The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation.

Immune cell trafficking constitutes a fundamental component of immunological response to tissue injury, but the contribution of intrinsic RNA nucleotide modifications to this response remains elusive. We report that RNA editor ADAR2 exerts a tissue- and stress-specific regulation of endothelial responses to interleukin-6 (IL-6), which tightly controls leukocyte trafficking in IL-6-inflamed and ischemic tissues. Genetic ablation of ADAR2 from vascular endothelial cells diminished myeloid cell rolling and adhesion on vascular walls and reduced immune cell infiltration within ischemic tissues. ADAR2 was required in the endothelium for the expression of the IL-6 receptor subunit, IL-6 signal transducer (IL6ST; gp130), and subsequently, for IL-6 trans-signaling responses. ADAR2-induced adenosine-to-inosine RNA editing suppressed the Drosha-dependent primary microRNA processing, thereby overwriting the default endothelial transcriptional program to safeguard gp130 expression. This work demonstrates a role for ADAR2 epitranscriptional activity as a checkpoint in IL-6 trans-signaling and immune cell trafficking to sites of tissue injury.

Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Inhibition of autophagy prevents cardiac dysfunction at early stages of cardiomyopathy in Bag3-deficient hearts.

The HSP70 co-chaperone BAG3 targets unfolded proteins to degradation via chaperone assisted selective autophagy (CASA), thereby playing pivotal roles in the proteostasis of adult cardiomyocytes (CMs). However, the complex functions of BAG3 for regulating autophagy in cardiac disease are not completely understood. Here, we demonstrate that conditional inactivation of Bag3 in murine CMs leads to age-dependent dysregulation of autophagy, associated with progressive cardiomyopathy. Surprisingly, Bag3-deficient CMs show increased canonical and non-canonical autophagic flux in the juvenile period when first signs of cardiac dysfunction appear, but reduced autophagy during later stages of the disease. Juvenile Bag3-deficient CMs are characterized by decreased levels of soluble proteins involved in synchronous contraction of the heart, including the gap junction protein Connexin 43 (CX43). Reiterative administration of chloroquine (CQ), an inhibitor of canonical and non-canonical autophagy, but not inactivation of Atg5, restores normal concentrations of soluble cardiac proteins in juvenile Bag3-deficient CMs without an increase of detergent-insoluble proteins, leading to complete recovery of early-stage cardiac dysfunction in Bag3-deficient mice. We conclude that loss of Bag3 in CMs leads to age-dependent differences in autophagy and cardiac dysfunction. Increased non-canonical autophagic flux in the juvenile period removes soluble proteins involved in cardiac contraction, leading to early-stage cardiomyopathy, which is prevented by reiterative CQ treatment.

Adherence to the Mediterranean Diet and its association with gastric cancer: health benefits from a Planeterranean perspective.

The Mediterranean Diet (MD) has garnered increasing attention for its potential protective effects against gastric cancer (GC). The MD's rich content of antioxidants, polyphenols, and other bioactive compounds contributes to its ability to modulate gene expression, inhibit tumor growth, and regulate apoptosis. Studies have shown significant reductions in inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) among individuals adhering to the MD, suggesting its pivotal role in mitigating chronic inflammation-associated with cancer development. Furthermore, the MD's anti-angiogenic properties, particularly in components like olive oil, red wine, fish, and tomatoes, offer promising avenues for reducing GC risk by inhibiting tumor angiogenesis. Additionally, the MD's influence on intestinal microbiota composition underscores its potential in maintaining immune homeostasis and reducing systemic inflammation, factors crucial in GC prevention. Despite challenges such as variability in dietary adherence scoring systems and the need for further gender and geographical-specific studies, evidence supports the MD as a cost-effective and holistic approach to GC prevention. Emphasizing the role of nutrition in public health is a promising strategy with broad implications for global health and cancer prevention initiatives. Therefore, this review explores the multifaceted impacts of the MD on GC prevention, delving into its anti-inflammatory, anti-angiogenic, and molecular mechanisms.

