SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants1-4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells5-9. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes. Here we show that boosting with an mRNA vaccine against the original monovalent SARS-CoV-2 mRNA vaccine or the bivalent B.1.351 and B.1.617.2 (Beta/Delta) mRNA vaccine induced robust spike-specific germinal centre B cell responses in humans. The germinal centre response persisted for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Spike-binding monoclonal antibodies derived from memory B cells isolated from individuals boosted with either the original SARS-CoV-2 spike protein, bivalent Beta/Delta vaccine or a monovalent Omicron BA.1-based vaccine predominantly recognized the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted sorting approach, we isolated monoclonal antibodies that recognized the BA.1 spike protein but not the original SARS-CoV-2 spike protein from individuals who received the mRNA-1273.529 booster; these antibodies were less mutated and recognized novel epitopes within the spike protein, suggesting that they originated from naive B cells. Thus, SARS-CoV-2 booster immunizations in humans induce robust germinal centre B cell responses and can generate de novo B cell responses targeting variant-specific epitopes.

Abnormal higher-order network interactions in Parkinson's disease visual hallucinations.

Visual hallucinations in Parkinson's disease can be viewed from a systems-level perspective, whereby dysfunctional communication between brain networks responsible for perception predisposes a person to hallucinate. To this end, abnormal functional interactions between higher-order and primary sensory networks have been implicated in the pathophysiology of visual hallucinations in Parkinson's disease, however the precise signatures remain to be determined. Dimensionality reduction techniques offer a novel means for simplifying the interpretation of multidimensional brain imaging data, identifying hierarchical patterns in the data that are driven by both within- and between-functional network changes. Here, we applied two complementary non-linear dimensionality reduction techniques-diffusion-map embedding and t-distributed stochastic neighbour embedding (t-SNE)-to resting state functional MRI data, in order to characterize the altered functional hierarchy associated with susceptibility to visual hallucinations. Our study involved 77 people with Parkinson's disease (31 with hallucinations; 46 without hallucinations) and 19 age-matched healthy control subjects. In patients with visual hallucinations, we found compression of the unimodal-heteromodal gradient consistent with increased functional integration between sensory and higher order networks. This was mirrored in a traditional functional connectivity analysis, which showed increased connectivity between the visual and default mode networks in the hallucinating group. Together, these results suggest a route by which higher-order regions may have excessive influence over earlier sensory processes, as proposed by theoretical models of hallucinations across disorders. By contrast, the t-SNE analysis identified distinct alterations in prefrontal regions, suggesting an additional layer of complexity in the functional brain network abnormalities implicated in hallucinations, which was not apparent in traditional functional connectivity analyses. Together, the results confirm abnormal brain organization associated with the hallucinating phenotype in Parkinson's disease and highlight the utility of applying convergent dimensionality reduction techniques to investigate complex clinical symptoms. In addition, the patterns we describe in Parkinson's disease converge with those seen in other conditions, suggesting that reduced hierarchical differentiation across sensory-perceptual systems may be a common transdiagnostic vulnerability in neuropsychiatric disorders with perceptual disturbances.

Sleep spindle architecture associated with distinct clinical phenotypes in older adults at risk for dementia.

Sleep spindles are a hallmark of non-REM sleep and play a fundamental role in memory consolidation. Alterations in these spindles are emerging as sensitive biomarkers for neurodegenerative diseases of ageing. Understanding the clinical presentations associated with spindle alterations may help to elucidate the functional role of these distinct electroencephalographic oscillations and the pathophysiology of sleep and neurodegenerative disorders. Here, we use a data-driven approach to examine the sleep, memory and default mode network connectivity phenotypes associated with sleep spindle architecture in older adults (mean age = 66 years). Participants were recruited from a specialist clinic for early diagnosis and intervention for cognitive decline, with a proportion showing mild cognitive deficits on neuropsychological testing. In a sample of 88 people who underwent memory assessment, overnight polysomnography and resting-state fMRI, a k-means cluster analysis was applied to spindle measures of interest: fast spindle density, spindle duration and spindle amplitude. This resulted in three clusters, characterised by preserved spindle architecture with higher fast spindle density and longer spindle duration (Cluster 1), and alterations in spindle architecture (Clusters 2 and 3). These clusters were further characterised by reduced memory (Clusters 2 and 3) and nocturnal hypoxemia, associated with sleep apnea (Cluster 3). Resting-state fMRI analysis confirmed that default mode connectivity was related to spindle architecture, although directionality of this relationship differed across the cluster groups. Together, these results confirm a diversity in spindle architecture in older adults, associated with clinically meaningful phenotypes, including memory function and sleep apnea. They suggest that resting-state default mode connectivity during the awake state can be associated with sleep spindle architecture; however, this is highly dependent on clinical phenotype. Establishing relationships between clinical and neuroimaging features and sleep spindle alterations will advance our understanding of the bidirectional relationships between sleep changes and neurodegenerative diseases of ageing.

