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Dexamethasone (DXM) was the first drug used to treat COVID-19, only a small part is metabolized and has been identified in wastewater and surface water, conventional treatments do not remove these compounds, therefore new technologies must be developed. A commercially injectable solution containing dexamethasone (DXM) was removed by heterogeneous sono/photo-Fenton (SPF) process using clinoptilolite zeolite (CZ) modified with Fe (CZ-Fe) by an electrodeposition method. The effect of initial concentration (1.2, 3, 5.5, 8, 9.7 mg/L), H 2 O 2 dose (9.8, 15, 22.5, 30, 35.1 mg/L) and hydraulic retention time (HRT, 39.5, 60, 90, 120, 140 min) were evaluated through central composite design (CCD). The frequency of the ultrasound was 140 kHz. The optimal conditions were 5.5 mg/L DXM, 22.5 mg/L H 2 O 2 and 140 min obtaining an 85.4% DXM by UV-Vis, 99% by high-performance liquid chromatography (HPLC) and 76% by chemical oxygen demand (COD) removal. The systems generated 12, 25, 40.5 and 45.5 mg/L of total oxidant at 20, 60, 100 and 140 kHz, respectively. In individual effects, UV radiation removed 23.6%, ultrasound 18.1% and H 2 O 2 14% of DXM. In kinetic studies, the best fit was obtained for the Behnajady-Modirshahla-Ghanbery (BMG) model. SPF improved the mass transfer within the reaction media, the oxidation rate and the consumption of H 2 O 2, and no sludge was generated. Finally, another oxidant formed during the process (H • , HO 2 • , O 2 -• ) contributed to DXM removal.

The finger tapping test (FTT) is a neuropsychological test that measures motor speed and coordination. It involves tapping a designated surface with a specific finger as quickly as possible for a certain duration. Touchscreen of smartphones has been used as interface to record the tap, what enables to extract information about the taps. The present study represents an initiative of construction for a national Database of Smartphone-Based FTT, which includes data from 176 healthy male and female adults ranging in age from 18 to 74 years. Participants were asked to perform the FTT using one or both hands, tapping on a central area of a smartphone as many times as possible within a 30-second interval. Data were extracted using an Android application, encompassing details such as touch timing, spatial coordinates, sex, smartphone model, hand used, and age. A Python-developed web visualization tool for individual and averaged analysis. This database serves as informative foundation for a healthy adult sample and supports further exploration and international comparative analyses of FTT performance., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/Objectives: Blood pressure (BP) readings are often rounded to the nearest zero end-digit. Guidelines permit rounding to the closest 2 mmHg. This paper investigated the effect of rounding systolic blood pressure (SBP) values on the prediction of cardiovascular disease (CVD) risk among the New Zealand population. A total of 427,299 individuals received opportunistic cardiovascular disease risk assessments at primary care facilities in New Zealand. Method: A total of 292,122 SBP readings possessed a non-zero terminal digit. These were rounded to the nearest zero end-digit. A survival model estimating a 5-year CVD risk was applied to both datasets, i.e., with and without rounding. Hazard ratios and misclassification rates were analysed to emphasise the notable differences. Financial impact was assessed by examining healthcare expenditures. Results: In total, 32% of SBP values exhibited a terminal digit of zero, and 2.85% and 4.24% of men were misclassified as moderate and high risk, respectively, while approximately 3.21% of women were misclassified into the same risk categories. Likewise, 1.19% and 0.47% of men, as well as 0.62% and 0.20% of women, were misclassified into the low and moderate risk categories, respectively. Conclusions: Precisely measuring SBP is crucial in accurately assessing CVD risk and managing healthcare resources effectively.

Context: Up to 20% of patients with X-linked hypophosphatemic rickets (XLH) have no causative variant identified on routine molecular diagnostic testing., Objective: To identify intronic variants causing PHEX mis-splicing in patients with XLH., Setting: The metabolic bone clinic of a paediatric orthopedic hospital., Participants: Four patients (age 6 to 12 years; 3 girls) with clinically diagnosed XLH and no PHEX variant on routine testing., Main Outcome Measures: RNA and DNA sequence analysis of PHEX., Methods: Urine-derived cells were cultured, and mRNA was extracted and transcribed to cDNA. PHEX cDNA was amplified by PCR, followed by sequencing of PCR products. Sequencing of PHEX intronic DNA regions was performed to identify variants causing mis-splicing observed on RNA analysis., Results: PHEX mis-splicing was identified in 3 of the 4 participants, and an intronic variant was identified in all 3 cases. In a 12-year-old boy, transcript analysis showed skipping of PHEX exon 13, while sequencing of PHEX intronic regions revealed a de novo 18 bp deletion in intron 13. In a 7-year-old girl, a pseudoexon in PHEX intron 17 was found, associated with a de novo deep intronic variant (c.1768+173A>G) that activated a cryptic splice donor site. Finally, an 84 bp pseudoexon in PHEX intron 21 caused by a recurrent de novo deep intronic variant (c.2147+1197A>G) was identified in an 11-year-old girl., Conclusions: Analysis of RNA from urine-derived cells combined with sequencing of PHEX introns can identify deep intronic variants in individuals with XLH without a detectable PHEX variant in routine exon-centric molecular diagnosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Lipid droplets are fat storage organelles composed of a protein envelope and lipid-rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all-trans-retinal to all-trans-retinol, is upregulated in the MITF LO /undifferentiated/neural crest-like melanoma cell state and reduced in the MITF HI /melanocytic state. Increased DHRS3 expression is sufficient to drive MITF HI /melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid-mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite being one of the most pristine regions in the world, Antarctica is currently also one of the most vulnerable to climate change. Antarctic vegetation comprises mostly lichens and bryophytes, complemented in some milder regions of Maritime Antarctica by two vascular plant species. Shifts in the spatial patterns of these three main vegetation groups have already been observed in response to climate change, highlighting the urgent need for the development of comprehensive large-scale ecological models of the effects of climate change. Besides climate, Antarctic terrestrial vegetation is also strongly influenced by non-climatic microscale conditions related to abiotic and biotic factors. Nevertheless, the quantification of their importance in determining vegetation patterns remains unclear. The objective of this work was to quantify the importance of abiotic and biotic microscale conditions in determining the spatial cover patterns of the major functional types, lichens, vascular plants and bryophytes, explicitly determining the likely confinement of each functional type to the microscale conditions, i.e., their ecological niche. Microscale explained >60 % of the spatial variation of lichens and bryophytes and 30 % of vascular plants, with the niche analysis suggesting that each of the three functional types may be likely confined to specific microscale conditions in the studied gradient. Models indicate that the main microscale ecological filters are abiotic but show the potential benefits of including biotic variables and point to the need for further clarification of vegetation biotic interactions' role in these ecosystems. Altogether, these results point to the need for the inclusion of microscale drivers in ecological models to track and forecast climate change effects, as they are crucial to explain present vegetation patterns in response to climate, and for the interpretation of ecological model results under a climate change perspective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3., (© 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

