Drought-Induced Xylem Embolism Limits the Recovery of Leaf Gas Exchange in Scots Pine.
Climate change increases the occurrence of prolonged drought periods with large implications for forest functioning. Scots pine (Pinus sylvestris) is one of the most abundant conifers worldwide, and evidence is rising that its resilience to severe drought is limited. However, we know little about its ability to recover from drought-induced embolism. To analyze postdrought hydraulic recovery, we investigated stress and recovery dynamics of leaf gas exchange, nonstructural carbohydrates, and hydraulic properties in 2.5-year-old Scots pine seedlings. We quantified the degree of xylem embolism by combining in vivo x-ray microtomography with intrusive techniques including measurements of hydraulic conductivity and dye staining during drought progression and short-term (2 d) and long-term (4 weeks) recovery. Seedlings were grown under controlled conditions, and irrigation was withheld until stomata closed and xylem water potential declined to -3.2 MPa on average, causing a 46% loss of stem hydraulic conductivity. Following drought release, we found a gradual recovery of leaf gas exchange to 50% to 60% of control values. This partial recovery indicates hydraulic limitations due to drought-induced damage. Whereas xylem water potential recovered close to control values within 2 d, both x-ray microtomography and intrusive measurements revealed no recovery of stem hydraulic conductivity. Moreover, we did not find indications for nonstructural carbohydrate reserves limiting hydraulic recovery. Our findings demonstrate that Scots pine is able to survive severe drought and to partially recover, although we assume that xylem development during the next growing season might compensate for some of the hydraulic impairment. Such drought-induced legacy effects are important when considering vegetation responses to extreme events.


Rapid identification of enterococci by reduction of litmus milk.
Of 100 strains of enterococci, 83% reduced litmus milk within 4 h. None of the 100 non-enterococcal streptococci tested were positive.


Photosensitive psoriasis. An epidemiologic study.
In this study of photosensitivity among psoriasis patients, a questionnaire was mailed to 2000 psoriasis patients living within the service area of Karolinska Hospital, Stockholm. Of the 88% patients who replied, 4.4% stated that their psoriasis always worsened after sun exposure, and 7.3% stated that this was sometimes so. After telephone interviews with an 80% sample of these allegedly photosensitive patients, half of them were considered nonphotosensitive. Thus an estimated prevalence of 5.5% photosensitivity was obtained. Forty-three percent of the light-sensitive patients had a history of polymorphous light eruption with secondary exacerbation of psoriasis lesions. Comparison between the photosensitive and the nonphotosensitive patients concerning background factors and symptoms showed a statistically significant increase (p less than or equal to 0.001) in the photosensitive group concerning skin type I, psoriasis affecting hands, heredity for photosensitivity, and advanced age.


Career satisfaction, commitment, and well-being among Taiwanese pediatricians.
Currently, the pediatrician shortage in Taiwan has raised concerns about pediatricians' workloads and wellbeing. This study aimed to understand in-hospital pediatricians' perceptions toward career satisfaction and their wellbeing. A questionnaire exploring pediatricians' life management, commitment to work, and work satisfaction was distributed to all the pediatricians (including attending physicians and residents) in 79 certified training institutions in Taiwan. After expert validation and pilot testing, 17 items with a five-point rating scale were developed to reflect the pediatricians' perceptions. There were 287 responses in total, including 180 attending physicians and 107 residents. Factor analysis was used to explore the construct structure underlying the 17 items. None of the 17 items had a "positive" mean score (≥4/5). Using factor analyses, five factors were extracted: commitment to medical career, self-care, benefit, work environment, and job satisfaction, which accounted for 66.97% of the variance. The factor with the lowest scores was self-care, followed by benefit. The mean score of factors ranged from 2.91 ± 0.17 to 1.64 ± 0.1, all considered "negative." Only 33.6% indicated satisfaction with their jobs. Only 60% of the pediatricians liked their medical career and work environment. The reliability alphas of the five factors ranged from 0.85 to 0.60. Currently, Taiwanese pediatricians are not satisfied with their jobs, having low commitment, poor self-care, and little wellbeing. This study provides a possible explanation for why young physicians leave the pediatric sector, and it also reveals the consequences of physician shortage in Taiwan.


The prevalence of sarcopenic obesity and its association with cognitive performance in type 2 diabetes in Singapore.
We aim to examine body composition, and association between SO and cognitive performance in Type 2 Diabetes (T2D) in an Asian population in Singapore. This was a cross-sectional study on 1235 patients with mean age 61.4 ± 8.0 years and T2D primary and secondary care attending diabetes care in Singapore. Body composition was assessed using tetrapolar multi-frequency BIA device analysis. Fat mass to fat-free mass (FM/FFM) ratio was categorized into 3 groups: Group 1, normal, <0.40; Group 2, obese and increase of FM is small relative to that in FFM, 0.40 to 0.80; and Group 3, SO, >0.80. Cognition was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Mini-Mental State Examination (MMSE). The distribution of body composition based on FM/FFM ratio was: Group 1, 20.2%; Group 2, 60.5%; and Group 3, 19.4%. SO (Group 3) was significantly associated with reduced RBANS total score with β-1.44 (95%CI -2.82 to -0.06; p = 0.041) in multivariable linear regression adjusted for demographics, education, depressive symptom(s) and clinical covariates. SO was significantly associated with reduced index scores for immediate memory and language in fully adjusted models with corresponding βs -2.71 (95%CI -5.06 to -0.36; p = 0.024) and -2.48 (95%CI -4.87 to -0.08; p = 0.043). Association between SO and reduced MMSE score was similarly observed. The prevalence of SO in Asians with T2D is relatively high. There is consistent and independent association of SO with reduced cognitive performance, especially in domains of memory and language, which may impair complex executive function such as adherence to diabetes self-care management.


Conventional and Microwave-Assisted Synthesis, Antitubercular Activity, and Molecular Docking Studies of Pyrazole and Oxadiazole Hybrids.
Microwave-assisted organic reaction enhancement (MORE) has become more important in synthetic organic chemistry for efficient resource utilization. In this study, we synthesized bioactive compounds using both traditional and microwave methods. Microwave-assisted synthesis takes less time and produces higher yields and quality than conventional approaches. We reported the synthesis of N'-(1-(2-(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazol-3(2H)-yl)ethylidene) substituted hydrazides (4a-t). We also tested them against two strains: M. tuberculosis H37Ra and M. bovis BCG. Against M. tuberculosis H37Ra, the compounds 4e, 4h, 4k, 4p, and 4s were the most effective. Compounds 4f, 4g, and 4s showed significant activity against M. bovis BCG. The structures of newly synthesized molecules were determined using spectral methods. Furthermore, molecular docking investigations into the active site of mycobacterial InhA yielded well-clustered solutions for these compounds' binding modalities producing a binding affinity in the range of -10.366 to -8.037. Theoretical results were in good accord with the observed experimental values. The docking score of compound 4e was -10.366, and the Glide energy was -66.459 kcal/mol.


Effects of Neutrophil Extracellular Traps in Patients With Septic Coagulopathy and Their Interaction With Autophagy.
Neutrophil extracellular traps (NETs) act as a critical trigger of inflammation and coagulation. We hypothesized that NETs are associated with septic hypercoagulability. In total, 82 patients admitted with sepsis in the Department of Critical Care Medicine of Peking Union Medical College Hospital were enrolled between February 2017 and April 2018. Clinical and hematological parameters and thrombotic or hemorrhagic events were recorded. Blood samples were obtained to assess biomarkers of NET formation, including neutrophil elastase 2 (ELA2) and citrullinated histone H3, and endothelial-derived biomarker syndecan-1. Autophagy levels and their regulation pathway were also examined to explore their interaction with NETs. Sepsis patients with disseminated intravascular coagulation (DIC) showed significantly higher levels of NET formation [ELA2, 1,247 (86-625) vs. 2,039 (1,544-2,534), p < 0.0001; H3, 140 (47-233) vs. 307 (199-415), p < 0.0001]. NET formation was independently associated with DIC risk [ELA2, OR 1.0028, 95% CI, 1.0010-1.0045; H3, OR 1.0104, 95% CI, 1.0032-1.0176] and mortality [ELA2, HR 1.0014, 95% CI, 1.0004-1.0024; H3, HR 1.0056, 95% CI, 1.0008-1.0115]. The area under the curve value for ELA2 in predicting DIC occurrence was 0.902 (95% CI, 0.816-0.957), and that of H3 was 0.870 (95% CI, 0.778-0.934). Furthermore, biomarkers of NET formation, endothelial cells, and autophagy exhibited a significant correlation [ELA2 and Syn (r = 0.5985, p < 0.0001), LC3B (r = -0.4224, p < 0.0001); H3 and Syn (r = 0.6383, p < 0.0001), LC3B (r = -0.3005, p = 0.0061)]. Increased NET formation is significantly associated with sepsis-induced DIC incidence and mortality in sepsis patients, revealing a significant relationship with the autophagy pathway. chictr.org.cn, identifier ChiCTR-ROC-17010750.


Regional lung functional impairment in acute airway obstruction and pulmonary embolic dog models assessed with gadolinium-based aerosol ventilation and perfusion magnetic resonance imaging.
Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-based aerosol ventilation and perfusion magnetic resonance (MR) images were used to define regional functional impairment in acute airway obstruction (AO) and pulmonary embolic (PE) dog models. The aerosol study was performed in 10 anesthetized normal dogs in a supine position during 20-minute spontaneous inhalation of an aerosol of 100- or 200-mmol-Gd/L Gd-DTPA solute produced by an ultrasonic nebulizer in an open-circuit delivery system, combined with a dynamic perfusion study after a 3-second intravenous bolus injection of a 0.1 mmol/kg dose of Gd-DTPA. These MR studies were also performed in the same 10 dogs approximately 30 minutes after obstructing the segmental (n = 6) or lobar (n = 4) bronchus with a balloon catheter, and in another six dogs after segmental (n = 6) and lobar (n = 4) pulmonary arterial embolization with enbucrilate. Regional lung enhancement was assessed on time-signal intensity (SI)-curves and ventilation- and perfusion-weighted images produced by a subtraction technique. The normal lungs were gradually and gravity-dependently enhanced with time after Gd-DTPA aerosol inhalation regardless of the respiratory SI changes, except for three animals with the fastest breathing rate. The averaged maximal relative lung SI increase against the baseline in the successful animals was significantly greater in the slowly and deeply breathing animals than in the fast and shallow breathing animals, regardless of the difference in Gd-concentration (100 mmol Gd/L: 153.3% +/- 69.7% vs. 54.2% +/- 23%; P < 0.001; and 200 mmol Gd/L: 189.7% +/- 68.0% vs. 75.6% +/- 42.2%; P < 0.0001, respectively). There was an additional enhancement of 382% +/- 101 in the ventral lung and 722% +/- 160 in the dorsal lung on the pulmonary arterial phase perfusion image even in the slowly and deeply breathing animals who inhaled 200-mmol-Gd/L aerosol, and the enhancement effect was significantly greater compared with that with the aerosol (P < 0.0001). The ventilation- and perfusion-weighted images clearly defined the regionally matched perfusion-ventilation deficits in all the AO models, and the regionally mismatched perfusion-ventilation in all the PE models. Gd-based aerosol can provide efficient lung enhancement in spontaneously and adequately breathing animals, using a relatively noninvasive aerosol delivery system. The combined use of Gd-based perfusion MR imaging may be acceptable for defining regionally impaired function associated with acute AO and PE.


