Short and long-term temperature variations drive recruitment variability in marine and estuarine juvenile fishes.

Understanding the long-term effects of climatic factors on key species' recruitment is crucial to species management and conservation. Here, we analysed the recruitment variability of key species (Dicentrarchus labrax, Platichthys flesus, Solea solea, Pomatoschistus microps and Pomatoschistus minutus) in an estuary between 2003 and 2019, and related it with the prevailing local and large-scale environmental factors. Using a dynamic factor analysis (DFA), juvenile abundance data were grouped into three common trends linked to different habitat uses and life cycle characteristics, with significant effect of temperature-related variables on fish recruitment: Sea surface temperature and the Atlantic Multidecadal Oscillation. In 2010, a regime shift in the North Atlantic coincided with a shift in the common trends, particularly a decline in P. flesus and S. solea trend. This work highlights the thermophilic character of fish recruitment and the necessity to investigate key biological processes in the context of species-specific responses to climate change.

A global synthesis of microplastic contamination in wild fish species: Challenges for conservation, implications for sustainability of wild fish stocks and future directions.

Research on the occurrence of microplastics in wild fish populations is a constantly growing area, requiring continuous reviews to properly keep up with the fast pace of publications and guide future work. This review analyses the scientific output of 260 field studies covering 1053 different fish taxa for the presence of microplastics. To date, microplastics have been recorded in 830 wild fish species, including 606 species of interest to commercial and subsistence fisheries. Among these, based on IUCN Red List status, 34 species are globally classified in one of the three threatened categories (Critically Endangered, Endangered or Vulnerable) and another 22 species were assessed as "Near Threatened". Of the species for which the IUCN Red List tracks population trend data, the fish species reported to have microplastics so far include 81 which are recorded as declining, 134 as stable and just 16 as increasing. This review highlights the potential implications of fish microplastic contamination to biodiversity conservation, sustainability of wild fish stocks, and human food safety and security. Finally, recommendations for future research are presented.

Gallstone Ileus: An Improbable Cause of Mechanical Small Bowel Obstruction.

Gallstone ileus (GI) is a rare complication of cholelithiasis and a rare cause of small bowel obstruction. It usually affects elderly women and the symptoms are nonspecific, both contributing to a delay in diagnosis and a high mortality rate. It is necessary to have a high suspicion index for diagnosis and abdominal CT is the gold standard imaging for the diagnosis. We present a case report of an 87-year-old man who presented to the ED with abdominal pain and vomiting for the last 20 days. A GI was diagnosed and he underwent enterolithotomy to remove the stone. Unfortunately, the patient died on the 13th postoperative day with multiorgan failure. The treatment and the time at which it is performed must be adapted to each patient.

Gastric Volvulus: A Complication of Hiatal Hernia.

Gastric volvulus is a rare but potentially life-threatening condition, with difficult diagnosis. We present a case report of a demented woman aged 65 years that attended the emergency department with epigastric pain and vomiting for the past 10 days. The chest plain revealed a retrocardiac air-filled mass and the abdomino-pelvic computed tomography confirmed the diagnosis of gastric volvulus. The patient was admitted. A nasogastric tube was introduced, antibiotics and parenteric nutrition were started and the patient didn't eat anything. The patient was operated at fifth day of admission by laparoscopy. There weren't signs of gastric necrosis, so the stomach was mobilized for its natural position on abdominal cavity, the hiatal defect was closed and a Nissen fundoplicature was performed. The post operative period was uneventful and the patient was discharged on the third post-operative day, without any complication. This case illustrates a sub acute presentation form of gastric volvulus and a differed minimally invasive approach attending at the patient's clinical stability.

Applying Artificial Intelligence Methods for the Estimation of Disease Incidence: The Utility of Language Models.

