PHA4GE quality control contextual data tags: standardized annotations for sharing public health sequence datasets with known quality issues to facilitate testing and training.

As public health laboratories expand their genomic sequencing and bioinformatics capacity for the surveillance of different pathogens, labs must carry out robust validation, training, and optimization of wet- and dry-lab procedures. Achieving these goals for algorithms, pipelines and instruments often requires that lower quality datasets be made available for analysis and comparison alongside those of higher quality. This range of data quality in reference sets can complicate the sharing of sub-optimal datasets that are vital for the community and for the reproducibility of assays. Sharing of useful, but sub-optimal datasets requires careful annotation and documentation of known issues to enable appropriate interpretation, avoid being mistaken for better quality information, and for these data (and their derivatives) to be easily identifiable in repositories. Unfortunately, there are currently no standardized attributes or mechanisms for tagging poor-quality datasets, or datasets generated for a specific purpose, to maximize their utility, searchability, accessibility and reuse. The Public Health Alliance for Genomic Epidemiology (PHA4GE) is an international community of scientists from public health, industry and academia focused on improving the reproducibility, interoperability, portability, and openness of public health bioinformatic software, skills, tools and data. To address the challenges of sharing lower quality datasets, PHA4GE has developed a set of standardized contextual data tags, namely fields and terms, that can be included in public repository submissions as a means of flagging pathogen sequence data with known quality issues, increasing their discoverability. The contextual data tags were developed through consultations with the community including input from the International Nucleotide Sequence Data Collaboration (INSDC), and have been standardized using ontologies - community-based resources for defining the tag properties and the relationships between them. The standardized tags are agnostic to the organism and the sequencing technique used and thus can be applied to data generated from any pathogen using an array of sequencing techniques. The tags can also be applied to synthetic (lab created) data. The list of standardized tags is maintained by PHA4GE and can be found at https://github.com/pha4ge/contextual_data_QC_tags. Definitions, ontology IDs, examples of use, as well as a JSON representation, are provided. The PHA4GE QC tags were tested, and are now implemented, by the FDA's GenomeTrakr laboratory network as part of its routine submission process for SARS-CoV-2 wastewater surveillance. We hope that these simple, standardized tags will help improve communication regarding quality control in public repositories, in addition to making datasets of variable quality more easily identifiable. Suggestions for additional tags can be submitted to PHA4GE via the New Term Request Form in the GitHub repository. By providing a mechanism for feedback and suggestions, we also expect that the tags will evolve with the needs of the community.

New Forms of Neuroactive Phospholipids for DHA Enrichment in Brain.

Low levels of docosahexaenoic acid (DHA) in the brain have been related to neurological disorders, like Alzheimer's disease (AD). After ingestion, dietary DHA must cross the blood-brain barrier, where it is absorbed as lysophosphatidylcholine (LPC), due to its role as a preferential DHA carrier in the brain. This work aimed at the production of LPC-DHA extracts to be used in supplementation/food fortification intended neural enrichment in DHA. As it is rich in DHA, especially its phospholipids (PL), Atlantic mackerel (Scomber scombrus, caught in Spring/2022) was used as a raw material. The polar lipids fraction was separated and hydrolysed with Rhizomucor miehei lipase, to enzymatically convert phosphatidylcholine (PC) into LPC. The fish (muscle and by-products) lipids fraction was used for total lipids (TL) content, lipid classes (LC) and fatty acid (FA) profile evaluation, whilst polar lipids extracts were studied for LC production and FA analysis. Muscle TL ranged between 1.45 and 4.64 g/100 g (WW), while by-products accounted for 7.56-8.96 g/100 g, with the highest contents being found in March. However, PL were more abundant in muscle (22.46-32.20% of TL). For polar lipids extracts, PL represented 50.79% of TL, among which PC corresponded to 57.76% and phosphatidylethanolamine to 42.24%. After hydrolysis, nearly half of this PC was converted into LPC. When compared to the initial PC, DHA relative content (33.6% of total FA) was significantly higher after hydrolysis: 55.6% in PC and 73.6% in LPC. Such extract, obtained from this undervalued species, may represent a promising strategy to increase DHA uptake into brain cells while allowing this species to upgrade.