[A case of Whipple disease with a pseudotumorous presentation: differential diagnosis with mesenteric panniculitis].
A case of Whipple's disease initially presenting as an inflammatory, granulomatous and pseudotumorous infiltration of the mesenterium is discussed. The initial diagnosis of mesenteric panniculitis was invalidated by the typical histological findings of Whipple's disease in a duodenal biopsy performed 18 months later for malabsorption syndrome. This case illustrates the difficulties besetting differential diagnosis of inflammatory and granulomatous lesions of the mesenterium.


Tuning the infrared resonance of thermal emission from metasurfaces working in near-infrared.
We simulated numerically and demonstrated experimentally that the thermal emittance of a metasurface consisting of an array of rectangular metallic meta-atoms patterned on a layered periodic dielectric structure grown on top of a metallic layer can be tuned by changing several parameters. The resonance frequency, designed to be in the near-infrared spectral region, can be tuned by modifying the number of dielectric periods, and the polarization and incidence angle of the incoming radiation. In addition, the absorbance/emittance value at the resonant wavelength can be tuned by modifying the orientation of meta-atoms with respect to the illumination direction.


Fibroblast growth factor-mediated growth regulation and receptor expression in embryonal carcinoma and embryonic stem cells and human germ cell tumours.
FGFs have been implicated in the induction of mesoderm in amphibian development and are present in the mouse embryo at stages that would be appropriate for a similar function in mammals. Primitive ectoderm would then be the target tissue. We have now changes in the expression of receptors for FGFs during the differentiation of embryonal carcinoma (EC) and embryonic stem (ES) cells from the mouse. These cells resemble those of the inner cell mass and later primitive ectoderm. On Northern blots of mRNA from undifferentiated cells, transcripts for FGF R1, R2 and R3 are expressed. All are upregulated during differentiation of ES cells and are upregulated or remain constant as EC cells differentiate. FGF R4 is only expressed after differentiation to derivatives resembling parietal endoderm. By contrast in human EC cells, FGF R2 is downregulated during differentiation, FGF R1 and FGF R3 are unchanged and FGF R4 is expressed before and after differentiation. In both human and mouse EC cells three members of the FGF family (a FGF, b FGF and k FGF, also known as FGFs 1,2 and 4) are mitogenic in serum-free medium and one (KGF or FGF 7) appears to have no effect on growth although cellular morphology is altered. Differences between human and mouse cells are primarily in the effects of heparin on the FGF-induced response.


Echinodorus grandiflorus: Ethnobotanical, phytochemical and pharmacological overview of a medicinal plant used in Brazil.
Echinodorus grandiflorus (Cham. & Schltdl.) Micheli is a native Brazilian species used in traditional practices for the treatment of several conditions such as inflammatory diseases, arthritis and hypertension. Through a systematic review of the accumulated knowledge about the species E. grandiflorus, the botanical, phytochemistry, ethnobotanical and pharmacological properties of this medicinal plant demonstrates its potential to naturally provide anti-inflammatory and anti-oxidant with a special emphasis on anti-hypertensive and cardioprotective effects. The body of literature reports that the chemical composition of crude E. grandiflorus extracts are notably composed of diterpenoids and flavonoids metabolites. Pharmacological studies have shown that oral treatments using the hydroalcoholic extracts of leaves from this plant has a significant anti-inflammatory, anti-hypertensive, diuretic and cardioprotective effects in rats with no toxicity. The holistic activities of complex extracts are corroborated by the individuals mechanisms of action, as well as, synergistic benefits attributed to the isolated chemical major constituents in this species. In light of the serious health concerns ascribed, it is important to investigate medicinal plant species with histories of traditional use for circulatory problems to meet the growing demands by scientifically validating their use and safety.


Prediction of Ovarian Cancer Response to Therapy Based on Deep Learning Analysis of Histopathology Images.
Ovarian cancer remains the leading gynecological cause of cancer mortality. Predicting the sensitivity of ovarian cancer to chemotherapy at the time of pathological diagnosis is a goal of precision medicine research that we have addressed in this study using a novel deep-learning neural network framework to analyze the histopathological images. We have developed a method based on the Inception V3 deep learning algorithm that complements other methods for predicting response to standard platinum-based therapy of the disease. For the study, we used histopathological H&E images (pre-treatment) of high-grade serous carcinoma from The Cancer Genome Atlas (TCGA) Genomic Data Commons portal to train the Inception V3 convolutional neural network system to predict whether cancers had independently been labeled as sensitive or resistant to subsequent platinum-based chemotherapy. The trained model was then tested using data from patients left out of the training process. We used receiver operating characteristic (ROC) and confusion matrix analyses to evaluate model performance and Kaplan-Meier survival analysis to correlate the predicted probability of resistance with patient outcome. Finally, occlusion sensitivity analysis was piloted as a start toward correlating histopathological features with a response. The study dataset consisted of 248 patients with stage 2 to 4 serous ovarian cancer. For a held-out test set of forty patients, the trained deep learning network model distinguished sensitive from resistant cancers with an area under the curve (AUC) of 0.846 ± 0.009 (SE). The probability of resistance calculated from the deep-learning network was also significantly correlated with patient survival and progression-free survival. In confusion matrix analysis, the network classifier achieved an overall predictive accuracy of 85% with a sensitivity of 73% and specificity of 90% for this cohort based on the Youden-J cut-off. Stage, grade, and patient age were not statistically significant for this cohort size. Occlusion sensitivity analysis suggested histopathological features learned by the network that may be associated with sensitivity or resistance to the chemotherapy, but multiple marker studies will be necessary to follow up on those preliminary results. This type of analysis has the potential, if further developed, to improve the prediction of response to therapy of high-grade serous ovarian cancer and perhaps be useful as a factor in deciding between platinum-based and other therapies. More broadly, it may increase our understanding of the histopathological variables that predict response and may be adaptable to other cancer types and imaging modalities.


Somatic currents contribute to frequency-dependent spike-broadening in supraoptic neuroendocrine cells.
Voltage-gated K and Ca currents were recorded in acutely dissociated neuroendocrine cells of the supraoptic nucleus. The effect of repeated activation of the currents by trains of (10) voltage pulses over a range of pulse-repetition frequencies were examined. There was a significant reduction of K-current amplitude and a significant increase of Ca-current amplitude during trains with high repetition frequencies. Frequency-dependent changes in K and Ca conductances may contribute to frequency-dependent spike-broadening which is exhibited during bursts of action potentials generated by these neurons.


Challenges and results of a school-based intervention to manage excess weight among school children in Tunisia 2012-2014.
Obesity is a serious health issue and predisposes individuals to an increased risk of morbidity and mortality. Its prevalence in children has increased worldwide. To demonstrate the feasibility and effectiveness of a school-based management program based on healthy lifestyle promotion for obese and overweight adolescents in Sousse, Tunisia. We conducted a quasi-experimental study among overweight and obese school children enrolled in 7th and 8th grades in Sousse, Tunisia with two groups, intervention and control. The 1-year intervention was based on promoting healthy eating and physical activity through a collective intervention for all recruited children and an individual intervention only for obese children who require intensive managing. Data collection was done before, at the end and at a 4-month follow up of the intervention, both in intervention and control groups. The body mass index Z score decreased significantly from pre-intervention to post-intervention (1.89±0.57 to 1.76±0.63, p<0.001) and from post-intervention to the follow-up (1.76±0.63 to 1.55±0.68, p<0.001) in the intervention group. In the control group, it decreased significantly from pre-intervention to post-intervention but not significantly from post-intervention to follow-up assessment. Calorie intake decreased significantly both in intervention and control groups. This project began with introducing a new culture of health management in schools on one side and with increasing awareness of the importance of obesity prevention and treatment. The support of authorities for this type of action is very important to guarantee its sustainability.


Urinary amino acid excretion: comparison of normal individuals and patients with bladder cancer.
The excretion levels of urinary amino acids obtained from acid hydrolysates were studied by gas chromatographic analysis in 29 normal individuals and 118 patients with bladder carcinoma. Leucine and isoleucine excretion were elevated in patients with bladder carcinoma as compared with normal subjects under the same experimental condition. Mathematical computer-assisted programs developed to aid in determining clusters of amino acid variables suggested that excretion of glycine, leucine, proline, and glutamic acid in men and concentrations of valine, serine, aspartic acid, phenylalanine, and lysine in women vary according to the invasiveness of the disease. These findings suggest that measurements of urinary amino acids may provide a useful parameter for the detection and aid in the staging of bladder carcinoma.


