Lifestyle interventions have not efficaciously reduced complications caused by maternal weight on fetal growth, requiring insight into explanatory mediators.

We hypothesized that maternal mediators, including adiponectin, leptin, insulin, and glucose, mediate effects of pregestational BMI (pBMI) and gestational weight gain (GWG) on birthweight and neonatal fat mass percentage (FM%) through placental weight and fetal mediators, including insulin levels (Ifv) and venous-arterial glucose difference (ΔGfva). Hypothesized confounders were maternal age, gestational age, and parity.

A cross-sectional study of healthy mother-offspring-pairs (n = 165) applying the 4-vessel in vivo sampling method at Oslo University Hospital, Norway. We obtained pBMI, GWG, birthweight, and placental weight. FM% was available and calculated for a subcohort (n = 84). We measured circulating levels of adiponectin, leptin, glucose, and insulin and performed path analysis and traditional mediation analyses based on linear regression models.

The total effect of pBMI and GWG on newborn size was estimated to be 30 g (range, 16-45 g) birthweight and 0.17 FM% (range, 0.04-0.29 FM%) per kg∙m-2 pBMI and 31 g (range, 18-44 g) and 0.24 FM% (range, 0.10-0.37 FM%) per kg GWG. The placental weight was the main mediator, mediating 25-g birthweight and 0.11 FM% per kg∙m-2 pBMI and 25-g birthweight and 0.13 FM% per kg GWG. The maternal mediators mediated a smaller part of the effect of pBMI (3.8-g birthweight and 0.023 FM% per kg∙m-2 pBMI) but not GWG.

Placental weight was the main mediator linking pBMI and GWG to birthweight and FM%. The effect of pBMI, but not GWG, on birthweight and FM%, was also mediated via the maternal and fetal mediators.

Placental weight was the main mediator linking pBMI and GWG to birthweight and FM%. The effect of pBMI, but not GWG, on birthweight and FM%, was also mediated via the maternal and fetal mediators.The self-renewal of mammalian spermatogonial stem cells (SSCs) supports spermatogenesis to produce spermatozoa, and this is precisely controlled in a stem niche microenvironment in the seminiferous tubules. Although studies have revealed the role of the surrounding factors in SSCs, little is known about whether the division of SSCs is controlled by extracellular vesicles. Here, extracellular vesicles were found in the basal compartment of seminiferous tubules in mouse, rat, rabbit and human testes. In the mice, the testicular extracellular vesicles are secreted by spermatogonia and are taken up by SSCs. Further, the extracellular vesicles from thy1-positive spermatogonia were purified by anti-Thy1-coupled magnetic beads, which suppress their proliferation of SSCs but do not lead to the apoptosis in vitro.BACKGROUND Primary cardiac tumors represent less than 5% of total cardiac tumors. Fibroelastoma is a rare benign cardiac tumor that is usually asymptomatic but is acknowledged for its emboligenic potential for causing cardiac, neurological, and vascular symptoms and increasing patient morbidity and mortality. CASE REPORT This report describes the clinical case of a 27-year-old woman who entered the Emergency Department with motor aphasia and hemiparesis in the right dimidium. A brain computed tomography scan was performed at admission, which showed left frontal-parietal hypodensity. The diagnosis of ischemic stroke was made, but cerebral reperfusion therapy with intravenous recombinant tissue plasminogen activator was not instituted due to the time that had passed since ictus (15 h 40 min). On the first day of hospitalization, the patient had a fever, with no apparent infectious cause. She underwent transthoracic echocardiogram that showed a sessile, isoechoic mass adhered to the atrial surface of the anterior mitral valve leaflet, measuring 6.8×5.5 mm. Antibiotic therapy with ceftriaxone and gentamicin was initiated due to the initial diagnosis of infective endocarditis. Three blood culture samples had negative results. Given a differential diagnosis of fibroelastoma, transesophageal echocardiography and cardiac resonance imaging were performed, and the findings were compatible with a diagnosis of mitral valve fibroelastoma. After clinical discussion, the patient was referred to cardiac surgery and underwent tumor resection with anatomopathological diagnosis of papillary fibroelastoma of the heart valve. CONCLUSIONS Young patients with ischemic stroke must be investigated with transthoracic and transesophageal echocardiograms. Papillary fibroelastoma is potential cause of ischemic stroke in young patients, and surgical resection is curative and has excellent prognosis.With the continued transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world, identification of highly suspected COVID-19 patients remains an urgent priority. In this study, we developed and validated COVID-19 risk scores to identify patients with COVID-19. In this study, for patient-wise analysis, three signatures, including the risk score using radiomic features only, the risk score using clinical factors only, and the risk score combining radiomic features and clinical variables, show an excellent performance in differentiating COVID-19 from other viral-induced pneumonias in the validation set. For lesion-wise analysis, the risk score using three radiomic features only also achieved an excellent AUC value. In contrast, the performance of 130 radiologists based on the chest CT images alone without the clinical characteristics included was moderate as compared to the risk scores developed. The risk scores depicting the correlation of CT radiomics and clinical factors with COVID-19 could be used to accurately identify patients with COVID-19, which would have clinically translatable diagnostic and therapeutic implications from a precision medicine perspective.