Background: AI-driven digital health tools often rely on estimates of disease incidence or prevalence, but obtaining these estimates is costly and time-consuming. We explored the use of machine learning models that leverage contextual information about diseases from unstructured text, to estimate disease incidence. Methods: We used a class of machine learning models, called language models, to extract contextual information relating to disease incidence. We evaluated three different language models: BioBERT, Global Vectors for Word Representation (GloVe), and the Universal Sentence Encoder (USE), as well as an approach which uses all jointly. The output of these models is a mathematical representation of the underlying data, known as "embeddings." We used these to train neural network models to predict disease incidence. The neural networks were trained and validated using data from the Global Burden of Disease study, and tested using independent data sourced from the epidemiological literature. Findings: A variety of language models can be used to encode contextual information of diseases. We found that, on average, BioBERT embeddings were the best for disease names across multiple tasks. In particular, BioBERT was the best performing model when predicting specific disease-country pairs, whilst a fusion model combining BioBERT, GloVe, and USE performed best on average when predicting disease incidence in unseen countries. We also found that GloVe embeddings performed better than BioBERT embeddings when applied to country names. However, we also noticed that the models were limited in view of predicting previously unseen diseases. Further limitations were also observed with substantial variations across age groups and notably lower performance for diseases that are highly dependent on location and climate. Interpretation: We demonstrate that context-aware machine learning models can be used for estimating disease incidence. This method is quicker to implement than traditional epidemiological approaches. We therefore suggest it complements existing modeling efforts, where data is required more rapidly or at larger scale. This may particularly benefit AI-driven digital health products where the data will undergo further processing and a validated approximation of the disease incidence is adequate.

Albumin-binding domain from Streptococcus zooepidemicus protein Zag as a novel strategy to improve the half-life of therapeutic proteins.

Recombinant antibody fragments belong to the promising class of biopharmaceuticals with high potential for future therapeutic applications. However, due to their small size they are rapidly cleared from circulation. Binding to serum proteins can be an effective approach to improve pharmacokinetic properties of short half-life molecules. Herein, we have investigated the Zag albumin-binding domain (ABD) derived from Streptococcus zooepidemicus as a novel strategy to improve the pharmacokinetic properties of therapeutic molecules. To validate our approach, the Zag ABD was fused with an anti-TNFα single-domain antibody (sdAb). Our results demonstrated that the sdAb-Zag fusion protein was highly expressed and specifically recognizes human, rat and mouse serum albumins with affinities in the nanomolar range. Moreover, data also demonstrated that the sdAb activity against the therapeutic target (TNFα) was not affected when fused with Zag ABD. Importantly, the Zag ABD increased the sdAb half-life ∼39-fold (47min for sdAb versus 31h for sdAb-Zag). These findings demonstrate that the Zag ABD fusion is a promising approach to increase the half-life of small recombinant antibodies molecules without affecting their therapeutic efficacy. Moreover, the present study strongly suggests that the Zag ABD fusion strategy can be potentially used as a universal method to improve the pharmokinetics properties of many others therapeutics proteins and peptides in order to improve their dosing schedule and clinical effects.

Intergenerational educational trajectories and lower back pain in young women and men.

We examined the association between intergenerational educational trajectories and lower back pain (LBP) outcomes in young women and men from the general population. Participants were part of the 21 years old follow-up of the EPITeen cohort study, which was set up during the 2003/2004 school year and recruited subjects born in 1990 attending schools in Porto, Portugal (n=1657, 51.6% women). Parental and individual educational levels were used to define intergenerational educational trajectories as stable-high, upward, stable-low, and downward. Data on the presence, severity and chronicity of LBP were also assessed. Gender-specific adjusted odds ratios (OR) with 95% confidence intervals (95% CI) were computed to estimate the associations between educational trajectories and LBP outcomes. When compared to women with stable-high educational trajectories, those with stable-low educational trajectories were significantly more likely to report moderate/severe (adjusted OR=1.76, 95% CI: 1.21-2.57) and chronic (adjusted OR=1.82, 95% CI: 1.02-3.22) LBP. The magnitude of these associations was even stronger among females with downward educational trajectories (moderate/severe: adjusted OR=2.58, 95% CI: 1.49-4.46; chronic: adjusted OR=2.42, 95% CI: 1.12-5.27). Educational trajectories were not significantly associated to LBP outcomes among men. In conclusion, intergenerational educational trajectories may contribute to LBP as reported in early adulthood, particularly in women.

