Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

Positive species interactions structure rhodolith bed communities at a global scale.

Rhodolith beds are diverse and globally distributed habitats. Nonetheless, the role of rhodoliths in structuring the associated species community through a hierarchy of positive interactions is yet to be recognised. In this review, we provide evidence that rhodoliths can function as foundation species of multi-level facilitation cascades and, hence, are fundamental for the persistence of hierarchically structured communities within coastal oceans. Rhodoliths generate facilitation cascades by buffering physical stress, reducing consumer pressure and enhancing resource availability. Due to large variations in their shape, size and density, a single rhodolith bed can support multiple taxonomically distant and architecturally distinct habitat-forming species, such as primary producers, sponges or bivalves, thus encompassing a broad range of functional traits and providing a wealth of secondary microhabitat and food resources. In addition, rhodoliths are often mobile, and thus can redistribute associated species, potentially expanding the distribution of species with short-distance dispersal abilities. Key knowledge gaps we have identified include: the experimental assessment of the role of rhodoliths as basal facilitators; the length and temporal stability of facilitation cascades; variations in species interactions within cascades across environmental gradients; and the role of rhodolith beds as climate refugia. Addressing these research priorities will allow the development of evidence-based policy decisions and elevate rhodolith beds within marine conservation strategies.

Proteomic Profiling of Tears in Blau Syndrome Patients in Identification of Potential Disease Biomarkers.

Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils' azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies.

Clinical and biochemical data for the diagnosis of endogenous hypercortisolism: the "Cushingomic" approach.

CONTEXT: The clinical presentation of Cushing's syndrome (CS) overlaps with common conditions. Recommended screening tests are serum cortisol after 1-mg overnight dexamethasone suppression test (DST), urinary free cortisol (UFC), and late-night salivary cortisol (LNSC). METHODS: We analyzed the diagnostic accuracy of screening tests in 615 patients without CS (263 suspected CS, 319 adrenal and 33 pituitary incidentaloma) and 40 with CS. Principal component analysis, K-means clustering, and neural network were used to compute an integrated analysis among tests, comorbidities, and signs/symptoms of hypercortisolism. RESULTS: The diagnostic accuracy of screening tests for CS was high, DST and UFC were slightly superior to LNSC. The threshold of DST should be adapted to the population considered, especially in adrenal incidentaloma with mild autonomous cortisol secretion: the cutoff to differentiate CS should be increased to 196 nmol/L. Diabetes, hypertension, and obesity were more common in patients without CS: the direction of their vectors was not aligned and their correlation with screening tests was poor. Clustering allowed us to differentiate those patients without CS in cluster one (aged osteoporotic patients with impaired screening tests), cluster two (hypertensive and metabolic phenotype), and cluster three (young subjects with a low likelihood of overt CS). A neural network model that combined screening tests and clinical presentation was able to predict the CS diagnosis in the validation cohort with 99% precision and 86% accuracy. CONCLUSIONS: Despite the high diagnostic accuracy of screening tests to detect CS, cortisol-related comorbidities or adrenal incidentaloma should be considered when interpreting a positive test.

Colorectal cancer and inflammatory bowel diseases share common salivary proteomic pathways.

Inflammatory bowels diseases (IBD) are high risk conditions for colorectal cancer (CRC). The discovery of IBD and CRC noninvasive protein/peptide biomarkers using saliva and feces was the aim of this study involving 20 controls, 25 IBD (12 Crohn's Disease-CD), 37 CRC. By untargeted proteomic (LTQ-Orbitrap/MS), a total of 152 proteins were identified in saliva. Absent in controls, 73 proteins were present in both IBD and CRC, being mainly related to cell-adhesion, cadherin-binding and enzyme activity regulation (g-Profiler). Among the remaining 79 proteins, 14 were highly expressed in CD and 11 in CRC. These proteins clustered in DNA replication/expression and innate/adaptive immunity. In stool, endogenous peptides from 30 different proteins were identified, two being salivary and CD-associated: Basic Proline-rich Protein 1 (PRBs) and Acidic Proline-rich Phosphoprotein. Biological effects of the PRBs-related peptides GQ-15 and GG-17 found in CD stool were evaluated using CRC cell lines. These peptides induced cell proliferation and activated Erk1/2, Akt and p38 pathways. In conclusion, the salivary proteome unveiled DNA stability and immunity clusters shared between IBD and CRC. Salivary PRB-derived peptides, enriched in CD stool, stimulate CRC cell proliferation and the pro-oncogenic RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways suggesting a potential involvement of PRBs in IBD and cancer pathogenesis.

Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk.

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.