Lymphovenous Bypass for Immediate Lymphatic Reconstruction in Breast Cancer Patients Undergoing Axillary Lymph Node Dissection: Minimizing the Risk of Upper Extremity Lymphedema.

BACKGROUND: Studies have shown a significant reduction in breast cancer-related lymphedema (BCRL) rates in patients undergoing complete axillary lymph node dissection (cALND) combined with immediate lymphatic reconstruction (ILR) using lymphovenous bypass (LVB).The purpose of this study was to determine if ILR with LVB at the time of cALND results in a decreased incidence of BCRL and its impact on patient quality of life (QOL). METHODS: In this prospective cohort study, patients ≥ 18 years requiring cALND underwent ILR from 2019 to 2021. The primary outcome was bilateral upper limb volumes measured by Brørson's truncated cone formula and the Pero-System (3D Körper Scanner). The secondary outcome was QOL measured by the Lymphedema Quality of Life (LYMQOL) arm patient-reported outcome measurement. RESULTS: Forty-two patients consented to ILR using LVB. ILR was completed in 41 patients with a mean of 1.9 ± 0.9 lymphovenous anastomosis performed. Mean age of patients was 52.4 ± 10.5 years with a mean body mass index of 27.5 ± 4.9 kg/m2. All patients (n = 39, 100%) received adjuvant therapy after ILR. Mean follow-up was 15.2 ± 5.1 months. Five patients met criteria for lymphedema throughout the duration of the study (12.8%), with two patients having resolution, with an overall incidence of 7.7% by the end of the study period. Patients with lymphedema were found to have statistically significant lower total LYMQOL values at 18 months (8.44 ± 1.17 vs. 3.23 ± 0.56, p < 0.001). A mean increase of 0.73 ± 3.5 points was observed for overall QOL average for upper limb function at 18 months compared with 3 months (t = 0.823, p = 0.425). CONCLUSION: This study showed an incidence of 7.7% lymphedema development throughout the duration of study. We also showed that ILR has the potential to reduce the significant long-term adverse outcomes of lymphedema and improve QOL for patients undergoing cALND.

Preconditioning program reduces the incidence of prolonged hospital stay after lung cancer surgery: Results from the Move For Surgery randomized clinical trial.

BACKGROUND: Lung cancer resection is associated with high rates of prolonged hospital stay. It is presumed that preconditioning with aerobic exercise can shorten the postoperative duration of hospital stay, but this has not yet been demonstrated in trials after lung cancer surgery. The aim of this study was to perform a RCT to determine whether Move For Surgery (MFS), a home-based and wearable technology-enhanced preconditioning program before lung cancer surgery, is associated with a lower incidence of prolonged hospital stay when compared to usual preoperative care. METHODS: Patients undergoing lung resection for early-stage non-small cell lung cancer were enrolled before surgery into this blinded, single-site RCT, and randomized to either the MFS or control group in a 1 : 1 ratio. Patients in the MFS group were given a wearable activity tracker, and education about deep breathing exercises, nutrition, sleep hygiene, and smoking cessation. Participants were motivated/encouraged to reach incrementally increasing fitness goals remotely. Patients in the control group received usual preoperative care. The primary outcome was the difference in proportion of patients with hospital stay lasting more than 5 days between the MFS and control groups. RESULTS: Of 117 patients screened, 102 (87.2 per cent) were eligible, enrolled, and randomized (51 per trial arm). The majority (95 of 102, 93.1 per cent) completed the trial. Mean(s.d.) age was 67.2(8.8) years and there were 55 women (58 per cent). Type of surgery and rates of thoracotomy were not different between arms. The proportion of patients with duration of hospital stay over 5 days was 3 of 45 (7 per cent) in the MFS arm compared to 12 of 50 (24 per cent) in the control arm (P = 0.021). CONCLUSION: MFS, a home-based and wearable technology-enhanced preconditioning program before lung cancer surgery, decreased the proportion of patients with a prolonged hospital stay. Registration number: NCT03689634 (http://www.clinicaltrials.gov).

