Tandem mass spectrometric determination of atypical 3β-hydroxy-Δ5-bile acids in patients with 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency: application to diagnosis and monitoring of bile acid therapeutic response.
3β-Hydroxy-Δ(5)-C27-steroid oxidoreductase (HSD3B7) deficiency, a progressive cholestatic liver disease, is the most common genetic defect in bile acid synthesis. Early diagnosis is important because patients respond to oral primary bile acid therapy, which targets the negative feedback regulation for bile acid synthesis to reduce the production of hepatotoxic 3β-hydroxy-Δ(5)-bile acids. These atypical bile acids are highly labile and difficult to accurately measure, yet a method for accurate determination of 3β-hydroxy-Δ(5)-bile acid sulfates is critical for dose titration and monitoring response to therapy. We describe a electrospray ionization LC-MS/MS method for the direct measurement of atypical 3β-hydroxy-Δ(5)-bile acid sulfates in urine from patients with HSD3B7 deficiency that overcomes the deficiencies of previously used GC-MS methods. Separation of sulfated 3β-hydroxy-Δ(5)-bile acids was achieved by reversed-phase HPLC in a 12-min analytical run. The mean (SE) urinary concentration of the total 3β-sulfated-Δ(5)-cholenoic acids in patients with HSD3B7 deficiency was 4650 (1711) μmol/L, approximately 1000-fold higher than in noncholestatic and cholestatic patients with intact primary bile acid synthesis. GC-MS was not reliable for measuring 3β-hydroxy-Δ(5)-bile acid sulfates; however, direct analysis of urine by fast atom bombardment mass spectrometry yielded meaningful semiquantitative assessment of urinary excretion. The tandem mass spectrometry method described here for the measurement of 3β-hydroxy-Δ(5)-bile acid sulfates in urine can be applied to the diagnosis and accurate monitoring of responses to primary bile acid therapy in HSD3B7 patients.


Rest tremor in Parkinson's disease: the theta and beta sides of the coin.
This scientific commentary refers to 'Independently together: subthalamic theta and beta opposite roles in predicting Parkinson's tremor', by Asch et al. (https://doi.org/10.1093/braincomms/fcaa074).


Complications of complex lower urinary tract reconstruction in patients with neurogenic versus nonneurogenic bladder--is there a difference?
The complications of lower urinary tract reconstruction have been well documented in children with neurogenic bladders. While most series include small numbers of nonneurogenic diagnoses, this group is typically underrepresented. Despite a number of fundamental anatomical and functional differences, a direct comparison of surgical complications of lower urinary tract reconstruction in patients with neurogenic vs nonneurogenic bladders has not been performed. We identified patients undergoing lower urinary tract reconstruction incorporating enterocystoplasty from 1996 to 2006. We performed a retrospective review of operative notes and medical records of patients who met inclusion criteria. Patients were divided into a neurogenic group and a nonneurogenic group based on the underlying diagnosis. The 2 groups were compared with respect to demographics, historical data, operative techniques, perioperative morbidity, long-term complications and need for surgical revision. Of the 127 patients who met inclusion criteria 72 were assigned to the nonneurogenic group and 55 to the neurogenic group. Overall the rates of significant perioperative morbidity (39%), long-term complications (54%) and need for surgical revision (39%) were substantial. The rates of catheter related complications, rehospitalization for dehydration and spontaneous bladder rupture were higher in the neurogenic group (p <0.05). Reconstruction of the lower urinary tract in children is associated with a considerable rate of complications and need for surgical revision regardless of whether the bladder is neurogenic or nonneurogenic. Children with neurogenic bladders are more prone to spontaneous rupture, catheter mishaps and early rehospitalization for dehydration.


Neuroethology of bat navigation.
Once a year about 15 million Mexican free-tailed bats (Tadarida brasiliensis) migrate up to 1,500 kilometers from wintering grounds, seamlessly flying over the Mexican border to enter the United States. Their destination is the Bracken Cave in southern Texas, which will be their summer home between the months of March through October. While residing there, these bats emerge every night at dusk from the narrow 100-foot-wide opening of this enormous cave and begin their nightly commute to foraging grounds located up to 50 kilometers away. Upon arrival, they will spend the night hunting for insects in mid-air while providing a valuable service to local farmers by keeping crop pests in check. Close to the break of dawn, as the night of hunting comes to an end, these bats will begin making their trip back to the roost.


The rhythmic relation between antler and bone porosity in Danish deer.
The interrelationship between porosity of antlers and metacarpal bones and annual physiologic osteopenia has been investigated in mature Danish male Roe deer (Capreolus capreolus). The study shows a highly significant inverse correlation between porosity in the antlers and porosity in the metacarpal bones, indicating a necessary calcium mobilization from the bones for the mineralization of the antlers. The investigation further suggests that the decreasing porosity of the antlers throughout the antler period, reaching very low values, may be the cause of antler shedding.


Type I allergy to insulin: case report and review of localized and systemic reactions to insulin.
Allergic reactions to insulin preparations are not uncommon. Although patients often present with skin symptoms, most articles on insulin allergy are published in endocrinology and allergy journals. The purpose of this report is to describe a case of localized type I allergy to insulin as well as provide a review of the classification of insulin allergy, methods of evaluation, and management options.


On the use of classic epidemiological formulae for estimating the intensity of endemic malaria transmission by vectors in the Amazon.
Although various reports have described entomological inoculation rates of malaria vector species, most were limited to providing descriptive field data. Here, we report biting rates and survival data for two important malaria vectors in the Amazon, Anopheles darlingi (Root) and Anopheles albitarsis E (Lynch-Arribalzaga) (Diptera: Culicidae), in the state of Roraima, Brazil. We calculated theoretical sporozoite infection rates and critical vector biting rates for these species during 1 year, comprising six bimestrial collections. Anopheles darlingi had higher sporozoite rates and lower critical biting rates, indicating that it would be the more efficient vector at the beginning of epidemic malaria transmission. Our data, together with compiled information from the literature in the Amazon, suggest that epidemic malaria transmission may be initiated by the primary vector, such as A. darlingi, while secondary vectors, such as A. albitarsis E, may only become epidemiologically important when there is an increase in the prevalence of human malaria. We propose that mathematical modeling may be able to quantify the relative importance of secondary vector species in malaria epidemiology.


Foreperiod duration and motor preparation during childhood.
The purpose of this experiment was to examine the development of motor preparation across three groups of children aged 6, 8 and 10 years old. The foreperiod duration (500, 1000, 2000 and 4000 ms) and the motor preparation conditions were manipulated using a priming procedure. Two type of primes were provided: (1), a prime carrying no advanced information (neutral condition); and (2), a prime giving advanced information on the nature of the motor response to execute, allowing the participant to prepare for it (selective condition). Reaction time and response errors were analyzed. Results showed that under both conditions, the optimal motor preparation was reached within the same time frame which decreased as age increased. As to the optimal alertness level (neutral preparation), it is maintained longer as age increases, whereas the optimal motor programming level (selective preparation) is reached only for specific foreperiod duration.