Plasma lipids paediatric reference intervals: Indirect estimation using a large 14-year database.

OBJECTIVES: Establishing direct reference intervals (RIs) for paediatric patients is a very challenging endeavour. Indirect RIs can address this problem, using existing clinical laboratory databases from real-world data research. Compared to the traditional direct method, the indirect approach is highly practical, widely applicable, and low-cost. Considering the relevance of dyslipidemia in the paediatric age, to provide better laboratory services to the local paediatric population, we established population-specific lipid RIs via data mining. METHODS: Our laboratory information system was searched for cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) of patients aged less than 18 years, performed from January 2009 until December 2022. RIs were estimated using RefineR algorithm. RESULTS: Values from 215,594 patients were initially collected. After refining data on the basis of specific exclusion criteria that left 17,933 patients, we determined the RIs for each analyte, including corresponding 95% confidence interval (95% CI). Age and sex partitions were required for proper stratification of the heterogenous subpopulations. Age-related variations in TC and TG values were observed mainly in children until 5 years. RIs were defined for children less than 3 years and for those of 3-18 years. In our population, the obtained RIs were comparable with those of the literature, but the upper TG limit in subjects under the age of 3 (2.03 mmol/L with 95% CI: 1.45-2.86) was lower than that previously reported. CONCLUSIONS: Our RIs, necessary for paediatric lipid monitoring, are tailored to the serviced patient population as should be done whenever possible.

Evaluation of the Comparability of Wantai Wan200+ Instrument with Routine Laboratory Assays for 21 Different Analytes.

Background: We compared the performance of 21 different assays performed by the Wantai Wan200+ (Wantai BioPharm, Beijing, China) with respect to other methods in use at the University Hospital of Padova (AOPD), Italy. Methods: The plasma (P) or serum (S) of 5027 leftover samples, collected from May to Sept 2023, was either analyzed or frozen at -20 °C. Beckman DXI800 (DXI), Roche Cobas 8000 e801 (RC), Snibe Maglumi 4000 plus (SM), DiaSorin Liaison XL (DL) and Binding Site Optilite (BS) equipment were used at the AOPD. P-procalcitonin (PCT), DXI; P-Troponin I (TnI), DXI; S-CA125, DXI; S-free PSA (f-PSA), DXI; S-total PSA (t-PSA), DXI; S-IL6, SM; P-Troponin T (TnT), RC; P-NT-proBNP, RC; P-Neuron-Specific Enolase (NSE), RC; S-CA15-3, DL; S-CA19-9, DL; S-AFP, DL; and S-CEA, DL were tested in fresh samples. P-Myoglobin (Myo), DXI; P-Cyfra21-1, RC; S-ß2 microglobulin (B2MIC), BS; S-HE4, SM; S-PGI, SM; S-PGII, SM; S-CA72-4, SM; and S-CA50, SM were analyzed in frozen and thawed samples. Bland-Altman (BA), Passing-Bablok (PB) and Cohen's Kappa (CKa) metrics were used as statistics. Results: An excellent comparability profile was found for 11 analytes. For example, the t-PSA CKa was 0.94 (95%CI: 0.90 to 0.98), and the PB slope and intercept were 1.02 (95%CI: 0.99 to 1.03) and 0.02 (95%CI: 0.01 to 0.03), respectively; the BA bias was 2.25 (95%CI: -0.43 to 4.93). Ten tested measurands demonstrated a suboptimal comparability profile. Biological variation in EFLM (EuBIVAS) performance specifications was evaluated to assess the clinical relevance of measured biases. Conclusions: Evaluation of the Wantai Wan200+'s performance suggests that between-method differences did not exceed the calculated bias. Metrological traceability may influence the comparisons obtained for some measurands.

Flow Cytometry Analysis in Breast Implant-Associated Anaplastic Large Cell Lymphoma: Three Case Reports.

Breast Implant-Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL) is a rare T-cell non-Hodgkin lymphoma associated with breast prosthetic implants and represents a diagnostic challenge. The National Comprehensive Cancer Network (NCCN) guidelines, updated in 2024, recommend for diagnosis an integrated work-up that should include cell morphology, CD30 immunohistochemistry (IHC), and flow cytometry (FCM). CD30 IHC, although the test of choice for BIA-ALCL diagnosis, is not pathognomonic, and this supports the recommendation to apply a multidisciplinary approach. A close collaboration between pathologists and laboratory professionals allowed the diagnosis of three BIA-ALCLs, presented as case reports, within a series of 35 patients subjected to periprosthetic effusions aspiration from 2018 to 2023. In one case, rare neoplastic cells were identified by FCM, and this result was essential in leading the anatomopathological picture as indicative of this neoplasm. In fact, the distinction between a lymphomatous infiltrate from reactive cells may be very complex in the cytopathology and IHC setting when neoplastic cells are rare. On the other hand, one limitation of FCM analysis is the need for fresh samples. In this study, we provide evidence that a dedicated fixative allows the maintenance of an unaltered CD30 expression on the cell surface for up to 72 h.

