Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10.

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.

Pseudohypoxia in paraganglioma and pheochromocytoma is associated with an immunosuppressive phenotype.

Metastatic pheochromocytoma and paraganglioma (PPGL) have poor prognosis and limited therapeutic options. The recent advent of immunotherapies showing remarkable clinical efficacies against various cancer types offers the possibility of novel opportunities also for metastatic PPGL. Most PPGLs are pathogenically linked to inactivating mutations in genes encoding different succinate dehydrogenase (SDH) subunits. This causes activation of the hypoxia-inducible factor 2 (HIF2)-mediated transcriptional program in the absence of decreased intratumoral oxygen levels, a phenomenon known as pseudohypoxia. Genuine hypoxia in a tumor creates an immunosuppressive tumor microenvironment. However, the impact of pseudohypoxia in the immune landscape of tumors remains largely unexplored. In this study, tumoral expression of programmed death-ligand 1 (PD-L1) and HIF2α and tumor infiltration of CD8 T lymphocytes (CTLs) were examined in PPGL specimens from 102 patients. We assessed associations between PD-L1, CTL infiltration, HIF2α expression, and the mutational status of SDH genes. Our results show that high PD-L1 expression levels in tumor cells and CTL tumor infiltration were more frequent in metastatic than nonmetastatic PPGL. However, this phenotype was negatively associated with SDH mutations and high HIF2α protein expression. These data were validated by analysis of mRNA levels of genes expressing PD-L1, CD8, and HIF2α in PPGL included in The Cancer Genome Atlas database. Further, PD-L1 and CD8 expression was lower in norepinephrine than epinephrine-secreting PPGL. This in silico analysis also revealed the low PD-L1 or CD8 expression levels in tumors with inactivating mutations in VHL or activating mutations in the HIF2α-coding gene, EPAS1, which, together with SDH-mutated tumors, comprise the pseudohypoxic molecular subtype of PPGL. These findings suggest that pseudohypoxic tumor cells induce extrinsic signaling toward the immune cells promoting the development of an immunosuppressive environment. It also provides compelling support to explore the differential response of metastatic PPGL to immune checkpoint inhibitors. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Investigation of the Performance of Various Low-Cost Radon Monitors under Variable Environmental Conditions.

A comparison of low-cost radon monitors was conducted at the Laboratory of Natural Radiation (LNR). The monitors we evaluated were EcoQube, RadonEye, RadonEye Plus2, Spirit, ViewPlus, ViewRadon and WavePlus. An AlphaGUARD monitor calibrated at the Laboratory of Environmental Radioactivity of the University of Cantabria (LaRUC), accredited for testing and calibration according to ISO/IEC 17025, provided the reference value of radon concentration. The temporal stability of the monitors was studied, obtaining a percentage of missing records ranged from 1% to 19% of the data. The main technical characteristics studied were temporal stability, measurement ranges, accuracy, correlation and response time. The main results show that the measurement ranges align with those specified by their manufacturers, with percentage differences with respect to the reference monitor of between 5% and 16%. The diversity found for response time is remarkable, with values ranging from 1 to 15 h, with Pearson correlation factors between 0.63 and 0.90.

Validation of an ex vivo Flow Model Including Magnetic Resonance Imaging to Study the Effects of Endovascular Treatments on the Arterial Wall.

Endovascular revascularization is the preferred treatment for peripheral arterial disease. Restenosis often occurs as a response to procedure-induced arterial damage. Reducing vascular injury during endovascular revascularization may improve its success rate. This study developed and validated an ex vivo flow model using porcine iliac arteries, obtained from a local abattoir. Twenty arteries (of 10 pigs) were equally allocated to two groups: a mock-treated control group and an endovascular intervention group. Arteries of both groups were perfused with porcine blood for 9 min, including 3 min of balloon angioplasty in the intervention group. Vessel injury was assessed by calculating the presence of endothelial cell denudation, vasomotor function, and histopathological analysis. MR imaging displayed balloon positioning and inflation. Endothelial cell staining showed 76% of denudation after ballooning compared to 6% in the control group (p < 0.001). This was confirmed by histopathological analysis, showing a significantly reduced endothelial nuclei count after ballooning compared to the controls (median: 22 vs. 37 nuclei/mm, p = 0.022). In the intervention group, vasoconstriction and endothelium-dependent relaxation were significantly reduced (p < 0.05).We present an ex vivo flow model to test the effects of endovascular therapy on the vessel's wall morphology, endothelial denudation, and endothelial-dependent vasomotor function under physiological conditions. Additionally, it allows the future testing of human arterial tissue.