Neurotransmission is critical for brain function, allowing neurons to communicate through neurotransmitters and neuropeptides. RVD-hemopressin (RVD-Hp), a novel peptide identified in noradrenergic neurons, modulates cannabinoid receptors CB1 and CB2. Unlike hemopressin (Hp), which induces anxiogenic behaviors via transient receptor potential vanilloid 1 (TRPV1) activation, RVD-Hp counteracts these effects, suggesting that it may block TRPV1. This study investigates RVD-Hp's role as a TRPV1 channel blocker using HEK293 cells expressing TRPV1-GFP. Calcium imaging and patch-clamp recordings demonstrated that RVD-Hp reduces TRPV1-mediated calcium influx and TRPV1 ion currents. Molecular docking and dynamics simulations indicated that RVD-Hp interacts with TRPV1's selectivity filter, forming stable hydrogen bonds and van der Waals contacts, thus preventing ion permeation. These findings highlight RVD-Hp's potential as a therapeutic agent for conditions involving TRPV1 activation, such as pain and anxiety.

Microbially induced carbonate precipitation (MICP) immobilizes toxic metals and reduces their bioavailability in aqueous systems. However, its application in the treatment of acid mine drainage (AMD) is poorly understood. In this study, the genomes of Sporosarcina sp. UB5 and UB10 were sequenced. Urease, carbonic anhydrases, and metal resistance genes were identified and enzymatic assays were performed for their validation. The geochemical mechanism of precipitation in AMD was elucidated through geo-mineralogical analysis. Sporosarcina sp. UB5 was shown to be a new genomospecies, with an average nucleotide identity < 95 % (ANI) and DNA-DNA hybridization < 70 % (DDH) whereas UB10 is close to S. pasteurii. UB5 contained two urease operons, whereas only one was identified in UB10. The ureolytic activities of UB5 and UB10 were 122.67 ± 15.74 and 131.70 ± 14.35 mM NH 4 + min -1 , respectively. Both strains feature several carbonic anhydrases of the α, β, or γ families, which catalyzed the precipitation of CaCO 3 . Only Sporosarcina sp. UB5 was able to immobilize metals and neutralize AMD. Geo-mineralogical analyses revealed that UB5 directly immobilized Fe (1-23 %), Mn (0.65-1.33 %) and Zn (0.8-3 %) in AMD via MICP and indirectly through adsorption to calcite and binding to bacterial cell walls. The MICP-treated AMD exhibited high removal rates (>67 %) for Ag, Al, As, Ca, Cd, Co, Cu, Fe, Mn, Pb, and Zn, and a removal rate of 15 % for Mg. This study provides new insights into the MICP process and its applications to AMD treatment using autochthonous strains., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Keratinocytes, the dominant cell type in the melanoma microenvironment during tumor initiation, exhibit diverse effects on melanoma progression. Using a zebrafish model of melanoma and human cell co-cultures, we observed that keratinocytes undergo an Epithelial-Mesenchymal Transition (EMT)-like transformation in the presence of melanoma, reminiscent of their behavior during wound healing. Surprisingly, overexpression of the EMT transcription factor Twist in keratinocytes led to improved overall survival in zebrafish melanoma models, despite no change in tumor initiation rates. This survival benefit was attributed to reduced melanoma invasion, as confirmed by human cell co-culture assays. Single-cell RNA-sequencing revealed a unique melanoma cell cluster in the Twist-overexpressing condition, exhibiting a more differentiated, less invasive phenotype. Further analysis nominated homotypic jam3b-jam3b and pgrn-sort1a interactions between Twist-overexpressing keratinocytes and melanoma cells as potential mediators of the invasive restraint. Our findings suggest that EMT in the tumor microenvironment (TME) may limit melanoma invasion through altered cell-cell interactions.

Rainwater Electro-Galvanic Alkalization (EGA) was performed using copper and magnesium (1:1) electrode. Efficiently removal of pollutants without external energy consumption was carried out, in addition essential ions were dosed for alkalization of rainwater. The optimal system conditions were obtained using response surface methodology (RSM) by considering the following operating variables: flow rate and concentration of the supporting electrolyte (NaCl and CaCl 2 ). Furthermore, the maximum efficiency of nitrate, ammoniacal nitrogen, colour, and turbidity removal was evaluated. The results showed that the response variables were mainly sensitive to the type of supporting electrolyte used and the flow rate. Under experimental conditions of 0.009 M (NaCl) and 20 mL min -1 , the removal rate was 74.19%, 72.49%, and 81.43% for nitrates, colour, and turbidity, respectively, and the lowest concentration of ammoniacal nitrogen ( 0.99 mg L - 1 ) was obtained. The kinetic models for nitrate and colour were fitted to zero-order models with k = 0.33 mg L - 1 mi n - 1 and k = 0.933 Pt - Co , respectively. In addition, turbidity was fitted to a first-order model ( k = 0.1661 mi n - 1 ) , and ammoniacal nitrogen was fitted to a second-order model ( k = 0.0217 L m g - 1 mi n - 1 ) . The concentration increases of minerals such as Ca and Mg, which rises the rainwater alkalinity after treatment (pH shift from 6.1 to 8.91), was determined by inductively coupled plasma (ICP) analysis.