A call-to-action for energy conservation and sustainability in the clinical laboratory: Experiences from the University of Padova.

OBJECTIVES: Healthcare has a considerable environmental impact, yet it has been largely overlooked. Clinical laboratories, in particular, consume significantly more energy and water per unit area compared to standard office buildings. It is crucial to raise awareness among laboratories about the significance of embracing eco-friendly practices. Numerous energy-saving measures do not incur additional costs but necessitate a shift in organizational culture and mindset. DESIGN & METHODS: This paper conducts a cost-benefit analysis of energy consumption at the Laboratory Medicine Unit of University Hospital of Padova, beginning with laboratory refrigerators and freezers. RESULTS: The need to rationalize the existing units, especially the combined refrigerators-freezers, and reorganize the contents of the Ultra-Low Temperature freezers with an energy-saving perspective has emerged. CONCLUSIONS: By implementing these practices, this initiative can gradually expand to encompass more green activities in the future.

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

Clinical and Analytical Performance of ELISA Salivary Serologic Assay to Detect SARS-CoV-2 IgG in Children and Adults.

Saliva is a promising matrix with several purposes. Our aim is to verify if salivary anti-SARS-CoV-2 antibody determination is suitable for monitoring immune responses. One hundred eighty-seven subjects were enrolled at University-Hospital Padova: 105 females (56.1%) and 82 males (43.9%), 95 (50.8%) children and 92 (49.2%) adults. Subjects self-collected saliva using Salivette; nineteen subjects collected three different samples within the day. A serum sample was obtained for all individuals. The N/S anti-SARS-CoV-2 salivary IgG (sal-IgG) and serum anti-SARS-CoV-2 S-RBD IgG (ser-IgG) were used for determining anti-SARS-CoV-2 antibodies. The mean (min-max) age was 9.0 (1-18) for children and 42.5 (20-61) for adults. Of 187 samples, 63 were negative for sal-IgG (33.7%), while 7 were negative for ser-IgG (3.7%). Spearman's correlation was 0.56 (p < 0.001). Sal-IgG and ser-IgG levels were correlated with age but not with gender, comorbidities, prolonged therapy, previous SARS-CoV-2 infection, or time from last COVID-19 infection/vaccination. The repeatability ranged from 23.8% (7.4 kAU/L) to 4.0% (3.77 kAU/L). The linearity of the assay was missed in 4/6 samples. No significant intrasubject differences were observed in sal-IgG across samples collected at different time points. Sal-IgG has good agreement with ser-IgG. Noninvasive saliva collection represents an alternative method for antibody measurement, especially in children.

Analytical and clinical evaluations of SNIBE Maglumi chemiluminescent immunoassay for the detection of SARS-CoV-2 antigen in salivary samples.

OBJECTIVES: In this study, we describe the analytical and clinical performances of the SNIBE Maglumi SARS-CoV-2 antigen fully-automated chemiluminescent immunoassay (MAG-CLIA) on salivary samples. METHODS: Limit of detection (LOD), linearity and precision were tested for values close to or below the declared LOD. Clinical performance of MAG-CLIA was evaluated on leftover salivary samples from the healthcare workers (HCW) surveillance program, at the University-Hospital of Padova. Salivary samples were analyzed by Lumipulse G SARS-CoV-2 Ag, and in case where the values exceeded 0.41 ng/L, further testing was conducted using TaqPathTM COVID-19 RT-PCR (Applied Biosystems, Thermo Fisher Scientific). RESULTS: The estimated MAG-CLIA LOD was 3 ng/L, with repeatability of 7.5 %. Good linearity was demonstrated by diluting two samples at 52.7 ng/L and 211.4 ng/L. Of the 228 HCW samples, 59/228 (25.9 %) were positive, 169/228 (74.1 %) were negative. MAG-CLIA SARS-CoV-2 sAg median level (and interquartile range [IQR]) was 5.03 ng/L (<0.001-35.8 ng/L) for positive and <0.001 ng/L (<0.001 ng/L) for negative samples. MAG-CLIA AUC was 0.795 (95 % CI: 0.720-0.871). Using the best cut-off, 3.5 ng/L, sensitivity and specificity were 57.1 % (95 % CI: 42.2-71.2 %) and 97.0 % (95 % CI: 93.2-99.0 %), respectively. The agreement with the molecular assay was 88.1 % (Cohen's kappa 0.606 [SE=0.066, p<0.001]). CONCLUSIONS: The analytical performances of MAG-CLIA are satisfactory, also when values below LOD were tested. In saliva samples, although specificity was elevated, clinical performance was not comparable with that on nasopharyngeal swabs (NPS).

