Palliative care considerations in frail older adults.

Frailty is a common geriatric syndrome characterized by a decline in physical and cognitive abilities and an increased vulnerability to stressors such as illnesses and injuries. As the global population is aging, the prevalence of frailty is growing. Frail older adults are at substantial risk of developing mobility and self-care difficulties, hospitalization, and death. Frailty is also associated with a high symptom burden and psychosocial stress, including malnutrition, pain, fatigue, weakness, cognitive loss, depression, falls, and sleep disorders, among others. The role of palliative care is gaining attention in medical literature because frailty is associated with increased morbidity and mortality. While there are no specific guidelines yet for when palliative care should be consulted in older patients with frailty, it has been proposed that palliative care should be considered in frail patients with continued functional decline, increased healthcare utilization, and uncontrolled symptoms. Palliative care can aid in communication with patients and families, establishing goals of care and treatment preferences, improving pain and symptom control, addressing psychosocial and spiritual needs, advance care planning, caregiver needs, and end-of-life care. Once frailty is identified, a comprehensive evaluation of the patient's physical, psychosocial, and spiritual aspects of care is essential for establishing a patient-centered treatment plan. This paper aims to guide clinicians in providing patientcentered care for older adults with frailty in the outpatient setting. Through a comprehensive literature review, we describe the leading models of frailty, frailty screening tools used in the clinical setting, and the assessment and management of palliative care needs in frail patients. We also describe emerging models of care focusing on palliative care for older adults with frailty and discuss issues related to access to palliative care for this population.

Influence of antipsychotic drugs on microRNA expression in schizophrenia patients - A systematic review.

Schizophrenia (SCZ) is a severe psychiatric disorder with unclear pathophysiology. Moreover, there is no specific biological marker to help clinicians to define a diagnosis, and medication is decided according to the psychiatrist's experience. In this scenario, microRNAs (miRNAs), which are small noncoding RNA molecules that regulate several genes, emerge as potential peripheral biomarkers to help not only the evaluation of the disease state but also the treatment response. Here, we systematically reviewed indexed literature and evaluated follow-up studies investigating the changes in miRNA expression due to antipsychotic treatment. We also assessed target genes and performed pathway enrichment analysis of miRNAs listed in this systematic review. A total of 11 studies were selected according to research criteria, and we observed that 28 miRNAs play a relevant role in schizophrenia pathogenesis or response to antipsychotic treatment, seven of those of extreme interest as possible biomarkers either for condition or treatment. Predicted targets of the miRNAs reviewed here were previously associated with schizophrenia in genome-wide studies, and pathway analysis showed enrichment for genes related to neural processes. With this review, we expect to highlight the importance of miRNAs in schizophrenia pathogenesis and its treatment and point out interesting miRNAs to future studies.

Genetic tuning of intrinsically photosensitive retinal ganglion cell subtype identity to drive visual behavior.

The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) comprise a subset of the ∼40 retinal ganglion cell types in the mouse retina and drive a diverse array of light-evoked behaviors from circadian photoentrainment to pupil constriction to contrast sensitivity for visual perception. Central to the ability of ipRGCs to control this diverse array of behaviors is the distinct complement of morphophysiological features and gene expression patterns found in the M1-M6 ipRGC subtypes. However, the genetic regulatory programs that give rise to subtypes of ipRGCs are unknown. Here, we identify the transcription factor Brn3b (Pou4f2) as a key genetic regulator that shapes the unique functions of ipRGC subtypes and their diverse downstream visual behaviors.

Diagnostic and therapeutic complexity of Susac syndrome.

A 40-year-old man who attended the emergency department with a scotoma in right eye. He mentioned hearing difficulties and headache for months and he had sensory and motor deficits in the previous days. In the ophthalmic examination, the right eye had areas of arterial occlusion. MRI revealed hyperintense lesions. The patient was diagnosed with Susac syndrome. He was treated with systemic steroids, however, it was not enough to control the condition. Rituximab and intravenous immunoglobulins were added, which allowed the improvement of neurological symptoms, but the alteration of the visual field and the hearing defect did not recover. Early diagnosis of this pathology is essential, since delaying treatment can cause irreversible consequences. Sometimes it is difficult given the wide variety of symptoms and the course of the disease. Ocular manifestations may raise suspicion when the general symptoms are nonspecific.

An ethologically relevant paradigm to assess defensive response to looming visual contrast stimuli.

In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones > > rods > > > ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.

Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells.