A substantial number of patients with esophageal squamous cell carcinoma (ESCC) do not achieve complete remission after definitive concurrent chemoradiotherapy (dCRT). We performed this retrospective study to evaluate the efficacy and safety of apatinib combined with S-1/capecitabine as the oral maintenance therapy for these patients.

Thirty-nine ESCC patients with residual disease after dCRT were included. Patients were treated with apatinib combined with S-1 /capecitabine after dCRT. Efficacy, toxicity, and survival were analyzed.

Of the 39 patients, 5 (12.8%) achieved a partial response and 29 (74.4%) achieved stable disease, yielding a disease control rate of 87.2%. The median progression-free survival (PFS) and overall survival (OS) were 27.5 (95%CI 14.9 – 40.1) and 38.1 (95%CI 31.3 – 44.8) months. Most frequent adverse events were of grade 1 to 2. Multivariate analysis revealed the occurrence of any adverse events (HR = 0.274, 95%[CI] = 0.119 – 0.630) correlated to better PFS and occurrence of proteinuria (HR = 0.108, 95%[CI] = 0.025 – 0.456) predicted better OS.

The oral combination therapy consisting of apatinib and S-1/capecitabine showed a tolerable toxicity profile and achieved satisfactory disease control in ESCC patients with residual disease after dCRT.

The oral combination therapy consisting of apatinib and S-1/capecitabine showed a tolerable toxicity profile and achieved satisfactory disease control in ESCC patients with residual disease after dCRT.

The study aimed to investigate the effect of varying testosterone levels in the morning and evening on the depth of anaesthesia in patients who underwent a septoplasty.

Male patients who underwent septoplasty under general anaesthesia between September 2016 and September 2017 were included in the study. The patients were divided into two groups. The first group consisted of patients who were operated on in the morning hours (between 8.00 and 10.00) when the testosterone level was the highest and the second group consisted of patients who had the lowest testosterone level in the afternoon (between 14.00 and 16.00). Blood was taken from the brachial vein to measure the testosterone level of the patients and blood testosterone levels were measured by mass spectrometry before the induction of anaesthesia.

Sixty patients were included in the study. The mean age of the patients was 33.77±10.98years. The rocuronium and propofol doses used in the morning group were significantly higher (P=.012 for propofol, P=.002 for rocuronium, P<.001 for rocuronium dose) (Table2). Additionally, the time to reach saturation of sevoflurane doses in expirium and inspiration was later in the morning group (morning group at 15th minute, evening group at 10th minute).

Sedation anaesthesia applied in patients who underwent septoplasty operation was associated with testosterone level and it was more difficult for patients to switch to sedation with increased testosterone level.

Sedation anaesthesia applied in patients who underwent septoplasty operation was associated with testosterone level and it was more difficult for patients to switch to sedation with increased testosterone level.Our understanding of the viral communities associated to animals has not yet reached the level attained on the bacteriome. This situation is due to, among others, technical challenges in adapting metagenomics using high-throughput sequencing to the study of RNA viromes in animals. Although important developments have been achieved in most steps of viral metagenomics, there is yet a key step that has received little attention the library preparation. This situation differs from bacteriome studies in which developments in library preparation have largely contributed to the democratisation of metagenomics. Here, we present a library preparation optimized for metagenomics of RNA viruses from insect vectors of viral diseases. The library design allows a simple PCR-based preparation, such as those routinely used in bacterial metabarcoding, that is adapted to shotgun sequencing as required in viral metagenomics. We first optimized our library preparation using mock viral communities and then validated a full metagenomic approach incorporating our preparation in two pilot studies with field-caught insect vectors; one including a comparison with a published metagenomic protocol. Our approach provided a fold increase in virus-like sequences compared to other studies, and nearly-full genomes from new virus species. Moreover, our results suggested conserved trends in virome composition within a population of a mosquito species. Finally, the sensitivity of our approach was compared to a commercial diagnostic PCR for the detection of an arbovirus in field-caught insect vectors. Our approach could facilitate studies on viral communities from animals and the democratization of metagenomics in community ecology of viruses.C-C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant-associated infections (OIAI), but whether CCR2-mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic-grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2-deficient mice. In vivo bioluminescent signals significantly increased in CCR2-deficient mice compared with wt mice at later time points (Days 14-28), which was confirmed with ex vivo colony-forming unit enumeration. S. aureus γ-hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ-hemolysin-deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ-hemolysin virulence. Although CCR2-deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2-deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread.

In order to understand the role of long noncoding RNAs (lncRNAs) played in the mechanisms of glyphosate neurotoxicity in neuronal development.

Perinatal glyphosate exposure (PGE) mouse model was constructed, and a lncRNA microarray was used to study the lncRNA expression changes in the hippocampus tissue of perinatal glyphosate exposure mice. Then we used GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases to analyze the function of the differentially expressed mRNAs and lncRNAs.