ADAR1 Prevents Autoinflammatory Processes in the Heart Mediated by IRF7.

BACKGROUND: ADAR1 (adenosine deaminase acting on RNA-1)-mediated adenosine to inosine (A-to-I) RNA editing plays an essential role for distinguishing endogenous from exogenous RNAs, preventing autoinflammatory ADAR1 also regulates cellular processes by recoding specific mRNAs, thereby altering protein functions, but may also act in an editing-independent manner. The specific role of ADAR1 in cardiomyocytes and its mode of action in the heart is not fully understood. To determine the role of ADAR1 in the heart, we used different mutant mouse strains, which allows to distinguish immunogenic, editing-dependent, and editing-independent functions of ADAR1. METHODS: Different Adar1-mutant mouse strains were employed for gene deletion or specific inactivation of ADAR1 enzymatic activity in cardiomyocytes, either alone or in combination with Ifih1 (interferon induced with helicase C domain 1) or Irf7 (interferon regulatory factor 7) gene inactivation. Mutant mice were investigated by immunofluorescence, Western blot, RNAseq, proteomics, and functional MRI analysis. RESULTS: Inactivation of Adar1 in cardiomyocytes resulted in late-onset autoinflammatory myocarditis progressing into dilated cardiomyopathy and heart failure at 6 months of age. Adar1 depletion activated interferon signaling genes but not NFκB (nuclear factor kappa B) signaling or apoptosis and reduced cardiac hypertrophy during pressure overload via induction of Irf7. Additional inactivation of the cytosolic RNA sensor MDA5 (melanoma differentiation-associated gene 5; encoded by the Ifih1 gene) in Adar1 mutant mice prevented activation of interferon signaling gene and delayed heart failure but did not prevent lethality after 8.5 months. In contrast, compound mutants only expressing catalytically inactive ADAR1 in an Ifih1-mutant background were completely normal. Inactivation of Irf7 attenuated the phenotype of Adar1-deficient cardiomyocytes to a similar extent as Ifih1 depletion, identifying IRF7 as the main mediator of autoinflammatory responses caused by the absence of ADAR1 in cardiomyocytes. CONCLUSIONS: Enzymatically active ADAR1 prevents IRF7-mediated autoinflammatory reactions in the heart triggered by endogenous nonedited RNAs. In addition to RNA editing, ADAR1 also serves editing-independent roles in the heart required for long-term cardiac function and survival.

Comparison of gradient diffusion and molecular methods using Allplex™ NG&DR assay (Seegene®) for macrolide and fluoroquinolone screening resistance in Neisseria gonorrhoeae.

Antimicrobial resistance in Neisseria gonorrhoeae (NG) is increasing worldwide. Second-line treatments with macrolides or fluoroquinolones are an option for NG infections in some cases following the STI guideline recommendations. In our study, we compared the gradient diffusion test using EUCAST 2024 breakpoints with a new molecular method using the Allplex™ NG&DR assay (Seegene®) including A2059G/C2611 mutations (23S rRNA) associated with high/moderate-level macrolide resistance and S91F mutation (gyrA) relationship with fluoroquinolone resistance in NG isolates (n = 100). We calculated the sensitivity, specificity, and correlation of the molecular test for fluoroquinolone using the gradient diffusion as the reference method. In twenty-three strains was not detected any mutation associated with macrolides or fluoroquinolone resistance. No A2059G/C2611T mutations were detected, and the S91F mutations were detected in 77 out of the 100 isolates screened. Twenty-three NG isolates were reported to be resistant to azithromycin (ECOFF: >1 mg/L), and 78 NG isolates were resistant to ciprofloxacin (MIC: >0.06 mg/L). The molecular method showed a sensitivity of 96.1% and, a specificity of 90.9% for fluoroquinolone susceptibility, but the statistical analysis between the molecular test and gradient diffusion test was not statistically significant for fluoroquinolone resistance (p = 1). Statistical analysis was not performed for macrolides because of the absence of positive RT-PCR results. According to our data, Allplex™ assay cannot replace the gradient diffusion test for macrolide resistance. However, the assay could be used to test fluoroquinolone resistance in NG isolates as a replacement for phenotypic methods.