Protective role of genetic polymorphism of heat shock protein 70-2 for gastric cancer risk.
Heat shock protein 70-2 (HSP70-2) has a cytoprotective role in various conditions and also protects the gastric mucosa. Recently, polymorphism of HSP70-2 at position 1267 was suggested to be associated with carcinogenesis. We investigated the association of this polymorphism with the risk of gastric cancer in the present study. We examined 223 patients (159 men and 64 women, mean age 64.8 years) with gastric cancer who underwent gastrointestinal endoscopy at our department. The controls were 200 age-matched patients (140 men and 60 women) without gastric cancer diagnosed by gastrointestinal endoscopy. Genotyping was done by PCR-based restriction fragment length polymorphism analysis, and the PCR products were digested with PstI. The two allelic forms, corresponding to the presence or absence of the PstI site, were designated as the P1 allele and P2 allele, respectively. Logistic regression analysis was performed to calculate an odds ratios (ORs) for differences of HSP70-2 polymorphism between the two groups. Among the 223 patients with gastric cancer, 46 (20.6%) had P1/P1, 177 (79.4%) were P1 carriers, and 6 (2.7%) were P2/P2. In the control group, 33 (16.5%) patients had P1/P1 polymorphism, 167 (83.5%) were P1 carriers, and 12 (6.0%) were P2/P2. The OR for gastric cancer of subjects with P2/P2 polymorphism relative to P1 carriers was 0.43 (95% CI = 0.16-1.17) (P = 0.097). Among females, the OR for gastric cancer of subjects with P2/P2 polymorphism relative to P1 carriers was 0.10 (95% CI = 0.012-0.838) (P = 0.014). This polymorphism was also associated with a lower risk of middle third cancer (OR = 0.13; 95% CI = 0.02-1.00). P2/P2 polymorphism of HSP70-2 at position 1267 was associated with a lower risk of gastric cancer in females.


Activation of PD-1 Protects Intestinal Immune Defense Through IL-10/miR-155 Pathway After Intestinal Ischemia Reperfusion.
To date, mechanisms of intestinal immunoglobulin (Ig) dysfunction following intestinal ischemia/reperfusion (I/R) remain unclear. Programmed death 1 (PD-1) is associated with immune responses of lymphocytes. We aimed to verify the hypothesis that activation of PD-1 may improve intestinal immune dysfunction by regulating IL-10/miR-155 production after intestinal IR injury. Intestinal I/R injury was induced in mice by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-L1 fusion Ig, anti-interleukin (IL)-10 monoclonal antibody (mAb), and microRNA (miR)-155 agomir were administered. PD-1 expression, IL-10 mRNA, and protein expression in Peyer's patches (PP) CD4+ cells were measured. MiR-155 levels, tumor necrosis factor (TNF)-α and IL-1β concentration, and activation-induced cytidine deaminase (AID), a key enzyme for intestinal immune antibodies, in PP tissues were measured, respectively. Importantly, the production and cecal bacteria-binding capacity of IgA and IgM were detected. Intestinal I/R led to decreased PD-1 expression, imbalanced production, and impaired bacteria-binding capacity of IgA and IgM. Activating PD-1 by PD-L1 Ig facilitated IL-10 synthesis, then decreased miR-155 levels, and subsequently promoted AID expression and reduced TNF-α, IL-1β concentration. Upregulation of AID improved the disruptions of intestinal immune barrier caused by IgA and IgM dysfunction. Anti-IL-10 mAb and miR-155 agomir abolished the protective effects of PD-L1 Ig on the intestinal immune defense. Activation of PD-1 with PD-L1 Ig relieves intestinal immune defensive injury through IL-10/miR-155 pathway following intestinal I/R attack. PD-1, IL-10, and miR-155 may be potential targets for the damages of intestinal barrier and immunity.


A little healthy competition: using mixed methods to pilot a team-based digital game for boosting medical student engagement with anatomy and histology content.
Digital games have been demonstrated to be beneficial for a range of non-recreational purposes, with a particular focus on their value for education. There is a limited amount of research supporting their use for medical education, but their are several studies on their use in areas such as surgical training, and life-support re-training. However, a significant gap exists in demonstrating how they engage with learners and games can be used most effectively in medical education. This pilot study assessed the value of digital games for teaching anatomy, by evaluating participant engagement and their attitudes towards a team-based strategy game. A digital game platform was designed, and then populated with anatomy questions developed by subject matter experts. Second year medical students were recruited to play three matches of the game. At the end of each match participants were asked to complete a Likert rating of their experiences of the game across five domains. Semi-structured interviews were conducted to assess engagement with the platform and perceived value to learners. Sixteen participants volunteered to participate. Post-match ratings indicated that participants had a generally positive experience with the game, with 89 % of respondents agreeing the game was engaging, 93 % of respondents agreeing the game was challenging and 74 % indicating they would like to play the game again if given the opportunity. A total of fourteen participants agreed to be interviewed after playing three matches of the game. Interview responses supported the findings of the post-match ratings that the game was considered enjoyable and engaging. Participants noted they particularly enjoyed the competitive aspect of the game, particularly the opportunity to play against peers they consider their academic equals. In addition to finding the game engaging interview participants indicated they perceived the game impacted on their knowledge around anatomy. In particular, participants noted that the game provided them unique insight into their knowledge strengths and deficits. This study demonstrated that digital games can engage medical students in traditionally-challenging areas such as anatomy and offer learners unique insights into their knowledge strengths and deficits.


The effect of bupivacaine on myocardial tissue hypoxia and acidosis during ventricular fibrillation.
Previously we observed that during bupivacaine-induced circulatory collapse, myocardial tissue pH declined more slowly than expected. Here we evaluated the effect of bupivacaine on myocardial acidosis induced by ventricular fibrillation. Sixteen dogs were anesthetized with 1.5% end-tidal isoflurane, the chest was opened, and a probe that measured oxygen pressure (PmO(2)), carbon dioxide pressure, pH, and temperature was inserted into myocardial tissue. After baseline measures, each dog received either 10 mg/kg bupivacaine (n = 8) or a sham saline treatment (n = 8). Three minutes later ventricular fibrillation was initiated electrically, and the rate of change in PmO(2) and pH during ventricular fibrillation was measured. Baseline physiological measures were similar in the two groups of dogs. During ventricular fibrillation there was a rapid decrease in PmO(2), and the rate of decrease was not different between sham- and bupivacaine-treated dogs. Tissue pH decreased during ventricular fibrillation, and the rate of decrease was 4 times faster in sham- compared with bupivacaine-treated dogs (P < 0.05). These results show that bupivacaine attenuated myocardial tissue acidosis during ventricular fibrillation. This potentially beneficial effect may be a result of bupivacaine's ability to inhibit myocardial lactate and carbon dioxide production. This suggests a potential clinical application of bupivacaine for myocardial preservation. In this animal study pretreatment with bupivacaine attenuated the progression of myocardial acidosis during ventricular fibrillation. The dogs regained normal hemodynamic variables after lipid infusion. The findings suggest such that bupivacaine may protect the heart against ischemic acidosis.


Requirement of Smad3 for mast cell growth.
The involvement of the TGF-beta family in cell growth of bone marrow-derived mast cells (BMMC) cultured with medium containing pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM) was examined. Doubling time of BMMC from Smad3-null mice was longer than that from wild-type (WT) mice, and the differences tended to be larger with time of culture. Consistent with the results, uptake and reduction of [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] was lower in Smad3-deficient BMMC. Cell cycle analyses revealed no apparent differences between WT BMMC and Smad3-deficient BMMC, suggesting that longer doubling time in Smad3-deficient BMMC resulted from increased cell death. TGF-beta and activin A were supplied by PWM-SCM rather than by self-production by BMMC. Blocking the TGF-beta pathway by anti-TGF-beta neutralizing antibody or an inhibitor for the type I receptors for ligands including TGF-beta and activin, SB431542, inhibited MTS uptake and reduction in WT BMMC, whereas anti-activin A antibody and SB431542 tended to inhibit them in Smad3-deficient BMMC. The present results suggest that TGF-beta-induced and Smad3-mediated signaling is essential for maximal cell growth in mast cells, and that the activin pathway may be required for it when mast cell context is modulated by Smad3 depletion.


Sublethal effects of nine insecticides on Drosophila suzukii and its major pupal parasitoid Trichopria drosophilae.
Although the pupal parasitoid Trichopria drosophilae is used in conservative and augmentative biocontrol of Drosophila suzukii infestations, current pest management strategies mostly rely on multiple insecticide applications. In this context, the aim of the study was to investigate the baseline toxicity of nine insecticides on D. suzukii larvae and their multiple sublethal effects (LC10 ) on immature stages of the pest feeding on contaminated diet and T. drosophilae developing within the intoxicated host. Chlorpyriphos and azadirachtin showed the lowest and the highest LC10 , the values of which were 9.78 × 1013 and 1.46 × 103 times lower than their recommended label field rate, respectively. Among tested insecticides, imidacloprid, malathion and dimethoate were the only treatments that did not affect the juvenile development time of D. suzukii, while spinosad and the organophosphates chlorpyriphos and dimethoate did not influence fly pupal size. No sublethal effects were recorded on T. drosophilae degree of infestation (DI) and juvenile development time. On the contrary, cyazypyr and dimethoate negatively affected the success of parasitism (SP) and the number of progeny of the pupal parasitoid, in association with malathion for the first parameter and spinosad for the fertility. Compared to the untreated control, more female progeny emerged following azadirachtin exposure, while dimethoate caused the opposite effect. Imidacloprid, lambda-cyhalothrin and spinetoram decreased hind tibia length of emerged parasitoids. This study provides new insights on the (eco)toxicological profile of nine insecticides and new information needed to support the deployment of T. drosophilae in the field within the sustainable management techniques against D. suzukii. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Liver complications in lymphomas treated with a combination of chemotherapy and radiotherapy: preliminary results.
From May 1978 to May 1981, a total of 20 patients (18 patients with Non Hodgkin Lymphomas + 2 patients with Stage IV Hodgkin's disease) were treated with chemotherapy and whole or upper abdominal radiotherapy. All the patients were in complete remission at the time of irradiation. Shielding of the kidneys was effected at the start of treatment and the right lobe of the liver was shielded after a dose of 20 Gy was delivered. As of January 1982, 17 of the patients were alive and free of disease with a follow-up ranging from 6 to 32 months (mean follow-up of 18.5 months). Two patients were dead from their disease. Alterations in liver chemistry were observed in 5 patients, clinical jaundice or transient hepatomegaly along with changes in liver chemistry in 4 patients, classical veno-occlusive disease in 2 patients and 7 of the patients did not develop any complication. No death from complications were observed. The contribution of the following factors such as radiotherapy dose to the liver, drugs, nutritional status and associated medical conditions, towards the development of complications have been analyzed in detail.


Pancreas specification: a budding question.
Much recent investigation has been carried out into the mechanisms by which the pancreas is specified from the early endoderm. Recent advances have highlighted important roles for retinoic acid and bone morphogenetic protein signalling in patterning the endoderm at late gastrulation. Subsequently, interactions with the endothelium of the aorta in the dorsal pancreas domain and lateral plate mesoderm in the ventral pancreas domain are the source of essential pancreas-inductive signals. Additionally, the transcription factor Ptf1a has been demonstrated to have a previously unappreciated role in distinguishing pancreas from surrounding duodenal fates.