Heat inactivation of SARS-CoV 2 enabled the measurement of salivary cortisol during COVID-19 pandemic.

BACKGROUND AND AIM: Salivary cortisol has become an essential tool in the management of cortisol-related disease. In 2020 the sudden outbreak of COVID-19 pandemic caused several concerns about the use of saliva, due to the risk of contamination, and a European consensus further discourage using salivary cortisol. To decrease infectious risk, we handled specimens by applying a heat treatment to inactivate viral particles, further evaluating the impact of the COVID-19 pandemic on the use of salivary cortisol in clinical practice. MATERIAL AND METHODS: Saliva samples were exposed for 10 min at 70 °C, then cortisol was measured using LC-MS/MS. The number of salivary cortisol examinations from 2013 to 2022 was extracted from the local electronic database: those performed in 2019, 2020, and 2021 were analyzed and compared with the historical data. RESULTS: During 2020 we observed a decrease of 408 (-20%) examinations (p = 0.05) compared to 2019; especially in salivary cortisol daily rhythm and salivary cortisol/cortisone ratio (respectively reduction of 47% and 88%, p = 0.003 and p = 0.001). Analyzing year 2021 compared with 2020 we reported an increase of 420 examinations (+20%, p = 0.01), with a complete recovery of salivary cortisol measurement (considering 2019: p = 0.71). Major differences were observed between morning salivary cortisol (-20%, p = 0.017), LNSC (-21%, p = 0.012) and salivary cortisol rhythm (-22%, p = 0.056). No Sars-Cov2 infections related to working exposure were reported among laboratory's employers. CONCLUSIONS: We speculate that the adoption of an appropriate technique to inactivate viral particles in saliva specimens allowed the safety maintenance of salivary collections, also during the Sars-CoV-2 outbreak.

Circulating haematopoietic stem cells and long-term outcomes of COVID-19.

BACKGROUND AND AIMS: An acute depletion of circulating haematopoietic stem/progenitor cells (HSPCs) occurs during COVID-19, especially among patients with a poorer disease course. We herein examined whether HSPCs levels at hospital admission for COVID-19 predict 1-year mortality and the long-COVID syndrome. MATERIALS AND METHODS: Patients hospitalized for COVID-19 in an infectious disease ward were consecutively enrolled. Circulating HSPC levels were assessed by flow cytometry as cells expressing CD34 and/or CD133. Follow-up was performed for 12 months after hospitalization through the review of electronic medical records and demographic local registers. RESULTS: The study included 100 patients, 36 of whom reported symptoms of long-COVID and 20 died during follow-up. The reduction of 1-SD of HSPCs was associated with a 3- to 5-fold increase in the risk of 1-year mortality. Age, admission hyperglycaemia, C-reactive protein peak, liver enzymes, the need of high-flow oxygen and/or invasive ventilation were predictors of mortality at univariate analysis. Among pre-existing comorbidities, coronary heart disease and chronic kidney disease, but not diabetes, were associated with 1-year mortality. In multivariate analyses, HSPCs remained significantly associated with 1-year mortality independently of confounders. The development of pneumonia an in-hospital treatment with glucocorticoids and convalescent plasma were associated with long-COVID symptoms at follow-up. HSPCs, diabetes and other comorbidities were not predictors of long-COVID. CONCLUSIONS: In a cohort of patients hospitalized for COVID-19, lower HSPC levels at the time of admission were independent predictors of 1-year mortality. However, COVID-19 severity, but not HSPC level, was significantly associated with the development of long-COVID symptoms.

Troponin T in spinal and bulbar muscular atrophy (SBMA).