After lung cancer surgery, many patients are admitted to hospital for a prolonged amount of time. It is believed that exercises undertaken before surgery can shorten the stay in hospital, but this has not yet been studied. This study aimed to find out whether Move For Surgery (MFS), a home-based exercise (preconditioning) program using wearable technology before lung cancer surgery, can decrease the number of patients who are admitted to hospital for a prolonged amount of time. Patients with lung cancer were invited to enter this trial 3­4 weeks before surgery. They were randomly put into the MFS or control group. Patients in the MFS group were given a wearable activity tracker, and education about deep breathing exercises, nutrition, sleep hygiene, and quitting smoking. Participants were encouraged to reach increasing fitness goals each week. Patients in the control group underwent usual preoperative care. The difference between the MFS and control groups in the proportion of patients with duration of stay in hospital exceeding 5 days was studied. There were 102 participants in total, 51 in each group. The majority (95 of 102, 93.1 per cent) completed the trial. The average age of participants was 67 years, and 58 per cent were women. Type of surgery and number of open operations were no different between groups. The proportion of patients with duration of stay greater than 5 days was 3 of 45 (7 per cent) in the MFS group compared with 12 of 50 (24 per cent) in the control group. Therefore, MFS before lung cancer surgery was shown to decrease the number of patients admitted to hospital for a prolonged amount of time.

Symptoms and associated impact in pre- and postmenopausal women with sexual arousal disorder: a concept elicitation study.

BACKGROUND: Approximately 26% of adult women in the United States suffer from female sexual arousal disorder (FSAD), yet little has been done to compare the experience of FSAD in pre- and postmenopausal women, which is critical to enhance the current understanding of FSAD and inform the development and assessment of treatment options for these patient populations. AIM: To explore the experience of condition-associated symptoms and the relative importance of FSAD symptoms, including their severity, bother, and impact, on participants' health-related quality of life (HRQoL) in pre- and postmenopausal women with FSAD. METHODS: In-depth, qualitative, semistructured concept elicitation interviews were conducted with premenopausal (n = 23) and postmenopausal (n = 13) women who were clinically diagnosed with FSAD by a trained sexual medicine clinician. All interviews were audio recorded and transcribed verbatim by a professional transcription company. Thematic analysis was performed with the assistance of NVivo qualitative analysis software. OUTCOMES: Outcomes included qualitative interview data about FSAD symptoms and HRQoL, as well as a comparison between pre- and postmenopausal populations. RESULTS: The most frequently reported symptom in both cohorts was "inability or difficulty with orgasm" (premenopausal, n = 21; postmenopausal, n = 13). The symptom that premenopausal women most desired to have treated was lubrication, and for postmenopausal women, it was a lack of lubrication or wetness and loss of feeling/sensation. In total, 21 of 23 premenopausal women and all 13 postmenopausal women reported a lack of feeling or sensation in the genitals. The most frequently reported HRQoL impact in both groups was decreased confidence. CLINICAL IMPLICATIONS: Results from this study suggest that the manifestation and experience of FSAD are similar in pre- and postmenopausal women and that the unmet need for an FSAD treatment in the postmenopausal population is just as great as that of the premenopausal population. STRENGTHS AND LIMITATIONS: This study involved in-depth qualitative interviews with a relatively small group of women (N = 36) recruited from only 5 study sites across the United States. CONCLUSION: The analysis of qualitative data from the concept elicitation interviews revealed a substantial physical and emotional burden of FSAD, underscoring the need for Food and Drug Administration-approved treatment options for pre- and postmenopausal women with FSAD.

Dietary sodium restriction alters muscle lipidomics that relates to insulin resistance in mice.