Sex differences in visuospatial cognition- a female advantage in jigsaw puzzle solving.

Mentally visualizing objects, understanding relationships between two- or three- dimensional objects, and manipulating objects in space are some examples of visuospatial abilities. Numerous studies have shown that male participants outperform female participants in visuospatial tasks, particularly in mental rotation. One exception is solving jigsaw puzzles. Performance by seven- to eight-year-old girls was found to be superior to that of boys of the same age (Kocijan et al. 2017). No study, however, has confirmed this finding in an adult population, where sex differences are often detectable. Seventy-nine young adult participants were given four different jigsaw puzzles and the Shepard and Metzler mental rotation test (MRT) with two main goals: First, to investigate possible sex differences in jigsaw puzzle solving, and second, to explore a potential relationship between mental rotation and jigsaw puzzle solving. We hypothesized that female participants would outperform males in the jigsaw puzzles but males would outperform females in the MRT. The findings confirmed this hypothesis. Notably, the male performance in jigsaw puzzle solving was attributed to their sex and mediated by their higher MRT scores. These results yielded two key insights. First, they indicate a dissociation between these two visuospatial abilities, jigsaw puzzle solving and mental rotation; and second, female and male participants capitalize on their distinct cognitive strengths when solving visuospatial tasks.

SWI2/SNF2 ATPase CHR2 remodels pri-miRNAs via Serrate to impede miRNA production.

Chromatin remodelling factors (CHRs) typically function to alter chromatin structure. CHRs also reside in ribonucleoprotein complexes, but little is known about their RNA-related functions. Here we show that CHR2 (also known as BRM), the ATPase subunit of the large switch/sucrose non-fermentable (SWI/SNF) complex, is a partner of the Microprocessor component Serrate (SE). CHR2 promotes the transcription of primary microRNA precursors (pri-miRNAs) while repressing miRNA accumulation in vivo. Direct interaction with SE is required for post-transcriptional inhibition of miRNA accumulation by CHR2 but not for its transcriptional activity. CHR2 can directly bind to and unwind pri-miRNAs and inhibit their processing, and this inhibition requires the remodelling and helicase activity of CHR2 in vitro and in vivo. Furthermore, the secondary structures of pri-miRNAs differed between wild-type Arabidopsis thaliana and chr2 mutants. We conclude that CHR2 accesses pri-miRNAs through SE and remodels their secondary structures, preventing downstream processing by DCL1 and HYL1. Our study uncovers pri-miRNAs as a substrate of CHR2, and an additional regulatory layer upstream of Microprocessor activity to control miRNA accumulation.

High-Resolution Ultrasound of Odontogenic Cutaneous Sinus Tract: An International Multicentric Experience and a Review of the Literature.