Highly Adaptive Nature of Group 15 Tris(quinolyl) Ligands─Studies with Coinage Metals.

The substitution of heavier, more metallic atoms into classical organic ligand frameworks provides an important strategy for tuning ligand properties, such as ligand bite and donor character, and is the basis for the emerging area of main-group supramolecular chemistry. In this paper, we explore two new ligands [E(2-Me-8-qy)3] [E = Sb (1), Bi (2); qy = quinolyl], allowing a fundamental comparison of their coordination behavior with classical tris(2-pyridyl) ligands of the type [E'(2-py)3] (E = a range of bridgehead atoms and groups, py = pyridyl). A range of new coordination modes to Cu+, Ag+, and Au+ is seen for 1 and 2, in the absence of steric constraints at the bridgehead and with their more remote N-donor atoms. A particular feature is the adaptive nature of these new ligands, with the ability to adjust coordination mode in response to the hard-soft character of coordinated metal ions, influenced also by the character of the bridgehead atom (Sb or Bi). These features can be seen in a comparison between [Cu2{Sb(2-Me-8-qy)3}2](PF6)2 (1·CuPF6) and [Cu{Bi(2-Me-8-qy)3}](PF6) (2·CuPF6), the first containing a dimeric cation in which 1 adopts an unprecedented intramolecular N,N,Sb-coordination mode while in the second, 2 adopts an unusual N,N,(π-)C coordination mode. In contrast, the previously reported analogous ligands [E(6-Me-2-py)3] (E = Sb, Bi; 2-py = 2-pyridyl) show a tris-chelating mode in their complexes with CuPF6, which is typical for the extensive tris(2-pyridyl) family with a range of metals. The greater polarity of the Bi-C bond in 2 results in ligand transfer reactions with Au(I). Although this reactivity is not in itself unusual, the characterization of several products by single-crystal X-ray diffraction provides snapshots of the ligand transfer reaction involved, with one of the products (the bimetallic complex [(BiCl){ClAu2(2-Me-8-qy)3}] (8)) containing a Au2Bi core in which the shortest Au → Bi donor-acceptor bond to date is observed.

Noncovalent Dualism in Perylene-Diimide-Based Keggin Anion Complexes: Theoretical and Experimental studies.

We report the synthesis and comprehensive characterization of organic-inorganic hybrid salts formed by bis-cationic N,N'-bis(2-(trimethylammonium)ethylene)perylene-3,4,9,10-tetracarboxylic acid bisimide (PTCD2+) and Keggin-type [XW12O40]n- (X = Si, n = 4; X = P, n = 3) polyoxometalates. (PTCD)3[PW12O40]2·3DMSO·2H2O (2) and (PTCD)2[SiW12O40]·DMSO·2H2O (3) were structurally characterized by single crystal X-ray diffraction. The cations in both structures exhibited infinite chainlike arrangements through π-π interactions, contrasting with the previously reported cation-anion stacking observed in naphthalene diimide derivatives. A detailed theoretical study employing topological analysis of the electron density distribution within the quantum theory of atoms in molecules approach provided further insights into this structural dualism. Atomic force microscopy analyses revealed the formation of self-assembled supramolecular structures on graphite from molecular monolayers (3 nm of thick) to submicrometer aggregates for 2. Hyperspectral Raman spectroscopy imaging revealed that such heterostructures are likely formed by an enhanced π-π interactions. Both complexes demonstrated interesting electrochemical behavior, photoluminescence and X-ray-induced luminescence. Electron spin resonance analysis confirmed charge separation in both compounds, with enhanced efficiency observed in compound 2. Our findings of these perylene-based organic-inorganic hybrid salts offer the potential for their application in optoelectronic devices and functional materials.

The effects of deep transcranial magnetic stimulation on Alzheimer's disease: a case report examining cognitive functioning, memory, and QEEG.