Endothelial cell-smooth muscle cell co-culture in a perfusion bioreactor system.
Vascular endothelial cells (EC) are exposed to a complex biomechanical environment in vivo and are responsible for relaying important messages to the underlying tissue. EC and smooth muscle cells (SMC) communicate to regulate vascular development and function. In this work, a vascular perfusion bioreactor is used to grow tubular constructs seeded with EC and SMC under pulsatile shear stress in long-term co-culture to study the effects of EC on SMC function. SMC seeded into porous poly(glycolic acid) tubular scaffolds are cultured in the bioreactor for 25 days. Constructs are seeded with EC on day 10 or day 23 creating 2-day (short-term) or 15-day (long-term) EC and SMC co-cultures. Long-term EC-SMC co-culture significantly increases cell proliferation and downregulates collagen and proteoglycan deposition compared to short-term co-culture. After 25 days of culture, 15-day co-culture constructs have a more uniform cell distribution across the construct thickness and SMC express a more contractile phenotype compared to 2-day co-culture constructs. These data demonstrate strong interactions between SMC and EC in the bioreactor under physiologically relevant conditions. Thus, the vascular construct perfusion bioreactor is an important tool to investigate cell-cell and cell-extracellular matrix interactions in vascular cell biology and tissue engineering.


Associative symmetry and item availability: evidence for qualitative age differences in acquisition strategies.
The concept of associative symmetry was investigated under three instructional conditions with standard instructional conditions producing associative asymmetry in old subjects and symmetry in young subjects. Analysis of response-stimulus item availability for young and old subjects led to the suggestion that young and old subjects utilize qualitatively different acquisition strategies to process information and that deficits in PA learning in old subjects may begin in the associative learning stage.


Navel Healing and Calf Fitness for Transport.
Dairy male calves are at risk of welfare compromise as they are usually transported at a very young age. The European Union has set a "completely healed navel" requirement for calf transport; moreover, a minimum age is established for longer journeys. However, this requirement has proven to be prone to misinterpretation. This study aimed to clarify what is meant by "navel healing" and to provide strong elements for reaching a consensus. The navels of 299 dairy calves (55 males, 244 females) aged 0-90 days were examined and scored 1 to 5 according to their healing status. Based on our results, a completely dry and shriveled navel (score 3) would imply a 25.5-38.0% risk of transporting too young calves. Alternatively, the presence of a scab covering the umbilical wound (score 4) would entail a 4.3% risk of transporting calves less than 10 days old and could be considered good practice for transporting calves (except for journeys exceeding 8 h). Conversely, complete navel healing (score 5) guarantees that calves that are too young are not transported; therefore, it should be considered best practice for transporting calves in general and the minimum requirement for transporting calves for journeys exceeding 8 h.


[Prognosis and therapy of congenital diaphragmatic hernia depending on the time of clinical presentation - experience of a highly specialized referral centre].
Congenital diaphragmatic hernia (CDH) is a diagnosis with multiple, mostly unknown origin. Therefore its clinical presentation is highly variable. In case of prenatal detection prognosis and amount of interventions in neonatal intensive care is predictable. The results reported by high volume centres for CDH improved continuously during the last years. In neonates suffering from CDH without prenatal diagnosis severe respiratory distress is the leading clinical sign. Presenting symptom of late-onset CDH can also be gastrointestinal problems. Due to more subtle symptoms late presenting CDH is more difficult to diagnose. Prognosis is good, but it still requires surgical intervention to alleviate the symptoms.


Visual and linguistic semantic representations are aligned at the border of human visual cortex.
Semantic information in the human brain is organized into multiple networks, but the fine-grain relationships between them are poorly understood. In this study, we compared semantic maps obtained from two functional magnetic resonance imaging experiments in the same participants: one that used silent movies as stimuli and another that used narrative stories. Movies evoked activity from a network of modality-specific, semantically selective areas in visual cortex. Stories evoked activity from another network of semantically selective areas immediately anterior to visual cortex. Remarkably, the pattern of semantic selectivity in these two distinct networks corresponded along the boundary of visual cortex: for visual categories represented posterior to the boundary, the same categories were represented linguistically on the anterior side. These results suggest that these two networks are smoothly joined to form one contiguous map.


Bond strengths of silicoated and acrylic resin bonding systems to metal.
The Kevloc bonding system is based on the bond of acrylic resin with the metal surface, in contrast to the Silicoater system, which covers the metal surface with a SiOx-C layer. Bonding prevents the occurrence of the marginal gap between the metal and the resin, which causes weaker bond strengths and discoloration. This investigation examined the bond strength values achieved by using the Kevloc technique on Ag-Pd and Co-Cr alloys, and compared them with those obtained by the Silicoater technique. After artificial aging, shear testing of the specimens was performed. A microscope image analyzer measured the thickness of bonding layers to reveal any marginal gap. No marginal gap was noticed for either technique. The Kevloc technique provided better results than Silicoater regardless of alloy used. Immersion in water (7.64 to 8. 05 MPa) and thermocycling (6.12 to 6.95 MPa) reduced the initial bond strength values (12.52 to 12.94 MPa), but the breakdown occurred between the opaque layers or between the opaque and the resin, thus giving a cohesive type of failure. The dental alloy used did not affect bond strengths and artificial aging caused reduction in bond strengths. The Kevloc bonding system exhibited higher bond strengths than Silicoater, but the marginal gap was not seen for either bonding system.


Epilepsy in the UK: misdiagnosis, mistreatment, and undertreatment? The Wrexham area epilepsy project.
To assess the diagnostic and therapeutic difficulties in patients with epilepsy who had never come into contact with specialist services. Assessment was offered to 676 patients diagnosed as having epilepsy and receiving anti-epileptic drug therapy (AED), who had no previous contact with the local epilepsy services. Two hundred and seventy-five patients gave consent and attended for reassessment. We identified the proportion of patients (a) who had previously seen a neurologist, (b) in whom the diagnosis of epilepsy was not secure, (c) in whom planned AED withdrawal could be considered (d) in whom seizure control could be improved. 53/275 (19.3%) of those attending for review had previously been seen by a neurologist. 87/275 (31.6%) patients ultimately received continued specialist care. Diagnostic doubt was expressed in 3/53 (5.6%) and 42/222 (18.9%) of patients diagnosed by neurologist and non-specialist, respectively. Of 133/219 (60.7%) of patients whose epilepsy was in remission, only 6 elected to withdraw or change medication. Of 18 patients with diagnostic doubt who accepted follow-up, 12 successfully stopped treatment. 17/55 (30.9%) patients with active epilepsy (10 partial, 7 generalised) achieved at least a 1 year remission consequent upon treatment in this clinic. In 15 cases this was a first ever remission. Approximately 55% of the population of adults receiving treatment for epilepsy have never received specialist advice. Reassessment of these patients uncovers diagnostic uncertainty, failure to classify (leading to sub-optimal therapy) and lack of information and advice about all aspects of epilepsy care. The development of integrated services for people with epilepsy (PWE) must take account of this hidden need. The new General Medical Services contract for general practitioners will bring this need to our attention, and our experience will help predict the measures required to deal with the under-treatent and mistreatment of this group. The majority of PWE, not currently receiving shared care, merit reassessment and approximately one-third will require continued specialist care. Existing services do not have the capacity to process a marked increase in rate of referral. This project informs prioritisation of referrals and service reorganisation.


Muramyl peptides augment cytotoxic effect of tumor necrosis factor-alpha in combination with cytotoxic drugs on tumor cells.
We have demonstrated that biologically active muramyl peptides, in particular, glucosaminylmuramyl dipeptide (GMDP), augmented in vitro cytotoxic activity of tumor necrosis factor-alpha (TNF-alpha) against murine fibrosarcoma L929 cells. The introduction of GMDP resulted in cytotoxic effect characteristic for substantially higher dose of cytokine. Even more potent was the combination of GMDP, TNF-alpha and Actinomycin D (ActD). According to clonogenic and MTT assays 100% L929 cells could be killed in culture with low doses of TNF-alpha and ActD if GMDP was present. When cisplatin was substituted for ActD similar results were obtained. GMDP also enhanced cytotoxicity of TNF-alpha and cisplatin against human breast carcinoma MCF7 and histiocytic lymphoma U937 cells. Normal cells, namely human peripheral blood leucocytes and murine peritoneal macrophages, were resistant to selected doses of TNF-alpha/cisplatin/GMDP.


Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus.
In the United States, more than ten million women use contraceptive hormones. Ethinyl estradiol and levonorgestrel have been mainstay contraceptive hormones for the last four decades. Surprisingly, there is scant information regarding their action on the central nervous system and behavior. Intact female rats received three weeks of subcutaneous ethinyl estradiol (10 or 30μg/rat/day), levonorgestrel (20 or 60μg/rat/day), a combination of both (10/20μg/rat/day and 30/60μg/rat/day), or vehicle. Subsequently, the rats were tested in three versions of the novel object recognition test to assess learning and memory, and a battery of tests for anxiety-like behavior. Serum estradiol and ovarian weights were measured. All treatment groups exhibited low endogenous 17β-estradiol levels at the time of testing. Dose-dependent effects of drug treatment manifested in both cognitive and anxiety tests. All low dose drugs decreased anxiety-like behavior and impaired performance on novel object recognition. In contrast, the high dose ethinyl estradiol increased anxiety-like behavior and improved performance in cognitive testing. In the cell molecular analyses, low doses of all drugs induced a decrease in tyrosine hydroxylase mRNA and protein in the locus coeruleus. At the same time, low doses of ethinyl estradiol and ethinyl estradiol/levonorgestrel increased galanin protein in this structure. Consistent with the findings above, the low dose treatments of ethinyl estradiol and combination ethinyl estradiol/levonorgestrel reduced brain-derived neurotrophic factor mRNA in the hippocampus. These effects of ethinyl estradiol 10μg alone and in combination with levonorgestrel 20μg suggest a diminution of norepinephrine input into the hippocampus resulting in a decline in learning and memory.