The pathophysiology of many neuropsychiatric disorders is still poorly understood. Identification of biomarkers for these diseases could benefit patients due to better classification and stratification. Exosomes excreted into the circulatory system can cross the blood-brain barrier and carry a cell type-specific set of molecules. Thus, exosomes are a source of potential biomarkers for many diseases, including neuropsychiatric disorders. Here, we investigated exosomal proteins produced from human-induced pluripotent stem cells (iPSCs) and iPSC-derived neural stem cells, neural progenitors, neurons, astrocytes, microglia-like cells, and brain capillary endothelial cells. Of the 31 exosome surface markers analyzed, a subset of biomarkers were significantly enriched in astrocytes (CD29, CD44, and CD49e), microglia-like cells (CD44), and neural stem cells (SSEA4). To identify molecular fingerprints associated with disease, circulating exosomes derived from healthy control (HC) individuals were compared against schizophrenia (SCZ) patients and late-onset Alzheimer's disease (LOAD) patients. A significant epitope pattern was identified for LOAD (CD1c and CD2) but not for SCZ compared to HC. Thus, analysis of cell type- and disease-specific exosome signatures of iPSC-derived cell cultures may provide a valuable model system to explore proteomic biomarkers for the identification of novel disease profiles.

An ethologically relevant paradigm to assess visual contrast sensitivity in rodents.

In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones ˃> rods ˃>>ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.

Extraction of High Value Products from Zingiber officinale Roscoe (Ginger) and Utilization of Residual Biomass.

Zingiber officinale Roscoe (ginger) is a plant from the Zingiberaceae family, and its extracts have been found to contain several compounds with beneficial bioactivities. Nowadays, the use of environmentally friendly and sustainable extraction methods has attracted considerable interest. The main objective of this study was to evaluate subcritical propane (scPropane), supercritical CO2 (scCO2), and supercritical CO2 with ethanol (scCO2 + EtOH) as co-solvent methods for the extraction of high value products from ginger. In addition, the reuse/recycling of the secondary biomass in a second extraction as a part of the circular economy was evaluated. Both the primary and the secondary biomass led to high yield percentages, ranging from 1.23% to 6.42%. The highest yield was observed in the scCO2 + EtOH, with biomass prior used to scCO2 extraction. All extracts presented with high similarities as far as their total phenolic contents, antioxidant capacity, and chemical composition. The most abundant compounds, identified by the two different gas chromatography-mass spectrometry (GC-MS) systems present, were a-zingiberene, ß- sesquiphellandrene, a-farnesene, ß-bisabolene, zingerone, gingerol, a-curcumene, and γ-muurolene. Interestingly, the reuse/recycling of the secondary biomass was found to be promising, as the extracts showed high antioxidant capacity and consisted of significant amounts of compounds with beneficial properties.

Cardioprotective Effects of Leucine Supplementation against Doxorubicin-Induced Cardiotoxicit.

Doxorubicin is one of the most important antitumor drugs used in oncology; however, its cardiotoxic effect limits the therapeutic use and raises concerns regarding patient prognosis. Leucine is a branched-chain amino acid used in dietary supplementation and has been studied to attenuate the toxic effects of doxorubicin in animals, which increases oxidative stress. Oxidative stress in different organs can be estimated using several methods, including catalase expression analysis. This study aimed to analyze the effect of leucine on catalase levels in rat hearts after doxorubicin administration. Adult male Wistar rats were separated into two groups: Standard diet (SD) and 5% Leucine-Enriched Diet (LED). The animals had free access to diet from D0 to D28. At D14, the groups were subdivided in animals injected with Doxorubicin and animals injected with vehicle, until D28, and the groups were SD, SD + Dox, LED and LED + Dox. At D28, the animals were submitted do Transthoracic Echocardiography and euthanized. Despite Dox groups had impaired body weight gain, raw heart weight was not different between the groups. No substantial alterations were observed in macroscopic evaluation of the heart. Although, Doxorubicin treatment increased total interstitial collagen in the heart, which in addition to Type I collagen, is lower in LED groups. Western blot analysis showed that catalase expression in the heart of LED groups was lower than that in SD groups. In conclusion, leucine supplementation reduced both the precocious Dox-induced cardiac remodeling and catalase levels in the heart.

Detection of atmospheric aerosols and terrestrial nanoparticles collected in a populous city in southern Brazil.