OBJECTIVES: To investigate the role of high-resolution ultrasound (HR-US) in the initial and differential diagnosis of the Odontogenic Cutaneous Sinus Tract (OCST) in a multicentric setting. METHODS: Skin HR-US examinations of OCSTs performed between January 2019 and June 2023 at different Institutions were retrospectively reviewed. Epidemiological and clinical data (age, gender, location of the skin lesion, causative tooth, and the clinical suspicion) as well as HR-US imaging findings (morphology and length of the sinus tract, Doppler signal, and cortical bone interruption of maxilla or mandible) were collected. US examinations were performed by expert radiologists using a high-performance US scanner, employing a high-frequency linear probe (15 MHz or higher frequencies). In only one patient the HR-US exam was integrated with strain elastography (SE). RESULTS: Sixteen patients were enrolled with a median age of 37.6 years (range 16-70 years). The most frequent clinical suspicion was epidermal cyst, while OCST was suspected in only two cases. In all cases, HR-US depicted the sinus tract as a nodular, triangular or "champignon-shaped" lesion in the subcutaneous layer, which continued with a slightly tortuous band structure, up to the focally interrupted cortical bone plate. Furthermore, color Doppler evaluation showed color signals around and/or within the lesion, expression of inflammation. On SE, the sinus tract showed a hard pattern, due to fibrous and granulomatous tissue. CONCLUSIONS: HR-US, thanks to its high spatial resolution, allows the evaluation of OCST, and play a crucial diagnostic role, mainly when the clinical suspicious is different.

NLRP3 Contributes to Sarcopenia Associated to Dependency Recapitulating Inflammatory-Associated Muscle Degeneration.

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1ß and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.

Genetic Characterization of Extensively Drug-Resistant Shigella sonnei Infections, Spain, 2021-2022.

In 2022, the United Kingdom reported an increase in drug resistance in Shigella sonnei isolates. We report 33 cases in Spain genetically related to the UK cases and 4 cases with similar antimicrobial resistance profiles infected with genetically distant strains. Our results suggest circulation of multiple genetic clusters of multidrug-resistant S. sonnei in Spain.

The distorted hand: systematic but 'independent' distortions in both explicit and implicit hand representations in young female adults.

It has long been assumed that an accurate representation of the size and shape of one's body is necessary to successfully interact with the environment. Previous research has shown accurate representations when healthy participants make overt judgments (i.e. explicit) about the size of their bodies. However, when body size is judged implicitly, studies have shown systematic distortions. One suggestion for these differences, is that explicit and implicit representations are informed by different sensory modalities. Explicit representations rely on vision whereas implicit representations are informed by haptics. We designed an experiment to investigate if explicit representations that are informed by haptics are more like implicit representation featuring systematic distortions. We asked female participants to estimate the size of their fingers and hands in three different tasks: an explicit-haptic, an implicit, and an explicit-vision task. The results showed that all three representations were distorted and furthermore, the distortions for each representation were different from one another. These results suggest that inaccurate finger and hand length are a stereotypical feature of body representation that is present in both visual and haptic domains. We discuss the results in relation to theories of body representation.

COVID-19 in Pediatric Cancer Patients and Hematopoietic Stem Cell Transplant Recipients in a Tertiary Care Hospital in Argentina.

The outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer pediatric patients was initially uncertain. The objective of this study was to describe the characteristics and outcome of cancer patients and hematopoietic stem cell transplant recipients from 0 to 19 years with detectable SARS-CoV-2 from April 23, 2020, to April 30, 2022, treated in a tertiary-level hospital in Argentina. A total of 348 cases were registered in 339 patients. The median age was 89.5 (3 to 224) months. The sex was predominantly male: 193 (55.5%). The most common malignant disease was leukemia (42.8%). One hundred four cases (29.9%) had comorbidities. Of the 346 cases with an available blood count, 17.6% had a lymphocyte count <300/mm 3 . Fever was the most common symptom. In most cases (93.1%) presented asymptomatic or mild disease. Twenty-one cases (6%) presented severe or critical status. Eleven of 24 admissions to the intensive care unit were due to COVID-19 (coronavirus disease 2019). Eight patients (2.3%) died. Two deaths were attributable to SARS-CoV-2 (0.6%). Being older, having fever, lymphopenia at diagnosis, and having received hematopoietic stem cell transplant were associated with a more severe disease. Around 90% of the children continued their cancer treatment without any change.

Can Ultrasound Examinations Generate Pain in Hidradenitis Suppurativa Patients? Results from a Multicentric Cross-Sectional Study.