Psychosocial Work Environment and Musculoskeletal Symptoms among 21-Year-Old Workers: A Population-Based Investigation (2011-2013).

BACKGROUND: The current labour market is becoming more flexible and informal, with job insecurity selectively affecting young workers. However, the role of these increasing adverse psychosocial working conditions on health outcomes remains little known among newly employed workers. OBJECTIVE: To estimate the associations between psychosocial work environment and musculoskeletal outcomes (widespread pain syndrome features and regional pain) in a population-based sample of young workers. METHODS: Cross-sectional data from workers aged 21 years were collected during the third wave of the EPITeen cohort study (2011-2013; n=650). The Job Content Questionnaire was used to characterize the psychosocial work environment according to the demand-control-support model. Data on pain and non-pain dimensions of the widespread pain syndrome (Fibromyalgia Survey Questionnaire) as well as on regional musculoskeletal pain (Nordic Musculoskeletal Questionnaire) were also collected. Crude and adjusted odds ratios (OR) with 95% confidence intervals (95% CI) were computed using logistic regression and all estimates were adjusted for sex, education and occupational biomechanical demands. RESULTS: Job insecurity was significantly associated to the non-pain dimension of the widespread pain syndrome (adjusted OR [95% CI]=1.51 [1.08, 2.12]). Young workers with strain jobs were significantly more likely to report high levels of non-pain symptoms when compared with those with no-strain jobs and this effect was even stronger when social support was added to the main exposure: workers with strain jobs and low social support had twice the odds of reporting high levels of non-pain features than those with high strain but high social support jobs (adjusted OR=1.86, 95% CI: 1.04, 3.31). These significant associations were not observed when widespread pain or multisite regional pain were the outcomes. CONCLUSION: In the beginning of professional life, high strain jobs were associated to non-pain complaints, especially when the work environment provided also low social support.

Gender and psychosocial context as determinants of fibromyalgia symptoms (fibromyalgia research criteria) in young adults from the general population.

OBJECTIVE: To quantify the prevalence of FM (FM research criteria), to describe its components-symptom severity score (SSS) and widespread pain index (WPI)-and to identify biopsychosocial predictors of the severity of SSS as well as WPI using a population-based sample of young adults. METHODS: Participants were part of the 21-year-old follow-up of the EPITeen cohort, which was set up during the 2003-04 school year and comprised subjects born in 1990 attending schools in Porto, Portugal (n = 1719, 51.4% women). Data on biopsychosocial characteristics were collected, and FM-related information was gathered using the Fibromyalgia Survey Questionnaire. Sex-specific multivariate log-binomial regression coefficients (ß) and 95% CI were used to quantify the associations between adverse biopsychosocial characteristics and high scores in SSS and WPI. RESULTS: The overall point-prevalence of FM was 1.0%. Women scored significantly higher in SSS and WPI when compared with men. Global psychological distress was strongly and significantly associated with high scores in SSS in women and men (respectively, low sleep quality, ß = 1.44, 95% CI 1.05, 1.84 and ß = 1.19, 95% CI 0.78, 1.61; depressive symptoms, ß = 1.64, 95% CI 1.23, 2.06 and ß = 1.14, 95% CI 0.60, 1.70; eating disorders, ß = 1.17, 95% CI 0.71, 1.63 and ß = 1.15, 95% CI 0.52, 1.78). In women, adverse socioeconomic factors were predictors of high scores in SSS, whereas in men these contexts were significantly associated with high scores in WPI. CONCLUSION: In young adulthood, psychological distress was particularly consistent in predicting SSS and may become useful as a red flag for the establishment of clinical disease.

Patterns of biomechanical demands are associated with musculoskeletal pain in the beginning of professional life: a population-based study.