The main objective of this study is to analyze hazardous elements in nanoparticles (NPs) (smaller than 100 nm) and ultrafine particles (smaller than 1 µm) in Porto Alegre City, southern Brazil using a self-made passive sampler and Sentinel-3B SYN satellite images in 32 collection points. The Aerosol Optical Thickness proportion (T550) identification was conducted using images of the Sentinel-3B SYN satellite at 634 points sampled in 2019, 2020, 2021, and 2022. Focused ion beam scanning electron microscopy analyses were performed to identify chemical elements present in NPs and ultrafine particles, followed by single-stage cascade impactor to be processed by high-resolution transmission electron microscopy. This process was coupled with energy-dispersive X-ray spectroscopy and later analysis via secondary ion mass spectrometry. Data was acquired from Sentinel-3B SYN images, normalized to a standard mean of 0.83 µg/mg, at moderate spatial resolution (260 m), and modeled in the Sentinel Application Platform (SNAP) software v.8.0. Statistical matrix data was generated in the JASP software (Jeffreys's Amazing Statistics Program) v.0.14.1.0 followed by a K-means cluster analysis. The results demonstrate the presence of between 1 and 100 nm particles of the following chemical elements: Si, Al, K, Mg, P, and Ti. Many people go through these areas daily and may inhale or absorb these elements that can harm human health. In the Sentinel-3B SYN satellite images, the sum of squares in cluster 6 is 168,265 and in cluster 7 a total of 21,583. The use of images from the Sentinel-3B SYN satellite to obtain T550 levels is of great importance as it reveals that atmospheric pollution can move through air currents contaminating large areas on a global scale.

Privacy-Preserving Automatic Collection of Acoustic Voiding Events.

Uroflowmetry is a non-invasive diagnostic test used to evaluate the function of the urinary tract. Despite its benefits, it has two main limitations: high intra-subject variability of flow parameters and the requirement for patients to urinate on demand. To overcome these limitations, we have developed a low-cost ultrasonic platform that utilizes machine learning (ML) models to automatically detect and record natural in-home voiding events, without any need for user intervention. This platform operates outside of human-audible frequencies, providing privacy-preserving, automatic uroflowmetries that can be conducted at home as part of daily routines. After evaluating several machine learning algorithms, we found that the Multi-layer Perceptron classifier performed exceptionally well, with a classification accuracy of 97.8% and a low false negative rate of 1.2%. Furthermore, even on lightweight SVM models, performance remains robust. Our results also showed that the voiding flow envelope, helpful for diagnosing underlying pathologies, remains intact even when using only inaudible frequencies.Clinical relevance- This classification task has the potential to be part of an essential toolkit for urology telemedicine. It is especially useful in areas that lack proper medical infrastructure but still host ubiquitous embedded privacy-preserving audio capture devices with Edge AI capabilities.

Classification of the Physical Surface in Sound-based Uroflowmetry.

This work constitutes a first approach to automatically classify the urination medium for non-invasive sound based uroflowmetry tests. Often the voiding flow impacts the toilet wall (often made of ceramic) instead of the water. This causes a reduction in the amplitude of the recorded audio signal, and thus a reduction in the amplitude of the extracted envelope. Analysing the envelope alone, it is not possible to tell accurately if the reduction in the amplitude is due to a low voiding flow or an impact on the toilet walls. In this work, we carry out a study on the classification of sound uroflowmetry data depending on the medium where the urine impacts within the toilet: water or ceramic. In the analysis, a classification algorithm is proposed to identify the physical medium automatically based on the urination acoustics. The classification algorithm takes as input the frequency spectrum, the variance, and the kurtosis of the audio signal corresponding to a voiding event.Clinical relevance- Sound uroflowmetry has a strong correlation with the standard uroflowmetry. It is useful for the non-invasive detection of pathologies associated with the urinary tract as a support tool for information processing and screening. It consists of a characterization of the urinary flow patterns by capturing the sound generated when the urine stream impacts the water in the toilet. Identifying the medium which originates the sound is of paramount importance to better interpret the sound uroflowmetry.

Análisis de interconsultas derivadas desde atención primaria y rechazadas por salud mental en el Departamento de Salud Arnau de Vilanova-Llíria (Valencia) / Analysis of Interconsultations Derived from Primary Care and Rejected by Mental Health in the Arnau de Vilanova-Llíria (Valencia) Health Department