BACKGROUND: Pain is not a trivial issue for hidradenitis suppurativa (HS) patients and has been considered a domain in the Core Outcome Set. To date, there is no evidence about pain caused by the ultrasound examinations. OBJECTIVE: The aim of the study was to assess the presence of pain generated by the ultrasound examinations of HS patients. METHODS: A multicentric cross-sectional study for detecting pain during the ultrasound examinations of HS patients using a validated verbal questionnaire immediately after the imaging studies. Statistical analysis included demographic data and possible associations with sex, age, location, clinical (Hurley), and ultrasonographic scoring (SOS-HS). The statistical tests were two proportions Z test, χ2 test, Student's t test, and ANOVA. A p < 0.05 was considered significant. RESULTS: 317 patients met the criteria. 77.3% of them did not present pain. Of cases with pain, 59.8% were mild, 16.7% moderate, and 23.6% severe. No significant association was found with sex, age, staging, location, or the number of affected regions. Although nonsignificant, severe pain cases were more frequent in the clinical Hurley III and ultrasonographic SOS-HS III stages. CONCLUSION: Pain generated by the ultrasound examination of HS patients is infrequent.

Exposure of 4-year to 24-year olds to tobacco imagery on prime-time Chilean television.

INTRODUCTION: The extent of the population's exposure to tobacco imagery across all genres of regular TV programming and the contribution of each of these genres is unknown, except for UK broadcast channels. The objective of this study is to estimate the exposure of young people to tobacco imagery on Chilean prime-time television and the programme source contributing to such exposure. METHODS: Programmes aired during 3 weeks in 2019 from the 15 highest audience channels in Chile were content-analysed for the occurrence of tobacco categorised as actual use, implied use, tobacco paraphernalia, tobacco brand appearances and whether they violated Chilean smoke-free law for each 1 min interval (92 639). The exposure of young people to tobacco content was estimated using media viewership figures. RESULTS: Young people received 29, 11 and 4 million tobacco impressions of any type, explicit use and smoke-free violation, respectively, at a rate of 21.8, 8.0 and 2.1 thousand impressions per hour of TV viewing. The main sources of exposure to tobacco impressions were feature films and animated productions, which were almost entirely non-Chilean. Finally, young people were exposed to tobacco brand impressions primarily through films, effectively circumventing the advertising ban in Chile. DISCUSSION: Television programming is a source of significant youth exposure to tobacco imagery, including branding impressions. To conform to the WHO FCTC, Chile should prohibit tobacco branding in any TV programme and require strong anti-tobacco advertisements prior to any TV programme portraying tobacco.

Tackling potentially inappropriate prescriptions in older adults: development of deprescribing criteria by consensus from experts in Colombia, Argentina, and Spain.

BACKGROUND: Potentially inappropriate medication use is prevalent among older adults in primary care, leading to increased morbidity, adverse drug reactions, hospitalizations, and mortality. This study aimed to develop and validate a tool for identifying PIMs in older adults within the primary care setting. The tool is composed of a list of criteria and was created based on consensus among experts from three Spanish-speaking countries, including two from Latin America. METHODS: A literature review was conducted to identify existing tools, and prescription patterns were evaluated in a cohort of 36,111 older adults. An electronic Delphi method, consisting of two rounds, was used to reach a formal expert consensus. The panel included 18 experts from Spain, Colombia, and Argentina. The content validity index, validity of each content item, and Kappa Fleiss statistical measure were used to establish reliability. RESULTS: Round one did not yield a consensus, but a definitive consensus was reached in round two. The resulting tool consisted of a list of 5 general recommendations per disease, along with 33 criteria related to potential problems, recommendations, and alternative therapeutic options. The overall content validity of the tool was 0.87, with a Kappa value of 0.69 (95% CI 0.64-0.73; Substantial). CONCLUSIONS: The developed criteria provide a novel list that allows for a comprehensive approach to pharmacotherapy in older adults, intending to reduce inappropriate medication use, ineffective treatments, prophylactic therapies, and treatments with an unfavorable risk-benefit ratio for the given condition. Further studies are necessary to evaluate the impact of these criteria on health outcomes.