OBJECTIVES: This study aimed to describe patterns of occupational biomechanical demands in the beginning of professional life and to quantify their association with the presence and intensity of regional musculoskeletal pain. METHODS: Cross-sectional data from 21-year-old participants were collected during the third wave of the EPITeen cohort study (N=1733, 37.5% were workers). Ten different work-related biomechanical tasks were characterized. Latent class analysis was conducted to identify empirical patterns of occupational biomechanical demands. The presence and intensity of regional musculoskeletal pain in the previous year were also evaluated. RESULTS: Four patterns of occupational biomechanical demands were found: "low demands", "sitting demands", "repetitive and asymmetric demands", and "high and vibrational demands". When compared to workers with low demands, those with repetitive and asymmetric demands or high and vibrational demands presented 80% higher adjusted odds ratio (OR adj) of reporting neck/shoulder pain. High and vibrational demands occupations were significantly associated with upper-/lower-back pain in comparison to low demands [OR adj1.80, 95% confidence interval (95% CI%) 1.09-2.96]. In addition, workers with sitting demands were more likely to report any or severe upper-/lower-back pain [OR adj1.56 (95% CI 0.99-2.45) and 1.66 (95% CI 1.03-2.66), respectively] when compared to those with low demands. CONCLUSIONS: Patterns of high work-related physical demands were associated with the presence of neck/shoulder pain and severity of upper-/lower-back pain. This emphasizes that even short-term biomechanical exposures at the workplace may be involved in the etiology of musculoskeletal complaints.

Osteoarthritis medical labelling and health-related quality of life in the general population.

BACKGROUND: Osteoarthritis is the most common chronic joint disease. In the absence of an effective medical treatment and due to the chronic nature of this condition, an osteoarthritis medical diagnosis may finally result in decreased health-related quality of life. Therefore, the aim of this study was to measure the impact of the osteoarthritis medical labelling on physical and mental health-related quality of life. METHODS: Subjects (n = 1132, 58.7% women) were approached as participants of an urban population-based cohort (EPIPorto). Self-reported information on previous diagnosis of knee, hip or hand osteoarthritis was obtained and rheumatologists established knee, hip or hand osteoarthritis clinical diagnosis in symptomatic individuals. Physical and mental dimensions of health-related quality of life were evaluated using the self-administered Medical Outcomes Study: 36-Item Short Form Survey. Crude and adjusted linear regression coefficients (beta) and the corresponding 95% confidence intervals (95% CI) were computed to estimate the associations between being labelled as an osteoarthritis case and health-related quality of life. RESULTS: Regardless of disease medical labelling, individuals with osteoarthritis scored significantly lower physical health-related quality of life when compared to those without joint disease (kneeunexposed: beta = -5.3, 95% CI: -7.6, -3.1; kneeexposed: beta = -6.0, 95% CI: -8.4, -3.7; hipunexposed: beta = -6.0, 95% CI: -9.8, -2.3; hipexposed: beta = -11.0, 95% CI: -15.6, -6.4; handunexposed: beta = -4.3, 95% CI: -6.5, -2.0; handexposed: beta = -4.3, 95% CI: -6.6, -2.1). The same was not observed regarding mental health-related quality of life. Among subjects with clinically confirmed osteoarthritis, the medical labelling of this joint disease was not significantly associated to health-related quality of life. CONCLUSIONS: The labelling of knee, hip and hand osteoarthritis diagnosis may not add specific benefit to osteoarthritis patients in terms of its capability to improve health-related quality of life.

Depressive symptoms are not associated with forearm bone accrual during adolescence.