Background: Pediatric uveitis poses challenges in diagnosis and treatment due to asymptomatic or oligosymptomatic presentations and high rates of intraocular complications., Objectives: This study aimed to characterize clinical manifestations and treatment approaches of pediatric uveitis patients in a northern Portuguese tertiary hospital., Methodology: A retrospective study was conducted involving 41 patients diagnosed with uveitis between 2006 and 2021. All individuals identified by the Opthalmology department were referred to Pediatric Rheumatology outpatient clinic. Demographic, clinical, treatment, and intraocular complications data were collected., Results: Of the patients, 78% had anterior uveitis, 17% had panuveitis, and 5% had intermediate uveitis. Uveitis associated with juvenile idiopathic arthritis (JIA) was the most common cause (43.9%), predominantly in the oligoarticular, anti-nuclear antibody-positive subgroup. Complications were identified in 80.5% of the patients. Uveitis associated with JIA was diagnosed earlier [5.0 years (3.0-10.5) vs. 9.0 years (5.5-14.0), P = .036], more frequently in asymptomatic patients (71% vs. 23%, P = .010), had a more insidious installation (71% vs. 17%, P = .004), and required more tumor necrosis factor (TNF) inhibitor treatment (70% vs. 39%, P = .027)., Conclusion: The high rates of intraocular complications and systemic pathology association highlight the need for a combined approach of ophthalmology and pediatric rheumatology in the diagnosis and treatment of pediatric uveitis., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Recent numerical and empirical results proved that high permittivity materials (HPM) used in pads placed near the subject or directly integrated with coils can increase the SNR and reduce the specific absorption rate (SAR) in MRI. In this paper, we propose an analytical investigation of the effect on the magnetic field distribution of a layer of HPM surrounding an anatomy-mimicking cylindrical sample., Methods: The study is based on a reformulation of the Mie scattering for cylindrical geometry, following an approach recently introduced for spherical samples. The total field in each medium is decomposed in terms of inward and outward electromagnetic waves, and the fields are expressed as series of cylindrical harmonics, whose coefficients can be interpreted as classical reflection and transmission coefficients., Results: Our new formulation allows a quantitative evaluation of the effect of the HPM layer for varying permittivity and thickness, and it provides an intuitive understanding of such effect in terms of propagation and scattering of the RF field., Conclusion: We show how HPM can filter out the modes that only contribute to the noise or RF power deposition, resulting in higher SNR or lower SAR, respectively. Our proposed framework provides physical insight on how to properly design HPM for MRI applications., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Haploinsufficiency of the short stature homeobox-containing (SHOX) gene leads to a phenotypic spectrum ranging from Leri-Weill dyschondrosteosis (LWD) to SHOX-deficient short stature. SHOX nullizygosity leads to Langer mesomelic dysplasia. Pathogenic variants can include whole or partial gene deletions or duplications, point mutations within the coding sequence, and deletions of upstream and downstream regulatory elements. Here we report two families: a non-consanguineous family with a deletion downstream of SHOX, in which the homozygous proband presented with isolated Madelung deformity, without LWD or short stature, as well as a 9-year-old girl with Madelung deformities, mesomelia, a dominant family history of Madelung deformity and a heterozygous deletion of the CNE9 region in the 3' downstream region of SHOX. These case reports provide additional information on the effects of 3' downstream deletions of SHOX, by demonstrating the limited phenotype associated with the recurrent 47.5 kb deletion in a homozygous state and the CNE9 deletion in a heterozygous state., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Pannexin1 hemichannels (Panx1 HCs) are found in the membrane of most mammalian cells and communicate the intracellular and extracellular spaces, enabling the passive transfer of ions and small molecules. They are involved in physiological and pathophysiological conditions. During apoptosis, the C-terminal tail of Panx1 is proteolytically cleaved, but the permeability features of hemichannels and their role in cell death remain elusive. To address these topics, HeLa cells transfected with full-length human Panx1 (fl-hPanx1) or C-terminal truncated hPanx1 (Δ371hPanx1) were exposed to alkaline extracellular saline solution, increasing the activity of Panx1 HCs. The Δ371hPanx1 HC was permeable to DAPI and Etd + , but not to propidium iodide, whereas fl-hPanx1 HC was only permeable to DAPI. Furthermore, the cytoplasmic Ca 2+ signal increased only in Δ371hPanx1 cells, which was supported by bioinformatics approaches. The influx of Ca 2+ through Δ371hPanx1 HCs was necessary to promote cell death up to about 95% of cells, whereas the exposure to alkaline saline solution without Ca 2+ failed to induce cell death, and the Ca 2+ ionophore A23187 promoted more than 80% cell death even in fl-hPanx1 transfectants. Moreover, cell death was prevented with carbenoxolone or 10 Panx1 in Δ371hPanx1 cells, whereas it was undetectable in HeLa Panx1 -/- cells. Pretreatment with Ferrostatin-1 and necrostatin-1 did not prevent cell death, suggesting that ferroptosis or necroptosis was not involved. In comparison, zVAD-FMK, a pancaspase inhibitor, reduced death by ~60%, suggesting the involvement of apoptosis. Therefore, alkaline pH increases the activity of Δ371hPanx1HCs, leading to a critical intracellular free-Ca 2+ overload that promotes cell death., Competing Interests: Competing interests statement:V.M.B., a reviewer, and J.C.S. were on a retrospective for Michael Bennett together this year (https://pubmed.ncbi.nlm.nih.gov/38278514/).

The advent of large-scale sequencing in both development and disease has identified large numbers of candidate genes that may be linked to important phenotypes. Validating the function of these candidates in vivo is challenging, due to low efficiency and low throughput of most model systems. We have developed a rapid, scalable system for assessing the role of candidate genes using zebrafish. We generated transgenic zebrafish in which Cas9 was knocked-in to the endogenous mitfa locus, a master transcription factor of the melanocyte lineage. We used this system to identify both cell-autonomous and non-cell autonomous regulators of normal melanocyte development. We then applied this to the melanoma setting to demonstrate that loss of genes required for melanocyte survival can paradoxically promote more aggressive phenotypes, highlighting that in vitro screens can mask in vivo phenotypes. Our high-efficiency genetic approach offers a versatile tool for exploring developmental processes and disease mechanisms that can readily be applied to other cell lineages.

Purpose of Review: Insomnia is the most common sleep disorder experienced by older adults. There is a wide range of pharmacological and non-pharmacological treatment options in existing literature. The purpose of this systematic review was to synthesize randomized controlled trials of insomnia treatment modalities for adults aged 55 and older over the last 5 years. We searched four databases, and after screening, there were 34 full-text manuscripts that met the inclusion/exclusion criteria., Recent Findings: We found non-pharmacological interventions, including exercise and behavioral/psychoeducational therapies, remain effective and favorable. Complementary and alternative therapies ranged across studies and warrant further testing in larger, more diverse samples. Dual orexin receptor antagonist medications were tested in a few studies with positive benefits for sleep and minimal side effects. Finally, measures of insomnia/sleep disturbance outcomes varied among the studies, with the Pittsburgh Sleep Quality Index being used most frequently., Summary: Non-pharmacological interventions for insomnia in older adults are effective, and some newer medications may be safer, with less side effects, at managing insomnia in this population., Competing Interests: Competing interests The authors declare no competing interests.