Mycoplasma pneumoniae causing nervous system lesion and SIADH in the absence of pneumonia.
A patient was admitted for fever and acute respiratory failure (ARF), rapidly progressive tetraparesis, delirium, behavioral abnormalities, and diplopia. Leukocytosis and a rise in C-reactive protein were present. A syndrome of inappropriate anti-diuretic hormone secretion (SIADH) was also diagnosed. Lumbar puncture yielded colorless CFS with mononuclear pleocytosis and protein rise. Electrodiagnosis revealed demyelinating polyneuropathy and axonal degeneration. Serum IgG and IgM for mycoplasma pneumoniae (MP) was consistent with acute infection, and erythromycin was started with rapid resolution of symptoms. Contrarily to most reports, an associated respiratory disease was not present and SIADH in association with MP has been reported only once, in a patient without direct central nervous system (CNS) involvement. Differential diagnosis and possible pathogenic mechanisms are discussed.


ADC correlation with Sirtuin1 to assess early chemoradiotherapy response of locally advanced esophageal carcinoma patients.
To determine the biological correlation between apparent diffusion coefficient (ADC) values and Sirtuin1 (SIRT1) levels of tumour tissues in patients with esophageal carcinoma (EC), and to ascertain the treatment biomarker of ADC in predicting the early response of patients undergoing definitive chemoradiotherapy (CRT). A total of 66 patients were enrolled, and the specimens of tumour tissues were collected before treatment to perform immunohistochemical (IHC) examinations and quantify the levels of SIRT1. Then all patients were given two esophageal magnetic resonance imaging (MRI) examinations with diffused weighed imaging (DWI) including pretreatment and intra-treatment (1~2 weeks after the start of radiotherapy). The regions of interest (ROIs) were contoured according to the stipulated rules in advance using off-line software, and the values of the ADC in the ROIs were generated automatically. Then, the values of the ADC at baseline and intra-treatment were labeled as pre-ADC and intra-ADC respectively, and ΔADC, ADCratio were calculated. Pearson's correlation coefficients were acquired to estimate the correlation between each of ADC values and SIRT1 levels. Spearman's rank correlation coefficients were acquired to estimate the correlation between early response and the values of each ADC. Receptor operation characteristics (ROC) curves were constructed to estimate the accuracy of the ADC in predicting the early response of CRT. The findings of this study showed different correlations between ADC values and the levels of SIRT1 (ΔADC: r = - 0.943, P = 0.002; ADCratio: r = - 0.911, P = 0.000; intra-ADC: r = - 0.748, P = 0.002; pre-ADC: r = 0.109, P = 0.558). There was a positive correlation between ΔADC and early response to treatment (ρ = 0.615, P = 0.023), and multivariable logistic regression revealed that ΔADC was significantly associated with short-term response of CRT in esophageal carcinoma patients. In summary, early increases in ADC may facilitate the predication of early CRT response in patients with esophageal squamous cell carcinoma (ESCC), which may be attributed to the different correlation between ADC changes and SIRT1 expression.


Baseline NT-proBNP Accurately Predicts Symptom Response to Transcatheter Aortic Valve Implantation.
Background Up to 30% of patients undergoing transcatheter aortic valve implantation (TAVI) experience minimal symptomatic benefit or die within 1 year, indicating an urgent need for enhanced patient selection. Previous analyses of baseline NT-proBNP (N-terminal pro-brain natriuretic peptide) and TAVI outcomes have assumed a linear relationship, yielding conflicting results. We reexamined the relationship between baseline NT-proBNP and symptomatic improvement after TAVI. Methods and Results Symptom status, clinical and echocardiographic data, and baseline NT-proBNP were reviewed from 144 consecutive patients undergoing TAVI for severe symptomatic aortic stenosis. The primary end point was change in New York Heart Association functional class at 1 year. There was a nonlinear, inverted-U relationship between log-baseline NT-proBNP and post-TAVI change in NYHA class (R2=0.4559). NT-proBNP thresholds of <800 and >10 000 ng/L accurately predicted no symptomatic improvement at 1 year (sensitivity 88%, specificity 83%, positive predictive value 72%, negative predictive value 93%). In adjusted analyses, baseline NT-proBNP outside this "sweet-spot" range was the only factor independently associated with poor functional outcome (high: NT-proBNP >10 000 ng/L, odds ratio [OR], 65; 95% CI, 6-664; low: NT-proBNP <800 ng/L, OR, 73; 95% CI, 7-738). Conclusions Baseline NT-proBNP is a useful prognostic marker to predict poor symptom relief after TAVI and may indicate when intervention is likely to be futile. Both low (<800 ng/L) and very high (>10 000 ng/L) levels are strongly associated with poor functional outcome, suggesting an alternative cause for symptoms in the former scenario and an irrevocably diseased left ventricle in the latter. Further evaluation of this relationship is warranted.


Flow and turbulence in unevenly obstructed channels with rigid and flexible vegetation.
The pattern of vegetation along the cross-section of macrophyte-dominated shallow waters is generally uneven, which affects water velocity and turbulence. This study examined the velocity and turbulence in the open channel with an uneven transverse distribution of vegetation in laboratory flume experiments. Two vegetation patterns were tested: emergent vegetation which covered part of the channel, and a symmetrical combination of submerged and emergent vegetation canopies along the lateral direction of the flume. The flow was measured using a three-dimensional Acoustic Doppler Velocimeter. The velocity and turbulence characteristics were analyzed under three vegetation densities and five discharge scenarios. Results showed that the longitudinal mean velocity changed with vegetation density and flow discharge when vegetation was unevenly distributed in a lateral direction. The strong variation in shear stress at the emergent vegetation-open water intersections and submerged-emergent vegetation intersections resulted in large-scale vortices at the interfaces. The formation processes of stem-scale turbulence and shear-scale turbulence under different vegetation scenarios were discussed. A turbulent kinetic energy model within partly obstructed vegetation canopies was established, which helped to identify the development of horizontal and vertical coherent vertices.


Lying posture affects sleep structures and cortical activities: a simultaneous EEG-fMRI imaging of the sleeping and waking brain.
Lying posture influences both neural activity and cognitive performance, and it is essential to sleep hygiene. Whereas, no neuroimaging research has investigated the effect of lying position on brain activity in waking and sleeping conditions. Therefore, we recruited 35 participants to perform a within-participant simultaneous EEG-fMRI recording with lying supine and lateral postures. Our results showed that sleep onset latency (SOL) was affected by both sleep position preference (SPP) and lying poses. SOL in supine was significantly shorter than that in lateral posture. The correlation analysis between SPP and sleep parameters indicated that individuals who prefer supine had less SOL and N2 sleep durations. However, we did not find this significant correlation in lateral-prefer individuals. Besides, different sleep positions mainly caused an alteration of the differences in brain activity patterns. In supine posture, the brain activities in the left precuneus, and anterior cingulate cortex were greater than those in lateral position. However, in the lateral posture, the status was just the opposite. Finally, we also found that the right putamen was sensitive to habitual sleep posture in the awake state. The participants who prefer to lie supine tend to have higher activity in the putamen. Our study may help with the understanding of the contribution of lying posture on brain activity and its relationship with posture preference in sleep.