LncRNA microarray analysis revealed that 1759 lncRNAs and 759 mRNAs were differentially expressed in the perinatal glyphosate exposure (PGE) mice group (G group) compared with the normal control mice group (C group). The functions of the DEmRNAs are involved in the cellular response to hormone stimulus. The ceRNA analysis showed that some interaction networks existed, including (ENSMUST00000137546, ENSMUST00000160950)/(miR-34a-3p, miR-130a-3p)/(Il12b, Irf1). Further analysis of the target mRNAs of miRNAs indicated that the possible functions involved the neuroactive ligand-receptor interaction and calcium signaling pathway, which are involved in perinatal glyphosate exposure-induced neurotoxicity.

The aberrant expression of lncRNAs is related to the perinatal glyphosate-exposed neurotoxicity. These lncRNAs affect the target gene expression level, might by regulating neuroactive ligand-receptor interactions. The (ENSMUST00000137546, ENSMUST00000160950)/ (miRNA-34a-5p, miR-130a-3p) / mRNAs (e.g., Il12b, Irf1) interaction network may functions in perinatal glyphosate exposure-induced neurotoxicity.

The aberrant expression of lncRNAs is related to the perinatal glyphosate-exposed neurotoxicity. These lncRNAs affect the target gene expression level, might by regulating neuroactive ligand-receptor interactions. The (ENSMUST00000137546, ENSMUST00000160950)/ (miRNA-34a-5p, miR-130a-3p) / mRNAs (e.g., Il12b, Irf1) interaction network may functions in perinatal glyphosate exposure-induced neurotoxicity.Metals play an important role in various metabolic activities in the human body, but above desired concentrations, a role reversal occurs that causes deadly outcomes viz., cancer. Metals cannot be cracked down and are non-biodegradable. It is the bioaccumulation of toxic metals inside the biomatrices, that further intensifies the research on different means of metal detoxification from different matrices. Among heavy toxic metals lead is a brutal carcinogen that requires pitiless sensors for its capturing. The use of heterocycles for metal sensing in supramolecular chemistry is preferred due to the strong chelation they offer to toxic metals. The C1-C3 probes were synthesized and studied for their Pb2+ binding ability. All the probes were prepared by treating bromoacetyl coumarin with camphor sulphonamide, 5-dimethylamino-1-naphthalene sulphonamide, and methyl-2-amino-sulphonyl benzoate at room temperature. The probes show selective binding with Pb2+ ions in aqueous acetonitrile among different tested metal ions viz., Cu2+ , Zn2+ , Ni2+ , Mn2+, and Pb2+ ions as shown in ultraviolet (UV)-visible, nuclear magnetic resonance (NMR), and high-performance liquid chromatography (HPLC) studies. These sulphur-containing probes bind very well with Pb2+ ions by offering selectivity in binding positions that capture lead ions at their minimum possible concentration.

In Wilms’ tumour (WT), secondary malignancies caused by the side effects of intensive treatments remain one of the important problems. Therefore, there is a need for new studies to identify low- and high-risk groups for WT and to improve the treatment regimens of children in the low-risk group. In our study, we aimed to determine the prognostic significance of the cyclooxygenase-2 (COX-2) biomarker in WT.

Our study included 24 patients diagnosed with WT between January 2010 and December 2019. The correlation between COX-2 expression and significant prognostic parameters was investigated by studying the COX-2 antibody using the immunohistochemical method.

COX-2 expression was observed in 22 of the patients and it was more evident in the epithelial component. No significant correlation was observed between COX-2 positivity and prognostic parameters. There was also no statistically significant difference between the two groups regarding survival (P=.563).

In our study, no significant relationship was found between significant prognostic parameters and COX-2 expression. Since COX-2 expression was observed in almost all patients, we consider that the COX-2 pathway is effective during the development phase of WT.

In our study, no significant relationship was found between significant prognostic parameters and COX-2 expression. Since COX-2 expression was observed in almost all patients, we consider that the COX-2 pathway is effective during the development phase of WT.Mass spectrometry is gaining momentum as a method of choice to de novo sequence antibodies (Abs). Adequate sequence coverage of the hypervariable regions remains one of the toughest identification challenges by either bottom-up or top-down workflows. Methods that efficiently generate mid-size Ab fragments would further facilitate top-down MS and decrease data complexity. Here, we explore the proteases Cathepsins L and D for forming protein fragments from three IgG1s, one IgG2, and one bispecific, knob-and-hole IgG1. We demonstrate that high-resolution native MS provides a sensitive method for the detection of clipping sites. Both Cathepsins produced multiple, albeit specific cleavages. The Abs were cleaved immediately after the CDR3 region, yielding ~ 12 kDa fragments, that is, ideal sequencing-sized. Cathepsin D, but not Cathepsin L, also cleaved directly below the Ab hinge, releasing the F(ab’)2. When constrained by the different disulfide bonds found in the IgG2 subtype or by the tertiary structure of the hole-containing bispecific IgG1, the hinge region digest product was not produced. The Cathepsin L and Cathepsin D clipping motifs were related to sequences of neutral amino acids and the tertiary structure of the Ab. A single pot (L + D) digestion protocol was optimized to achieve 100% efficiency. Nine protein fragments, corresponding to the VL, VH, CL, CH1, CH2, CH3, CL + CH1, and F(ab’)2, constituted ~ 70% of the summed intensities of all deconvolved proteolytic products. Cleavage sites were confirmed by the Edman degradation and validated with top-down sequencing. The described work offers a complementary method for middle-down analysis that may be applied to top-down Ab sequencing. ENZYMES Cathepsin L-EC 3.4.22.15, Cathepsin D-EC 3.4.23.5.

Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT.

This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON).

Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

The epidemiology of hepatitis B virus (HBV) infection differs between Asians and non-Asians, but little is known regarding the effect of ethnicity on outcomes of HBV-related hepatocellular carcinoma (HCC). We aim to characterize the presentation and survival outcomes in Asian and non-Asian patients with HBV-related HCC.

We analyzed the baseline characteristics and long-term survival of 613 Asian and 410 non-Asian patients with HBV-related HCC from three US and one Spanish centre.

Overall, non-Asian patients were more likely to have HIV or hepatitis C co-infection, cirrhosis, decompensated liver disease and advanced BCLC stage (all P≤.04). Compared with Asians, non-Asians were more likely to be listed for transplantation (P<.0001) and undergo HCC treatment with curative intent (P=.003). Propensity-score matching on HCC diagnosis year, gender and age was performed to balance the two groups for survival analysis and yielded 370 pairs of patients. There was no significant difference in survival overall (P=.43) and among patients with cirrhosis (P=.57). Among patients without cirrhosis, non-Asians had poorer 5-year survival compared with Asians (37.6% vs 53.7%, P=.01), and was associated with poorer survival after adjusting for age, gender, diabetes, alcohol, co-infections, diagnosis date, antiviral therapy, BCLC stage and HCC treatment (adjusted HR 2.01 [95% CI 1.07-3.74], P=.03).

Among HBV-related HCC patients, non-Asians presented with more advanced BCLC stage compared to Asians. Non-Asian ethnicity was independently associated with twice the risk of mortality among patients without cirrhosis, but not among those with cirrhosis. Additional studies are needed to clarify this disparity.

Among HBV-related HCC patients, non-Asians presented with more advanced BCLC stage compared to Asians. Non-Asian ethnicity was independently associated with twice the risk of mortality among patients without cirrhosis, but not among those with cirrhosis. Additional studies are needed to clarify this disparity.

This study focused on comparing the applicability and efficacy of the World Health Organization (WHO) growth standards and the China growth charts in diagnosing malnutrition and indicating nutritional interventions in preterm infants.

Six hundred and eighty-three preterm infants were involved and their anthropometric data were collected. The proportion of weight and head circumference less than the 10

percentile (P

), weight less than the 25

percentile (P

), and weight for length greater than the 90

percentile (P

) identified by the WHO growth standards and the China growth charts were compared.

At corrected age (CA) 1~<2 months (m), the proportion of head circumference <P

assessed by the WHO growth standards was higher than that assessed by the China growth charts by approximately 4.4% in boys and 6.6% in girls. During infancy, both boys and girls had lower proportions of weight <P

and weight <P

with the WHO growth standards than with the China growth charts 5.1% and 5.6%, respectively, for weight <P

and 7.0% and 8.8%, respectively, for weight <P

. For boys older than CA 1 m and for girls older than CA 3 m, the proportion of weight-for-length >P

assessed by the WHO growth standards was greater than that assessed by the China growth charts.

Compared with the China growth charts, the WHO growth standards can further reduce the number of diagnoses of abnormal physical growth, are more helpful in avoiding overnutrition interventions, and are more sensitive in the early detection of delayed head circumference growth.

Compared with the China growth charts, the WHO growth standards can further reduce the number of diagnoses of abnormal physical growth, are more helpful in avoiding overnutrition interventions, and are more sensitive in the early detection of delayed head circumference growth.

To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management.

Multicentre, double-blind, randomised placebo-controlled trial.

30 French hospitals.

Patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins.

Within 30minutes after introduction of prostaglandins, patients received either 3g fibrinogen concentrate or placebo.

Failure as composite primary efficacy endpoint at least 4g/dl of haemoglobin decrease and/or transfusion of at least two units of packed red blood cells within 48hours following investigational medicinal product administration. Secondary endpoints PPH evolution, need for haemostatic procedures and maternal morbidity-mortality within 6±2weeks after delivery.

437 patients were included 224 received FC and 213 placebo. At inclusion, blood loss (877±346ml) and plasma fibrinogen (4.1±0.9g/l) were similar in both groups (mean±SD). Failure rates were 40.0% and 42.4% in the fibrinogen and placebo groups, respectively (odds ratio [OR]=0.99) after adjustment for centre and baseline plasma fibrinogen; (95%CI 0.66-1.47; P=0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56g/l in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group versus two in the placebo group.

As previous placebo-controlled studies findings, early and systematic administration of 3g fibrinogen concentrate did not reduce blood loss, transfusion needs or postpartum anaemia, but did prevent plasma fibrinogen decrease without any subsequent thromboembolic events.

Early systematic blind 3g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.

Early systematic blind 3 g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.

Inhalation of welding fume may cause pulmonary disease known as welder’s lung. At our centre we came across a number of welders with systemic iron overload and prolonged occupational history and we aimed at characterizing this novel clinical form of iron overload.