Numerous treatment options are being studied for Alzheimer's disease (AD) given the rising prevalence of this condition worldwide. Transcranial Magnetic Stimulation (TMS) is a promising option for regulating specific neurological abnormalities pertaining to this condition. This case presents a patient with AD and co-occurring major depressive disorder that received 36 sessions of Deep TMS to the frontal and temporal lobes. This patient experienced improved general cognitive functioning and memory, remission from depression, and reduced slow-frequency theta activity in frontal and temporal sites. Following 7 months of weekly maintenance, additional improvements occurred. This report suggests that Deep TMS may be effective in mitigating AD symptoms, and maintenance sessions are advisable.

Polymorphism and Visible-Light-Driven Photocatalysis of Doped Bi2O3:M (M = S, Se, and Re).

δ-Bi2O3:M (M = S, Se, and Re) with an oxygen-defective fluorite-type structure is obtained by a coprecipitation method starting from the bismuth oxido cluster [Bi38O45(OMc)24(dmso)9]·2dmso·7H2O (A) in the presence of additives such as Na2SO4, Na2SeO4, NH4ReO4, Na2SeO3·5H2O, and Na2SO3. The coprecipitation of the starting materials with aqueous NaOH results in the formation of alkaline reaction mixtures, and the cubic bismuth(III)-based oxides Bi14O20(SO4) (1c), Bi14O20(SeO4) (2c), Bi14O20(ReO4.5) (3c), Bi12.25O16.625(SeO3)1.75 (4c), and Bi10.51O14.765(SO3)0.49(SO4)0.51 (5c) are obtained after microwave-assisted heating; formation of compound 5c is the result of partial oxidation of sulfur. The compounds 1c, 2c, 4c, and 5c absorb UV light only, whereas compound 3c absorbs in the visible-light region of the solar spectrum. Thermal treatment of the as-prepared metastable bismuth(III) oxide chalcogenates 1c and 2c at T = 600 °C provides a monotropic phase transition into their tetragonal polymorphs Bi14O20(SO4) (1t) and Bi14O20(SeO4) (2t), while compound 3c is transformed into the tetragonal modification of Bi14O20(ReO4.5) (3t) after calcination at T = 700 °C. Compounds of the systems Bi2O3-SOx (x = 2 and 3) and Bi2O3-Re2O7 are thermally stable up to T = 800 °C, whereas compounds of the system Bi2O3-SeO3 completely lose SeO3. Thermal treatment of 4c and 5c in air results in the oxidation of the tetravalent to hexavalent sulfur and selenium, respectively, upon heating to T = 400-500 °C. The as-prepared cubic bismuth(III)-based oxides 1c-5c were studied with regard to the photocatalytic decomposition of rhodamine B under visible-light irradiation with compound 3c showing the highest turnover and efficiency.

Sedation Usage in COVID-19 Acute Respiratory Distress Syndrome: A Multicenter Study.

BACKGROUND: Patients with COVID-19 acute respiratory distress syndrome (ARDS) have been shown to have high sedation requirements. OBJECTIVE: The purpose of this study was to compare sedative use between patients with COVID-19 ARDS and non-COVID-19 ARDS. METHODS: This was a retrospective study of patients with COVID-19 ARDS compared with historical controls of non-COVID-19 ARDS who were admitted to 2 hospitals from March 1, 2020, to April 30, 2020, and April 1, 2018, to December 31, 2019, respectively. The primary outcome was median cumulative dose of propofol (µg/kg) at 24 hours after intubation. RESULTS: There were 92 patients with COVID-19 ARDS and 37 patients with non-COVID-19 ARDS included. Within the first 24 hours of intubation, patients with COVID-19 ARDS required higher total median doses of propofol: 51 045 µg/kg (interquartile range, 26 150-62 365 µg/kg) versus 33 350 µg/kg (9632-51 455 µg/kg; P = 0.004). COVID-19 patients were more likely receive intravenous lorazepam (37% vs 14%; P = 0.02) and higher cumulative median doses of midazolam by days 5 (14 vs 4 mg; P = 0.04) and 7 of intubation (89 vs 4 mg; P = 0.03) to achieve the same median Richmond Analgesia-Sedation Scale scores. COVID-19 ARDS patients required more ventilator days (10 vs 6 days; P = 0.02). There was no difference in 30-day mortality. CONCLUSION AND RELEVANCE: Patients with COVID-19 ARDS required higher doses of propofol and benzodiazepines than patients with non-COVID-19 ARDS to achieve the same median levels of sedation.