The etiology and effect of age-related immune dysfunction in cancer is not completely understood. Here we show that limited priming of CD8 + T cells in the aged tumor microenvironment (TME) outweighs cell-intrinsic defects in limiting tumor control. Increased tumor growth in aging is associated with reduced CD8 + T cell infiltration and function. Transfer of T cells from young mice does not restore tumor control in aged mice owing to rapid induction of T cell dysfunction. Cell-extrinsic signals in the aged TME drive a tumor-infiltrating age-associated dysfunctional (T TAD ) cell state that is functionally, transcriptionally and epigenetically distinct from canonical T cell exhaustion. Altered natural killer cell-dendritic cell-CD8 + T cell cross-talk in aged tumors impairs T cell priming by conventional type 1 dendritic cells and promotes T TAD cell formation. Aged mice are thereby unable to benefit from therapeutic tumor vaccination. Critically, myeloid-targeted therapy to reinvigorate conventional type 1 dendritic cells can improve tumor control and restore CD8 + T cell immunity in aging., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: Retinitis pigmentosa (RP) comprises a genetically and clinically heterogeneous group of inherited retinal degenerations, where 20-30% of patients exhibit extra-ocular manifestations (syndromic RP). Understanding the genetic profile of RP has important implications for disease prognosis and genetic counseling. This study aimed to characterize the genetic profile of syndromic RP in Portugal., Methods: Multicenter, retrospective cohort study. Six Portuguese healthcare providers identified patients with a clinical diagnosis of syndromic RP and available genetic testing results. All patients had been previously subjected to a detailed ophthalmologic examination and clinically oriented genetic testing. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for disease etiology., Results: One hundred and twenty-two patients (53.3% males) from 100 families were included. Usher syndrome was the most frequent diagnosis (62.0%), followed by Bardet-Biedl (19.0%) and Senior-Løken syndromes (7.0%). Deleterious variants were identified in 86/100 families for a diagnostic yield of 86.0% (87.1% for Usher and 94.7% for Bardet-Biedl). A total of 81 genetic variants were identified in 25 different genes, 22 of which are novel. USH2A and MYO7A were responsible for most type II and type I Usher syndrome cases, respectively. BBS1 variants were the cause of Bardet-Biedl syndrome in 52.6% of families. Best-corrected visual acuity (BCVA) records were available at baseline and last visit for 99 patients (198 eyes), with a median follow-up of 62.0 months. The mean BCVA was 56.5 ETDRS letters at baseline (Snellen equivalent ~ 20/80), declining to 44.9 ETDRS letters (Snellen equivalent ~ 20/125) at the last available follow-up (p < 0.001)., Conclusion: This is the first multicenter study depicting the genetic profile of syndromic RP in Portugal, thus contributing toward a better understanding of this heterogeneous disease group. Usher and Bardet-Biedl syndromes were found to be the most common types of syndromic RP in this large Portuguese cohort. A high diagnostic yield was obtained, highlighting current genetic testing capabilities in providing a molecular diagnosis to most affected individuals. This has major implications in determining disease-related prognosis and providing targeted genetic counseling for syndromic RP patients in Portugal., (© 2024. The Author(s).)

We aimed to study the impact of polymorphisms in the genes encoding interleukin-6 (IL6) and tumor necrosis factor receptor-2 (TNFR2), reported to be mortality risk predictors, in patients with end-stage kidney disease (ESKD) undergoing dialysis. TNFRSF1B (rs3397, rs1061624, and rs1061622) and IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms were studied in patients with ESKD and controls; the genotype and allele frequencies and the associations with inflammatory and erythropoiesis markers were determined; deaths were recorded throughout the following two years. The genotype and allele frequencies for the TNFRSF1B rs3397 polymorphism were different in these patients compared to those in the controls and the global and European populations, and patients with the C allele were less common. Patients with the CC genotype for TNFRSF1B rs3397 presented higher hemoglobin and erythrocyte counts and lower TNF-α levels, suggesting a more favorable inflammatory response that seems to be associated with erythropoiesis improvement. Patients with the GG genotype for TNFRSF1B rs1061622 showed lower serum ferritin levels. None of the TNFRSF1B (rs3397, rs1061624, and rs1061622) or IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms had a significant impact on the all-cause mortality rate of Portuguese patients with ESKD.

Thyroxine (T4) is a drug extensively utilized for the treatment of hypothyroidism. However, the oral absorption of T4 presents certain limitations. This research investigates the efficacy of CO 2 nanobubbles in water as a potential oral carrier for T4 administration to C57BL/6 hypothyroid mice. Following 18 h of fasting, the formulation was administered to the mice, demonstrating that the combination of CO 2 nanobubbles and T4 enhanced the drug's absorption in blood serum by approximately 40%. To comprehend this observation at a molecular level, we explored the interaction mechanism through which T4 engages with the CO 2 nanobubbles, employing molecular simulations, semi-empirical quantum mechanics, and PMF calculations. Our simulations revealed a high affinity of T4 for the water-gas interface, driven by additive interactions between the hydrophobic region of T4 and the gas phase and electrostatic interactions of the polar groups of T4 with water at the water-gas interface. Concurrently, we observed that at the water-gas interface, the cluster of T4 formed in the water region disassembles, contributing to the drug's bioavailability. Furthermore, we examined how the gas within the nanobubbles aids in facilitating the drug's translocation through cell membranes. This research contributes to a deeper understanding of the role of CO 2 nanobubbles in drug absorption and subsequent release into the bloodstream. The findings suggest that utilizing CO 2 nanobubbles could enhance T4 bioavailability and cell permeability, leading to more efficient transport into cells. Additional research opens the possibility of employing lower concentrations of this class of drugs, thereby potentially reducing the associated side effects due to poor absorption.

Objectives: This study aims to comprehensively review and update the literature concerning the correlates of sleep disturbance among caregivers of persons living with Alzheimer's disease and related dementias to identify gaps in the literature and antecedent targets for interventions., Methods: We searched PubMed, CINAHL, PsycINFO, and Embase using terms related to "sleep," "caregiver," and "dementia.", Results: Thirty-six articles were included in this review. Based on the antecedents within the 3P model of insomnia, predisposing factors associated with caregiver sleep included caregiver demographics, and physiological factors like genotype and biomarkers. Precipitating factors related to caregiver sleep included caregiving status and responsibilities, and person living with dementia factors., Conclusions: Sleep disturbance is a significant issue for caregivers of persons living with dementia. However, this review has identified multiple precipitating factors that are modifiable targets for interventions to improve or enhance caregiver sleep., Clinical Implications: Numerous predisposing and precipitating factors contribute to caregivers of persons living with dementia being susceptible to sleep disturbance. Healthcare providers should ask patients about their caregiving status during annual visits. Healthcare providers should also evaluate caregivers' sleep patterns, and the predisposing and precipitating factors of sleep disturbance, with a focus on the modifiable factors, to enable timely intervention.

Objectives: To explore and characterize predisposing, precipitating, and perpetuating factors of subthreshold, moderate, and severe insomnia in cancer survivors., Sample & Setting: 135 cancer survivors who self-reported symptom severity on the Insomnia Severity Index during the baseline phase of a randomized clinical trial on insomnia treatment., Methods & Variables: Participants completed measures assessing predisposing factors (age, sex, race and ethnicity, body mass index), precipitating factors (number of years since cancer diagnosis, depression and anxiety symptoms, health-related quality of life), and perpetuating factors (frequency of consuming alcoholic and caffeinated beverages, napping behavior, dysfunctional beliefs about sleep)., Results: In the multivariate model, being female was protective against insomnia, and being a person of color, having higher anxiety, having more depression symptoms, and having stronger dysfunctional beliefs about sleep were significantly associated with greater insomnia severity., Implications for Nursing: By fostering interprofessional collaboration and implementing evidence-based interventions, nurses can contribute to the well-being of cancer survivors and address their sleep-related challenges. This study underscores the importance of regular insomnia screenings for cancer survivors, with nurses as essential facilitators.

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% ( n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N -terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: -0.407, 0.272, -0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.