[Prevention of arterial diseases in the 2010s: the European treatment guideline].
Reduction of risk factors at the population level forms the basis of the European recommendation of 2012 for the prevention of arterial diseases. Actions at the individual level arise from risk assessment. The risk of arterial disease is graded into four categories, the uppermost ones comprising patients who have already developed the disease, diabetics, those suffering from renal insufficiency and those carrying a serious gene defect. In Finland the risk among healthy people is assessed by using the FINRISKI tool. Non-smoking, healthy diet and regular exercise are suitable for all. Statins are an effective and safe means of prevention for those at high risk regardless of lipid values.


[Accumulation of glutamic acid and glycine in human cerebral tumors in vitro].
Preliminary results are given on transport of glycine and L-glutamate into human cerebral tissue, normal and tumoral. In comparison with normal tissue, glycine transport is diminished in meningioma and oligodendroblastoma, unaffected in neurinoma, sharply increased in medulloblastoma. Glutamic acid transport is lowered in neurinoma and oligodendroblastoma; increased in medulloblastoma. Such preliminary observations are briefly discussed.


Green tea polyphenols enhance sodium nitroprusside-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.
Oxidative stress is a main mediator in nitric oxide (NO) -induced neurotoxicity and has been implicated in the pathogenesis of many neurodegenerative disorders. Green tea polyphenols are usually expected as potent chemo-preventive agents due to their ability of scavenging free radicals and chelating metal ions. However, not all the actions of green tea polyphenols are necessarily beneficial. In the present study, we demonstrated that higher-concentration green tea ployphenols significantly enhanced the neurotoxicity by treatment of sodium nitroprusside (SNP), a nitric oxide donor. SNP induced apoptosis in human neuroblastoma SH-SY5Y cells in a concentration and time-dependent manner, as estimated by cell viability assessment, FACScan analysis and DNA fragmentation assay, whereas treatment with green tea polyphenols alone had no effect on cell viability. Pre-treatment with lower-dose green tea polyphenols (50 and 100 microm) had only a slightly deleterious effect in the presence of SNP, while higher-dose green tea polyphenols (200 and 500 microm) synergistically damaged the cells severely. Further research showed that co-incubation of green tea polyphenols and SNP caused loss of mitochondrial membrane potential, depletion of intracellular GSH and accumulation of reactive oxygen species, and exacerbated NO-induced neuronal apoptosis via a Bcl-2 sensitive pathway.


Ovarian activity and reproductive potential in a natural population of Drosophila melanogaster.
The ovarian state of Drosophila melanogaster females from a wild population in the south of France was studied by immediate dissection, in the field, during two different periods in the year: early in June and at the end of September. It was compared with either the reproductive capacities of aliquot females kept in laboratory conditions or the reproductive potential of the first laboratory generation.Among the wild flies, about 20% were young (less than 24 h). 85 to 90% of all females were inseminated and virgins were found among the youngest ones.In the field, the vitellogenetic activity appeared to be very low and noncontinuous. Females with active vitellogenesis were fairly rare but about 60% of the females presented eggs in retention in the ovaries and 50% had a fertilized egg waiting in the uterus. All these observations showed that fecundity in the field was certainly low.When wild females were studied in the laboratory, their daily egg production was relatively high, more than 50 eggs per day per female. This production was stimulated by insemination and decreased with adult population density.Daughter females reared in the laboratory were bigger, had more numerous ovarian tubes than their mothers (an average of 50 instead of 32), and their daily egg production was very high. However the daily overiole production in these two groups was very similar.The genetic reproductive potential of this natural French population seems to be very high but, under natural life conditions, this potential is not expressed. Wild flies do not seem to give priority to their reproductive effort but to individual survival and activity.


Velocity of axonal transport of phospholipid in rat sciatic nerve.
The difficulties involved in measuring axonal transport velocity for phospholipid in mammalian axons have been overcome by using a reversible local cold-block technique which causes a local accumulation of labeled phospholipid in rat sciatic nerve that follows injection of [methyl 3H]choline chloride into the L5 dorsal root ganglion. On rewarming the nerve a distinct front of [3H]-activity moves distally from the cold-block site at 17.8 mm X h-1, a velocity not significantly different from that previously determined for protein. This observation provides further support for the hypothesis that fast axonal transport conveys membranes assembled in the cell body.


Effects of diet on high-density lipoprotein cholesterol.
Multiple dietary factors have been shown to increase high-density lipoprotein cholesterol (HDL-C) concentrations, and HDL-C has been inversely associated with coronary heart disease (CHD) risk. Replacement of dietary carbohydrate with polyunsaturated, monounsaturated and saturated fat has been associated with progressively greater increases in HDL-C (7-12%) in addition to other lipid changes. Added sugars, but not high glycemic carbohydrates, have been associated with decreased HDL-C. Alcohol consumption has been associated with increased HDL-C (9.2%) independent of changes in other measured lipids. Modest effects on HDL-C (~4-5%) among other lipid and non-lipid CHD risk factors have also been observed with weight loss by dieting, omega-3 fatty acids, and a Mediterranean diet pattern. The CHD benefit of increasing HDL-C is unclear given the inconsistent evidence from HDL-raising pharmacologic trials. Furthermore, pleiotropic effects of diet preclude attribution of CHD benefit specifically to HDL-C. Investigation into functional or other properties of HDL may lend further insight.


EGFR mutation frequency in Middle East and African non-small cell lung cancer patients: a systematic review and meta-analysis.
Our goal was to investigate the prevalence of the epidermal growth factor receptor (EGFR) mutation in Middle East and African countries and to compare its prevalence with that shown in other populations. We used PubMed and the Cochrane Library databases to conduct a literature search using the terms "[EGFR] AND [mutation] AND [Non Small Cell Lung Cancer] AND [Middle East OR Africa]." We assessed studies published in English and French from 2004 until 2016. Ten relevant studies were included in this systematic review. Overall, 1215 patients with non-small cell lung cancer (NSCLC) were included in this analysis. The overall ratio of male to female patients was 2.15. Of total patients included, 41.1% had never smoked and 85.8% had been diagnosed with adenocarcinoma. In 8 of the 10 studies, polymerase chain reaction (PCR) analyses were conducted to identify EGFR mutations. In total, 257 patients had an EGFR mutation, corresponding to a prevalence of 21.2%. The most frequent abnormality detected in all of the studies was in exon 19. In addition, all studies concluded the presence of a correlation between EGFR mutation status and female sex, non-smoking status, and adenocarcinoma subtype. The EGFR mutation frequency in Middle East and African patients is higher than that shown in white populations but still lower than the frequency reported in Asian populations.


Primary fibrosarcoma of the heart presenting as obstruction at the tricuspid valve: diagnosis by cross-sectional echocardiography.
We report a case of primary fibrosarcoma of the heart which presented with features of obstruction to the tricuspid valve and superior caval vein. It was correctly diagnosed by cross-sectional echocardiography.


The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb.
Overexpression of the oncogene MYBL2 (B-Myb) is associated with increased cell proliferation and serves as a marker of poor prognosis in cancer. However, the mechanism by which B-Myb alters the cell cycle is not fully understood. In proliferating cells, B-Myb interacts with the MuvB core complex including LIN9, LIN37, LIN52, RBBP4, and LIN54, forming the MMB (Myb-MuvB) complex, and promotes transcription of genes required for mitosis. Alternatively, the MuvB core interacts with Rb-like protein p130 and E2F4-DP1 to form the DREAM complex that mediates global repression of cell cycle genes in G0/G1, including a subset of MMB target genes. Here, we show that overexpression of B-Myb disrupts the DREAM complex in human cells, and this activity depends on the intact MuvB-binding domain in B-Myb. Furthermore, we found that B-Myb regulates the protein expression levels of the MuvB core subunit LIN52, a key adapter for assembly of both the DREAM and MMB complexes, by a mechanism that requires S28 phosphorylation site in LIN52. Given that high expression of B-Myb correlates with global loss of repression of DREAM target genes in breast and ovarian cancer, our findings offer mechanistic insights for aggressiveness of cancers with MYBL2 amplification, and establish the rationale for targeting B-Myb to restore cell cycle control.


Evaluation of Concurrent Radiation, Temozolomide and ABT-888 Treatment Followed by Maintenance Therapy with Temozolomide and ABT-888 in a Genetically Engineered Glioblastoma Mouse Model.
Despite the use of ionizing radiation (IR) and temozolomide (TMZ), outcome for glioblastoma (GBM) patients remains dismal. Poly (ADP-ribose) polymerase (PARP) is important in repair pathways for IR-induced DNA damage and TMZ-induced alkylation at N7-methylguanine and N3-methyldenine. However, optimized protocols for administration of PARP inhibitors have not been delineated. In this study, the PARP inhibitor ABT-888 was evaluated in combination with and compared to current standard-of-care in a genetically engineered mouse GBM model. Results demonstrated that concomitant TMZ/IR/ABT-888 with adjuvant TMZ/ABT-888 was more effective in inducing apoptosis and reducing proliferation with significant tumor growth delay and improved overall survival over concomitant TMZ/IR with adjuvant TMZ. Diffusion-weighted MRI, an early translatable response biomarker detected changes in tumors reflecting response at 1 day post TMZ/IR/ABT-888 treatment. This study provides strong scientific rationale for the development of an optimized dosing regimen for a PARP inhibitor with TMZ/IR for upfront treatment of GBM.


Molecular convergence and transgenic evidence suggest a single origin of laryngeal echolocation in bats.
The laryngeal echolocation is regarded as one of the conspicuous traits that play major roles in flourishing bats. Whether the laryngeal echolocation in bats originated once, however, is still controversial. We here address this question by performing molecular convergence analyses between ancestral branches of bats and toothed whales. Compared with controls, the molecular convergences were enriched in hearing-related genes for the last common ancestor of bats (LCAB) and extant echolocating bats, but not for the LCA of Old World fruit bats (LCAP). And the convergent hearing gene prestin of the LCAB and the extant echolocating bats functionally converged. More importantly, the high-frequency hearing of the LCAP-prestin knock-in mice decreased with lower cochlear outer hair cell function compared with the LCAB-prestin knock-in mice. Together, our findings provide multiple lines of evidence suggesting a single origin of laryngeal echolocation in the LCAB and the subsequent loss in the LCAP.


TB granuloma: CD30 co-stimulation for CD4+ T cell co-operation.
Tuberculosis granuloma T cells express an array of mediators including the CD30 co-stimulatory receptor and its ligand, CD153. CD4 T effector cells require signals through CD30, potentially provided co-operatively by other T cells, to completely differentiate and protect against disease (Foreman et al., 2023. J. Exp. Med.https://doi.org/10.1084/jem.20222090).