Estrogenic activity response to best management practice implementation in agricultural watersheds in the Chesapeake Bay watershed.
Best management practices (BMPs) have been predominantly used throughout the Chesapeake Bay watershed (CBW) to reduce nutrients and sediments entering streams, rivers, and the bay. These practices have been successful in reducing loads entering the estuary and have shown the potential to reduce other contaminants (pesticides, hormonally active compounds, pathogens) in localized studies and modeled load estimates. However, further understanding of relationships between BMPs and non-nutrient contaminant reductions at regional scales using sampled data would be beneficial. Total estrogenic activity was measured in surface water samples collected over a decade (2008-2018) in 211 undeveloped NHDPlus V2.1 watersheds within the CBW. Bayesian hierarchical modeling between total estrogenic activity and landscape predictors including landcover, runoff, BMP intensity, and a BMP*agriculture intensity interaction term indicates a 96% posterior probability that BMP intensity on agricultural land is reducing total estrogenic activity. Additionally, watersheds with high agriculture and low BMPs had a 49% posterior probability of exceeding an effects-based threshold in aquatic organisms of 1 ng/L but only a 1% posterior probability of exceeding this threshold in high-agriculture, high-BMP watersheds.


Cultivar-specific kinetics of gene induction during downy mildew early infection in grapevine.
The oomycete pathogen Plasmopara viticola (Berk. et Curt.) Berl. et de Toni is the causing agent of the destructive downy mildew disease in grapevine. Despite the advances towards elucidation of grapevine resistance mechanisms to downy mildew, increased knowledge of the biological and genetic components of the pathosystem is important to design suitable breeding strategies. Previously, a cDNA microarray approach was used to compare two Vitis vinifera genotypes Regent and Trincadeira (resistant and susceptible to downy mildew, respectively) in field conditions. The same cDNA microarray chip was used to confirm field-based results and to compare both genotypes under greenhouse conditions at 0, 6, and 12 h post-inoculation with P. viticola. Results show that when comparing both cultivars after pathogen inoculation, there is a preferential modulation of several defense, signaling, and metabolism associated transcripts in Regent. Early transcriptional changes are discussed in terms of genetic background and resistance mechanism. This study is the first to directly compare resistant and susceptible cultivars responses as early as 6 hpi with P. viticola, providing several candidate genes potentially related to the expression of resistance traits.


Inflammatory human leucocyte antigen genotypes are not a risk factor in chronic subdural hematoma development.
Chronic subdural hematoma (CSDH) pathophysiology has undergone a paradigm shift from being regarded as solely traumatic to be driven mainly by inflammation. Human leucocyte antigen (HLA) is a gene complex involved in antigen processing and presentation to T lymphocytes, thereby mediating the adaptive immune responses. As specific HLA profiles are associated with inflammatory diseases, patients with a specific HLA profile may have a lower threshold for subdural inflammation, and therefore are predisposed for CSDH development. We hypothesized that (1) CSDH patients have a specific HLA profile compared to a Danish background population, and (2) patients with recurrent CSDH have a specific HLA profile compared to CSDH patients without recurrent CSDH. Three specific HLA class II haplotypes known to drive inflammatory-mediated diseases were determined in 68 patients with CSDH. The distribution of these three haplotypes in our CSDH population was compared to a Danish population of blood donors using Monte Carlo Pearson's chi-square test. Furthermore, the distribution of the haplotypes was compared between CSDH patients with and without recurrent CSDH. We found no significant association between either of the haplotypes and the risk of CSDH, and neither of the haplotypes were associated with increased risk of CSDH recurrence. This study did not show an association between selected HLA class II haplotypes and the risk of CSDH or recurrence of CSDH compared with a healthy background population.


Identification and characterization of a human smad3 splicing variant lacking part of the linker region.
Smad3 is one of the signal transducers that are activated in response to transforming growth factor-beta (TGF-beta). We have identified and characterized a splicing variant of smad3. The splicing variant (smad3-Delta3) lacks exon 3 resulting in a truncated linker region. We could detect mRNA expression of smad3-Delta3 in all investigated human tissues. Real-time PCR analyses demonstrated that the fraction of smad3-Delta3 mRNA compared to normal smad3 varies between tissues. The amount of spliced mRNA was estimated to represent 0.5-5% of the normal smad3 mRNA. When smad3-Delta3 is overexpressed in a fibrosarcoma cell line, the Smad3-Delta3 is translocated to the nucleus upon TGF-beta stimulation and binds the Smad responsive element. Using a CAGA luciferase reporter system, we demonstrate that Smad3-Delta3 has transcriptional activity and we conclude that Smad3-Delta3 possesses functional transactivating properties.


Submandibular gland endoscopic resection: a cadaveric study.
Recent advancement of head and neck surgery has been marked by the development of endoscopic and video-assisted minimally invasive surgery. This study reports the feasibility of endoscopic submandibular gland resection in human cadavers. Twelve submandibular gland resections were performed in six human cadavers. A 30 degrees angle endoscope and conventional surgical instruments were inserted through two 15 mm submandibular incisions. Dissection was carried out bluntly with scissors in an avascular plane superficial to the gland. No insufflation was needed since transcutaneous sutures lead to effective retraction. Facial vessels, the lingual nerve and Wharton's duct were identified and protected. Vascular ligatures were performed using surgical miniclips. After the procedure, an open submandibular dissection was performed to control the integrity of the anatomical structures. In all cases, the resection of the submandibular gland was successful without the need for an additional incision. Injuries of the facial artery and lingual nerve occurred when the procedure was carried out initially. The operative time decreased with training, from 120 min for the first cases to 35 min for the later ones. In conclusion, endoscopic submandibular gland resection is possible without major difficulty. Training and experience reduce the operative time and the complication rate.