En los últimos años se ha constatado un aumento de la demanda asistencial en los servicios de salud mental y, por tanto, un aumento de interconsultas que se reci-ben desde atención primaria, siendo necesario filtrar dichas derivaciones para poder llevar a cabo una atención adecuada. El principal objetivo de este estudio es la evaluación del modelo de derivación del Servicio de Salud Mental del Departamento del Arnau de Vila-nova-Llíria mediante un análisis descriptivo y el seguimiento a lo largo de 6 meses de las interconsultas derivadas desde atención primaria y rechazadas por salud mental en el año 2019. Durante esos meses se recibieron 2029 interconsultas, de las cuales 623 fueron rechazadas, correspondiéndose estas a 504 pacientes. De estas personas, 164 fueron finalmente citadas en salud mental tras realizar una nueva interconsulta. Este análisis pone de manifiesto la necesidad de implementar un modelo colaborativo entre atención primaria y salud mental que se traduzca en una mayor detección de casos, una mejor derivación y, en definitiva, una mejor atención a los y las pacientes. (AU)

In recent years, there has been an increase in the demand for care in Mental Health services and, therefore, an increase in interconsultations received from Primary Care, making it necessary to filter said referrals in order to carry out adequate care. The main objective of this study is to evaluate the referral model of the Mental Health Ser-vice of the Department of Arnau de Vilanova-Llíria through the descriptive analysis and follow-up over 6 months of interconsultations derived from Primary Care and rejected by Mental Health in 2019. During those months, 2029 interconsultations were received, of which 623 were rejected, corresponding to 504 patients. Of these patients, 164 were fi-nally attended to in Mental Health after carrying out a new interconsultation. This analysis shows the need to implement a collaborative model between Primary Care and Mental Health that turns into greater cases detection, better referral sand, ultimately, a better patient care. (AU)

Emerging and established biomarkers of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a rare, primarily autosomal dominant, late onset muscular dystrophy commonly presenting with ptosis, dysphagia, and subsequent weakness of proximal muscles. Although OPMD diagnosis can be confirmed with high confidence by genetic testing, the slow progression of OPMD poses a significant challenge to clinical monitoring and a barrier to assessing the efficacy of treatments during clinical trials. Accordingly, there is a pressing need for more sensitive measures of OPMD progression, particularly those which do not require a muscle biopsy. This review provides an overview of progress in OPMD biomarkers from clinical assessment, quantitative imaging, histological assessments, and genomics, as well as hypothesis-generating "omics" approaches. The ongoing search for biomarkers relevant to OPMD progression needs an integrative, longitudinal approach combining validated and experimental approaches which may include clinical, imaging, demographic, and biochemical assessment methods. A multi-omics approach to biochemical biomarker discovery could help provide context for differences found between individuals with varying levels of disease activity and provide insight into pathomechanisms and prognosis of OPMD.

All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration.

SUMMARY STATEMENT: Bone marrow cell transplant has proven to be an effective therapeutic approach to treat peripheral nervous system injuries as it not only promoted regeneration and remyelination of the injured nerve but also had a potent effect on neuropathic pain.

Chemical Recycling of PET Using Catalysts from Layered Double Hydroxides: Effect of Synthesis Method and Mg-Fe Biocompatible Metals.

The chemical recycling of poly(ethylene terephthalate) (PET) residues was performed via glycolysis with ethylene glycol (EG) over Mg-Fe and Mg-Al oxide catalysts derived from layered double hydroxides. Catalysts prepared using the high supersaturation method (h.s.c.) presented a higher surface area and larger particles, but this represented less PET conversion than those prepared by the low supersaturation method (l.s.c.). This difference was attributed to the smaller mass transfer limitations inside the (l.s.c.) catalysts. An artificial neural network model well fitted the PET conversion and bis(2-hydroxyethyl) terephthalate (BHET) yield. The influence of Fe in place of Al resulted in a higher PET conversion of the Mg-Fe-h.s.c. catalyst (~95.8%) than of Mg-Al-h.s.c. (~63%). Mg-Fe catalysts could be reused four to five times with final conversions of up to 97% with reaction conditions of EG: PET = 5:1 and catalyst: PET = 0.5%. These results confirm the Mg-Fe oxides as a biocompatible novel catalyst for the chemical recycling of PET residues to obtain non-toxic BHET for further polymerization, and use in food and beverage packaging.

Acute inhibition of nicotinamide adenine dinucleotide phosphate oxidase in the commissural nucleus of the solitary tract reduces arterial pressure and renal sympathetic nerve activity in renovascular hypertension.