After exclusion of other known causes of iron overload, 20 welders were fully evaluated for working history, hepatic, metabolic and iron status. MRI iron assessment was performed in 19 patients and liver biopsy in 12. We included 40 HFE-HH patients and 24 healthy controls for comparison.

75% of patients showed lung HRCT alterations; 90% had s-FERR>1000ng/mL and 60% had TSAT>45%. Liver iron overload was mild in 8 and moderate-severe in 12. The median iron removed was 7.8g. Welders showed significantly lower TSAT and higher SIS and SIS/TIS ratio than HFE-HH patients. Serum hepcidin was significantly higher in welders than in HFE-HH patients and healthy controls. At liver biopsy, 50% showed liver fibrosis that was mild in four, and moderate-severe in two. Liver staging correlated with liver iron overload.

Welders with prolonged fume exposure can develop severe liver iron overload. The mechanism of liver iron accumulation is quite different to that of HFE-HH suggesting that reticuloendothelial cells may be the initial site of deposition. We recommend routine measurement of serum iron indices in welders to provide adequate diagnosis and therapy, and the inclusion of prolonged welding fume exposure in the list of acquired causes of hyperferritinemia and iron overload.

Welders with prolonged fume exposure can develop severe liver iron overload. The mechanism of liver iron accumulation is quite different to that of HFE-HH suggesting that reticuloendothelial cells may be the initial site of deposition. We recommend routine measurement of serum iron indices in welders to provide adequate diagnosis and therapy, and the inclusion of prolonged welding fume exposure in the list of acquired causes of hyperferritinemia and iron overload.

Physiologic reserve is an important prognostic indicator. Due to its complexity, no single test can measure an individual’s physiologic reserve. Frailty is the phenotypic expression of decreased reserve and portends poor prognosis. Both subjective and objective tools have been used to measure one or more components of physiologic reserve. Most of these tools appear to predict pre-transplant mortality, but only some predict post-transplant survival.

Incorporation of these measures of physiologic reserve in the clinical and research settings including prediction models will be reviewed and the applicability to patient related outcomes discussed.

Commonly used tools, in patients with cirrhosis, that have been associated with clinical outcomes were reviewed.

The strength of subjective tools lies in low cost, wide availability and quick assessments at bedside. A disadvantage of these tools is the manipulative capacity, restricting their value in allocation processes. The strength of objective tests lies in objective measurements and the ability to measure change. The disadvantages include complexity, increased cost, and limited accessibility.

Heterogeneity in definitions and tools used has prevented further advancement or a clear role in transplant assessment. Consistent use of objective tools including six-minute walk test, gait speed, liver frailty index or short physical performance battery are recommended in clinical and research settings.

Heterogeneity in definitions and tools used has prevented further advancement or a clear role in transplant assessment. Consistent use of objective tools including six-minute walk test, gait speed, liver frailty index or short physical performance battery are recommended in clinical and research settings.

Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter-cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell-derived extracellular vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis.

Immune cell-derived EV were measured in cirrhosis patients [Child-Turcotte-Pugh (Child) score A, n=15; B n=16; C n=43 and Child-C with sepsis (n=38)], and healthy controls (HC, n=11). In vitro and in vivo functional relevance of EV in cirrhosis and associated sepsis was investigated.

Monocyte, neutrophil and hematopoietic stem cells associated EV progressively increased with higher Child score (P<.001)and correlated with liver disease severity indices (r

>0.3, P<.001), which further increased in Child C sepsis than without sepsis(P<.001); monocyte EV showing the highest association with disease stage [P=.013; Odds ratio-4.14(1.34-12.42)]. A threshold level of monocyte EV early stratification of sicker patients.

To create a personalised machine learning model for prediction of severe adverse neonatal outcomes (SANO) during the second stage of labour.

Retrospective Electronic-Medical-Record (EMR) -based study.

A cohort of 73868 singleton, term deliveries that reached the second stage of labour, including 1346 (1.8%) deliveries with SANO.

A gradient boosting model was created, analysing 21 million data points from antepartum features (e.g. gravidity and parity) gathered at admission to the delivery unit, and intrapartum data (e.g. cervical dilatation and effacement) gathered during the first stage of labour. Deliveries were allocated to high-risk and low-risk groups based on the Youden index to maximise sensitivity and specificity.

SANO was defined as either umbilical cord pH levels ≤7.1 or 1-minute or 5-minute Apgar score ≤7.

The model for prediction of SANO yielded an area under the receiver operating curve (AUC) of 0.761 (95% CI 0.748-0.774). A third of the cohort (33.5%, n=24721) were allocated to a high-risk group for SANO, which captured up to 72.1% of these cases (odds ratio 5.3, 95% CI 4.7-6.0; high-risk versus low-risk groups).

Data acquired throughout the first stage of labour can be used to predict SANO during the second stage of labour using a machine learning model. Stratifying parturients at the beginning of the second stage of labour in a 'time out’ session, can direct a personalised approach to management of this challenging aspect of labour, as well as improve allocation of staff and resources.

Personalised prediction score for severe adverse neonatal outcomes in labour using machine learning model.