Magnetic resonance imaging investigation of age-related morphological changes in the pancreases of 226 Chinese.
To investigate the morphological changes with age in the pancreases of healthy individuals undergoing magnetic resonance imaging (MRI). The participants were selected from adults who were undergoing physical examinations from January 2017 to September 2020 at Huadong Hospital. They were divided according to age, as broken down by decades into seven groups ranging from 20 to 29 years to ≥80 years of age. There were 30 to 35 cases for each decade. They were then divided into a young and middle-aged group (<60 years of age) and an elderly group (≥60 years of age). The morphological characteristics of the pancreases of each participant in the group were measured on magnetic resonance images. The characteristics included the pancreatic anteroposterior diameters and volumes. The relationships between the anteroposterior diameters of the pancreatic head, body, and tail and pancreatic volume and age were analyzed. A total of 226 magnetic resonance images from 112 (49.56%) men and 114 (50.44%) women, aged 22-93 (54.68 ± 19.52) years. The age ranges of the seven groups consisted of the following: 20-29 years (n = 33), 30-39 years (n = 32), 40-49 years (n = 32), 50-59 years (n = 31), 60-69 years (n = 35), 70-79 years (n = 33) and ≥80 years (n = 30). The age range and numbers of patients in the young and middle-aged group was 22-59 (40.09 ± 10.88) years (n = 128) and in the elderly group was 60-93 (73.74 ± 8.99) years (n = 98). The MRI findings characteristic of aging included pancreatic atrophy (especially of the pancreatic tail), pancreatic lobulation, uneven signal intensity, fatty degeneration, and widening of the main pancreatic duct. The respective anteroposterior diameters of the pancreatic head, body, and tail and the pancreatic volumes peaked at 30 to 39 years as follows: 28.03 ± 4.45 mm, 24.10 ± 4.27 mm, 24.57 ± 4.94 mm, 98.54 ± 26.56 cm3; and then gradually decreased to 19.05 ± 3.59 mm, 16.00 ± 3.81 mm, 13.83 ± 3.39 mm, 45.02 ± 9.15 cm3 at ≥80 years, for respective decreases of 32.03%, 33.60%, 43.71%, and 54.31%. The respective anteroposterior diameters of the pancreatic head, body, tail, and pancreatic volume in the elderly patients were 21.45 ± 4.15 mm, 18.14 ± 4.09 mm, 16.81 ± 4.37 mm, and 59.02 ± 21.44 cm3, which were significantly smaller than the respective corresponding measurements in the young and middle-aged patients (26.09 ± 4.40 mm, 22.30 ± 4.42 mm, 22.08 ± 4.53 mm, and 88.32 ± 23.92 cm3). The differences were statistically significant (t = 8.06, 7.24, 8.79, 9.54, respectively, p < 0.001). The anteroposterior diameters of the pancreatic head, body, tail, and pancreatic volume were negatively correlated with age (r = -0.53, -0.47, -0.56, -0.57, respectively, p < 0.001). The anteroposterior diameters of the pancreatic head, body, tail, and the pancreatic volume all peaked at the age range of 30-39 years and then gradually decreased with increasing age. After the age of 60 years, pancreatic atrophy became increasingly obvious, with changes in shape and widening with age of the main pancreatic duct.


Exome sequencing of contralateral breast cancer identifies metastatic disease.
Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastases.


Elevation of serum creatine kinase B-subunit levels by radiographic contrast agents in patients with neurologic disorders.
The effect of radiographic contrast agents on the central nervous system was evaluated by measurement of serum creatine kinase B-subunit (CKB) levels with use of radioimmunoassay in 58 patients who underwent computed tomographic (CT) scanning and 46 patients who underwent cerebral angiography for evaluation of cerebrovascular diseases, brain tumors, and other neurologic disorders. In 11 patients (10.6%), the CKB increased to abnormally high levels within 4 hours after the radiographic procedures, and the median value after 30 minutes was significantly higher than the corresponding precontrast value (P less than 0.01). Eight of the 11 patients had recent ischemic cerebrovascular diseases, and 7 of the 11 had undergone CT scanning. On the basis of the information available in the literature, elevation of the serum CKB levels may be interpreted as reflecting breakdown of the blood-brain barrier and neural damage. Intravascularly administered radiographic media are generally safe, but the results of the current investigation suggested the potential for detrimental effects, particularly in patients with recent cerebrovascular diseases.


The MUC1-C oncoprotein binds to the BH3 domain of the pro-apoptotic BAX protein and blocks BAX function.
The pro-apoptotic BAX protein contains a BH3 domain that is necessary for its dimerization and for activation of the intrinsic apoptotic pathway. The MUC1 (mucin 1) heterodimeric protein is overexpressed in diverse human carcinomas and blocks apoptosis in the response to stress. In this study, we demonstrate that the oncogenic MUC1-C subunit associates with BAX in human cancer cells. MUC1-C·BAX complexes are detectable in the cytoplasm and mitochondria and are induced by genotoxic and oxidative stress. The association between MUC1-C and BAX is supported by the demonstration that the MUC1-C cytoplasmic domain is sufficient for the interaction with BAX. The results further show that the MUC1-C cytoplasmic domain CQC motif binds directly to the BAX BH3 domain at Cys-62. Consistent with binding to the BAX BH3 domain, MUC1-C blocked BAX dimerization in response to (i) truncated BID in vitro and (ii) treatment of cancer cells with DNA-damaging agents. In concert with these results, MUC1-C attenuated localization of BAX to mitochondria and the release of cytochrome c. These findings indicate that the MUC1-C oncoprotein binds directly to the BAX BH3 domain and thereby blocks BAX function in activating the mitochondrial death pathway.


Subnormal cerebellum in fetuses with spina bifida.
The results of a prospective ultrasound study of the posterior fossa structures in 19 fetuses with spina bifida are reported. The transverse cerebellar diameter is below the normal limits and the cisterna magna is obliterated in all cases. Decreased cerebellar size and failure to visualize the cerebellum appear to be specific findings for spina bifida since they are not present in a group of 17 fetuses with isolated hydrocephalus. The results of this study indicate that ultrasound investigation of the posterior fossa may prove useful in the prenatal diagnosis of spina bifida.


Laparoscopic transposition of lower pole vessels--the 'vascular hitch': an alternative to dismembered pyeloplasty for pelvi-ureteric junction obstruction in children.
Dismembered pyeloplasty is the traditional technique in the management of ureterovascular pelvi-ureteric junction obstruction (PUJO) in children. Controversy remains regarding the role of lower pole vessels as the sole aetiology for PUJO. Endopyelotomy and concomitant laparoscopic transposition of lower pole vessels for PUJO has been described in adults. We describe our technique of laparoscopic transposition of lower pole vessels in children with PUJO, leaving the PUJ intact. Thirteen patients (seven boys and six girls) with a mean age of 10.2 years (range 7-16 years) underwent laparoscopic transposition of lower pole vessels. Surgery was indicated on the basis of intermittent pain and ultrasound/MAG3 appearance of obstruction with or without reduced function. The technique involved laparoscopic transperitoneal mobilization of the lower pole vessels from the region of the PUJ thereby freeing the junction and transposing them superiorly onto the anterior wall of the pelvis. The main outcome measures were relief of pain and improvement in ultrasound appearance or drainage parameters on a postoperative MAG3 renogram performed within 4-6 weeks of surgery. Median operating time was 92 min. All patients were discharged within 36 h of surgery. All patients remain pain free at a median of 6 months (range 3-18 months). Twelve patients showed good drainage on the postoperative MAG3 renogram and improvement in ultrasound appearance. One patient had recurrent symptoms requiring insertion of a JJ stent. She has undergone further laparoscopic exploration. The vessels were in their transposed position and there was a kink at the PUJ which was released. She had a vertical pyelotomy and transverse closure over the JJ stent with good results. This technique is simple and requires less operating time. No anastomosis or temporary JJ stent is required. Our early results are very encouraging with no serious complications.


Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial.
Intrauterine insemination with controlled ovarian hyperstimulation is commonly used as first-line treatment for couples with unexplained subfertility. Since such treatment increases the risk of multiple pregnancy, a couple's chances of achieving an ongoing pregnancy without it should be considered to identify those most likely to benefit from treatment. We aimed to assess the incremental effectiveness of intrauterine insemination with controlled ovarian hyperstimulation compared with expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy. 253 couples with unexplained subfertility and a 30-40% probability of a spontaneous ongoing pregnancy within 12 months were randomly assigned either intrauterine insemination with controlled ovarian hyperstimulation for 6 months or expectant management for 6 months. The primary endpoint of this hospital-based study was ongoing pregnancy within 6 months. Analysis was by intention to treat. This trial is registered with the Dutch Trial Register and as an International Standard Randomised Clinical Trial, number ISRCTN72675518. Of the 253 couples enrolled, 127 were assigned intrauterine insemination with controlled ovarian hyperstimulation and 126 expectant management. In the intervention group, 42 (33%) women conceived and 29 (23%) pregnancies were ongoing. In the expectant management group, 40 (32%) women conceived and 34 (27%) pregnancies were ongoing (relative risk 0.85, 95% CI 0.63-1.1). There was one twin pregnancy in each study group, and one woman in the intervention group conceived triplets. A large beneficial effect of intrauterine insemination with controlled ovarian hyperstimulation in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for 6 months is therefore justified in these couples.


The levels of leptin, adiponectin, and resistin in normal weight, overweight, and obese pregnant women with and without preeclampsia.
The purpose of this study was to compare adipokines' levels between women with and without preeclampsia based on maternal body mass index (BMI). This was a cross-sectional study among third-trimester pregnancies with preeclampsia (PIH) compared with normotensive controls. Serum levels of adiponectin, leptin, and resistin were measured before delivery by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). The study included 22 normotensive and 77 PIH women. Leptin levels increased with maternal BMI. In patients with severe preeclampsia, overweight, and obese women had increased leptin levels (33.4 +/- 14.8 vs 23.0 +/- 10.8 ng/mL respectively, P = .02), and decreased adiponectin levels (8.4 +/- 5.3 vs 12.6 +/- 6.0 ng/mL, P = .03) compared with normal weight women. In women with BMI <25 kg/m2, adiponectin levels increased in patients with preeclampsia compared with controls (11.5 +/- 5.6 vs 9.6 +/- 4.6 and 7.0 +/- 3.2 ng/mL, respectively, P = .005). There was no association between resistin levels and preeclampsia or maternal BMI. Women with severe preeclampsia and BMI > or = 25 kg/m2 have decreased adiponectin and increased leptin levels, while normal weight women with preeclampsia have increased adiponectin levels.


The effect of fertilizer treatments on yield of seed and volatile oil of fennel (Foeniculum vulgare Mill.).
Nitrogen fertilization gave higher number of compound umbels and increased oil percentage, seed yield and oil yield with increase in dose. Phosphorus and potassium produced significant increase in the previons aspects with the second dose only.


The omlA gene is involved in multidrug resistance and its expression is inhibited by coumarins in Xanthomonas campestris pv. phaseoli.
A gene encoding the outer membrane lipoprotein, OmlA, from the bacterial phytopathogen Xanthomonas campestris pv. phaseoli was isolated and characterized. An omlA insertion mutant showed an increased susceptibility to novobiocin and coumermycin, antibiotics with gyrase inhibitor activity. The omlA mutant accumulated novobiocin. Additionally, the omlA mutant was more sensitive than the wild type to chloramphenicol, a protein synthesis inhibitor; SDS, a detergent; and menadione, a superoxide generator. The susceptibility of the mutant to unrelated chemicals indicated a general role for OmlA in maintaining membrane integrity. Transcription of omlA was downregulated in the presence of both gyrase inhibitors, suggesting that DNA supercoiling might regulate the synthesis of OmlA. The omlA gene was divergently transcribed from the gene encoding the ferric uptake regulator Fur. Although the promoters of omlA and fur overlapped, Fur did not play any regulatory role in the expression of omlA due to the fact that inactivation of Fur did not affect the expression of omlA either in the presence or absence of iron.


Association Between Family History of Diabetes, Irrational Beliefs, and Health Anxiety with 10-Year Risk of Type 2 Diabetes Mellitus: the ATTICA Epidemiological Study (2002-2012).
This study aimed to examine the relationship between family history of diabetes, irrational beliefs, and health anxiety in the development of type 2 diabetes mellitus (T2DM). ATTICA is a prospective, cohort study (2002-2012). The working sample included 845 participants (18-89 years), free of diabetes at baseline. Α detailed biochemical, clinical, and lifestyle evaluation was performed, while participants' irrational beliefs and health anxiety were assessed through the Irrational Beliefs Inventory and the Whiteley index scale, respectively. We evaluated the association between the participants' family history of diabetes mellitus with the 10-year risk of diabetes mellitus, both in the total study's sample and separately according to their levels of health anxiety and irrational beliefs. The crude 10-year risk of T2DM was 12.9% (95%CI: 10.4, 15.4), with 191 cases of T2DM. Family history of diabetes was associated with 2.5 times higher odds (2.53, 95%CI 1.71, 3.75) of T2DM compared to those without family history. Among participants with family history of diabetes, the highest likelihood of developing T2DM, regarding their tested psychological features (i.e., low/high irrational beliefs in the entire group, low/high health anxiety in the entire group, and low/high irrational beliefs, low/high healthy anxiety), had people with high irrational beliefs, low health anxiety (OR 3.70, 95%CI 1.83, 7.48). The findings underline the important moderating role of irrational beliefs and health anxiety in the prevention of T2DM, among participants at increased risk of T2DM.


Stability of SARS-CoV-2 in cold-chain transportation environments and the efficacy of disinfection measures.
Low temperature is conducive to the survival of COVID-19. Some studies suggest that cold-chain environment may prolong the survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increase the risk of transmission. However, the effect of cold-chain environmental factors and packaging materials on SARS-CoV-2 stability remains unclear. This study aimed to reveal cold-chain environmental factors that preserve the stability of SARS-CoV-2 and further explore effective disinfection measures for SARS-CoV-2 in the cold-chain environment. The decay rate of SARS-CoV-2 pseudovirus in the cold-chain environment, on various types of packaging material surfaces, i.e., polyethylene plastic, stainless steel, Teflon and cardboard, and in frozen seawater was investigated. The influence of visible light (wavelength 450 nm-780 nm) and airflow on the stability of SARS-CoV-2 pseudovirus at -18°C was subsequently assessed. Experimental data show that SARS-CoV-2 pseudovirus decayed more rapidly on porous cardboard surfaces than on nonporous surfaces, including polyethylene (PE) plastic, stainless steel, and Teflon. Compared with that at 25°C, the decay rate of SARS-CoV-2 pseudovirus was significantly lower at low temperatures. Seawater preserved viral stability both at -18°C and with repeated freeze-thaw cycles compared with that in deionized water. Visible light from light-emitting diode (LED) illumination and airflow at -18°C reduced SARS-CoV-2 pseudovirus stability. Our studies indicate that temperature and seawater in the cold chain are risk factors for SARS-CoV-2 transmission, and LED visible light irradiation and increased airflow may be used as disinfection measures for SARS-CoV-2 in the cold-chain environment.