UNLABELLED: Although depression has been associated to worst bone physical properties in adulthood, this study showed that depressive symptoms were not significantly associated to bone mineral density measured at the forearm during adolescence. PURPOSE: Depressive conditions have been related to the reduction of bone mineral density (BMD) in adulthood. Though it is possible to hypothesize that depressive symptoms present similar effects in bone mineral accrual during adolescence, such association is poorly researched. Therefore, we aimed to study the relation between depressive symptoms and forearm BMD during adolescence. METHODS: The study is based on the Epidemiological Health Investigation of Teenagers cohort that sampled adolescents born in 1990 and enrolled in public and private schools of Porto during the 2003/2004 academic year. At baseline (n = 2,160) and at 17 years of age (n = 1,716), depressive symptoms were evaluated using the Beck Depression Inventory-II (BDI-II). BMD (grams per square centimetre) was measured at the non-dominant forearm using dual-energy X-ray absorptiometry. Sex-specific crude and adjusted linear regression coefficients (ß) and the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the cross-sectional and prospective associations between depressive symptoms and forearm BMD. RESULTS: In both sexes, in early and late adolescence, depressive symptoms presented no statistically significant association with forearm BMD (ß Girls13 = 0.09, 95 % CI = -0.43 to 0.61; ß Girls17 = 0.10, 95 % CI = -0.43 to 0.64; ß Boys13 = -0.10, 95 % CI = -0.96 to 0.76; ß Boys17 = 0.49, 95 % CI = -0.96 to 1.93). Similarly, there were no significant associations between depressive symptoms and the annual forearm BMD change during adolescence in girls and boys (ß Girls_BDI-II_13-17_remained_lowest = -0.85, 95 % CI = -4.62 to 2.92 vs. ß Girls_BDI-II_13-17_remained_highest = -1.87, 95 % CI = -5.06 to 1.31; ß Boys_BDI-II_13-17_remained_lowest = 0.48, 95 % CI = -5.30 to 6.26 vs. ß Boys_BDI-II_13-17_remained_highest = 1.36, 95 % CI = -3.25 to 5.97). CONCLUSIONS: Depressive symptoms, with the range of severity observed in the general adolescent population, were not associated with changes in forearm bone mineral density during adolescence. Further research based on measurements of different skeletal sites is needed in order to detect a systemic effect of depression on growing bone.

Biodistribution of a (67)Ga-labeled anti-TNF VHH single-domain antibody containing a bacterial albumin-binding domain (Zag).

INTRODUCTION: Small domain antibodies (sdAbs) present high potential for both molecular in vivo imaging and therapy. Owing to the low molecular weight they are rapidly cleared from blood circulation, and new strategies to extend their half-lifes are needed for therapeutic applications. We have selected a bacterial albumin-binding domain (ABD) from protein Zag to be fused to an anti-tumor necrosis factor (TNF) single variable-domain heavy-chain region antibody (VHH) to delay blood clearance, and evaluated the biodistribution profile of the fusion protein. METHODS: The anti-TNF VHH and the fusion protein VHH-Zag were conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA). The anti-TNF and albumin-binding properties of the conjugates NOTA-VHH and NOTA-VHH-Zag were assessed by enzyme-linked immunosorbent assay (ELISA). The radioconjugates (67)Ga-NOTA-VHH and (67)Ga-NOTA-VHH-Zag were obtained by reaction of (67)GaCl3 with the corresponding conjugates at room temperature. Biodistribution studies were performed in healthy female CD-1 mice. RESULTS: The immunoreactivity of the VHH-based proteins is preserved upon conjugation to NOTA as well as after radiometallation. The radiochemical purity of the radioconjugates was higher than 95% as determined by ITLC-SG after purification by gel filtration. The biodistribution studies showed that the Zag domain affected the pharmacokinetic properties of VHH, with impressive differences in blood clearance (0.028 ± 0.004 vs 1.7 ± 0.8 % I.A./g) and total excretion (97.8 ± 0.6 vs 25.5 ± 2.1 % I.A.) for (67)Ga-NOTA-VHH and (67)Ga-NOTA-VHH-Zag, respectively, at 24h p.i. CONCLUSION: The Zag domain prolonged the circulation time of VHH by reducing the blood clearance of the labeled fusion protein (67)Ga-NOTA-VHH-Zag. In this way, the anti-TNF VHH in fusion with the Zag ABD presents a higher therapeutic potential than the unmodified VHH.