Personalised prediction score for severe adverse neonatal outcomes in labour using machine learning model.Staphylococcus aureus is a common organism in orthopedic infections, but little is known about the genetic diversity of strains during an infectious process. Using periprosthetic joint infection (PJI) as a model, a prospective study was designed to quantify genetic variation among S. aureus strains both among and within patients. Whole genome sequencing and multilocus sequence typing was performed to genotype these two populations at high resolution. In nasal cultures, 78% of strains were of clonal complexes CC5, CC8, and CC30. In PJI cultures, only 63% could be classified in these common clonal complexes. The PJI cultures had a larger proportion of atypical strains, and these atypical strains were associated with poor host status and compromised immune conditions. Mutations in genes involved in fibronectin binding (ebh, fnbA, clfA, and clfB) systematically distinguished later PJI isolates from the first PJI isolate from each patient. Repeated mutations in S. aureus genes associated with extracellular matrix binding were identified, suggesting adaptive, parallel evolution of S. aureus during the development of PJI.Parallel evolution is considered strong evidence for natural selection. However, few studies have investigated the process of parallel selection as it plays out in real time. The common approach is to study historical signatures of selection in populations already well adapted to different environments. Here, to document selection under natural conditions, we study six populations of threespine stickleback (Gasterosteus aculeatus) inhabiting bar-built estuaries that undergo seasonal cycles of environmental changes. Estuaries are periodically isolated from the ocean due to sandbar formation during dry summer months, with concurrent environmental shifts that resemble the long-term changes associated with postglacial colonization of freshwater habitats by marine populations. We used pooled whole-genome sequencing to track seasonal allele frequency changes in six of these populations and search for signatures of natural selection. We found consistent changes in allele frequency across estuaries, suggesting a potential role for parallel selection. Functional enrichment among candidate genes included transmembrane ion transport and calcium binding, which are important for osmoregulation and ion balance. The genomic changes that occur in threespine stickleback from bar-built estuaries could provide a glimpse into the early stages of adaptation that have occurred in many historical marine to freshwater transitions.

Brief interventions (BIs) in primary health care (PHC) settings can be effective in addressing behavioural risk factors of chronic conditions. However, the impact of the characteristics of BI training programs on the uptake of the program and implementation of BIs in Indigenous PHC settings is not fully understood. The B.strong Program was an Indigenous health worker BI training program delivered in Queensland from 2017 to 2020. This study examines the impact of the characteristics of the B.strong Program on its uptake and implementation in PHC settings.

Semi-structured interviews were conducted in 2019 and 2020 with 20 B.strong Program trainees and four health service managers from eight purposively sampled Queensland PHC services, and one Queensland Department of Health manager, to collect their perceptions of the implementation of the B.strong Program. The Consolidated Framework for Implementation Research guided data collection.

Key program characteristics that facilitated both the program uptake anlivery processes.

Relevance to practice, easy access, program credibility and measures taken to ensure cultural appropriateness of the B.strong Program in development, in engagement stages with health services, and in program delivery facilitated program uptake and implementation of BIs. Online BI training may be of limited value compared to face-to-face training in this setting. SO WHAT? To enhance participation by Indigenous PHC services in health worker BI training programs and implementation of BIs posttraining by health staff, it is important to ensure the cultural appropriateness of the program’s characteristics, and its development, engagement and delivery processes.Telomerase reverse transcriptase (TERT) maintains telomere homeostasis, thus ensuring chromosome stability and cell proliferation. In addition, several telomere-independent functions of human TERT have been described. In this study, we report that TERT binds directly to the TCF binding elements located upstream of the oncomiR miR500A, and induces its transcription. This function was independent of the telomerase activity, as shown with experiments using catalytically inactive TERT and inhibitors of TERT and the TERT RNA component. miR500A was in turn found to target three key components of the Hedgehog signalling pathway Patched 1; Gli family zinc finger 3; and Cullin 3, thereby promoting cell invasion. Our results point to the crucial role of the TERT-miR500A-Hedgehog axis in tumour aggressiveness and highlight the therapeutic potential of targeting noncanonical TERT functions in cancer.

The objectives of this study were to characterize the craniofacial and airway morphology of oculo-auriculo-vertebral spectrum (OAVS) individuals using computed tomography (CT) examination.

This sample included individuals in the age range from 5 to 14years, consisted of a group of 18 OAVS individuals (12 females and 6 males), Pruzansky-Kaban

IIB and III and by a paired control group matched by age and sex for comparison of morphometric and airway variables.

Through the CT examination, airway analysis was performed using Dolphin Imaging® Software, and seven morphometric measurements were performed to evaluate craniofacial morphology by Materialize Mimics® Software. To compare airway and morphometric variables, the control group was used. Student’s t test and Mann-Whitney U test were performed to compare differences between the groups.

Statistically significant differences were showed between the control and OAVS groups for the variables total airway (TA) area, volume and MAA, RP area, RP volume, RP MAA, RG volume, RG MAA, total posterior height diff, Md incl and y-axis asymmetry. Pearson and Spearman’s correlation showed mostly moderate correlations between Mand Occlusal canting AS with TA area and RP volume, Ax-Gn with TA area and Hy-C3 with TA volume.