Therapeutic effects of ghrelin on endotoxic shock in rats.
We investigated the effects of ghrelin in a rat endotoxic shock model, and also observed the direct role of endotoxin on ghrelin generation in gastric mucosa. About 55% (11/20) of rats treated with lipopolysaccharide (5 mg/kg i.v.) alone died within 24 h of endotoxin injection. However, administration of ghrelin either at the same time as lipopolysaccharide injection (early treatment) or 12 h after lipopolysaccharide injection (late treatment) significantly decreased the mortality rate and ameliorated the hypotension seen in rats with endotoxic shock. Early and late treatment with ghrelin increased markedly the plasma glucose concentration and decreased the plasma lactate concentration. Early treatment with ghrelin attenuated significantly the deficiency in myocardial ATP content, but late treatment with ghrelin had no effect on myocardial ATP content. The plasma ghrelin level was significantly increased in the rats with endotoxin shock, and it increased further after ghrelin administration. Exposure of rat gastric mucosa in vitro to lipopolysaccharide (1.0 to 100 microg/ml) triggered the release of ghrelin from mucosa tissue in a dose- and time-dependent manner, meaning that lipopolysaccharide stimulated directly gastric mucosa to synthesize and secrete ghrelin. The results suggest that ghrelin could have therapeutic value for endotoxic shock.


Water deficit and aluminum interactive effects on generation of reactive oxygen species and responses of antioxidative enzymes in the seedlings of two rice cultivars differing in stress tolerance.
Aluminum (Al) is a major constraint to crop productivity in acid soils, whereas water deficit severely limits crop production in arid and semi-arid regions of the world. The objective of the present study was to examine the effects of both stresses, Al excess and water deficit, individually and in combination on the production of the reactive oxygen species (ROS) superoxide anion (O2˙(-)), hydrogen peroxide (H2O2), hydroxyl radical, and lipid peroxidation and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (GPX) in the seedlings of two rice (Oryza sativa L.) cvs. Malviya-36 (sensitive to water deficit and Al) and Vandana (tolerant to water deficit and Al). When 15-day grown seedlings were exposed to water deficit (created with 15% polyethylene glycol, PEG-6000) or Al (1 mM AlCl3) treatment or both treatments together for 24-72 h, the lengths and fresh weights of root/shoot declined in the seedlings of the sensitive cultivar, whereas in the tolerant seedlings, either little or insignificant decline in these parameters was observed due to the treatments. Biochemical determinations and histochemical studies revealed that under a similar level of water deficit, Al, or combined treatment, seedlings of sensitive cultivar showed a higher level of production of O2˙(-), H2O2, hydroxyl radical, and lipid peroxides compared to the tolerant seedlings. Seedlings of tolerant cultivars, both in roots and shoots, had constitutively higher activity levels of antioxidative enzymes SOD, CAT, and GPX and showed a greater increase in activity under water deficit or Al treatment alone or in combination compared to the similarly treated seedlings of sensitive cultivar. Our results suggest that a lower constitutive level of ROS and a high antioxidative enzyme capacity are associated with tolerance to both water deficit and Al excess in rice seedlings.


Elevation of aversive threshold in rats by intra-amygdaloid injection of morphine sulphate.
Bilateral micro-injection of morphine sulphate (10 microgram, 20 microgram) into the cortico-medial amygdala produced a dose-dependent increase in aversive threshold. Similar injections into the basolateral amygdala or caudate-putamen failed to have any consistent effect on aversive thresholds. Whilst overall activity levels remained unaffected by morphine injection into either amygdaloid site, caudate animals exhibited a significant decrement in total activity in response to both morphine and control injections. Results are discussed with reference to a possible role for limbic mechanisms in morphine analgesia.


Granular natural-killer cells develop into mucus-secreting cells.
Colonies of granular natural-killer cells selectively develop in lymph-node cell cultures of nude mice after stimulation with rat T-cell growth factor. When these cells are grown on X-irradiated monolayers prepared from 16-18-day-old mouse embryos, they are triggered to synthesize and secrete a sulphated glycoprotein that can be identified as mucus. As a result of an erosive process of the granules, the mucoid material accumulates in pools in the cytoplasm matrix. The secretion is operated through a process of budding of double-membrane-bound vesicles. The successful triggering of mucous synthesis is interpreted by the successful growth of those mesenchymal cells in the embryonic monolayer that function in the induction of epithelial morphogenesis in the developing embryo.


Event-Related Spectral Perturbation, Inter Trial Coherence, and Functional Connectivity in motor execution: A comparative EEG study of old and young subjects.
The motor-related bioelectric brain activity of healthy young and old subjects was studied to understand the effect of aging on motor execution. A visually cued finger tapping movement paradigm and high-density EEG were used to examine the time and frequency characteristics. Twenty-two young and 22 healthy elderly adults participated in the study. Repeated trials of left and right index finger movements were recorded with a 128-channel EEG. Event-Related Spectral Perturbation (ERSP), Inter Trial Coherence (ITC), and Functional Connectivity were computed and compared between the age groups. An age-dependent theta and alpha band ERSP decrease was observed over the frontal-midline area. Decrease of beta band ERSP was found over the ipsilateral central-parietal regions. Significant ITC differences were found in the delta and theta bands between old and young subjects over the contralateral parietal-occipital areas. The spatial extent of increased ITC values was larger in old subjects. The movement execution of older subjects showed higher global efficiency in the delta and theta bands, and higher local efficiency and node strengths in the delta, theta, alpha, and beta bands. As functional compensation of aging, elderly motor networks involve more nonmotor, parietal-occipital, and frontal areas, with higher global and local efficiency, node strength. ERSP and ITC changes seem to be sensitive and complementary biomarkers of age-related motor execution.


Complete sequence of the multi-resistance plasmid pV7037 from a porcine methicillin-resistant Staphylococcus aureus.
The aim of this study was to determine the complete sequence of the multi-resistance plasmid pV7037 to gain insight into the structure and organization of this plasmid. Of the four XbaI clones of pV7037, one clone of 17,577 bp has already been sequenced and shown to carry a multi-resistance gene cluster. The remaining three clones of approximately 12.5, 6.5 and 4.5 kb were sequenced, the entire plasmid sequence correctly assembled and investigated for reading frames. In addition, two reading frames one coding for an ABC transporter and the other coding for an rRNA methylase were cloned and expressed in a S. aureus host to see whether they confer antimicrobial resistance properties. Plasmid pV7037 proved to be 40,971 bp in size. Besides the previously determined resistance gene cluster, it carried a functionally active tet(L) gene for tetracycline resistance, a complete cadDX operon for cadmium resistance and also a variant of the β-lactamase transposon Tn552. Two single bp deletions, which resulted in frame shifts, functionally deleted the genes for the BlaZ β-lactamase and the signal transducer protein BlaR1 in this Tn552 variant of pV7037. Plasmid pV7037 seems to be composed of various parts previously known from plasmids and transposons of staphylococci and other Gram-positive bacteria. However, there are also parts of the plasmid which do not show any homology to so far known sequences deposited in the databases. The novel ABC transporter and rRNA methylase genes identified on pV7037 do not seem to play a role in antimicrobial resistance. The co-location of numerous antimicrobial resistance genes bears the risk of co-transfer and co-selection of resistance genes, but also persistence of resistance genes even if no direct selective pressure by the use of the respective antimicrobial agents is applied.


