-NPs) is synthesized, capable of coating a zone of injury, allowing the application of a low electrical current to decrease bacterial contamination. With a high conductivity of 1.5 S cm-1 , SF/Ag-NPs gels killed 80% of Escherichia coli in 1 min, no toxicity toward Chinese hamster ovary cells is observed. The mechanism of an electrical composite gel combined with electrical wound therapy is associated with silver ion (Ag+ ) release, and reactive oxygen species (ROS) production. The findings in the present study show a similar Ag+ release for treatment with gels and the combined effect, whereas ROS generation is 50% higher when a small electrical current is applied leading to a broad bactericidal effect.

Adult-onset methylenetetrahydrofolate reductase deficiency.

Severe hyperhomocysteinemia (>100 µmol/L) is often associated with inborn errors of homocysteine metabolism. It manifests typically in neonatal period with developmental delay, hypotonia, feeding problems or failure to thrive. Adult-onset forms are rare and include less severe manifestations. Early diagnosis is crucial because effective treatment is available. A 23-year-old man presented with a 3-week history of speech and gait impairment, and numbness in lower limbs. Neurological examination revealed dysarthria, decreased vibratory sensation in both legs and appendicular and gait ataxia. Brain MRI revealed T2-hyperintense symmetric white matter lesions and cortical atrophy. He had folate and vitamin B12 deficiency, a markedly elevated serum homocysteine and low methionine. Despite vitamin supplementation homocysteine levels remained elevated. Molecular studies of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene revealed a new pathogenic mutation (c.1003C>T (p.Arg335Cys)) and a polymorphism (C677T (p.Ala222Val)) associated with hyperhomocysteinemia, both in homozygosity. The patient started betaine with clinical and biochemical improvement.

APOEɛ4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer's Disease.

BACKGROUND: Mild cognitive impairment (MCI) has been considered as a pre-dementia stage, although the factors leading to Alzheimer's disease (AD) conversion remain controversial. OBJECTIVE: Evaluate whether TOMM40 poly-T (TOMM40' 523) polymorphism is associated with the risk and conversion time from MCI to AD and secondly with AD cerebrospinal fluid (CSF) biomarkers, disentangling the APOE genotype. METHODS: 147 AD patients, 102 MCI patients, and 105 cognitively normal controls were genotyped for poly-T polymorphism. MCI patients were subdivided into two groups, the group of patients that converted to AD (MCI-AD) and the group of those that remained stable (MCI-S). RESULTS: TOMM40' 523 L allele was significantly more frequent in the MCI-AD group and having at least one L allele significantly increased the risk of conversion from MCI to AD (OR = 8.346, p < 0.001, 95% CI: 2.830 to 24.617). However, when adjusted for the presence of APOEɛ4 allele, both the L allele and ɛ4 allele lost significance in the model (p > 0.05). We then analyzed the APOEɛ4-TOMM40' 523 L haplotype and observed that patients carrying this haplotype had significantly higher risk (OR = 5.83; 95% CI = 2.30-14.83) and mean lower times of conversion to AD (p = 0.003). This haplotype was also significantly associated with a biomarker profile compatible with AD (p = 0.007). CONCLUSION: This study shows that the APOEɛ4-TOMM40' 523 L haplotype is associated with a higher risk and shorter times of conversion from MCI to AD, possibly driven by CSF biomarkers and mitochondrial dysfunction.

Lower CSF Amyloid-Beta1-42 Predicts a Higher Mortality Rate in Frontotemporal Dementia.

Frontotemporal lobar degeneration, the neuropathological substrate of frontotemporal dementia (FTD), is characterized by the deposition of protein aggregates, including tau. Evidence has shown concomitant amyloid pathology in some of these patients, which seems to contribute to a more aggressive disease. Our aim was to evaluate cerebrospinal fluid (CSF) amyloid-beta as a predictor of the mortality of FTD patients. We included 99 patients diagnosed with FTD-both behavioral and language variants-with no associated motor neuron disease, from whom a CSF sample was collected. These patients were followed prospectively in our center, and demographic and clinical data were obtained. The survival analysis was carried through a Cox regression model. Patients who died during follow up had a significantly lower CSF amyloid-beta1-42 than those who did not. The survival analysis demonstrated that an increased death rate was associated with a lower CSF amyloid-beta1-42 (HR = 0.999, 95% CI = [0.997, 1.000], p = 0.049). Neither demographic nor clinical variables, nor CSF total tau or p-tau were significantly associated with this endpoint. These results suggest that amyloid deposition in FTD patients may be associated with a higher mortality.