The textile industry is an important economic sector; however, its wastewater generates a great impact on the environment. A heterogeneous solar Fenton (HSF) process was evaluated for denim wastewater treatment. The catalyst was obtained through ultrasonic modification of recycled polyethylene terephthalate (PET) with Fe nanoparticles (PET/NPs- Fe 3 O 4 ). The SFH process was optimized using surface response methodology with a face-centered central composite design considering the effects of the hydraulic retention time (10, 25, and 40 min), hydrogen peroxide dosage (500, 1000, and 1500 mg/L), and mass of the packed catalyst (4, 6 and 8 g) on the color, COD, and turbidity removal efficiencies. The operating conditions for maximum COD removal were H 2 O 2 541.7 mg/L, HRT 33.9 min, and PET/NPs- Fe 3 O 4 dose 7.9 g with solar radiation. The removal of 91.2% COD, 86.2% color, 90.4% turbidity, and 81.9% TOC was obtained at 14.2 kJ/L QUva. PET modification yielded 1.6 mg Fe/g PET, and the modification method does not allow Fe leaching. The effluent obtained from the SFH process complies with the maximum permissible limits in Mexican legislation in terms of COD, TOC, turbidity, and color and allows the reuse of PET., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To report two new cases with confirmed diagnosis of Heimler syndrome and describe their systemic and ophthalmic phenotype and visual rehabilitation., Methods: Retrospective review of medical records., Results: Both siblings were diagnosed as having sensori-neural hearing loss and retinal dystrophy with exuberant intraretinal cystoid spaces and cone-rod dysfunction. The older sibling also had amelogenesis imperfecta and neither had nail abnormalities. Genetic analysis identified homozygosity for the pathogenic variant c.2528G>A p.(Gly843Asp) in the PEX1 gene in both siblings. The parents were heterozygous carriers of the variant., Conclusions: The authors report a familial case of Heimler syndrome due to biallelic PEX1 pathogenic variants that manifested as macular dystrophy characterized by cone-rod dysfunction and complicated by intraretinal cystoid spaces. Review of the literature shows that ocular phenotype is variable in patients with Heimler syndrome. [ J Pediatr Ophthalmol Strabismus . 2024;61(1):59-66.] .

Background: Chemotherapy-induced adverse effects are an unresolved nightmare. In preclinical studies in rats, the food additive monosodium glutamate (MSG) improved some of the side effects caused by cisplatin, but its effects in other models of chemotherapy-treated animals are not well known. The aim of this study was to test if MSG may improve some of the adverse effects induced by vincristine in rats., Methods: Young male Wistar rats were exposed or not to MSG (4 g L -1 ) in drinking water from week 0 till 1 week after treatment (week 3). Rats received two cycles of five daily intraperitoneal (ip) injections (Monday to Friday, weeks 1 and 2) of either saline (2 mL kg -1 ) or vincristine (0.1 mg kg -1 ). Gastrointestinal motility was measured in vivo by radiological methods after the first and tenth ip administrations. On week 3, the threshold for mechanical somatic and colorectal sensitivity was recorded using Von Frey filaments applied to the paws and an intracolonic balloon, respectively. Finally, samples of the terminal ileum and distal colon were histologically evaluated in sections., Key Results: Vincristine reduced body weight gain, food intake, and upper gastrointestinal transit, caused somatic (but not visceral) hypersensitivity and increased the thickness of the submucosal and muscle layers of the small intestine. In vincristine-treated animals, MSG partially prevented gastrointestinal dysmotility and reduced visceral sensitivity but did not improve structural alterations of the small intestine., Conclusions & Inferences: MSG could be used as an adjuvant to conventional treatments to improve some gastrointestinal dysfunctions caused by chemotherapy., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

The pipeline from discovery to testing and then implementing evidence-based innovations in real-world contexts may take 2 decades or more to achieve. Implementation science innovations, such as hybrid studies that combine effectiveness and implementation research questions, may help to bridge the chasm between intervention testing and implementation in dementia care. This paper describes hybrid effectiveness studies and presents 3 examples of dementia care interventions conducted in various community-based settings. Studies that focus on outcomes and implementation processes simultaneously may result in a truncated and more efficient implementation pipeline, thereby providing older persons, their families, health care providers, and communities with the best evidence to improve quality of life and care more rapidly. We offer post-acute and long-term care researchers considerations related to study design, sampling, data collection, and analysis that they can apply to their own dementia and other chronic disease care investigations., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Sleep disturbances occur in >60% of persons living with cognitive impairment, affecting their quality of life (QOL). Regulating the sleep-wake cycle through engaging cognitive, physical, and sensory-based activities delivered at strategic times may reduce sleep disturbances and be a feasible nonpharmacological treatment for sleep problems. The objective of this trial was to test the efficacy of a timed-activity intervention in improving QOL and sleep disturbances in persons living with cognitive impairment., Research Design and Method: Randomized 2-group parallel design involving 209 dyads of community-residing persons living with cognitive impairment and care partners. Dyads were randomly assigned (1:1) to 1-hr home activity sessions administered weekly in the morning, afternoon, or evening over 4 weeks (the Healthy Patterns Sleep Program), or to an attention-control condition consisting of sleep hygiene training plus education on home safety and health promotion. QOL, objective and subjective sleep quality, and neuropsychiatric symptoms were assessed at baseline and 4 weeks later., Results: QOL was significantly improved in the intervention group compared to control ( p  = .0491). There were no significant effects on objective or subjective sleep or neuropsychiatric symptoms. In a subgroup analysis, subjective sleep as measured by the PROMIS (Patient Reported Outcomes Measurement Information System) Sleep-Related Impairment survey was significantly improved in the intervention group compared to the control group for individuals with symptoms of depression ( p  = .015) or poor observed sleep at baseline ( p  = .005)., Discussion and Implications: The Healthy Patterns Intervention may benefit QOL for persons living with cognitive impairment and those with poor subjective sleep. A longer dose may be necessary to elicit improvement in actigraphically measured sleep-wake activity., Clinical Trial Registration Number: NCT0368218 5., Competing Interests: None., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Purpose: To evaluate the visual impairment of patients with inherited retinal diseases (IRDs), as per the national table of disabilities (TNI)., Design: Retrospective, single-center cohort study., Participants: Patients with a clinical diagnosis of IRD were recruited at a referral center in Portugal., Methods: Demographics and clinical data were collected from each individual patient file. The estimated visual disability coefficient was calculated through the evaluation of 7 graduated categories: orbital or eyelid deformities, low vision, visual field change, loss of bi-foveolar fixation, oculomotor palsy, photophobia, and chronic conjunctivitis. The TNI provides minimum and maximum disability values for numerous conditions within each category, which were summed to calculate an overall summary disability coefficient for each patient., Main Outcome Measures: Demographic/clinical and estimated minimum and maximum visual disability coefficient according to the TNI for each patient., Results: This study included 253 patients from 214 families, aged 3 to 80 years, with a mean age of 39.8 ± 20.0 years. The mean estimated minimum and maximum visual disability coefficients as per the TNI were 0.6 ± 0.4 and 0.7 ± 0.4, respectively. The low vision was the single most frequent contributor category (21.7%) present in the calculation of visual impairment. Low vision and visual field changes were the most frequent double combination (18.2%), and the addition of loss of bi-foveolar fixation was the most frequent triple combination (8.3%)., Conclusions: This study found that IRD patients had a significant visual disability, with the majority having a disability coefficient ≥0.6, which would qualify them for a "multipurpose disability medical certificate.", Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article., (© 2023 by the American Academy of Ophthalmology.)