Efficacy and safety evaluation of intravenous infusion of cervus and cucumis polypeptides for treatment of avascular necrosis of the femoral head: a randomized clinical trial.
To investigate the efficacy and safety of intravenous cervus and cucumis polypeptides for treating avascular necrosis of the femoral head (ANFH) in regard to pain and hip function in a randomized clinical trial. A total of 96 subjects with ANFH who were recruited at the Orthopaedic Hospital Affiliated with Hebei United University and Qian Hai Femoral Head Hospital of Beijing were assigned by lottery to an intervention group (n = 48) or a control group (n = 48). All subjects underwent physical therapy and rehabilitation exercises. In addition, subjects in the intervention group were given intravenous infusions of cervus and cucumis polypeptides. Visual analogue scale (VAS), Harris hip score, and radiography or magnetic resonance imaging were applied to assess all subjects at the beginning of treatment and 3, 6, and 9 months afterward. All the subjects were followed up for 2 years. At the beginning of treatment, there were no statistically significant differences between the two groups in terms of the general condition of patients or the VAS and Harris hip scores (all P > 0.05). At 3, 6, and 9 months after treatment, however, the VAS score decreased and the Harris hip score increased in all patients, with the improvement of intervention group significantly greater than that of the control group (P < 0.05). The total effectiveness rates for the intervention and control groups were 89.58% and 70.83%, respectively, with the difference being statistically significant (P < 0.05). There was no statistically significant difference between the two groups in terms of the safety of the injections (P> 0.05). Intravenous infusion of cervus and cucumis polypeptides relieved pain and improved hip function of subjects with ANFH. Thus, the intravenous infusion of cervus and cucumis polypeptides was a safe, effective treatment for ANFH.


A sequential pulse generator for producing true biphasic stimuli.
The ability to generate biphasic pulses during electrical stimulation of nervous tissue has important advantages over monophasic or capacitively coupled stimulation. A comparatively simple circuit is described which, when used with standard electrophysiological laboratory equipment, can economically implement biphasic stimulation. The resultant system is quite flexible, yet easy to operate.


A nanoplatform-based aptasensor to electrochemically detect epinephrine produced by living cells.
A novel aptasensor has been designed for quantitative monitoring of epinephrine (EP) based on cerium metal-organic framework (CeMOF) loaded gold nanoparticles (AuNPs). The aptamer, specific to EP, is immobilized on a flexible screen-printed electrode modified with AuNPs@CeMOF, enabling highly selective binding to the target biomolecule. Under optimized operational conditions, the peak currents using voltammetric detection measured at voltage of 83 mV (vs. Ag/AgCl) for epinephrine exhibit a linear increase within concentration in the range 1 pM-10 nM. Following this detection strategy, a boasted limit of detection of 0.3 pM was achieved, surpassing the sensitivity of most reported methods. The developed biosensor showcased exceptional performance in detection of EP in spiked serum sample, with remarkable recovery range of 95.8-113% and precision reflected by low relative standard deviation (RSD) ranging from 2.23 to 6.19%. These results indicate the potential utility of this biosensor as a valuable clinical diagnostic tool. Furthermore, in vitro experiments were carried out using the presented biosensor to monitor the release of epinephrine from PC12 cells upon extracellular stimulation with K+ ions.


Effects of nifedipine and felodipine on adenosine and inosine release from the hypoxemic rat cerebral cortex.
The cerebral cortical cup technique has been used to study the effects of nifedipine and felodipine on adenosine and inosine release from the rat brain. After basal and hypoxia (8% 02)-evoked control levels of purine release had been established, these 1,4-dihydropyridine calcium antagonists were administered intraperitoneally (1 mg/kg). Both agents depressed basal levels of purine efflux and suppressed the hypoxia-evoked release of adenosine and inosine. An inhibition of the transporter that mediates purine efflux from brain cells is likely to account for the suppression of release from the cerebral cortex. A reduced release of adenosine into the interstitial space also explains the ability of both agents to block the increase in CBF evoked by hypoxic challenges.


[Schooling of patients exhibiting Autism Spectrum Disorders without mental retardation].
Autism Spectrum Disorders belong to Pervasive Development Disorders. Although access to education is recommended by the French National High Authority for Health (HAS), the practice remains limited and the reasons for the low education rate of these children have still not been sufficiently explored in the literature. The main objective of this study was to analyze the links between Autism Spectrum Disorder without mental retardation, psychiatric comorbidity and education. The secondary objective was to analyze the cognitive and contextual factors that could limit educational inclusion. Eighty-three autistic patients (3-18years old; 73 males and 10 females) with childhood autism, atypical autism or Asperger's syndrome (criteria from the International Classification of Diseases-10) without mental retardation and in education were assessed at the Alpine Centre for Early Diagnosis of Autism. The sample included 45 subjects with childhood autism, 12 subjects with atypical autism and 26 subjects with Asperger's syndrome. The diagnosis was based on the Autism Diagnostic Interview Revised (ADI-R), in accordance with the recommendations of the HAS, the Autism Diagnostic Observation Schedule (ADOS) and the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Our results showed that childhood autism and atypical autism were mainly found in nursery and primary school, whereas Asperger's syndrome was mainly found in secondary school (Chi(2)=18.23; df=6; P<.006). Individuals with childhood autism and atypical autism were more likely to receive the support of a special educational assistant (Chi(2)=15.61; df=2; P<.000) and underwent a higher number of consultations and treatment episodes than those with Asperger's syndrome (Chi(2)=27.83; df=14; P<.015). The cognitive profiles obtained with the WISC-IV also differed: the Verbal Comprehension Index (VCI) and Working Memory Index (WMI) were higher for Asperger's syndrome than for childhood autism and atypical autism (respectively, F=23.11, P<.000; df=2; partial η(2)=.576 and F=8.06, P<.001; df=2; partial η(2)=.357). Linear regression showed that the VCI and Processing Speed Index (PSI) were inversely correlated to the number of hours spent with a special educational assistant: the lower these indexes, the greater the amount of time spent with a special educational assistant. No link was found between psychiatric comorbidity, type of psychological and psychiatric treatment, and education. The use of special educational assistants seems to be linked to the diagnosis of Autism Spectrum Disorders and neuropsychological functioning, as assessed by WISC-IV, along a continuum that ranges from childhood autism (more needs and deficits) to atypical autism to Asperger's syndrome. The Verbal Comprehension Index (VCI) and the Processing Speed Index (PSI) could be used to evaluate the number of hours of support needed by children and to better target the deficits and specific needs of children without mental retardation who are in education. A study on a larger scale could help to more closely address the question of the cognitive abilities of children with Autism Spectrum Disorder without mental retardation, so as to better help them in their education.


[Amino acids as catalysts of the binding reaction of formaldehyde with adenine residue in polyadenylic acid].
Binding of formaldehyde and amino acids (Gly, Lys and Leu) with poly(A), poly(G), and poly(C) has been investigated in comparison with treatment with formaldehyde alone. It was found that in the case of poly(A) amino acids were found to catalyze the N-hydroxymethylation reaction on exocyclic amino groups of adenine. For example, at 20 degrees C and pH 6.0 the rate of this reaction increased about 10 fold in the presence of glycine.