Overcoming Microbiome-Acquired Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma.

Gastrointestinal cancers (GICs) are one of the most recurrent diseases in the world. Among all GICs, pancreatic cancer (PC) is one of the deadliest and continues to disrupt people's lives worldwide. The most frequent pancreatic cancer type is pancreatic ductal adenocarcinoma (PDAC), representing 90 to 95% of all pancreatic malignancies. PC is one of the cancers with the worst prognoses due to its non-specific symptoms that lead to a late diagnosis, but also due to the high resistance it develops to anticancer drugs. Gemcitabine is a standard treatment option for PDAC, however, resistance to this anticancer drug develops very fast. The microbiome was recently classified as a cancer hallmark and has emerged in several studies detailing how it promotes drug resistance. However, this area of study still has seen very little development, and more answers will help in developing personalized medicine. PC is one of the cancers with the highest mortality rates; therefore, it is crucial to explore how the microbiome may mold the response to reference drugs used in PDAC, such as gemcitabine. In this article, we provide a review of what has already been investigated regarding the impact that the microbiome has on the development of PDAC in terms of its effect on the gemcitabine pathway, which may influence the response to gemcitabine. Therapeutic advances in this type of GIC could bring innovative solutions and more effective therapeutic strategies for other types of GIC, such as colorectal cancer (CRC), due to its close relation with the microbiome.

Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function.

BACKGROUND: Aging and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak. OBJECTIVES: Two independent cross-sectional studies were designed to evaluate the association between age, sex, and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study 1) and in overweight and obese postmenopausal females (Study 2). METHODS: In Study 1, 40 young (20-49 y) and older (50-75 y) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable-isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m2) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined. RESULTS: In Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 µmol·h-1·kg-1 compared with 0.39 ± 0.10 µmol·h-1·kg-1, P = 0.01) but there was no evidence of a sex difference (P = 0.81). Plasma 25(OH)D concentration was not associated with PWV (r = 0.18, P = 0.28) or whole-body NO production (r = -0.20, P = 0.22). Plasma ADMA concentration was associated positively with age (r = 0.35, P = 0.03) and negatively with whole-body NO production (r = -0.33, P = 0.04). In Study 2, age was associated with lower PORH (r = -0.28, P = 0.02) and greater ADMA concentrations (r = 0.22, P = 0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r = -0.31, P = 0.004). CONCLUSIONS: Older age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in postmenopausal overweight females.

Development of a training programme in individual case formulation skills and a scale for assessing its effectiveness.

BACKGROUND: Little is known about the skills involved in clinical formulation. The individual case formulation (ICF) approach, based on functional analysis, employs clinical descriptions that are theory-free and depicts formulations constructed according to a set of basic conventions. AIMS: We report a test of whether this method could be taught and if the quality of the resulting diagrams could be reliably rated. METHOD: Participants (n=40) participated in a training course in formulation. A draft rating scale was refined in the course of rating formulation diagrams and basic inter-rater reliability established. RESULTS: Results of the study support further development of the ICF approach.

Empowerment-based nutrition interventions on blood pressure: a randomized comparative effectiveness trial.