BACKGROUND: A growing body of evidence suggests that oxidative stress plays a role in the pathophysiology of hypertension. However, the involvement of the reactive oxygen species (ROS) in the commissural nucleus of the solitary tract (commNTS) in development the of hypertension remains unclear. METHOD: We evaluated the hemodynamic and sympathetic responses to acute inhibition of NADPH oxidase in the commNTS in renovascular hypertensive rats. Under anesthesia, male Holtzman rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip (2K1C) hypertension. After six weeks, these rats were anesthetized and instrumented for recording mean arterial pressure (MAP), renal blood flow (RBF), renal vascular resistance (RVR), and renal sympathetic nerve activity (RSNA) during baseline and after injection of apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor), NSC 23766 (RAC inhibitor) or saline into the commNTS. RESULTS: Apocynin into the commNTS decreased MAP, RSNA, and RVR in 2K1C rats. NSC 23766 into the commNTS decreased MAP and RSNA, without changing RVR in 2K1C rats. CONCLUSION: These results demonstrate that the formation of ROS in the commNTS is important to maintain sympathoexcitation and hypertension in 2K1C rats and suggest that NADPH oxidase in the commNTS could be a potential target for therapeutics in renovascular hypertension.

Review: using rolled-up tubes for strain-tuning the optical properties of quantum emitters.

Rolled-up tubes based on released III-V heterostructures have been extensively studied and established as optical resonators in the last two decades. In this review, we discuss how light emitters (quantum wells and quantum dots) are influenced by the inherently asymmetric strain state of these tubes. Therefore, we briefly review whispering gallery mode resonators built from rolled-up III-V heterostructures. The curvature and its influence over the diameter of the rolled-up micro- and nanotubes are discussed, with emphasis on the different possible strain states that can be produced. Experimental techniques that access structural parameters are essential to obtain a complete and correct image of the strain state for the emitters inside the tube wall. In order to unambiguously extract such strain state, we discuss x-ray diffraction results in these systems, providing a much clearer scenario compared to a sole tube diameter analysis, which provides only a first indication of the lattice relaxation in a given tube. Further, the influence of the overall strain lattice state on the band structure is examined via numerical calculations. Finally, experimental results for the wavelength shift of emissions due to the tube strain state are presented and compared with theoretical calculations available in literature, showing that the possibility to use rolled-up tubes to permanently strain engineer the optical properties of build-in emitters is a consistent method to induce the appearance of electronic states unachievable by direct growth methods.

Activated carbon prepared from Brazil nut shells towards phenol removal from aqueous solutions.

The Brazil nut shell was used as a precursor material for preparing activated carbon by chemical activation with potassium hydroxide. The obtained material (BNSAC) was characterized, and the adsorptive features of phenol were investigated. The characterization showed that the activated carbon presented several rounded cavities along the surface, with a specific surface area of 332 m2 g-1. Concerning phenol adsorption, it was favored using an adsorbent dosage of 0.75 g L-1 and pH 6. The kinetic investigation revealed that the system approached the equilibrium in around 180 min, and the Elovich model represented the kinetic curves. The Sips model well represented the equilibrium isotherms. In addition, the increase in temperature from 25 to 55 °C favored the phenol adsorption, increasing the maximum adsorption capacity value (qs) from 83 to 99 mg g-1. According to the estimated thermodynamic parameters, the adsorption was spontaneous, favorable, endothermic, and governed by physical interactions. Therefore, the Brazil nut shell proved a good precursor material for preparing efficient activated carbon for phenol removal.

Preparation of carbonaceous materials from flotation-sludge of the poultry industry and its application in the methylene blue adsorption.

In this work, different carbonaceous materials based on floated sludge from a poultry industry wastewater treatment plant (PI-WTP) were synthesized. These materials were characterized and investigated in methylene blue dye (MB) adsorption. The influences of the initial pH solution, adsorbent dosage, kinetics, equilibrium, and thermodynamics were evaluated in the adsorption experiments. A simulation of a real textile effluent was also carried out to evaluate the adsorbent. The results of the adsorbents' characterization demonstrated that adding ZnCl2 + lime, followed by pyrolysis and acid leaching, significantly improved the material's properties, leading to abundant porosity and high surface area. The adsorption experiments indicated that the natural pH of the solution (8.0) and the AC-II dosage of 0.75 g L-1 are optimal for MB removal. Elovich and Sips' models (with a maximum adsorption capacity of 221.02 mg g-1 at 328 K) best fitted the experimental kinetic and equilibrium data, respectively. The adsorption process is spontaneous and endothermic according to thermodynamic parameters. The discoloration efficiency of the simulated effluent was 67.8%. In conclusion, the floated sludge, a residue produced on a large scale that needs to be disposed of correctly, can be converted into a value-added material (carbonaceous adsorbent) and applied to treat colored effluents.