A Fluorescent Cage for Supramolecular Sensing of 3-Nitrotyrosine in Human Blood Serum.

3-Nitrotyrosine (NT) is generated by the action of peroxynitrite and other reactive nitrogen species (RNS), and as a consequence it is accumulated in inflammation-associated conditions. This is particularly relevant in kidney disease, where NT concentration in blood is considerably high. Therefore, NT is a crucial biomarker of renal damage, although it has been underestimated in clinical diagnosis due to the lack of an appropriate sensing method. Herein we report the first fluorescent supramolecular sensor for such a relevant compound: Fluorescence by rotational restriction of tetraphenylethenes (TPE) in a covalent cage is selectively quenched in human blood serum by 3-nitrotyrosine (NT) that binds to the cage with high affinity, allowing a limit of detection within the reported physiological concentrations of NT in chronic kidney disease.

Effect of timing delay between visual and vestibular stimuli on heading perception.

Heading direction is perceived based on visual and inertial cues. The current study examined the effect of their relative timing on the ability of offset visual headings to influence inertial perception. Seven healthy human subjects experienced 2 s of translation along a heading of 0°, ±35°, ±70°, ±105°, or ±140°. These inertial headings were paired with 2-s duration visual headings that were presented at relative offsets of 0°, ±30°, ±60°, ±90°, or ±120°. The visual stimuli were also presented at 17 temporal delays ranging from -500 ms (visual lead) to 2,000 ms (visual delay) relative to the inertial stimulus. After each stimulus, subjects reported the direction of the inertial stimulus using a dial. The bias of the inertial heading toward the visual heading was robust at ±250 ms when examined across subjects during this period: 8.0° ± 0.5° with a 30° offset, 12.2° ± 0.5° with a 60° offset, 11.7° ± 0.6° with a 90° offset, and 9.8° ± 0.7° with a 120° offset (mean bias toward visual ± SE). The mean bias was much diminished with temporal misalignments of ±500 ms, and there was no longer any visual influence on the inertial heading when the visual stimulus was delayed by 1,000 ms or more. Although the amount of bias varied between subjects, the effect of delay was similar.NEW & NOTEWORTHY The effect of timing on visual-inertial integration on heading perception has not been previously examined. This study finds that visual direction influence inertial heading perception when timing differences are within 250 ms. This suggests visual-inertial stimuli can be integrated over a wider range than reported for visual-auditory integration and may be due to the unique nature of inertial sensation, which can only sense acceleration while the visual system senses position but encodes velocity.

Uncovering the Hidden Landscape of Tris(4-pyridyl) Ligands: Topological Complexity Derived from the Bridgehead.

Supramolecular main group chemistry is a developing field which parallels the conventional domain of metallo-organic chemistry. Little explored building blocks in this area are main group metal-based ligands which have the appropriate donor symmetry to build desired molecular or extended arrangements. Tris(pyridyl) main group ligands (E(py)3 , E=main group metal) are potentially highly versatile building blocks since shifting the N-donor arms from the 2- to the 3-positions and 4-positions provides a very simple way of changing the ligand character from mononuclear/chelating to multidentate/metal-bridging. Here, the coordination behaviour of the first main group metal tris(4-pyridyl) ligands, E(4-py)3 (E=Sb, Bi, Ph-Sn) is explored, as well as their ability to build metal-organic frameworks (MOFs). The complicated topology of these MOFs shows a marked influence on the counter anion and on the ability of the E(4-py)3 ligands to switch coordination mode, depending on the steric and donor character of the bridgehead. This structure-directing influence of the bridgehead provides a potential building strategy for future molecular and MOF design in this area.

Body Mass Index Is Significantly Associated With Disease Severity in Spinocerebellar Ataxia Type 2 Patients.