Novel chimerical endolysins with broad antimicrobial activity against methicillin-resistant Staphylococcus aureus.

Due to their bacterial lytic action, bacteriophage endolysins have recently gained great attention as a potential alternative to antibiotics in the combat of Gram-positive pathogenic bacteria, particularly those displaying multidrug resistance. However, large-scale production and purification of endolysins is frequently impaired due to their low solubility. In addition, a large number of endolysins appear to exhibit reduced lytic efficacy when compared with their action during phage infection. Here, we took advantage of the high solubility of two recently characterized enterococcal endolysins to construct chimeras targeting Staphylococcus aureus. The putative cell wall binding domain of these endolysins was substituted by that of a staphylococcal endolysin that showed poor solubility. Under appropriate conditions the resulting chimeras presented the high solubility of the parental enterococcal endolysins. In addition, they proved to be broadly active against a collection of the most relevant methicillin-resistant S. aureus epidemic clones and against other Gram-positive pathogens. Thus, fusion of endolysin domains of heterologous origin seems to be a suitable approach to design new potent endolysins with changed and/or extended lytic spectrum that are amenable to large-scale production.

Assessing combinatorial strategies to multimerize libraries of single-domain antibodies.

Single-domain antibodies (SDAs) are among the most studied and interesting antibody fragments. These molecules combine advantages of antibodies and small molecules. However, SDAs present a low efficiency of in vivo targeting because of their low binding avidity and fast clearance from blood circulation. Multimerization of SDA can overcome these drawbacks and increase their therapeutic potency. In this work, we developed and compared three strategies that allow construction of SDA dimers derived from rabbit light chains--PCR overlap, sticky PCR, and restriction/ligation. The restriction/ligation strategy proved to be the most efficient and feasible method to construct a successful library of SDA dimers. To further explore this technique, we constructed different libraries that differed in linker length between the two SDAs, and assessed its efficiency to deliver antigen-specific SDA dimers. We efficiently increased both the molecular size and avidity of antibody fragments, increasing the possibility of these molecules to bind to their antigen. Therefore, this work describes efficient tools for therapeutic development of SDA dimers.

Monoclonal antibodies recognize conformational epitopes on wild-type and recombinant mutant amidases from pseudomonas aeruginosa.

Hybridoma technology was used to raise monoclonal antibodies (MAbs) against wild-type amidase from Pseudomonas aeruginosa. Hybridoma clones secreting polyol-responsive MAbs (PR-MAbs) were screened that bind antigen tightly. but release under mild- and non-denaturing elution conditions, which can be used as ligands in immunoaffinity chromatography. Two of these hybridoma clones (C9E4 and B1E4) secreting MAbs against wild-type amidase were selected in order to check if they are PR-MAbs by using ELISA-elution assay. These hybridoma cell lines secreted MAbs of IgG class which were purified in a single step by Protein A-Sepharose CL-4B chromatography, which revealed two protein bands on SDS-PAGE. Specificity studies of MAb C9E4 revealed that it recognized a common epitope on wild-type and mutant T103I amidases as determined by direct ELISA, as well as by Western blotting under native conditions. This MAb exhibited a higher-affinity constant (K) for the mutant T103I amidase than for the wild-type enzyme. However, this MAb did not recognize either wild-type or mutant T103I enzymes under denaturing conditions suggesting that it binds to a conformation-sensitive epitope on amidase molecule. On the other hand, it also does not recognize either native or denatured forms of mutant C91A amidase suggesting that this substitution disrupted the conformational epitope present on amidase molecule. Furthermore, MAb C9E4 inhibited about 80% of wild-type amidase activity, whereas it activated about 80% of mutant amidase (T103I) activity. However, this MAb did not affect mutant C91A amidase activity which is in agreement with other results presented in this work. The data presented in this work suggest that this MAb acts as a powerful probe to detect conformational changes in native and denatured amidases as well as to differentiate wild-type and mutant (T103I and C91A) amidases.