Introduction: Empowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood pressure (BP) reduction: salt reduction-specific program vs. healthy lifestyle general program. Methods: Three hundred and eleven adults (median age of 44 years, IQR 34-54 years) were randomly assigned to a salt reduction (n = 147) or a healthy lifestyle program (n = 164). The outcome measures were urinary sodium (Na+) and potassium (K+) excretion, systolic (SBP) and diastolic (DBP) blood pressure, weight, and waist circumference. Results: There were no significant differences in primary and secondary outcomes between the two program groups. When comparing each program to baseline, the program focused on salt reduction was effective in lowering BP following a 12-week intervention with a mean change of -2.5 mm Hg in SBP (95% CI, -4.1 to -0.8) and - 2.7 mm Hg in DBP (95% CI, -3.8 to -1.5) in the intention-to-treat (ITT) analysis. In the complete-case (CC) analysis, the mean change was -2.1 mm Hg in SBP (95% CI, -3.7 to -0.5) and - 2.3 mm Hg in DBP (95% CI, -3.4 to -1.1). This effect increases in subjects with high-normal BP or hypertension [SBP - 7.9 mm Hg (95% CI, -12.5 to -3.3); DBP - 7.3 mm Hg (95% CI, -10.2 to -4.4)]. The healthy lifestyle group also exhibited BP improvements after 12 weeks; however, the changes were less pronounced compared to the salt reduction group and were observed only for DBP [mean change of -1.5 mm Hg (95% CI, -2.6 to -0.4) in ITT analysis and - 1.4 mm Hg (95% CI, -2.4 to -0.3) in CC analysis, relative to baseline]. Overall, improvements in Na+/K+ ratio, weight, and Mediterranean diet adherence resulted in clinically significant SBP decreases. Importantly, BP reduction is attributed to improved dietary quality, rather than being solely linked to changes in the Na+/K+ ratio. Conclusion: Salt-focused programs are effective public health tools mainly in managing individuals at high risk of hypertension. Nevertheless, in general, empowerment-based approaches are important strategies for lowering BP, by promoting health literacy that culminates in adherence to the Mediterranean diet and weight reduction.

How Can the Microbiome Induce Carcinogenesis and Modulate Drug Resistance in Cancer Therapy?

Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted therapies or immunotherapies. Drug resistance in cancer is one of the limiting factors contributing to unsuccessful therapies; therefore, understanding how cancer cells acquire this resistance is essential to help cure individuals affected by cancer. Recently, the altered microbiome was observed to be an important hallmark of cancer and therefore it represents a promising topic of cancer research. Our review aims to provide a global perspective of some cancer hallmarks, for instance how genetic and epigenetic modifications may be caused by an altered human microbiome. We also provide information on how an altered human microbiome can lead to cancer development as well as how the microbiome can influence drug resistance and ultimately targeted therapies. This may be useful to develop alternatives for cancer treatment, i.e., future personalized medicine that can help in cases where traditional cancer treatment is unsuccessful.

Salmonellosis in Children at a Portuguese Hospital: A Retrospective Study.

INTRODUCTION: Salmonellosis represents a considerable health, social and economic burden in both high- and low-income countries. Recently, in Portugal, most cases of Salmonella infections have been reported in children under 15 years of age. The main aim of this study was to characterize, from an epidemiological, microbiological, and clinical perspective, cases of Salmonella isolation among children. MATERIAL AND METHODS: The authors performed a descriptive study using retrospective analysis of cases of salmonellosis, in pediatric age, at a Portuguese Level II Hospital, between January 2015 and July 2020. RESULTS: The population included a total of 63 children, of which 81% were Portuguese. Ethnicity was identified in 13 children, most of whom were African. The median age at diagnosis was four years old (3.5 - 9 years old). Despite the small number of cases per year in our study (11), one-third were severe enough to require hospitalization. Overall, 13% of patients were treated with antibiotics. In 63% of the isolates, serotype was identified: Salmonella Enteriditis (38%), Salmonella Typhimurium (22%), and Salmonella Typhi (3%). Antibiotic resistance rates were 19% for ampicillin and 6.4% for amoxicillinclavulanic acid and cotrimoxazole. No resistance to third-generation cephalosporins was found. CONCLUSION: Given the obtained results, we intend to improve knowledge on salmonellosis in Portugal and, consequently improve prevention strategies, treatment and its notification. Although the incidence of salmonellosis has been decreasing in recent years it is the second most frequent gastrointestinal infection in the European Union, contributing to significant rates of hospitalizations and use of antibiotics in Portugal.

Acute Complications of Sickle Cell Disease in Children Under 5 Years at a Level II Hospital.