A low-sodium (LS) diet has been shown to reduce blood pressure (BP) and the incidence of cardiovascular diseases. However, severe dietary sodium restriction promotes insulin resistance (IR) and dyslipidemia in animal models and humans. Thus, further clarification of the long-term consequences of LS is needed. Here, we investigated the effects of chronic LS on gastrocnemius gene and protein expression and lipidomics and its association with IR and plasma lipids in LDL receptor knockout mice. Three-month-old male mice were fed a normal sodium diet (NS; 0.5% Na; n = 12-19) or LS (0.06% Na; n = 14-20) over 90 days. Body mass (BM), BP, plasma total cholesterol, triacylglycerol (TG), glucose, hematocrit, and IR were evaluated. LS increased BM (9%), plasma TG (51%), blood glucose (19%), and IR (46%) when compared with the NS. RT-qPCR analysis revealed that genes involved in lipid uptake and oxidation were increased by the LS: Fabp3 (106%), Prkaa1 (46%), and Cpt1 (74%). Genes and proteins (assessed by Western blotting) involved in insulin signaling were not changed by the LS. Similarly, lipid species classically involved in muscle IR, such as diacylglycerols and ceramides detected by ultra-high-performance liquid chromatography coupled to mass spectrometry, were also unchanged by LS. Species of phosphatidylcholines (68%), phosphatidylinositol (90%), and free fatty acids (59%) increased while cardiolipins (41%) and acylcarnitines (9%) decreased in gastrocnemius in response to LS and were associated with glucose disposal rate. Together these results suggest that chronic LS alters glycerophospholipid and fatty acids species in gastrocnemius that may contribute to glucose and lipid homeostasis derangements in mice.

The Impact of Bariatric Surgery on Assisted Reproductive Technology Outcomes: A Systematic Review.

OBJECTIVE: There is a paucity of literature on the impact of bariatric surgery on artificial reproductive technology (ART) outcomes. This topic should be examined, given that most bariatric surgery candidates are of reproductive age and those with obesity are significantly more likely to experience poor fertility outcomes. This systematic review aimed to determine if bariatric surgery impacts ART outcomes and if effects vary between females and males. DATA SOURCES: MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials were searched for English studies published between January 1978 and May 2021. STUDY SELECTION: Studies with participants who had received bariatric surgery and subsequently underwent ART (i.e., in vitro fertilization or intracytoplasmic sperm injection) were eligible for inclusion. Screening, data abstraction, and risk of bias assessment were conducted independently and in duplicate. DATA EXTRACTION AND SYNTHESIS: Of the 279 articles screened for eligibility, 25 were sought for full text review, and 7 were included for analysis. Four studies (57%) examined ART interventions in females, while 3 (43%) examined interventions in males. Data on cumulative live birth rate (CLBR) was extracted for all 7 studies (N = 169). There were 50 live births with CLBRs ranging from 0.0% to 80.0%. Data on female secondary outcomes were varied. Data on male secondary outcomes were contradictory: 1 study indicated improved sperm parameters following bariatric surgery, while 2 showed decreased parameters, with certain participants seeing improvements after several months. CONCLUSION: Bariatric surgery prior to ART may have an impact on CLBRs; however, high-quality research is needed to delineate the direct effects of bariatric surgery on ART outcomes. Various sex-specific outcomes should be considered prior to recommending ART after bariatric surgery. Future research should determine the optimal type of bariatric surgery and timing of ART following bariatric surgery.

Robotic thoracic surgery in Canada: Are patients willing to pay out of pocket?

Robotic-assisted thoracoscopic surgery (RTS) is safe and effective, but is associated with high capital and operating costs that are not reimbursed by the Canadian government. Currently, patients have access to RTS only when it is supported by research or philanthropic funds. In a recent study, we assessed the extent of patient-reported satisfaction with RTS, whether patients would have been willing to pay out of pocket for it, and what factors were associated with patients' willingness to pay. Many patients (290 of 411 [70.56%]) stated that they would have paid the additional $2000 to supplement the government health care coverage to have access to RTS. Factors found to be significantly associated with participants' willingness to pay were an annual income of $60 000 or more (p = 0.034), private insurance coverage (p = 0.007), overall experience with RTS rated as 8 or higher out of 10 (p < 0.001), and overall postoperative postdischarge experience rated as satisfying or very satisfying (p = 0.004).

Use of Incentive Spirometry in Adults following Cardiac, Thoracic, and Upper Abdominal Surgery to Prevent Post-Operative Pulmonary Complications: A Systematic Review and Meta-Analysis.