BACKGROUND: Spinocerebellar ataxia type 2 is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Although weight loss has been associated with disease progression in several neurodegenerative conditions, it has been barely assessed in patients with spinocerebellar ataxia type 2. OBJECTIVE: The objective of this study was to test whether body mass index is altered in patients with spinocerebellar ataxia type 2 with varying expansion sizes from early to late disease stages. METHODS: A cross-sectional case-control study was performed, which included 222 clinically and molecularly diagnosed patients and 214 sex- and age-matched healthy individuals. ATXN2 genotypes and sex were considered as risk factors. Clinical outcomes included the body mass index, age at onset, disease duration, Scale for the Assessment and Rating of Ataxia score, disease stage, dysphagia, and progression rate. Multiple linear regression models were generated. RESULTS: Body mass index was significantly decreased in male patients, but not in female patients, relative to control subjects. In addition to sex, body mass index was significantly associated with age at onset and progression rate. Conversely, body mass index, along with repeat length in ATXN2 expanded alleles and disease duration, was associated with Scale for the Assessment and Rating of Ataxia score. In addition, body mass index, along with the age at onset and the repeat length in ATXN2 normal and expanded alleles, has a significant influence on progression rate. CONCLUSIONS: Body mass index might be a useful biomarker of disease severity, particularly in male patients with spinocerebellar ataxia type 2 in the context of nutritional interventions or clinical trials assessing the efficacy of promising new drugs. © 2021 International Parkinson and Movement Disorder Society.

Cation- and Anion-Mediated Supramolecular Assembly of Bismuth and Antimony Tris(3-pyridyl) Complexes.

The use of antimony and bismuth in supramolecular chemistry has been largely overlooked in comparison to the lighter elements of Group 15, and the coordination chemistry of the tripodal ligands [Sb(3-py)3] and [Bi(3-py)3] (L) containing the heaviest p-block element bridgehead atoms has been unexplored. We show that these ligands form a common hybrid metal-organic framework (MOF) structure with Cu(I) and Ag(I) (M) salts of weakly coordinating anions (PF6-, SbF6-, and OTf-), composed of a cationic substructure of rhombic cage (M)4(L)4 units linked by Sb/Bi-M bonding. The greater Lewis acidity of Bi compared to Sb can, however, allows anion···Bi interactions to overcome Bi-metal bonding in the case of BF4-, leading to collapse of the MOF structure (which is also seen where harder metals like Li+ are employed). This study therefore provides insight into the way in which the electronic effects of the bridgehead atom in these ligand systems can impact their supramolecular chemistry.

Sustainability of the Healthy Municipalities Strategy in Guatemala.

OBJECTIVE: Evaluate the sustainability of the Healthy Municipalities strategy in Guatemala in order to have solid evidence to support decision-making. METHODS: A concurrent mixed-methods study was carried out in five phases: 1) theoretical-conceptual (based on a narrative review of the literature on sustainability, dimensions and categories were proposed for evaluation); 2) empirical (four municipalities were selected for convenience and 29 semi-structured interviews and four focus groups were conducted with key actors to explore sustainability; with this information, a score was assigned to each category and dimension); 3) analytical, by category and dimension (content analysis was performed for qualitative information, and totals and averages were calculated for quantitative information); 4) integrative (qualitative data were integrated into matrices by category and dimension, and quantitative data were supported by qualitative information); and 5) meta-inference (consideration was given to the context and its influence on the results). RESULTS: Ninety-two (92) informants participated. In operational terms, progress was observed in the transfer and use of results, and in rotations in leadership. In the legal and political sphere, accountability and local planning were highlighted. In the economic sphere, progressive investment in health, water and sanitation was emphasized, as well as insufficient investment in social determinants of health. In the social sphere, few mechanisms were observed to promote and strengthen social participation. CONCLUSIONS: In the municipalities that participated in the study, a fair level of sustainability was observed in the Healthy Municipalities strategy.

[Sustainability of the Healthy Municipalities strategy in GuatemalaSustentabilidade da estratégia de Municípios Saudáveis na Guatemala]. / Sostenibilidad de la estrategia Municipios Saludables en Guatemala.