Acid mine drainage was evaluated using a galvanic (GV) electrochemical system, Al-Cu (anode/cathode), based on a 3 2 factorial design. The factors analyzed were anodic area/volume ratios (A/V) of 0.037, 0.072, and 0.112 cm 2 /cm 3 , and treatment time from 0.25-8 h, and analyses were performed in duplicate with 11 degrees of freedom. The response variables were the total dissolved solids and concentrations of As, Cu, Co, Cr, Pb, Fe, Ni, and S O 4 2 - . The pH, electrical conductivity, and temperature were monitored during the process. Significant differences between treatments were determined by analysis of variance with Tukey's test ( p  < 0.05) using Statgraphics Centurion XVI.I software. The results showed that a greater electrode surface, A/V ratio, and treatment time improved pollutant removal. The spontaneous reactions generated by the galvanic cell, through the current that flows owing to the potential difference between the Al and Cu electrodes, allows the removal of heavy metals, arsenic, and S O 4 2 - by coagulation and precipitation mechanisms. The removal efficiencies achieved were Cu (99.1%), As (76.6%), Ni (80.2%), Pb (83.6%), Cr (100%), Fe (93.71%), and 92.9% for sulfates. The X-ray diffraction and Raman analyses of the solid fraction indicated that cuprite was formed with a purity of 96%, and the recovery of Cu by the GV system may be a viable option for mining companies.

Biological treatments have become insufficient to treat municipal wastewater with greater toxicity and excess nitrogen and phosphate species, thus affecting the organisms that consume the water. In this work, a process was implemented for the removal of nutrients through three stages: stage A, complete aeration (24 h, 43 months); stage B, decreased aeration (12 h, 17 months); and stage C, decreased aeration with biocalcium (12 h, 19 months). The addition of biocalcium from eggshell promoted the formation of flocks, which resulted in the removal of nitrites (61 %), nitrates (84 %), total nitrogen (57 %), total phosphorus (8.3 %), sedimentable solids (50 %), total suspended solids (69 %), BOD 5 (76 %), helminth eggs (50 %) and fecal coliforms (54 %). The statistical analyses in the three stages indicated that there is a strong correlation between the concentration of fats and oils and the removal of sedimentable solids and total suspended solids, since these parameters were correlated by 97 and 89 %, respectively. Sedimentable solids were correlated with total suspended solids by 94 %, while nitrates and total nitrogen were correlated 92 %, which favors the removal of nutrients in wastewater . The increase in the concentration of nitrogen in the sludge in stage C generated a C:N ratio of 7.98. This ratio shows that the sludge is feasible for use as a mediator of soils and a biofertilizer because of the high contents of calcium, phosphorus and nitrogen. In addition, biocalcium promoted the precipitation of hydroxyapatite, struvite, calcite and quartz. In general, the three stages of the treatment contributed to the stabilization of the wastewater treatment plant (WWTP) in an efficient, economical, and safe way., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Our understanding of drug-microbe relationships has evolved from viewing microbes as mere drug producers to a dynamic, modifiable system where they can serve as drugs or targets of precision pharmacology. This review highlights recent findings on the gut microbiome, particularly focusing on four aspects of research: (i) drugs for bugs, covering recent strategies for targeting gut pathogens; (ii) bugs as drugs, including probiotics; (iii) drugs from bugs, including postbiotics; and (iv) bugs and drugs, discussing additional types of drug-microbe interactions. This review provides a perspective on future translational research, including efficient companion diagnostics in pharmaceutical interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘All authors, except for J.A.U. and V.M.M., were employees of Digbi Health and may hold stocks or stock options in Digbi Health. R.S. was the CEO and founder of Digbi Health. D.E.A. has received royalties from Kura Biotech. S.V.K., I.P., R.S., and D.E.A. have patents pending related to the topic of this review (US Applications 17/817,558 and 17/817,562, entitled Methods and Systems for Multi-omics Interventions; and US Application 18/299,571, entitled Methods and Systems for Multi-omics Interventions for Multiple Health Conditions), as well as one provisional patent application (US Application 63/482,796, entitled Methods and Systems for Multi-omics Stratification of Patient Populations). I.P., J.A.U., V.M.M., and D.E.A. have coauthored multiple patents and patents pending owned by third-party companies, which are available in public domain repositories. The former conflicts of interest did not influence our adherence to policies nor any of the concepts or opinions discussed in this review article, and the review does not focus unduly on our own research or products.’., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Daytime napping may improve cognitive function in older adults. However, the association can be complicated by specific features of napping and the older adult's health. This systematic review aims to synthesize the current literature on napping and cognition in older adults and provide recommendations for future research and daytime sleep practice in older adults., Methods: Systematic searches for relative research published between January 1995 and October 2022 were conducted at PubMed, MEDLINE, PsycINFO, and Google Scholar using keywords individually and in multiple combinations. Manual searches were performed to identify additional studies. All included studies were critically appraised by 2 authors., Results: Thirty-five studies, including 23 observational and 12 intervention studies, were reviewed. Findings from observational studies suggest a possible inverted U-shaped association between napping duration and cognitive function: short and moderate duration of naps benefited cognitive health in older adults compared with both non-napping and long or extended napping. Findings from intervention studies suggest one session of afternoon napping might improve psychomotor function and working memory, although with some inconsistency. The effect of multiple nap sessions on cognition was inconclusive due to a limited number of studies., Conclusion: More rigorous research studies are needed to investigate what causes different patterns of daytime napping, the associations between these distinct patterns and cognitive function, and to determine whether interventions targeting napping patterns can improve cognition in older adults. In addition, future research needs to comprehensively assess daytime napping using a combination of measures such as sleep diary and actigraphy., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A 17-year-old male was taken to the emergency department for decreased left visual acuity and floaters beginning that same day. There was a history of exposure to pulmonary tuberculosis five years before (mother as index case) followed by a four-month period of isoniazid prophylaxis. The ophthalmic examination showed posterior and intermediate uveitis in the left eye. Laboratory tests were normal; IgG for herpes simplex 1 was positive and both the varicella-zoster virus and remaining serologic tests were negative. Chest radiography was normal. Two weeks later, an epiretinal membrane with risk of tractional retinal detachment was observed. The Mantoux tuberculin skin test showed an induration of 15 mm and the IGRA test was positive. Sputum and vitreous humor samples were collected. Quadruple therapy and prednisolone were started. Ten days later, a posterior vitreous detachment with underlying vitreous hematoma was observed. Posterior vitrectomy and peripheral endolaser were performed without complications. One month later, the microbiological results became available, with the identification of Mycobacterium tuberculosis. Corticosteroids were weaned progressively. Antituberculous drugs were maintained for six months. The patient made a full recovery.