BACKGROUND: Currently, consensus on the effectiveness of incentive spirometry (IS) following cardiac, thoracic, and upper abdominal surgery has been based on randomized controlled trials (RCTs) and systematic reviews of lower methodological quality. To improve the quality of the research and to account for the effects of IS following thoracic surgery, in addition to cardiac and upper abdominal surgery, we performed a meta-analysis with thorough application of the Grading of Recommendations Assessment, Development and Evaluation scoring system and extensive reference to the Cochrane Handbook for Systematic Reviews of Interventions. OBJECTIVE: The objective of this study was to determine, with rigorous methodology, whether IS for adult patients (18 years of age or older) undergoing cardiac, thoracic, or upper abdominal surgery significantly reduces30-day post-operative pulmonary complications (PPCs), 30-day mortality, and length of hospital stay (LHS) when compared to other rehabilitation strategies. METHODS: The literature was searched using Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and Web of Science for RCTs between the databases' inception and March 2019. A random-effect model was selected to calculate risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Thirty-one RCTs involving 3,776 adults undergoing cardiac, thoracic, or upper abdominal surgery were included. By comparing the use of IS to other chest rehabilitation strategies, we found that IS alone did not significantly reduce 30-day PPCs (RR = 1.00, 95% CI: 0.88-1.13) or 30-day mortality (RR = 0.73, 95% CI: 0.42-1.25). Likewise, there was no difference in LHS (mean difference = -0.17,95% CI: -0.65 to 0.30) between IS and the other rehabilitation strategies. None of the included trials significantly impacted the sensitivity analysis and publication bias was not detected. CONCLUSIONS: This meta-analysis showed that IS alone likely results in little to no reduction in the number of adult patients with PPCs, in mortality, or in the LHS, following cardiac, thoracic, and upper abdominal surgery.

Fish Quality Index Method: Principles, weaknesses, validation, and alternatives-A review.

Fish is a high nutritional value matrix of which production and consumption have been increasing in the last years. Advancements in the efficient evaluation of freshness are essential to optimize the quality assessment, to improve consumer safety, and to reduce raw material losses. Therefore, it is necessary to use rapid, nondestructive, and objective methodologies to evaluate the quality of this matrix. Quality Index Method (QIM) is a tool applied to indicate fish freshness through a sensory evaluation performed by a group of assessors. However, the use of QIM as an official method for quality assessment is limited by the protocol, sampling size, specificities of the species, storage conditions, and assessor's experience, which make this method subjective. Also, QIM may present divergences regarding the development of microorganisms and chemical analysis. In this way, novel quality evaluation methods such as electronic noses, electronic tongues, machine vision system, and colorimetric sensors have been proposed, and novel technologies such as proteomics and mitochondrial analysis have been developed. In this review, the weaknesses of QIM were exposed, and novel methodologies for quality evaluation were presented. The consolidation of these novel methodologies and their use as methods of quality assessment are an alternative to sensory methods, and their understanding enables a more effective fish quality control.

Assessing the Impact of ED Triage Directives on Febrile Oncology Patient Wait Times.

INTRODUCTION: Fever during chemotherapy is a common and potentially severe complication being increasingly evaluated in emergency departments to minimize morbidity and mortality. Streamlining triage of these patients may improve health outcomes and wait times in the health care system. METHODS: A retrospective chart review of febrile patients undergoing chemotherapy was conducted at a local emergency department to assess the impact of nurse-initiated protocols on wait times. RESULTS: We identified 315 patients undergoing current chemotherapy presenting with fever. Of these, 140 (44%) and 87 (28%) were initiated on the sepsis and febrile neutropenia nurse-initiated protocols, respectively. In total, 197 (63%) were admitted. The febrile neutropenia protocol had a shorter wait time from triage to disposition than the sepsis protocol (403 minutes [SD = 23] vs 329 minutes [SD = 19], t = 1.71, P = 0.01). Furthermore, the febrile neutropenia protocol demonstrated shorter times from both triage to lab results reported, in addition to the physician initial assessment in the admitted patient subgroup. DISCUSSION: Decreased wait times from triage associated with the use of a febrile neutropenia protocol could be accounted for by a lower number of lab results required through this protocol in addition to shorter physician assessment times in the admitted population. This study shows that nurse-initiated protocols may influence door-to-antibiotic time for patients undergoing chemotherapy. By having a targeted protocol for the cancer population, health care centers may be able to demonstrate decreased health care expenditure and increased resource availability. Furthermore, as the current population of patients undergoing chemotherapy is at a high risk for neutropenia, prompt management is crucial to minimize mortality.

Mass Spectrometry Characterization of Thiol Conjugates Linked to Polyoxygenated Polyunsaturated Fatty Acid Species.