Establishment of reference intervals for complete blood count in times of COVID-19 and vaccination.
COVID-19 and vaccination may affect some parameters of the complete blood count (CBC). The aim of this study was to determine reference intervals (RI) of CBC in healthy population with different COVID-19 and vaccination backgrounds and compare them with those established previously. A cross-sectional study was conducted in donors who attended the Traumatology Hospital "Dr. Victorio de la Fuente Narváez" (HTVFN) from June to September 2021. Reference intervals were established using the non-parametric method on Sysmex XN-1000. For differences between groups with different COVID-19 and vaccination backgrounds, non-parametric tests were used. The RI were established in 156 men and 128 women. Haemoglobin (Hb), haematocrit (Hct), red blood cells (RBC), platelets (Plt), mean platelets volume (MPV), monocytes and relative neutrophils were higher in men than women (P < 0.001). The percentiles of Hb, Hct, RBC, MPV and relative monocytes showed higher values; Plt, white blood cells (WBC), lymphocytes, monocytes, neutrophils, eosinophils and absolute basophils, the 2.5th was higher and the 97.5th was lower; for lymphocytes and relative neutrophils, both percentiles had a trend toward lower values, compared to previous RI. Differences between groups with different COVID-19 and vaccination backgrounds, in lymphocytes (P = 0.038), neutrophils (P = 0.017) and eosinophils (P = 0.018) in men; Hct (P = 0.014), RDW (P = 0.023) in women and MPV (P = 0.001) in both, were not considered pathological. The RI for the CBC were established in a Mestizo-Mexican population with different COVID-19 and vaccination backgrounds, so should be updated and validated in different hospitals close to the HTVFN that use the same analyser.


Estimation of metabolite networks with regard to a specific covariable: applications to plant and human data.
In systems biology, where a main goal is acquiring knowledge of biological systems, one of the challenges is inferring biochemical interactions from different molecular entities such as metabolites. In this area, the metabolome possesses a unique place for reflecting "true exposure" by being sensitive to variation coming from genetics, time, and environmental stimuli. While influenced by many different reactions, often the research interest needs to be focused on variation coming from a certain source, i.e. a certain covariable [Formula: see text]. Here, we use network analysis methods to recover a set of metabolite relationships, by finding metabolites sharing a similar relation to [Formula: see text]. Metabolite values are based on information coming from individuals' [Formula: see text] status which might interact with other covariables. Alternative to using the original metabolite values, the total information is decomposed by utilizing a linear regression model and the part relevant to [Formula: see text] is further used. For two datasets, two different network estimation methods are considered. The first is weighted gene co-expression network analysis based on correlation coefficients. The second method is graphical LASSO based on partial correlations. We observed that when using the parts related to the specific covariable of interest, resulting estimated networks display higher interconnectedness. Additionally, several groups of biologically associated metabolites (very large density lipoproteins, lipoproteins, etc.) were identified in the human data example. This work demonstrates how information on the study design can be incorporated to estimate metabolite networks. As a result, sets of interconnected metabolites can be clustered together with respect to their relation to a covariable of interest.


Health professionals' perceptions of weight loss programmes and recommendations for future implementation: a qualitative study.
Obesity is an increasing public health challenge and most weight loss programmes are still inadequate to support sustainable weight loss. One reason for the continued lack of success might be the dominant biomedical, individualised approach to weight loss. Holistic approaches that focus on overall health and well-being in addition to weight loss are increasingly recommended. In Denmark, health professionals in the municipalities are responsible for developing and conducting weight loss programmes. The objective of this study was to explore what health professional's perceived as an ideal, holistic weight loss programme that could be feasibly implemented in the municipalities. A phenomenological-hermeneutical qualitative study was performed using semistructured interviews. Thirty-two Danish municipalities were weight loss programmes are developed and conducted. Thirty-five health professionals with experience conducting weight loss programmes. Three themes emerged from the analysis: Support from the social network are important both during and after a weight loss, Changing the self-belief by positive discussions and doing activities, Maintaining changes through daily life. Future municipal weight loss programmes should emphasise overall health and well-being instead of weight loss and adopt a holistic approach including a focus on social relationships, meaningful activities and successes as part of a balanced daily life.


Adverse childhood experiences among early care and education teachers: Prevalence and associations with observed quality of classroom social and emotional climate.
This study examines the prevalence of self-reported adverse childhood experiences (ACEs) among a sample of 349 early care and education teachers. Seventy-three percent of the sample reported experiencing at least one ACE and 22% reported experiencing 4 or more ACEs. Live observational assessments of the quality of the social and emotional climate in teacher's classrooms were conducted for a subsample of 58 teachers. Within this subsample, reporting a higher number of ACEs was associated with facilitating a lower quality social and emotional classroom climate. Individual ACEs were also examined. Teachers who reported experiencing incarceration of a family member, physical abuse, or emotional abuse were observed to facilitate a lower quality social and emotional classroom climate. This study provides preliminary insight into the prevalence of ACEs among members of the early care and education workforce. Further, it extends previous work examining the multi-generational impacts of ACEs within families by showing that ACEs may influence the care that is provided to children in childcare settings.


Relationship between pelvic sensations and lifetime exposure to receptive anal intercourse among people with prostates.
Despite the negative stigma on receptive anal intercourse (RAI), this behavior has a positive influence on individuals' sexual and relationship health. No large studies have previously looked at specific sensations experienced during RAI and how these sensations may change with experience. In this study we aimed to quantify commonly reported pelvic sensations during RAI and determine whether their presentation changes with increasing experience of RAI. An internet survey was conducted on sensations felt during RAI among people with prostates from July 2022-January 2023. The survey content was developed based on a mixed-methods qualitative study and inquired about demographic and sexual histories as well as sensations (pleasure, pain, urinary, and bowel) experienced during RAI. We used descriptive statistics to describe demographic and sexual histories. All data were stratified by lifetime exposure to RAI. The primary outcomes assessed included the quantification of both the primary sensations experienced during RAI and the associated bother. In total, 975 participants completed the survey. The median age was 32 (range 18-78) years. The average age of first participation in RAI was 21 ± 6.6 years. Most respondents were having sex at least once a week (65%). Nine percent of respondents reported fewer than 10 experiences with RAI, 26% reported 11-50 RAI experiences, 32% reported 51-200 experiences, 16% reported 201-500 experiences, and 18% reported >500 experiences. As the number of experiences with RAI increased (from <10 to >500 exposures), the reported frequency of pleasurable sensation increased from 41% to 92% (P < .0001), whereas severe insertional pain and symptoms of bowel urgency decreased from 39% to 13% and from 21% to 6%, respectively (P < .0001). Urinary urgency sensation did not differ by lifetime RAI experience. Lifetime RAI exposure can be readily assessed and correlates not only with pelvic sensation but also many other aspects of sexual health. These results imply that the etiology of dissatisfaction with pleasure or anodyspareunia during RAI may differ by lifetime RAI exposure. This is the first study to our knowledge to assess pelvic sensations experienced during RAI among a large sample of individuals. This is a cross-sectional study, and we cannot conclude how pelvic sensations change over time among individuals. Internet-based participants may not be representative of clinical populations. Lifetime exposure to RAI is positively associated with pleasure and is negatively associated with pain and bowel urgency. Pelvic sensations experienced during RAI appear to be dependent on lifetime RAI exposure history regardless of age.


Closed reduction of constrained total hip arthroplasty in the ED.
A dislocated hip prosthesis is a common occurrence in the Emergency Department. To combat this problem, orthopedists use constraint devices in an attempt to reduce the incidence of dislocation. However, when these devices fail, a more complicated case arises. We discuss a case report in which a patient presented with a dislocation of his hip after implantation of a constrained total hip arthroplasty. We describe a closed reduction procedure using deep sedation, fluoroscopy, and adequate assistance.


Passive mechanical properties of porcine left circumflex artery and its mathematical description.
The aim of this study was to analyze the pseudoelastic behavior of the coronary wall in vitro and to describe this behavior with three alternative strain energy functions frequently used in arterial mechanics. Six tubular segments of artery were subjected to various levels of simultaneous transmural pressure and axial force encompassing the physiological range of loading. Measured data on force, pressure, stress-free geometry and vessel deformation were used to compute components of the Green strain tensor and to determine by least squares fit the values of constants appearing in the following strain energy functions: Fung's exponential function, a combined polynomial-exponential form and a neo-Hookean plus exponential expression. The results obtained showed large biological variability. A comparison of the relative magnitude of the strain components did not reveal significant deviations from orthotropy under the given experimental conditions, hence shear terms were not included in the present constitutive formulations. The deformational behavior of the coronary artery displayed the high non-linearity typical for arteries of the muscular type. For states of equibiaxial stress the corresponding strains in the axial direction were larger than those in the circumferential direction, at least for loads in the upper and physiological range. All these aspects of coronary elasticity were mimicked fairly well by all three functions, although with slightly different degrees of accuracy.


Adriamycin extravasation: surgical treatment and possible prevention of skin and soft-tissue injuries.
In a material consisting of approximately 6,000 injections of Adriamycin during a 2-year period, eleven moderate and five severe extravasation injuries have been observed. Even a small leakage of the drug may cause a permanent lesion. The most serious injuries were caused by large doses and on the dorsum of the hand. Plastic surgical operations were successfully performed in the severe cases. An active surgical intervention after primary neutralization of the extravasated Adriamycin is recommended.


Controlled nanoparticle synthesis of Ag/Fe co-doped hydroxyapatite system for cancer cell treatment.
Diagnosis of cancer by chemotherapy treatment, severe side effects caused by high dosages of cancer drugs include non-controlled cytotoxicity to bone marrow cells and immune cells. To overcome, we have synthesized nanoparticles with controlled sized hydroxyapatite (nHAp) materials doped and co-doped with silver and iron by co-precipitation, yielding materials that can treat both the infections and malignant tumors with non-cytotoxic nature to normal cells. Spherical and rod like morphologies were observed for the samples with higher Ag+ doping concentrations with average size of 50 ± 5 nm and (75 × 22) ± 5 nm2, whereas higher Ag+/Fe2+ co-doping concentrations yielded samples with spherical, rod-like, and flake-like structures. For samples nHAp and Ag+-nHAp samples were diamagnetic, whereas the Fe2+-nHAp and Ag+/Fe2+ co-doped samples were superparamagnetic. The in vitro biological toxicity study revealed that the Ag+/Fe2+-nHAp nanoparticles are effective for targeting to kill cancerous cells, for example, human cervical cancer (HeLa) cells efficiently while they are non-toxic to normal cells. Applying these nanoparticles for drug delivery system, 5-fluorouracil was loaded in the nanoparticles and studied its release kinetics. In the case of Ag+/Fe2+co-doped nHAp samples, a pulsatile drug release profile was observed, which the drug was released for about a week on varying the Ag+ and Fe2+ concentrations. The 5-fluorouracil release kinetics was well fitted by the first-order model with diffusion. Thus, nHAps co-doped with Ag+/Fe2+ material have the potential to lag the time on delivering the drug at site-specific could be with an application in biomedicine such as to treat malignant tumor without any bacterial side effect.