The aim of this study was to characterize the acute complications that required hospitalization in children under 5 years with Sickle Cell Disease. The population included 70 patients, 64% of African ascendency and 95.7% homozygotic for the HbS. We analyzed data from 337 hospitalizations. The first hospitalization occurred before 12 months in 38.6% and the average hospital admission per child was 3.92. The mean duration per hospitalization was 5.36 days. The most common diagnosis was vaso-occlusive crisis (36.8%) followed by fever, upper airway infections, bacterial pneumonia and splenic sequestration. Hemoglobin values at admission were between 6 and 7 g/dL in 22.3%, with 44.2% requiring at least 1 blood transfusion. There are several acute complications of SCD, being vaso-occlusive crisis the most common. Splenic sequestration generally occurs during the first 2 years and is associated with the need of transfusion. They represent a significant burden, with each child spending approximately 3 weeks hospitalized.

The association between anxiety and cardiac interoceptive accuracy: A systematic review and meta-analysis.

Anxiety is often conceptualised as the prototypical disorder of interoception (one's perception of bodily states). Whilst theoretical models predict an association between interoceptive accuracy and anxiety, empirical work has produced mixed results. This manuscript presents a pre-registered systematic review (https://osf.io/2h5xz) and meta-analysis of 55 studies, obtained via a Pubmed search on 9th November 2020, examining the relationship between state and trait anxiety and objectively measured cardiac interoceptive accuracy as assessed by heartbeat counting and discrimination tasks. Potential moderators of this relationship - the age, gender and clinical diagnoses of participants, the anxiety measures used and the study design - were also explored. Overall, we found no evidence for an association between cardiac interoceptive accuracy and anxiety, with none of the factors examined moderating this finding. We discuss the implications these findings have for future research, with a particular focus on the need for further investigation of the relationship between anxiety and other facets of interoception.

Iodine status, dietary iodine intake and iodized salt in school-aged children in São Miguel Island, Azores, Portugal.

OBJECTIVE: School-aged children in São Miguel Island, Azores, Portugal, are a population with a long history of iodine deficiency, and a recent governmental program for iodized salt (IS) consumption was implemented. This study investigated urinary iodine concentration (UIC), household and school IS consumption, and iodine-rich food intake in school-aged children. METHODS: In this cross-sectional study, spot urine samples and dietary iodine intake were collected. Urinary iodine concentration was evaluated using the fast colorimetric method. Dietary iodine intake was calculated by determining the iodine content of reported food intake using a Food Frequency Questionnaire (FFQ). RESULTS: The median UIC was 106.7 µg/L, and 55.5% of children had UIC >100 µg/L. Iodized salt was used by 100% of schools and 48.3% of school-aged children's households. Excluding iodine in IS, the median dietary iodine intake was 105.5 µg/d. No significant correlation was found between UIC and dietary iodine intake. Milk and dairy products, with a median intake of 311.1 g/d, provided 81.5 µg iodine/d. Seafood, with a median intake of 30.5 g/d, provided 16.8 µg iodine/d. Dairy product intake was not statistically correlated with UIC (P = 0.567). CONCLUSIONS: School-aged children in São Miguel Island did not have iodine deficiency after the governmental program for IS consumption. Adequate iodine status of school-aged children probably reflects not only an increase in iodine intake, through IS, but also an improvement of food intake patterns. Future studies are needed to ensure the sufficient iodine status of school-aged children in the Azores, and political commitment and efforts are required to prevent the possible reemergence of iodine deficiency.

Intracardiac versus extracardiac shunt in a young man with ischaemic stroke.

A 24-year-old man with a history of recent ischaemic stroke was diagnosed with patent foramen ovale (PFO) and referred for closure at our hospital. At admission, besides low peripheral oxygen saturation (88%), physical examination was otherwise normal. We performed intraprocedural transoesophageal echocardiogram that revealed no PFO, although agitated saline injection demonstrated bubbles lately on the left atrium. The atrial septum could not be crossed. We suspected an extracardiac shunt, so pulmonary angiograms were performed that revealed the presence of a left pulmonary arteriovenous malformation (PAVM). A Konar-MF Occluder was used to occlude the PAVM, with a satisfactory result. At 6 months follow-up, the patient had normal peripheral oxygen saturation and a new pulmonary angiogram showed no residual shunt. Intrapulmonary shunts are a rare and under-recognised cause of paradoxical emboli in young patients; physicians should be aware of this diagnosis as percutaneous occlusion is indicated and critical to avoid recurrent ischaemic episodes.