Radical mediated oxidation of polyunsaturated fatty acids (PUFA) is known to generate a series of polyoxygenated cyclic products (PUFA-On, n ≥ 3). Here, we describe the characterization of glutathione (GSH) conjugates bound to polyoxygenated docosahexaenoic (DHA-On, n = 3-9), arachidonic (ARA-On, n = 3-7), α-linolenic (ALA-O3), and linoleic (LA-O3) acid species. Similar conjugates were also characterized for N-acetylcysteine (NAC) and Cu,Zn-superoxide dismutase (SOD1). Extensive LC-MS/MS characterization using a synthetic α-linolenic hydroxy-endoperoxide (ALA-O3) derivative revealed at least two types of mechanisms leading to thiol adduction: a mechanism involving the nucleophilic attack by thiolate anion on 1,2-dioxolane to form a sulfenate ester-bonded conjugate and a mechanism involving cleavage of the dioxolane to form a α,ß-unsaturated carbonyl followed by the Michael addition reaction. Finally, we detected a GSH conjugate with hydroxy-endoperoxide derived from linoleic acid (LA-O3) in mice liver. In summary, our study reveals the formation of a series of thiol conjugates that are bound to highly oxygenated PUFA species. GSH conjugates described in our study may potentially play relevant roles in redox and inflammatory processes, especially under high oxygen tension conditions.

Pulmonary hypertension during respiratory syncytial virus bronchiolitis: a risk factor for severity of illness.

BACKGROUND: Respiratory syncytial virus infection is the most frequent cause of acute lower respiratory tract disease in infants. A few reports have suggested that pulmonary hypertension is associated with increased severity of respiratory syncytial virus infection. We sought to determine the association between the pulmonary hypertension detected by echocardiography during respiratory syncytial virus bronchiolitis and clinical outcomes. METHODS: We retrospectively reviewed 154 children admitted with respiratory syncytial virus bronchiolitis who had an echocardiography performed during the admission. The association between pulmonary hypertension and clinical outcomes including mortality, intensive care unit (ICU) admission, prolonged ICU stay (>10 days), tracheal intubation, and need of high frequency oscillator ventilation was evaluated. RESULTS: Echocardiography detected pulmonary hypertension in 29 patients (18.7%). Pulmonary hypertension was observed more frequently in patients with congenital heart disease (CHD) (n = 11/33, 33%), chronic lung disease of infancy (n = 12/25, 48%), prematurity (<37 weeks gestational age, n = 17/59, 29%), and Down syndrome (n = 4/10, 40%). The presence of pulmonary hypertension was associated with morbidity (p < 0.001) and mortality (p = 0.02). However, in patients without these risk factors (n = 68), pulmonary hypertension was detected in five patients who presented with shock or poor perfusion. Chronic lung disease was associated with pulmonary hypertension (OR = 5.9, 95% CI 2.2-16.3, p = 0.0005). Multivariate logistic analysis demonstrated that pulmonary hypertension is associated with ICU admission (OR = 6.4, 95% CI 2.2-18.8, p = 0.0007), intubation (OR = 4.7, 95% CI 1.8-12.3, p = 0.002), high frequency oscillator ventilation (OR = 8.4, 95% CI 2.95-23.98, p < 0.0001), and prolonged ICU stay (OR = 4.9, 95% CI 2.0-11.7, p = 0.0004). CONCLUSIONS: Pulmonary hypertension detected by echocardiography during respiratory syncytial virus infection was associated with increased morbidity and mortality. Chronic lung disease was associated with pulmonary hypertension detected during respiratory syncytial virus bronchiolitis. Routine echocardiography is not warranted for previously healthy, haemodynamically stable patients with respiratory syncytial virus bronchiolitis.

Study on the developmental toxicity of ß-ionone in the rat.