OBJECTIVE: Evaluate the sustainability of the Healthy Municipalities strategy in Guatemala in order to have solid evidence to support decision-making. METHODS: A concurrent mixed-methods study was carried out in five phases: 1) theoretical-conceptual (based on a narrative review of the literature on sustainability, dimensions and categories were proposed for evaluation); (2) empirical (four municipalities were selected for convenience and 29 semi-structured interviews and four focus groups were conducted with key actors to explore sustainability; with this information, a score was assigned to each category and dimension); (3) analytical, by category and dimension (content analysis was performed for qualitative information, and totals and averages were calculated for quantitative information); (4) integrative (qualitative data were integrated into matrices by category and dimension, and quantitative data were supported by qualitative information); and 5) meta-inference (consideration was given to the context and its influence on the results). RESULTS: Ninety-two (92) informants participated. In operational terms, progress was observed in the transfer and use of results, and in rotations in leadership. In the legal and political sphere, accountability and local planning were highlighted. In the economic sphere, progressive investment in health, water and sanitation was emphasized, as well as insufficient investment in social determinants of health. In the social sphere, few mechanisms were observed to promote and strengthen social participation. CONCLUSIONS: In the municipalities that participated in the study, a fair level of sustainability was observed in the Healthy Municipalities strategy.

OBJETIVO: Avaliar a sustentabilidade da estratégia de Municípios Saudáveis na Guatemala para dispor de evidências sólidas para apoiar o processo decisório. MÉTODOS: Foi realizado um estudo de método misto concorrente em cinco fases: 1) fase teórica-conceitual em que foi feita a revisão narrativa da literatura em sustentabilidade a partir da qual foram propostas dimensões e categorias a serem avaliadas; 2) fase empírica em que foi feita a seleção por conveniência de quatro municípios, com 29 entrevistas semiestruturadas e quatro grupos de discussão com as principais partes interessadas para explorar a sustentabilidade; a partir das informações coletadas, foi dada uma pontuação a cada categoria e dimensão; 3) fase analítica, por categoria e dimensão, em que foi realizada a análise do conteúdo para os dados qualitativos e feito o cálculo de somatórias e médias para os dados quantitativos; 4) fase integrativa em que os dados qualitativos foram integrados em matrizes por categoria e dimensão e os dados quantitativos foram respaldados com a informação qualitativa e 5) metainferência em que foi analisado o contexto e sua influência nos resultados. RESULTADOS: O estudo incluiu 92 participantes. Na dimensão operacional, destacam-se os avanços na transferência e no uso de resultados, bem como a ênfase em liderança. Na dimensão jurídico-política, destacam-se a prestação de contas e os planos locais. Na dimensão econômica, destaca-se o investimento progressivo em saúde, água e saneamento, com investimento inadequado nos determinantes sociais da saúde. Na dimensão social, observam-se poucos mecanismos para incentivar e reforçar a participação social. CONCLUSÕES: Foi observado nos municípios participantes do estudo um nível constante de sustentabilidade da estratégia de Municípios Saudáveis.

A Review of Nanocomposite-Modified Electrochemical Sensors for Water Quality Monitoring.

Electrochemical sensors play a significant role in detecting chemical ions, molecules, and pathogens in water and other applications. These sensors are sensitive, portable, fast, inexpensive, and suitable for online and in-situ measurements compared to other methods. They can provide the detection for any compound that can undergo certain transformations within a potential window. It enables applications in multiple ion detection, mainly since these sensors are primarily non-specific. In this paper, we provide a survey of electrochemical sensors for the detection of water contaminants, i.e., pesticides, nitrate, nitrite, phosphorus, water hardeners, disinfectant, and other emergent contaminants (phenol, estrogen, gallic acid etc.). We focus on the influence of surface modification of the working electrodes by carbon nanomaterials, metallic nanostructures, imprinted polymers and evaluate the corresponding sensing performance. Especially for pesticides, which are challenging and need special care, we highlight biosensors, such as enzymatic sensors, immunobiosensor, aptasensors, and biomimetic sensors. We discuss the sensors' overall performance, especially concerning real-sample performance and the capability for actual field application.

Common causation and offset effects in human visual-inertial heading direction integration.