Serum biomarkers that might detect clinical progression are currently lacking for Spinal and bulbar muscular atrophy (SBMA), thus limiting the effectiveness of possible future pharmacological trials. Elevation of cardiac troponin T (cTnT) unrelated to myocardial damage in a motor neuron (MN) disease as amyotrophic lateral sclerosis (ALS) was associated to disease severity. We enrolled 47 SBMA patients and 5 Spinal muscular atrophy (SMA) type 3 adult patients as control group; each SBMA patient was evaluated at baseline and at one-year follow-up visit. Demographic and clinical data including functional scores (SBMAFRS) were collected; serum was collected as standard of care and tested for cardiac troponins. Levels of cTnT but not cTnI were increased in SBMA with respect to reference values; unlike other neuromuscular diseases, SMA patients had overall normal cTnT values. Median cTnT concentrations did not change after one year and values were correlated to motor function, particularly with lower limb subdomain, at baseline only. Variations of cTnT and of SBMAFRS were unrelated. The cautiously promising results of cTnT as potential biomarker should undergo a more extensive clinical validation, including studies with longer follow-up period. When evaluating SBMA patients for a potential cardiac damage cTnI testing should be coupled or preferred to cTnT.

Short-term impact assessment of ocean liming: A copepod exposure test.

Ocean liming (OL) is a potential carbon dioxide removal (CDR) method that aims to increase the ocean's capacity to absorb atmospheric CO2 by adding hydrated lime to the surface ocean. Modeling studies indicate that OL may cause temporary pH spikes lasting several minutes, depending on the lime sparging rate. Little is known about the short-term effects of these spikes on marine organisms. Aim of the present study is to investigate these effects on the copepod Acartia tonsa. Copepods were exposed to different pH conditions (9, 10, 11, 12) by dosing different hydrated lime solutions. Copepod mortality, movements, and behavior were recorded. At pH 9 for short exposure times (<6 h), no negative effects were observed indicating a potential tolerable threshold for OL applications. At longer exposure times (>6 h) and pH higher than 9, negative effects (mortality and sublethal effects) were found significantly higher than in the control.

Managing Circadian Disruption due to Hospitalization: A Pilot Randomized Controlled Trial of the CircadianCare Inpatient Management System.

The objective of the present study was to test the effects of an inpatient management system (CircadianCare) aimed at limiting the negative impact of hospitalization on sleep by enhancing circadian rhythmicity. Fifty inpatients were randomized to either CircadianCare (n = 25; 18 males, 62.4 ± 1.9 years) or standard of care (n = 25; 14 males, 64.5 ± 2.3 years). On admission, all underwent a full sleep-wake evaluation; they then completed daily sleep diaries and wore an actigraph for the whole length of hospitalization. On days 1 (T0), 7 (T1), and 14 (T2, if still hospitalized), salivary melatonin for dim light melatonin onset (DLMO) and 24-h skin temperature were recorded. In addition, environmental noise, temperature, and illuminance were monitored. Patients in the CircadianCare arm followed 1 of 3 schedules for light/dark, meal, and physical activity timings, based on their diurnal preference/habits. They wore short-wavelength-enriched light-emitting glasses for 45 min after awakening and short-wavelength light filter shades from 18:00 h until sleep onset. While the first, primary registered outcome (reduced sleep-onset latency on actigraphy or diary) was not met, based on sleep diaries, there was a trend (0.05 < p < 0.1) toward an advance in bedtime for CircadianCare compared to standard of care patients between T0 and T1. Similarly, DLMO time significantly advanced in the small group of patients for whom it could be computed on both occasions, with untreated ones starting from earlier baseline values. Patients sleeping near the window had significantly higher sleep efficiency, regardless of treatment arm. As noise fluctuation increased, so did the number of night awakenings, regardless of treatment arm. In conclusion, the CircadianCare management system showed positive results in terms of advancing sleep timing and the circadian rhythm of melatonin. Furthermore, our study identified a combination of environmental noise and lighting indices, which could be easily modulated to prevent hospitalization-related insomnia.

Evaluation of a new molecular test for the detection of SARS-CoV-2 nucleic acid in salivary samples.

Background: Molecular testing is considered the gold standard for the detection of SARS-CoV-2. This study aimed to compare the performance of the P742H SARS-CoV-2 Nucleic Acid Multiplex Detection Kit in salivary samples, with respect to the 732HF Novel Coronavirus (2019-nCoV) Nucleic Acid Detection Kit and the TaqPath COVID-19 CEIVD RT-PCR Kit, used at University-Hospital of Padova, Italy. Methods: One hundred twenty-four salivary samples selfcollected by healthcare workers (HCW) during the screening program at University-Hospital of Padova, Italy, from Oct to Nov 2022, were included in the study. RNA extraction was performed by Viral DNA and RNA Extraction Kit (Technogenetics, Lodi, Italy) and amplification by P742H and 732HF (Technogenetics, Lodi, Italy). RNA was extracted using MagNa Pure 96 DNA and Viral NA Small Volume Kit (Roche, Switzerland) for TaqPath analysis (Thermo Fisher Scientific, USA).