Background: When caregivers have a high level of caregiver mastery, their care recipients with cognitive impairment have less behavioral health problems. However, the relationship between caregiver mastery and anxiety among care recipients over time is unknown. Therefore, this study was conducted to examine that better caregiver mastery is associated with less anxiety in individuals with cognitive impairment over time., Methods: A secondary data analysis was conducted using the Healthy Patterns Clinical Trial (NCT03682185) dataset and guided by Factors Associated with Behavioral and Psychological Symptoms of Dementia conceptual framework. This study included 154 dyads of individuals with cognitive impairment and their caregivers. Multiple linear regression analyses were performed on changes in anxiety. Model 1 included variables at the level of neurodegeneration (i.e., cognitive impairment and age). Model 2 added patient factors (i.e., sleep problems and depression) with the Model 1. Finally, Model 3 included caregiver factor (i.e., caregiver mastery) with the Model 2 to examine how changes in caregiver mastery influence changes in anxiety of care recipients., Results: Model 3 was statistically significant; after controlling for variables at the level of neurodegeneration associated with cognitive impairment and patient factors, improvement of caregiver mastery over time (β =-0.230, p = 0.015) was related to decreased anxiety over time (R 2  = 0.1099)., Conclusions: Caregivers with high caregiver mastery may have better knowledge on how to care for their loved ones and how to manage their neuropsychiatric symptoms. Therefore, improving the level of caregiver mastery by providing psychoeducational programs and resources that family caregivers need will help reduce the frequency of anxiety in individuals with cognitive impairment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs. Twenty RCTs were included in the updated systematic review. Physical activity significantly reduced fatigue (standardized mean difference -0.44, 95% confidence interval -0.64 to -0.24; n = 8 RCTs). Using the 2018 recommendations as a basis, the panel continued to make strong recommendations to use physical activity, and to offer relaxation, mindfulness or both, to manage fatigue in pediatric patients. Cognitive or cognitive behavioral therapies may be offered. Pharmacological approaches should not be routinely used. The panel made a new good practice statement to routinely assess for fatigue, ideally using a validated scale., Competing Interests: PSH received grants or research support from NIH; royalties or licenses from Lippincott; consulting fees from MSKCC and participated on the REACH Board at Nemours, Delaware. SNCR received grants from CIHR, CCS and Kids Cancer Care-IMPACT. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2023 The Author(s).)

Cisplatin is clinically proven to combat different cancers, including sarcomas, soft tissue cancers, bones, muscles, and blood. However, renal and cardiovascular toxicities are important limitations in cisplatin therapeutical use. Immunoinflammation could be key factor in cisplatin-induced toxicity. The aim of the present study was to evaluate the activation of the inflammatory TLR4/NLRP3 pathway as a common mechanism for cardiovascular and renal cisplatin's cycles treatment toxicity. Adult male Wistar rats were treated with saline, cisplatin 2 mg/kg or cisplatin 3 mg/kg (intraperitoneally once a week, for five experimental weeks). After treatments, plasma, cardiac, vascular, and renal tissues were collected. Plasma malondialdehyde (MDA) and inflammatory cytokines were determined. TLR4, MyD88, NF-κβ p65, NLRP3, and procaspase-1 tissue expressions were also analyzed. Cisplatin treatment induced a dose-dependent increase in plasma MDA and IL-18. In cardiovascular system, an increase in NLRP3 and in cleaved caspase-1 were observed in cardiac tissue and a moderate increase in TLR4, MyD88 appeared in mesenteric artery. In kidney, a significant dose-dependent increase in TLR4, MyD88 and NLRP3 and cleaved caspase 1 expressions were observed after cisplatin treatments. In conclusion, cisplatin cycles provoke a low grade pro-inflammatory systemic state. Kidney was more sensitive than cardiovascular tissues to this pro-inflammatory state. TLR4 and NLRP3 are key pathways involved in renal tissue damage, NLRP3 is the main pathway involved in cardiac toxicity and TLR4 pathway in resistance vessel toxicity., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Spatial variation in cellular phenotypes underlies heterogeneity in immune recognition and response to therapy in cancer and many other diseases. Spatial transcriptomics holds the potential to quantify such variation, but existing analysis methods are limited by their focus on individual tasks such as spot deconvolution. We present BayesTME, an end-to-end Bayesian method for analyzing spatial transcriptomics data. BayesTME unifies several previously distinct analysis goals under a single, holistic generative model. This unified approach enables BayesTME to deconvolve spots into cell phenotypes without any need for paired single-cell RNA-seq. BayesTME then goes beyond spot deconvolution to uncover spatial expression patterns among coordinated subsets of genes within phenotypes, which we term spatial transcriptional programs. BayesTME achieves state-of-the-art performance across myriad benchmarks. On human and zebrafish melanoma tissues, BayesTME identifies spatial transcriptional programs that capture fundamental biological phenomena such as bilateral symmetry and tumor-associated fibroblast and macrophage reprogramming. BayesTME is open source., Competing Interests: Declaration of interests R.M.W. is a paid consultant to N-of-One Therapeutics, a subsidiary of Qiagen. R.M.W. receives royalty payments for the use of the casper line from Carolina Biologicals., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Two experiments were designed to evaluate the effects of altering body condition score (BCS) and the profile of a fatty acid (FA) supplement on the metabolism of Bos indicus Nellore females. In experiment 1, 16 and 24 B. indicus heifers and nonlactating cows, respectively, were assigned to (1) maintenance diet (MNT-MNT; n = 10), (2) maintenance diet and BCS loss (MNT-LSS; n = 10), (3) maintenance diet supplemented with calcium salts of soybean oil for 30 d and BCS loss for 40 d (MNT+CFA-LSS; n = 10), and (4) maintenance diet for 30 d and BCS loss for 40 d with a diet containing calcium salts of soybean oil (MNT-LSS+CFA; n = 10). Following the BCS loss period, MNT-LSS, MNT+CFA-LSS, and MNT-LSS+CFA were fed a diet to promote the gain of BCS. In experiment 2, 40 Bos indicus nulliparous heifers were assigned to (1) maintenance diet (MNT-MNT; n = 10), (2) BCS loss followed by a BCS gain (LSS-REM; n = 10), (3) BCS loss followed by a BCS gain diet with CFA of palm oil (LSS-REM+PLM; n = 10), and (4) BCS loss followed by a BCS gain diet with CFA of soybean oil (LSS-REM+SOY; n = 10). Blood samples were obtained for serum haptoglobin and fecal samples for pH (experiment 2 only). In experiment 1, a treatment × day interaction was observed for BCS during the 60-d BCS loss and gain period. Animals assigned to MNT-MNT had a greater BCS than the other treatment groups on d 40 and 60 of the experiment, but no other differences were observed. Moreover, a treatment × day interaction was observed for serum haptoglobin, as on d 60, MNT-LSS had a greater mean serum haptoglobin concentration. In experiment 2, a treatment × day interaction was also observed for BCS. From d -4 to 0, LSS-REM and LSS-REM+SOY had a reduced BCS versus MNT-MNT, but also lower for LSS-REM versus MNT-MNT on d 1, and LSS-REM+PLM versus MNT-MNT on d -1 and 0. For serum haptoglobin, no treatment or treatment × day interaction was observed. A treatment × day interaction was observed for fecal pH. From d -10 to 0, MNT often had a lower fecal pH, but during realimentation, LSS-REM heifers had a reduced fecal pH on d 1, 4, and 10. In summary, we failed to demonstrate an increase in serum haptoglobin due to a BCS loss. Still, supplementation with calcium salts of FA alleviated the increase in haptoglobin and maintained fecal pH at more stable values during realimentation, regardless of the FA profile of the supplement., (© 2023.)