Erlangen Score as a tool to predict progression from mild cognitive impairment to dementia in Alzheimer's disease.

BACKGROUND: The previously described and validated Erlangen Score (ES) algorithm enables interpretation of the cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), ordering them on an ordinal scale: from neurochemically normal (ES = 0) through improbable AD (ES = 1), possible AD (ES = 2 or 3), to probable AD (ES = 4). Here we assess the accuracy of the ES in predicting hazards of progression from the mild cognitive impairment (MCI) stage of AD to the dementia stage of the disease (Alzheimer's disease dementia (ADD)) in a novel, single-center cohort. METHODS: Baseline CSF biomarkers (amyloid beta (Aß) 1-42, Aß42/40, Tau, and pTau181), interpreted according to the ES, were used to estimate time to progression from the MCI stage of AD to ADD, conditional on age, gender, APOE ε4 genotype, and Mini Mental State Examination score in 144 MCI subjects, using the Extended Cox Model; the subjects were followed-up until they developed dementia or until they had been cognitively stable for at least 2 years. In addition, ES distributions were studied in 168 ADD cases and 66 neurologic controls. Further, we stratified MCI patients into those who progressed to ADD faster (within 3 years, n = 47) and those who progressed slower (n = 74). RESULTS: The distributions of the ES categories across the four diagnostic groups (Controls, MCI-Stable, MCI-AD, and ADD) were highly significantly different (Kruskal-Wallis χ2(df = 3) = 151.4, p < 0.001), with significant contrasts between each pair (p < 0.005), except between the ADD and the MCI-AD groups (p = 1.0). MCI patients with ES = 2 or 3 had 6-8 times higher hazards to progress to ADD compared to patients with ES = 0 or 1 in the first 3 follow-up years, and then their hazards decreased to those of the group with ES = 0 or 1. Patients with ES = 4 had hazards 8-12 times higher compared to the ES = 0 or 1 group. Faster progressors with ES = 2 or 3 had, in comparison to slower progressors, significantly lower Aß1-42, Aß1-40, and Aß42/40, but comparable Tau and pTau181. A highly significant difference of the ES distributions between these two groups was observed (p < 0.001). CONCLUSIONS: Our current results reconfirm and extend the conclusions of the previously published report that the Erlangen Score is a useful tool facilitating interpretation of a complex pattern of the CSF AD biomarkers.

Metabolic Syndrome Features: Is There a Modulation Role by Mineral Water Consumption? A Review.

Metabolic syndrome (MetSyn) promotes, among others, the development of atherosclerotic cardiovascular disease and diabetes. Its prevalence increases with age, highlighting the relevance of promoting precocious MetSyn primary prevention and treatment with easy-to-implement lifestyle interventions. MetSyn features modulation through mineral water consumption was reviewed on Pubmed, Scopus and Google Scholar databases, using the following keywords: metabolic syndrome, hypertension, blood pressure (BP), cholesterol, triglycerides, apolipoprotein, chylomicron, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein (HDL), glucose, insulin, body weight, body mass index, waist circumference (WC), obesity and mineral(-rich) water. Twenty studies were selected: 12 evaluated BP, 13 assessed total-triglycerides and/or HDL-cholesterol, 10 analysed glucose and/or 3 measured WC. Mineral waters were tested in diverse protocols regarding type and composition of water, amount consumed, diet and type and duration of the study. Human and animal studies were performed in populations with different sizes and characteristics. Distinct sets of five studies showed beneficial effects upon BP, total-triglycerides, HDL-cholesterol and glucose. WC modulation was not reported. Minerals/elements and active ions/molecules present in mineral waters (and their pH) are crucial to counterbalance their inadequate intake and body status as well as metabolic dysfunction and increased diet-induced acid-load observed in MetSyn. Study characteristics and molecular/physiologic mechanisms that could explain the different effects observed are discussed. Further studies are warranted for determining the mechanisms involved in the putative protective action of mineral water consumption against MetSyn features.