Visualization Analysis of CRISPR Gene-editing Knowledge Map based on Citespace.
CRISPR is an adaptive immune defense system found in bacteria and archaea that is resistant to heterologous invasive genetic material. Later studies showed that the CRISPR system can be used for gene-editing. This study used the Web of Science database as a search object, then visually analyzed the literature related to CRISPR gene-editing technology with CiteSpace IV. The results show that publications had increased year by year. USA ranked first in terms of publications. China is second, but the centrality is very low. Doudna JA and Zhang F have made outstanding contributions. There are close connections between the internal institutions of the various states, but there are few links between the states. The hot spot and frontier are the application of CRISPR in animals, plants, detection, diagnosis, and clinical treatment.


Sensors based on galvanic cell generated electrochemiluminescence and its application.
In this paper, a novel electrochemiluminescence (ECL) imaging sensor array was developed for determination of hydrogen peroxide (H2O2), which was based on Cu/Zn alloy galvanic cell generated ECL. In alkaline solution, Cu/Zn galvanic cell was formed because of corrosion effect, the galvanic cell could supply stable potential for ECL generation of luminol, and the weak ECL emission could be enhanced by H(2)O(2). The galvanic cell sensor array was designed by putting Cu/Zn alloy in 96-well microtiter plates separately. The relative ECL intensity was proportional with the concentration of hydrogen peroxide in the range of 1.0 x 10(-6) to 1.0 x 10(-4) mol l(-1) and the detection limit was 3.0 x 10(-7) mol l(-1) (3sigma), the relative standard deviation (R.S.D.) for 11 parallel measurements of 1.0 x 10(-5)mol l(-1) H2O2 was 4.0%.


Role of puboperinealis and rectourethralis muscles as a urethral support system to maintain urinary continence after robot-assisted radical prostatectomy.
The present study investigated the role of a urethral support system to maintain urinary continence after robot-assisted radical prostatectomy (RARP), with a focus on pelvic floor muscles, such as the puboperinealis muscle (PPM) and rectourethralis muscle (RUM). Finally, 323 patients who underwent RARP were analyzed in this study. All patients performed a one-hour pad test 1, 3, 6, 9, and 12 months after RARP to assess urinary incontinence and MRI before and 9 months after RARP to evaluate the pelvic anatomical structure. The preoperative cross-sectional area of PPM (2.21 ± 0.69 cm2) was significantly reduced by 19% after RARP (1.79 ± 0.60 cm2; p < 0.01). Positive correlations were observed between the amount of urinary leakage according to the 1-h pad test 1, 3, 6, 9, and 12 months after RARP and the change in the cross-sectional area of PPM by RARP (p < 0.01, < 0.001, < 0.001, < 0.001, and < 0.001, respectively). A positive correlation was also noted between the amount of urinary leakage 6 and 12 months after RARP and the preoperative RUM diameter (p < 0.05). The amount of urinary leakage 1, 3, 6, 9, and 12 months after RARP negatively correlated with the change in the antero-posterior diameter of the membranous urethra (MU diameter) from the static to dynamic phases during the Valsalva maneuver by cine MRI. Furthermore, the change in the MU diameter negatively correlated with the change in the cross-sectional area of PPM (p < 0.05). PPM and RUM play significant roles as a supportive mechanism to maintain urinary continence by functioning as a urethral support.


Self-concept and physical self-concept in psychiatric children and adolescents.
Self-concept is a widely examined construct in the area of psychiatric disorders. This study compared the Physical Self-Description Questionnaire (PSDQ) scores of adolescents with psychiatric disorders (N=103) with the results of a matched group of non-clinical adolescents (N=103). Self-concept and Physical self-concept were lower in the clinical than in the non-clinical group. Girls (N=59) scored lower than boys (N=44) in both groups. In the different diagnostic groups specific domains were affected in line with symptomatology, which has implications for therapy.


Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction.
Left ventricular mechanical dyssynchrony has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic significance is not known. Of 3445 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, dyssynchrony analysis was performed on 424 patients (12%) by multiple speckle tracking echocardiography strain-based criteria. The primary dyssynchrony analysis was the standard deviation of the time to peak longitudinal strain (SD T2P LS). Cox proportional hazards models assessed the association of dyssynchrony with the composite outcome of cardiovascular death or heart failure hospitalization. Mean age was 70 ± 10 years, LVEF was 60 ± 8%, and QRS duration was 101 ± 27 ms. Worse dyssynchrony, reflected in SD T2P LS, was associated with wider QRS, prior myocardial infarction, larger LV volume and mass, and worse systolic (lower LVEF and global longitudinal strain) and diastolic (lower e' and higher E/e') function. During a median follow-up of 2.6 (interquartile range 1.5-3.8) years, 107 patients experienced the composite outcome. Worse dyssynchrony was associated with the composite outcome in unadjusted analysis [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.07; P = 0.021, per 10 ms increase], but not after adjusting for clinical characteristics, or after further adjustment for LVEF, AF, NYHA class, stroke, heart rate, creatinine, haematocrit, and QRS duration (HR 1.03, 95% CI 0.99-1.06; P = 0.16, per 10 ms increase). Worse LV mechanical dyssynchrony, assessed by speckle tracking echocardiography, is not an independent predictor of adverse outcomes in HFpEF, suggesting that mechanical dyssynchrony is unlikely to be an important mechanism underlying this syndrome. These findings warrant validation in an independent study specifically designed to assess the prognostic utility of mechanical dyssynchrony in HFpEF. NCT00094302.


Use of amantadine as substrate for SSAT-1 activity as a reliable clinical diagnostic assay for breast and lung cancer.
Spermidine/spermine N1-acetyltransferase (SSAT-1) plays a critical role in cell growth, proliferation and death, and is known to be activated in human cancer cells. Amantadine, a US FDA-approved antiviral drug, is a substrate for SSAT-1 and can be used to indirectly measure SSAT-1 activity because of its conversion to acetylamantadine (AA). This study was undertaken to further validate SSAT-1 activity in breast and lung cancer patients. An increase in the urinary concentration of AA in lung and breast cancer patients was observed. The 0-2 h collection time point was determined to be optimal in revealing significant differences in urinary AA concentration between healthy controls and cancer patients. The high urine concentration of AA could be used as a simple and useful test for the detection of breast and lung cancer.


Cataract surgery in patients with age-related maculopathy: preoperative diagnosis and postoperative visual acuity.
To report the reliability in detecting age-related maculopathy (ARM) lesions before cataract surgery and postoperative visual acuity (VA) in cataract surgery patients with ARM. Medical records of surgical patients in a large public hospital, west of Sydney, were reviewed retrospectively. Detection of ARM lesions was compared before and after surgery to determine sensitivity and specificity of preoperative diagnoses. Postoperative VA was assessed 4 weeks after surgery. Data were available for 721/784 eyes (92.0%) of 656 patients aged 60 years or older. ARM lesions were detected in 98 eyes (13.6%) before and 92 eyes (12.8%) after surgery. Sensitivities for detecting late ARM lesions, soft drusen and retinal pigment epithelium abnormalities preoperatively were 100%, 94% and 69%, respectively. Corresponding specificities were 100%, 100% and 77%, respectively. Postoperative VA achieved or remained 6/12 or better in 81.6% of eyes. A high sensitivity and specificity in detecting late ARM lesions and soft drusen preoperatively, and a good postoperative VA outcome is achievable in patients with preoperative early ARM lesions.


An audit of fresh frozen plasma usage and effect of fresh frozen plasma on the pre-transfusion international normalized ratio.
To audit the usage of fresh frozen plasma (FFP) and to study the effect of FFP on the pre-transfusion international normalized ratio (INR). Medical records of 100 consecutive patients who received FFP in our institute were retrospectively studied. FFP usage was classified as appropriate or inappropriate based on the guidelines by the National Health and Medical Research Council and The Australasian Society for Blood Transfusion. Pre-and post-transfusion INR were recorded and the effect of FFP on the pre-transfusion INR was studied in patients who appropriately received FFP. Relationship between the pre-transfusion INR and improvement in the INR per unit of FFP was studied using Pearson's correlation. Total 325 units were issued for the 100 patients (37 males and 63 females, mean age 33 years, range 1-65 years). Obstetrics and gynecology and medicine departments requested most units of FFP. Total 197 units (60.6%) in 67 patients were appropriately transfused and 128 units (39.4%) in 33 patients were inappropriately used. Mean improvement in the pre-transfusion INR per unit of FFP was 0.79 (median 0.53, range 0-3.5, SD 0.94). A significant improvement in the pre-transfusion INR per unit of FFP was seen in 64.9% patients. A linear relationship was noted between the pre-transfusion INR and improvement in INR per unit of FFP (r=0.89, degree of freedom 55). Proportion of inappropriate FFP usage remains high. A significant improvement in INR is more likely with a high pre-transfusion INR. The improvement in INR per unit of FFP is also more with higher pre-transfusion INR.


Impairment of short-term memory associated with low iron stores in a volunteer multidose plateletpheresis donor.
A platelet donor may lose 80-100 mL of blood both in the harness and by blood sampling at each donation, the equivalent of four to five whole blood donations per annum for a donor attending at 2-weekly intervals. A 54-year-old male multidose platelet donor had donated platelets at regular 2-weekly intervals for 6 years. He developed an impairment of anterograde memory (new learning). A self-rating scale revealed a moderate degree of depression [Beck Depression Inventory (BDI) score 22]. Memory testing (Doors and People Memory Battery) showed low scores, particularly for verbal recall and verbal recognition memory. He was found to have a normal haemoglobin of 157 g L(-1) with normal red blood cell indices, but a low serum ferritin (15 ng mL(-1)) and a low serum iron (8.1 mmol L(-1)). Following iron therapy and a return of his iron stores to normal levels, there was an improved BDI score of 13 (minimal level of depression) and a marked improvement in memory test scores. This has been maintained even though he has resumed platelet donation but at reduced intervals.