Accelerated idioventricular rhythm in a healthy newborn: frightening but non-threatening.

Accelerated idioventricular rhythm is a rare but benign form of ventricular tachycardia which might be challenging to differentiate from other more worrisome forms. We present the case of a healthy newborn diagnosed with an accelerated idioventricular rhythm which is spontaneously terminated without the need for medical therapy.

Indirect Calorimetry as an Instrument of Research to Identify the Effect of Hypermetabolism in Critical Patients' Prognosis.

BACKGROUND: Energy expenditure (EE) evaluation in Intensive Care Unit (ICU) patients can be very challenging. Critical illness is characterized by great variability in EE, which is influenced by the disease itself and the effects of treatment. Indirect calorimetry (IC) is currently the gold standard to measure EE in Intensive Care Unit (ICU) patients. However, calorimeters are not widely available, and predictive formulas (PF) are still commonly used, leading to under or overfeeding and deleterious consequences.Important metabolic changes occur and catabolism becomes prominent in critically ill patients.Both hyper and hypometabolism can be observed, but hypermetabolic patients appear to have higher mortality rates compared to metabolically normal patients. This study aimed to assess hypermetabolism incidence and compare clinical outcomes between hypermetabolic and normometabolic patients in ICU. METHODS: A single-center, retrospective, and observational study was conducted in the ICU of the Hospital do Divino Espírito Santo in Ponta Delgada, between August 2018 and February 2021. Only invasively mechanically ventilated patients were included. Resting energy expenditure (REE) was predicted by 25 kcal/kg/day formula to obtain predicted resting energy expenditure (PREE), and REE was measured by IC to obtain measured resting energy expenditure (MREE). According to their metabolic state (PREE/MREE), patients were divided into hypermetabolic (≥1.3) and normometabolic (<1.3). To determine the limits of agreement between PREE and MREE, we performed a Bland-Altman (BA) analysis. Baseline characteristics, severity criteria, nutritional status, and main diagnosis on admission were compared. The primary outcome considered was 30-day mortality. Other outcomes such as the ICU length of stay (LOS), in-hospital LOS, and length of invasive ventilation were also evaluated. RESULTS: Among the 80 ICU patients included in the final analysis, 67 patients were normometabolic (83.4%). Patients admitted due to pneumonia were more hypermetabolic, 8 (61.5%) vs. 10 (14.9%); p<0.001. Hypermetabolism was found also in patients admitted due to sepsis/septic shock, 7 (53.8%) vs. 16 (23.9%); p=0.029. Hypermetabolic patients had lower body mass index (22.5 [interquartile range (IQR): 21.5-24.9] vs. 27.7 [IQR: 25.0-32.4] kg/m2; p=0.001) and higher MREE (2715.0 [2399.0-3090.0] vs. 1690.0 [1410.0-2190.0] kcal/day; p<0.001). Bland-Altman analysis showed a mean difference of -5.6 ± 744.7 Kcal/day between the PREE and MREE by IC. No statistically significant difference was found between the two groups, neither in 30-day mortality nor in the other outcomes considered. CONCLUSIONS: Hypermetabolism was not seen to present a greater risk of death in mechanically ventilated patients in ICU. Lower BMI, sepsis/septic shock, and pneumonia appear to be associated with a hypermetabolic state.

Production of rayon fibres from cellulosic pulps: State of the art and current developments.

The increasing demand for cellulosic fibres is continuously driven by the growing earth population and requirements of the textile industry. The annual cotton production of ca. 25 million tons is no longer enough to meet the market demands. This market gap of cellulosic fibres is progressively filled by regenerated cellulosic fibres derived from the dissolving pulp. The conventional industrial process of viscose production is far from being environmentally friendly due to the use of hazardous reagents. Alternatively, new trends in the production of regenerated fibres are related to the direct dissolution of cellulose in appropriate environmentally sound recyclable solvents, allowing high quality rayon fibres. This article reviews the sources of dissolving pulps used for the production of viscose and its quality parameters related to the performance of viscose production. The prospective cellulose regeneration processes, both commercialized and under development, are reviewed regarding current and future developments in the area.