Arabidopsis retains vertebrate-type telomerase accessory proteins via a plant-specific assembly.

The recent discovery of the bona-fide telomerase RNA (TR) from plants reveals conserved and unique secondary structure elements and the opportunity for new insight into the telomerase RNP. Here we examine how two highly conserved proteins previously implicated in Arabidopsis telomere maintenance, AtPOT1a and AtNAP57 (dyskerin), engage plant telomerase. We report that AtPOT1a associates with Arabidopsis telomerase via interaction with TERT. While loss of AtPOT1a does not impact AtTR stability, the templating domain is more accessible in pot1a mutants, supporting the conclusion that AtPOT1a stimulates telomerase activity but does not facilitate telomerase RNP assembly. We also show, that despite the absence of a canonical H/ACA binding motif within AtTR, dyskerin binds AtTR with high affinity and specificity in vitro via a plant specific three-way junction (TWJ). A core element of the TWJ is the P1a stem, which unites the 5' and 3' ends of AtTR. P1a is required for dyskerin-mediated stimulation of telomerase repeat addition processivity in vitro, and for AtTR accumulation and telomerase activity in vivo. The deployment of vertebrate-like accessory proteins and unique RNA structural elements by Arabidopsis telomerase provides a new platform for exploring telomerase biogenesis and evolution.

Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities.

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.

Benefits of the Neurogenic Potential of Melatonin for Treating Neurological and Neuropsychiatric Disorders.

There are several neurological diseases under which processes related to adult brain neurogenesis, such cell proliferation, neural differentiation and neuronal maturation, are affected. Melatonin can exert a relevant benefit for treating neurological disorders, given its well-known antioxidant and anti-inflammatory properties as well as its pro-survival effects. In addition, melatonin is able to modulate cell proliferation and neural differentiation processes in neural stem/progenitor cells while improving neuronal maturation of neural precursor cells and newly created postmitotic neurons. Thus, melatonin shows relevant pro-neurogenic properties that may have benefits for neurological conditions associated with impairments in adult brain neurogenesis. For instance, the anti-aging properties of melatonin seem to be linked to its neurogenic properties. Modulation of neurogenesis by melatonin is beneficial under conditions of stress, anxiety and depression as well as for the ischemic brain or after a brain stroke. Pro-neurogenic actions of melatonin may also be beneficial for treating dementias, after a traumatic brain injury, and under conditions of epilepsy, schizophrenia and amyotrophic lateral sclerosis. Melatonin may represent a pro-neurogenic treatment effective for retarding the progression of neuropathology associated with Down syndrome. Finally, more studies are necessary to elucidate the benefits of melatonin treatments under brain disorders related to impairments in glucose and insulin homeostasis.

Asymmetric encryption by optical Kerr nonlinearities exhibited by electrochromic NiO thin films.

Herein is analyzed how an electric field can induce a band gap shift in NiO films to generate an enhancement in their third-order optical nonlinearities. An electrochromic effect seems to be responsible for changes in absorbance and modification in off-resonance nonlinear refractive index. The optical Kerr effect was determined as the dominant physical mechanism emerging from the third-order optical susceptibility processes present in a nanosecond two-wave mixing configuration at 532 nm wavelength. Absence of any important multi-photonic absorption was validated by the constant trace of high-irradiance optical transmittance in single-beam mode. The inspection of nonlinear optical signals allowed us to propose an exclusive disjunctive logic gate assisted by an electrochromic effect in an optical Kerr gate. Asymmetric encryption by our XOR system with the influence of a switchable probe beam transmittance and electrical signals in the sample was studied. Immediate applications for developing multifunctional quantum systems driven by dynamic parameters in electrochromic and nonlinear optical materials were highlighted.