Aim: The aim of this study was to explore nurse practitioner (NP) students' perceptions of a sleep e-learning program., Background: Sleep assessment is uncommon as nursing curricula lack sleep education. By preparing NPs to conduct sleep assessment and screening and understand basic sleep diagnostics, sleep health is more likely to be part of the differential diagnosis., Method: The study is a qualitative descriptive study utilizing two focus groups. A directed content analysis, guided by the Kirkpatrick model, was used for analysis., Results: Twenty-four students participated in focus groups. Two overarching themes emerged: perceptions of course design and content. Asynchronous, case-based scenarios and quizzes were favorable. Students spoke of content relevance to themselves and patients and intentions to adopt sleep assessment practices., Conclusion: NP students embraced sleep education and declared intention to apply learned skills in practice. This study highlights the feasibility of increasing curricular exposure to sleep education and ensuring NPs have skills to recognize implications of poor and disordered sleep in patients., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2023 National League for Nursing.)

Insomnia symptoms are prevalent in older adults with mild cognitive impairment (MCI) and can pose treatment challenges. We tested the feasibility, acceptability, and preliminary efficacy of assisted relaxation therapy (ART) to improve insomnia symptoms in community-dwelling older adults with MCI. In this pilot RCT, 25 participants were assigned to intervention or control groups for 2 weeks. The final sample ( n  = 20) consisted of all Black, primarily female (70%) older adults (mean age 69.10; SD  = 7.45) with mean Montreal Cognitive Assessment scores of 21.10 ( SD  = 2.49). Recruitment was timely; attrition was low (80%). Participants were able to use ART (average use 7.00; SD  = 5.07 days). Participants in the ART group improved on Insomnia Severity Index (ISI) (- 7.10; 95% CI [-11.63, -2.55]; p  = .004) compared to baseline. There were clinically meaningful mean change scores on ISI for the intervention group compared to the control (- 7.10 vs. - 4.33). Results provide justification for testing ART in a fully powered clinical trial.

Objective: To assess the cardiovascular risk (CV risk) change following bilateral phacoemulsification cataract surgery., Methods: We performed a retrospective observation cohort study on 112 selected patients who underwent uncomplicated bilateral cataract surgery at Centro Hospitalar de Entre o Douro e Vouga (CHEDV) between 2018 and 2019. This patient cohort was further subdivided in 2 different groups: Good VA - no to mild visual impairment, ≤0.48 LogMAR; Bad VA - moderate to severe visual impairment, >0.48 LogMAR. We compared the changes in the CV risk score components in our patient cohort and between subgroups Good VA and Bad VA, before and after surgery, using paired t-test or Wilcoxon rank-sum test, and repeated measures ANOVA with Tukey post-hoc tests, respectively. Visual Acuity (VA) before and after surgery was correlated with the patients' CV risk score. At last, linear regression models were built to explain changes in CV risk variables considering the change in VA., Results: Cataract surgery resulted in improved VA. Notably, following surgery our patient cohort showed reduced low-density lipoprotein (LDL) levels after surgery, from 111.17±36.26 mg/dL to 104.22±37.53 mg/dL, and reduced systolic arterial pressure (SAP), from 139.1±15.0 mmHg to 133.7±12.0 mmHg. Ultimately, this translated to an improved CV risk score within 6 months of cataract surgery, from 17.39±11.44% to 16.51±11.27%. Of note, these improvements were mostly present in the Bad VA group of patients, where baseline VA and incidence of dyslipidemia were worse., Conclusion: Our results suggest that phacoemulsification cataract surgery may be an important tool in addressing CV risk.

There are more than 900 genetic syndromes associated with oral manifestations. These syndromes can have serious health implications, and left undiagnosed, can hamper treatment and prognosis later in life. About 6.67% of the population will develop a rare disease during their lifetime, some of which are difficult to diagnose. The establishment of a data and tissue bank of rare diseases with oral manifestations in Quebec will help medical professionals identify the genes involved, will improve knowledge on the rare genetic diseases, and will also lead to improved patient management. It will also allow samples and information sharing with other clinicians and investigators. As an example of a condition requiring additional research, dental ankylosis is a condition in which the tooth's cementum fuses to the surrounding alveolar bone. This can be secondary to traumatic injury but is often idiopathic, and the genes involved in the idiopathic cases, if any, are poorly known. To date, patients with both identified and unidentified genetic etiology for their dental anomalies were recruited through dental and genetics clinics for the study. They underwent sequencing of selected genes or exome sequencing depending on the manifestation. We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A , EDAR , AMBN , PLOD1 , TSPEAR , PRKAR1A , FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS . Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

H 2 S is a gaseous compound that contributes to air pollution. In this work, the electrochemical oxidation treatment of gaseous streams polluted with H 2 S is evaluated using a jet mixer and electrochemical cell device, in which the performance of electrolytic and electro-Fenton assisted absorption processes are compared. Results demonstrate the feasibility of both processes to remove H 2 S, reaching coulombic efficiencies of nearly 100% in the electrolytic assisted absorption, and 70-80% in the electro-Fenton assisted absorption. Aqueous solutions containing phosphate salts as electrolyte were found to be suitable as absorbents for the process. Efficiency in the cathodic production of H 2 O 2 in these solutions using the experimental device was found to be as high as 32.8% (1.184 mgH 2 O 2 /min) at 12 °C and atmospheric pressure. Sequential formation of SO 2 and SO 3 is obtained by the oxidation of H 2 S contained in the gas. These species are hydrolysed, and a part remained in the absorbent as SO 3 2- and SO 4 2- , while the rest is dragged in the outlet gas. SO 3 production is promoted by electrolytic assisted absorption and polysulphides by the electro-Fenton technology. Low concentrations of elemental sulphur are detected in the solid suspensions formed during the process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)