Movement direction can be determined from a combination of visual and inertial cues. Visual motion (optic flow) can represent self-motion through a fixed environment or environmental motion relative to an observer. Simultaneous visual and inertial heading cues present the question of whether the cues have a common cause (i.e., should be integrated) or whether they should be considered independent. This was studied in eight healthy human subjects who experienced 12 visual and inertial headings in the horizontal plane divided in 30° increments. The headings were estimated in two unisensory and six multisensory trial blocks. Each unisensory block included 72 stimulus presentations, while each multisensory block included 144 stimulus presentations, including every possible combination of visual and inertial headings in random order. After each multisensory stimulus, subjects reported their perception of visual and inertial headings as congruous (i.e., having common causation) or not. In the multisensory trial blocks, subjects also reported visual or inertial heading direction (3 trial blocks for each). For aligned visual-inertial headings, the rate of common causation was higher during alignment in cardinal than noncardinal directions. When visual and inertial stimuli were separated by 30°, the rate of reported common causation remained >50%, but it decreased to 15% or less for separation of ≥90°. The inertial heading was biased toward the visual heading by 11-20° for separations of 30-120°. Thus there was sensory integration even in conditions without reported common causation. The visual heading was minimally influenced by inertial direction. When trials with common causation perception were compared with those without, inertial heading perception had a stronger bias toward visual stimulus direction.NEW & NOTEWORTHY Optic flow ambiguously represents self-motion or environmental motion. When these are in different directions, it is uncertain whether these are integrated into a common perception or not. This study looks at that issue by determining whether the two modalities are consistent and by measuring their perceived directions to get a degree of influence. The visual stimulus can have significant influence on the inertial stimulus even when they are perceived as inconsistent.

Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients.

The prevalence estimations of hereditary ataxias are biased since most epidemiological studies are confined to isolated geographical regions and few nationwide studies are available. The study aims to assess the prevalence, distribution, and neurological features of the Cuban population with hereditary ataxias. A nationwide epidemiological study of hereditary ataxias was conducted in Cuba between March 2017 and June 2018. Patients were scheduled at the Cuban ataxia research center, various hospitals, or at their homes. Demographic and clinical variables were obtained through standardized questionnaires and validated clinical tools. Overall, 1001 patients were diagnosed with hereditary ataxias for a nationwide prevalence of 8.91 cases/100.000 inhabitants. Spinocerebellar ataxia type 2 (SCA2) was the commonest subtype, with highest prevalences at Holguín province (47.86/100.000), and a broad dissemination in the whole country. Most of neurological features were common between all SCA cohorts, but the frequencies of some of them varied between distinct subtypes. Within the SCA2 cohort, significant influences of long mutation size and higher disease duration over the muscle atrophy and oculomotor disorders were observed. Besides, higher disease durations were associated with resting tremor and dysphagia, whereas shorter disease durations were associated with hyperreflexia. The spreading of SCA2 to whole country and the documented raising of its prevalence set the rationales for higher-scope medical care and research strategies, supported in collaborative research networks. The wide epidemiological, clinical, and genetic characterization of this founder SCA2 population identifies this homogeneous cohort as an attractive source for the development of future clinical-genetic and therapeutic researches.

Testosterone Levels Are Decreased and Associated with Disease Duration in Male Spinocerebellar Ataxia Type 2 Patients.

Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Despite clinical and experimental evidence indicating the relevance of the gonadotropic axis to the prognosis and therapeutics for several late-onset neurodegenerative disorders, its functioning and association with disease severity have not been previously explored in SCA2. To assess serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and their clinical relevance in SCA2 patients. A case-control study involving 94 Cuban SCA2 patients and 101 gender- and age-matched healthy controls was conducted. Testosterone, LH, and FSH serum levels were determined by radioimmunoassay or immunoradiometric assay systems. Clinical outcomes included age at onset, disease duration, Scale for the Assessment and Rating of Ataxia (SARA) score, and progression rate. Univariate general linear models were generated. Testosterone, LH, and FSH serum levels were significantly reduced in male SCA2 patients relative to control individuals. On average, there was a 35% reduction in testosterone levels in male patients versus male control individuals. Testosterone levels were associated with disease duration (r = 0.383; p = 0.025) and age at onset (r = 0.414; p = 0.011) in male SCA2 patients, but no association was observed between testosterone and CAG expansion size, SARA score, or progression rate. Testosterone levels might be a biomarker of disease progression in male SCA2 patients. Further studies are needed to explore the effects of low testosterone levels on non-motor symptoms, and to assess the potential of testosterone replacement therapy in male SCA2 patients.