ß-ionone (BIO) is used in fragrances, toiletries and non-cosmetic products, and as a flavor food additive. Notwithstanding the widespread human exposure, there are limited data on the reproductive toxicity of BIO. This study evaluated the developmental toxicity of BIO (0, 125, 250, 500 and 1000 mg/kg body weight/day) given orally to rats on days 6-15 of gestation (GD6-15). C-section was on GD21 and implantations, living and dead fetuses and resorptions were recorded. Fetuses were weighed, and examined for external abnormalities and skeleton and visceral anomalies. The embryotoxicity of a single oral dose of BIO (1000 mg/kg body wt) given on GD11 was evaluated as well. At the highest dose, BIO reduced weight gain and produced chromodacryorrhea and other signs of toxicity. BIO did not increase the frequency of malformations nor did it retard fetal growth. Nonetheless, BIO decreased the pregnancy rate in the group of females exposed on GD6-15, and increased the resorption rate in those treated on GD11 only. In conclusion, except for a higher embryolethality at a maternally toxic dose, BIO caused no embryotoxic effect over the dose range tested and the study NOAEL for maternal and developmental toxicity was 500 mg of BIO/ kg of body weight/day.

Reduction of the DNA damages, Hepatoprotective Effect and Antioxidant Potential of the Coconut Water, ascorbic and Caffeic Acids in Oxidative Stress Mediated by Ethanol.

Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18 µM), caffeic acid (1.1 µM), methyl caffeate (0.03 µM), quercetin (0.08 µM) and ferulic acid (0.02 µM) isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT) was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.

Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies.

BACKGROUND: A study in frog and chicken embryos, and reports of a high incidence of birth defects in regions of intensive GM-soy planting have raised concerns on the teratogenic potential of glyphosate-based herbicides. These public concerns prompted us to conduct a systematic review of the epidemiological studies testing hypotheses of associations between glyphosate exposure and adverse pregnancy outcomes including birth defects. METHODS: A systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Bireme-BVS and SCOPUS databases using different combinations of exposure and outcome terms. A case-control study on the association between pesticides and congenital malformations in areas of extensive GM soy crops in South America, and reports on the occurrence of birth defects in these regions were reviewed as well. RESULTS: The search found ten studies testing associations between glyphosate and birth defects, abortions, pre-term deliveries, small for gestational date births, childhood diseases or altered sex ratios. Two additional studies examined changes of time-to-pregnancy in glyphosate-exposed populations. Except for an excess of Attention Deficit Hyperactivity Disorder - ADHD (OR = 3.6, 1.3-9.6) among children born to glyphosate appliers, no significant associations between this herbicide and adverse pregnancy outcomes were described. Evidence that in South American regions of intensive GM-soy planting incidence of birth defects is high remains elusive. CONCLUSIONS: Current epidemiological evidence, albeit limited to a few studies using non-quantitative and indirect estimates and dichotomous analysis of exposures, does not lend support to public concerns that glyphosate-based pesticides might pose developmental risks to the unborn child. Nonetheless, owing to methodological limitations of existing analytical observational studies, and particularly to a lack of a direct measurement (urine and/or blood levels), or an indirect estimation of exposure that has proven valid, these negative findings cannot be taken as definitive evidence that GLY, at current levels of occupational and environmental exposures, brings no risk for human development and reproduction.

Stratification of Kidney Transplant Recipients Into Five Subgroups Based on Temporal Disease Trajectories.

Background: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Considerable clinical research has focused on improving graft survival and an increasing number of kidney recipients die with a functioning graft. There is a need to improve patient survival and to better understand the individualized risk of comorbidities and complications. Here, we developed a method to stratify recipients into similar subgroups based on previous comorbidities and subsequently identify complications and for a subpopulation, laboratory test values associated with survival. Methods: First, we identified significant disease patterns based on all hospital diagnoses from the Danish National Patient Registry for 5752 kidney transplant recipients from 1977 to 2018. Using hierarchical clustering, these longitudinal patterns of diseases segregate into 3 main clusters of glomerulonephritis, hypertension, and diabetes. As some recipients are diagnosed with diseases from >1 cluster, recipients are further stratified into 5 more fine-grained trajectory subgroups for which survival, stratified complication patterns as well as laboratory test values are analyzed. Results: The study replicated known associations indicating that diabetes and low levels of albumin are associated with worse survival when investigating all recipients. However, stratification of recipients by trajectory subgroup showed additional associations. For recipients with glomerulonephritis, higher levels of basophils are significantly associated with poor survival, and these patients are more often diagnosed with bacterial infections. Additional associations were also found. Conclusions: This study demonstrates that disease trajectories can confirm known comorbidities and furthermore stratify kidney transplant recipients into clinical subgroups in which we can characterize stratified risk factors. We hope to motivate future studies to stratify recipients into more fine-grained, homogenous subgroups to better discover associations relevant for the individual patient and thereby enable more personalized disease-management and improve long-term outcomes and survival.