The Effects of Shaking Duration on the Abundance and the Community of Aerobic Denitrifying Bacteria in Shrimp Pond Water and Sediment Samples.
With the rapid development of intensive aquaculture, the considerable release of nitrogenous organic compounds has become a serious threat to aquatic organisms. Currently, isolating autochthonous aerobic denitrifying bacteria (ADB) from aquaculture environments is essential for the biological elimination of nitrogenous pollutants. In this study, the enrichment of ADB from shrimp pond water and sediment samples was conducted under different shaking durations. The absolute abundance of total bacteria, nosZ-type, and the napA-type ADB was measured using qPCR. High-throughput sequencing of 16S rRNA, nosZ, and napA genes was performed to reveal the community structure of bacteria and ADB, respectively. Our data revealed that absolute abundance and the community structure of the total bacteria, nosZ-type and napA-type ADB, were significantly altered under different shaking durations. Specifically, the order Pseudomonadales, possessing both nosZ and napA genes, was significantly enriched in water and sediment samples under both 12/12 and 24/0 shaking/static cycles. However, in water samples, compared to the 24/0 shaking/static cycles, the 12/12 shaking/static cycles could lead to a higher enrichment rate of aerobic denitrification bacteria indicated by the higher absolute abundance of bacteria and the higher accounting percentage of orders Oceanospirillales and Vibrionales. Moreover, although the order Pseudomonadales notably increased under the 12/12 of shake/static cycle compared to the 24/0 shaking/static cycle, considering the relative higher abundance of ADB in 24/0 shaking/static cycle, the enrichment of ADB in sediment may be efficient with the 24/0 shaking/static cycle.


Development and evaluation of a rehabilitation training compliance scale for patients with urinary incontinence.
Urinary incontinence treatment includes conservative treatment, physical devices, medication, and surgery. Pelvic floor muscle training combined with bladder training is among the most effective, non-invasive, and economical ways to treat urinary incontinence, and compliance with training is essential in urinary incontinence treatment. Several instruments assess pelvic floor muscle training and bladder training. However, no tool has been found that assesses compliance with pelvic floor muscle training when combined with bladder training for urinary incontinence. This study aimed to develop a rehabilitation training compliance scale for patients with urinary incontinence and to evaluate its validity and reliability. This study was performed in two tertiary hospitals in Hainan, China between December 2020 and July 2021, 123 patients were included. A literature review, group discussions, and two rounds of letter consultations were performed to acquire the item pool and finalise the 12 items for this scale. Exploratory and confirmatory factor analysis, Cronbach's α, split-half reliability, test-retest reliability, content validity, construct validity, convergent and discriminant validity, and criterion-related validity were used to examine the items in the scale. A 12-item scale comprising three factors accounted for 85.99% of the variance in the data. The Cronbach's α, split-half reliability, test-retest reliability, and content validity index of the scale were 0.95, 0.89, 0.86, and 0.93, respectively. Comparison with the Chen pelvic floor muscle exercise self-efficacy scale showed high calibration correlation validity (coefficient = 0.89). The training compliance scale developed in this study is a valid and reliable measurement tool to assess pelvic floor muscle training and bladder training compliance in patients with urinary incontinence.


The relation of communication to risk judgment and preventive behavior related to lead in tap water.
More and more communities are becoming concerned about health risks posed by lead and other health hazards in their drinking water. Our study, applying the model of innovation diffusion to the adoption of preventive health behaviors, found that reliance on health professionals for information about lead in tap water was associated with residents perceiving risk from this hazard, their sense of efficacy in dealing with it, and their adoption of preventive behaviors. Mass media and pamphlets mailed directly to residents were relatively ineffective. Results suggest that interpersonal channels may be the best way to reach individuals who live in areas of highest risk from tap water lead.


Leprosy in French Guiana, 2015 to 2021: Dynamics of a Persistent Public Health Problem.
A resurgence of leprosy as a public health problem in French Guiana was reported over the period 2007 to 2014, particularly among Brazilians gold miners. Prolonged multidrug therapy and reversal reactions represent a therapeutic challenge. The objective of this study was to assess the evolution of leprosy in this European overseas territory. All patients with leprosy confirmed in histopathology between 1 January 2015 and 31 December 2021 were included. A total of 86 patients were included, including 64 new cases and 22 previously diagnosed cases. Sixty patients (70%) were male, 6 cases were paediatric. Brazilian gold miners represented 44.1% of reported occupations (15/34). Maroons represented the second community (13 patients, 15%). Multibacillary and paucibacillary forms were found in 53 (71%) and 22 (29%) patients, respectively. The annual prevalence never exceeded the threshold of 1/10,000. The mean incidence and prevalence were significantly lower than during the period 2007 to 2014 (p < 0.0001). Reversal reactions were found in 29 patients and almost always required a long course of steroids. Infliximab allowed a reduction in the length of treatment with steroids in 2/2 cases. In conclusion, the prevalence of leprosy has decreased significantly in French Guiana, but remains driven by the population of illegal gold miners. Anti-tumour necrosis factor (anti-TNF) drugs represent a promising option in the management of reversal reactions.


Emerging trends in the application of the social sciences to health and medicine.
Tensions are inevitable between funders seeking to solve specific health care issues within existing frameworks and many social scientists who see health and health care as reflections of societal stratification and processes of power and control. Many current and impending issues require deep scrutiny of values and meaning systems as they relate to class, gender, ethnicity and other forms of social differentiation. Interdisciplinary efforts provide social scientists important problem-solving opportunities but also occasions to refine disciplinary theories and methods. In recent years such efforts have resulted in increased sensitivity to demographic imperatives, prospective investigations, social experimentation, a growing appreciation of the complexity of life trajectories, development of more complex models of causation and remediation, and a revival of interest in meaning systems and their effects on ultimate outcomes. Social scientists have come to play a variety of roles in health services and policy research that contribute to a fruitful interplay of theory and practice. Major roles include helping to frame issues and how they are attacked; anticipating emerging trends, issues and problems; monitoring health and the provision of health services; evaluation and assessment; and implementation processes. The contributions of the social sciences to understanding complex organizational arrangements, structures, cultures, managerial approaches, financial arrangements and regulatory processes are increasingly evident and part of a culture of informed thinking.


Constraints in estimating the proton density fat fraction.
The study evaluates four physically motivated constraints in the estimation of the proton density fat fraction (PDFF). Least squares approaches were developed for constraining the parameters in PDFF quantification based on the physics of magnetic resonance imaging. These were smooth fieldmap, smooth initial phase, nonnegative proton density and moderate R2∗ values. The constraints were evaluated in terms of their influence on the bias and standard deviation of the estimated parameters using numerical simulations and in vivo data acquired at 0.35 T. Results show that unconstrained least squares estimation is noisy and biased and that constraints can be effective at reducing both the standard deviation and bias.


Gastrointestinal Absorption and Toxicity of Nanoparticles and Microparticles: Myth, Reality and Pitfalls explored through Titanium Dioxide.
Daily oral exposure to vast numbers (>1013/adult/day) of micron or nano-sized persistent particles has become the norm for many populations. Significant airborne particle exposure is deleterious, so what about ingestion? Titanium dioxide in food grade form (fgTiO2) , which is an additive to some foods, capsules, tablets and toothpaste, may provide clues. Certainly, exposed human populations accumulate these particles in specialised intestinal cells at the base of large lymphoid follicles (Peyer's patches) and it's likely that a degree of absorption goes beyond this- i.e. lymphatics to blood circulation to tissues. We critically review the evidence and pathways. Regarding potential adverse effects, our primary message, for today's state-of-art, is that in vivo models have not been good enough and at times woeful. We provide a 'caveats list' to improve approaches and experimentation and illustrate why studies on biomarkers of particle uptake, and lower gut/mesenteric lymph nodes as targets, should be prioritized.


A novel deployment design of vena cava filters might be the solution to their blockage problem.
The blockage of a vena cava filter (VCF) by the captured blood clots presents a serious problem to the patients. Commercially available cone-shaped VCFs such as the Gunther Tulip filter has an inherent structural flaw that leads the captured blood clots to be trapped in their front spire areas where the flow-induced shear stress is relatively low so that the clots cannot dissolve fast enough and will accumulate, gradually block the central passages of the filters. It is well known that for a Hagen-Poiseuille flow in a circular tube, the flow-induced shear stress is highest at the wall of the tube and lowest along its axis. Herein, we hypothesize that by reversely deploying a cone-shaped filter in the vena cava, the filter's blockage problem might be prevented. First of all, this kind of deployment scenario can force the captured blood clots to stay in the peripheral areas of the vena cava and keep the central passage of the filter unblocked. Secondly, this scenario can expose the captured blood clots to relatively high shear stress that may dissolve the clots faster.


The START domain mediates Arabidopsis GLABRA2 dimerization and turnover independently of homeodomain DNA binding.
Class IV homeodomain leucine-zipper transcription factors (HD-Zip IV TFs) are key regulators of epidermal differentiation that are characterized by a DNA-binding HD in conjunction with a lipid-binding domain termed steroidogenic acute regulatory-related lipid transfer (START). Previous work established that the START domain of GLABRA2 (GL2), a HD-Zip IV member from Arabidopsis (Arabidopsis thaliana), is required for TF activity. Here, we addressed the functions and possible interactions of START and the HD in DNA binding, dimerization, and protein turnover. Deletion analysis of the HD and missense mutations of a conserved lysine (K146) resulted in phenotypic defects in leaf trichomes, root hairs, and seed mucilage, similar to those observed for START domain mutants, despite nuclear localization of the respective proteins. In vitro and in vivo experiments demonstrated that while HD mutations impair binding to target DNA, the START domain is dispensable for DNA binding. Vice versa, protein interaction assays revealed impaired GL2 dimerization for multiple alleles of START mutants, but not HD mutants. Using in vivo cycloheximide chase experiments, we provided evidence for the role of START, but not HD, in maintaining protein stability. This work advances our mechanistic understanding of HD-Zip TFs as multidomain regulators of epidermal development in plants.