The OAVS’s airway was altered and worse than the control group. Our results suggest that the contralateral side of OAVS individuals is unaffected; however, longitudinal assessments are needed to confirm it. Hyoid bone and postural measures play an important role in interpreting airway features of individuals with and without OAVS.

The OAVS’s airway was altered and worse than the control group. Our results suggest that the contralateral side of OAVS individuals is unaffected; however, longitudinal assessments are needed to confirm it. Hyoid bone and postural measures play an important role in interpreting airway features of individuals with and without OAVS.Renal transplant recipients remain at risk of delayed-onset cytomegalovirus (CMV) infection occurring beyond a complete course of prophylaxis. In this retrospective cohort, all 278 patients who received renal allografts from deceased donors from 2014 to 2016 were followed until September 1, 2019. We determined the effect of early-vs late-onset acute rejection (EAR vs LAR [ie, occurring beyond 12 months after transplantation]) on CMV infection and subsequently long-term allograft outcome. Median (IQR) duration of follow-up was 1186.0 (904.7-1531.2) days. Seventy patients including 49 patients with EAR and 21 with LAR received augmented immunosuppression. In the same interval, 40 patients developed CMV infection (36 patients beyond 90 days after transplantation [90%]). In logistic regression analysis, D+/R- CMV serostatus (OR 5.5, 95% CI 2.5-12.2) and LAR (OR 7.9, 95% CI 2.8-22.2) significantly increased the risk of CMV infection. In Cox proportional hazard model, delayed-onset CMV infection (HR 2.51, 95% CI 1.08-5.86) and LAR (HR 5.46, 95% CI 2.26-13.14) significantly increased the risk of allograft loss. Patients with LAR are at risk of late-onset CMV infection. Post-LAR, targeted prophylaxis may reduce the risk of CMV infection and subsequently allograft loss. Further studies are required to demonstrate the effect of targeted prophylaxis following LAR.

Owing to the increase in the number of medical procedures performed every year, the frequency of filler injection-related complications has also increased. Although slow, gentle injections with low pressure are usually considered to be safe, the differences in ejection pressure during a filler injection remain to be determined. This study aimed to identify the optimal pressure during filler injections and evaluate its capacity to overcome the arterial blood pressure and reflux the filler material.

Twelve combinations of four hyaluronic acid (HA) fillers with different rheological properties and three needles of different diameters were assessed to determine the force exerted by the injection model. The ejection forces corresponding to varying injection forces were measured and HA filler ejection pressures were calculated.

The highest and lowest injection forces were achieved using 30- and 25-G needles, respectively. In accordance with the expected ejection force, high ejection pressure was achieved by administering the HA filler under a high injection force. Irrespective of the injection force, the ejection pressure was likely to be higher than the vascular pressure at the time of entry into the vessel, rendering the injection dangerous.

During filler injection, penetration of blood vessels and intravascular injection can be avoided by approaching the target area gently using a cannula or needle.

During filler injection, penetration of blood vessels and intravascular injection can be avoided by approaching the target area gently using a cannula or needle.Candida glabrata is an opportunistic pathogen of humans, responsible for up to 30% of disseminated candidiasis. Adherence of C. glabrata to host cells is mediated by adhesin-like proteins (ALPs), about half of which are encoded in the subtelomeres. We performed a de novo assembly of two C. glabrata strains, BG2 and BG3993, using long single-molecule real-time (SMRT) reads, and constructed high-quality telomere-to-telomere assemblies of all 13 chromosomes to assess differences between C. glabrata strains. We documented variation between strains, and in agreement with earlier studies, found high (~0.5%-1%) frequencies of SNVs across the genome, including within subtelomeric regions. We documented changes in ALP gene structure and complement there are large length differences in ALP genes in different strains, resulting from copy number variation in tandem repeats. We compared strains to characterize chromosome rearrangement events including within the poorly characterized subtelomeric regions. We show that rearrangements within the subtelomere regions all affect ALP-encoding genes, and 14/16 involve just the most terminal ALP gene. We present evidence that these rearrangements are mediated by break-induced replication. This study highlights the constrained nature of subtelomeric changes impacting ALP gene complement and subtelomere structure.

Dexamethasone added to incision-site infiltration has been routinely used to reduce pain after tonsillectomy in children. However, this has not been studied in pediatric craniotomy patients yet. We hypothesized that incision-site infiltration with a combination of ropivacaine and dexamethasone might provide superior analgesia to ropivacaine alone in pediatric craniotomy patients.

In this multicenter, double-blind, randomized, controlled trial, children aged 2-12years, scheduled for craniotomy, were prospectively enrolled at two study centers, from September 2, 2019, to July 5, 2020. Eighty children were randomly assigned (11) to either ropivacaine plus dexamethasone group who received pre-emptive incision-site infiltration with 0.2% ropivacaine plus 0.025% dexamethasone, or ropivacaine group who received 0.2% ropivacaine alone. Primary outcome was the modified Children’s Hospital of Eastern Ontario Pain Scale (mCHEOPS) at 24h postoperatively. Primary analysis was performed using the modified intention-to-rative incision-site infiltration has better postoperative analgesic effect than ropivacaine alone in pediatric craniotomy patients.

The addition of dexamethasone to ropivacaine for preoperative incision-site infiltration has better postoperative analgesic effect than ropivacaine alone in pediatric craniotomy patients.

Antipsychotics and lithium are widely used in psychiatry, particularly in schizophrenia and bipolar disorders. Recently, some cases of somnambulism or sleep-related eating disorder (SRED) have been reported in patients treated with these drugs. This study investigated the risk of reporting somnambulism or SRED associated with the use of antipsychotics and lithium.

The World Health Organization pharmacovigilance database (VigiBase), comprising >18 million adverse events, was queried. All somnambulism or SRED reports related to antipsychotics or lithium were identified. The association between antipsychotics or lithium and somnambulism or SRED was computed using the proportional reporting ratio (PRR) and information component.

Among the 5784 cases reporting somnambulism or SRED, 508 suspected at least 1 antipsychotic or lithium. Most patients were aged 18-64 years (62.0%), and 37.0% were men. In most cases (77.6%), antipsychotic or lithium were the only drug class involved, and 53.3% of cases suspected quetiapine. Somnambulism was reported in 88.6% of cases and SRED in 18.1%. A significant association was found for second-generation antipsychotics (PRR 3.44, 95% confidence interval 3.13) and lithium (PRR 2.03, [1.22; 3.37]), but not for first-generation antipsychotics (PRR 0.99, [0.68; 1.44]).

We found a significant signal of somnambulism or SRED related to second-generation antipsychotics and lithium. While case reports mentioned mostly quetiapine and olanzapine, almost all second-generation antipsychotics were associated with somnambulism or SRED.

We found a significant signal of somnambulism or SRED related to second-generation antipsychotics and lithium. While case reports mentioned mostly quetiapine and olanzapine, almost all second-generation antipsychotics were associated with somnambulism or SRED.

Malnutrition is associated with worse outcome in rehabilitation patients; however, appropriate malnutrition screening tools for this population have not been investigated. We examined the predictive validity of specific cut-off values of the Mini Nutritional Assessment Short-Form version 2 (MNA-SFv2) for Japanese rehabilitation patients.

This retrospective cohort study analyzed adult patients (≥20years) in the Japan Rehabilitation Nutrition Database who were in convalescent rehabilitation wards after stroke or hip fracture. Patients were classified into three categories based on MNA-SFv2 original (0-7, 8-11 and 12-14 points, respectively) or modified (0-5, 6-7 and 8-14 points, respectively) cut-off values malnutrition, at risk of malnutrition or well-nourished. Functional independence measure (FIM) and home discharge were compared between the categories.

Overall, 489 patients were analyzed. Based on the MNA-SFv2 original and modified cut-off values, 64.4% and 36.0% were malnourished, 32.3% and 28.4% were at risk of malnutrition, and 3.3% and 35.6% were well-nourished, respectively. Malnutrition defined by both cut-off values was significantly associated with the FIM at admission, whereas only those defined by modified cut-off values predicted the FIM at discharge (B, -7.1; 95% confidence interval=-12.3 to -1.9). Neither original, nor modified cut-off values predicted discharge to home and long-term care facilities.

An MNA-SFv2 score of 0-5 points may be useful to identify Japanese patients with poor outcomes in a rehabilitation setting.

An MNA-SFv2 score of 0-5 points may be useful to identify Japanese patients with poor outcomes in a rehabilitation setting.

Population cancer screening rates are around 50% for the general population and even lower in rural areas. This study aimed to explore knowledge, attitudes, behaviours, motivators and barriers to breast, bowel and cervical screening participation in under-screened men and women.

We used a qualitative research design. Focus groups were segmented by age, sex and screening participation. Participants were under-screened in at least one of the cancer screening programs, with separate groups for each of the programs. The discussion guides were designed around the Health Belief Model and group discussions were coded using a thematic content analysis approach.

Fourteen focus groups were held with 80 participants. Key themes were that the concept of cancer screening was not well understood, a low priority for preventive health behaviours, issues relating to local general practitioners (GP) and screening was unpleasant, embarrassing and/or inconvenient. A key determinant of participation in cancer screening was ent of messages for each of the screening programs should be further explored as factors that may influence rural population screening rates. SO WHAT? Addressing health attitudes, beliefs, knowledge, health practitioner and test-related barriers and improving messaging may increase cancer screening participation in under-screened rural populations.In modern process development, it is imperative to consider biocatalysis, and whole-cell catalysts often represent a favored form of such catalysts. However, the application of whole-cell catalysis in typical organic batch two-phase synthesis often struggles due to mass transfer limitations, emulsion formation, tedious work-up and, thus, low yields. Herein, we demonstrate that utilizing segmented flow tools enables the conduction of whole-cell biocatalysis efficiently in biphasic media. Exemplified for three different biotransformations, the power of such segmented flow processes is shown. For example, a 3-fold increase of conversion from 34 % to >99 % and a dramatic simplified work-up leading to a 1.5-fold higher yield from 44 % to 65 % compared to the analogous batch process was achieved in such a flow process.