Direct versus indirect measurement of digit ratio: New data from Austria and a critical consideration of clarity of report in 2D:4D studies.
Digit ratio (2D:4D), has been the subject of many studies. However, the best method of measuring digit length, either directly (d2D:4D) or indirectly (i2D:4D), is controversial. In many reports i2D:4D has been found to show a directional effect such that d2D:4D > i2D:4D. The exception is three studies from one group of researchers in Austria. Thus, it is unclear whether this effect is nation- or lab-specific. To examine evidence for effects of direct versus indirect measurements of mean 2D:4D in Austrians. We compared 2D:4D based on direct and indirect measurements of digit lengths of Austrians. There were 80 participants, 21 adults and 59 children. 2D:4D of right and left hands, measured directly (from the palm) and indirectly (from hand scans). Repeatability was high for both d2D:4D and i2D:4D, with the latter slightly higher than the former. d2D:4D and i2D:4D correlated strongly and the sex difference in 2D:4D (males < females) was greater for i2D:4D. With regard to directional differences, we found d2D:4D > i2D:4D for both right (d = -0.53) and left hands (d = -0.80). There was no evidence of an "Austrian" effect on direct versus indirect measurements of 2D:4D, i.e. mean d2D:4D was greater than i2D:4D. We discuss our findings in the light of issues regarding "clarity of report" from earlier Austrian studies.


Do American Colleges and Universities Support the Lactation Needs of Students?
Despite strong evidence for the health benefits of breastfeeding, many mothers cannot continue breastfeeding their infants upon their return to work or school. Students are especially affected by this transition because they do not have legal protection that requires designated lactation space or time to express milk to be provided by places of education. Furthermore, limited research has been completed that specifically addresses the return to school of mothers who are students. One hundred fifty-seven colleges and universities from across the United States were contacted through telephone and/or e-mail, and their websites were searched to assess the support they offer for lactating students. The presence of a formal policy for lactating students and designated lactation rooms, accessible to students, were the key measures. Information was gathered from 88.53% (n = 139) of the colleges and universities. A mere 3.6% (n = 5) had an official policy for lactating students and/or had the lactation spaces mentioned in the student handbook. However, more than half of the colleges and universities (54.68%; n = 76) had designated lactation spaces accessible to their students. The vast majority of the sample did not have a policy for lactating students, and almost half of the schools did not have designated space for milk expression accessible to students. Lactating students will likely encounter challenges in simultaneously sustaining breastfeeding and meeting their educational goals in these contexts. To meet the recommendation of the American Academy of Pediatrics of 6 months of exclusive breastfeeding and continued breastfeeding for 1 year or more, American colleges and universities must establish not only designated spaces for milk expression but also policies to support lactating students.


Hibernation: an opioid-dependent state?
Hibernation reduces substantially the heart rate of hamsters as well as the respiratory rate, the body temperature and the arousal level. The heart rate is reversed dramatically by the injection of low doses of Naloxone and in some cases the hamster arouses prematurely from hibernation. The effect is not due to the pain of the injection because saline injections do not produce such changes. The effect requires a pre-existing state of hibernation because Naloxone has no cardioacceleratory or arousal effect in non-hibernating hamsters that have had their heart rate and body temperature decreased substantially during hypothermia. These results suggest that endogenous opioids may contribute specifically to the state of hibernation. Moreover, a physiological role may exist for an anti-opioid system in the promotion of arousal from hibernation.


A closer look at the "Protopithecus" fossil assemblages: new genus and species from Bahia, Brazil.
The recently extinct large-bodied New World monkey Protopithecus brasiliensis Lund 1836 was named based on a distal humerus and proximal femur found in the Lagoa Santa cave system in the southeastern Brazilian state of Minas Gerais. These bones are from an animal about twice the size of the largest extant platyrrhines. One hundred and seventy-five years later, a nearly complete skeleton was discovered in the Toca da Boa Vista caves in the neighboring state of Bahia and was allocated to the same taxon as it was the first platyrrhine fossil of comparable size found since the originals. Our detailed study of the equivalent elements, however, reveals important morphological differences that do not correspond to intraspecific variation as we know it in related platyrrhine taxa. The presence of both an expanded brachioradialis flange on the humerus and gluteal tuberosity on the femur of the Bahian skeleton distinguishes it from the Lagoa Santa fossil as well as from all other platyrrhines. Further cranial and postcranial evidence suggests a closer relationship of the former with the alouattine Alouatta, while the limited Lund material fits more comfortably with the ateline clade. Therefore, we propose to limit P. brasiliensis Lund to the distal humerus and proximal femur from Lagoa Santa and erect a new genus and species for the skeleton from Toca da Boa Vista. Cartelles coimbrafilhoi was a large-bodied frugivore with a relatively small brain and diverse locomotor repertoire including both suspension and climbing that expands the range of platyrrhine biodiversity beyond the dimensions of the living neotropical primates.


Traitement médical de première ligne du cancer épithélial de l'ovaire de haut grade: First-line medical treatment of high-grade epithelial ovarian cancer.
In early stages, standard treatment is adjuvant chemotherapy, consisting of platinum-based combination for 6 cycles, especially in serous and endometrioid high grade carcinomas. In advanced stages, indication of neoadjuvant chemotherapy must be discussed on a case-by-case basis in multidisciplinary meetings (MDM). Bevacizumab can also be considered in the neoadjuvant setting in some circumstances, always after discussion in MDM. Carboplatin plus paclitaxel every 21 days, with or without bevacizumab remains the standard of care for first-line chemotherapy. Inhibitors of poly-(ADP-riboses) polymerases (PARPi) have been approved and are reimbursed as maintenance monotherapy in tumors carrying BRCA1 or BRCA2 mutation after complete or partial response to chemotherapy. Two recent studies demonstrated the efficacy of PARPi on progression free survival, one for niraparib single-agent in patients with high-grade ovarian carcinoma regardless of BRCA status, the other one for the combination of bevacizumab and olaparib in patients with high grade carcinoma, with positive test for homologous recombination DNA repair deficiency (regardless of BRCA status). These two new modalities of maintenance therapy are now available in compassionate use programs or post compassionate use programs. Depending on pending decisions upon reimbursement, these indications might be somewhat modified.


Treatment of chronic heart failure in long-term care facilities: implications of recent heart failure guidelines recommendations.
Use of angiotensin-converting enzyme inhibitor in heart failure with left ventricular systolic dysfunction has revolutionized management of heart failure and resulted in several national heart failure guidelines. However, studies have documented underutilization of these life saving drugs. Subsequently, results of other randomized clinical trials revealed the beneficial effects of angiotensin receptor blockers, beta-blockers, and spironolactone in heart failure with systolic dysfunction, which prompted several other guidelines. However, all these guidelines were primarily restricted to systolic dysfunction. Heart failure is as much a geriatric syndrome as it is a cardiac. Most heart failure patients are older adults. About half of the heart failure in older adults is not associated with left ventricular systolic dysfunction. Two recent heart failure guidelines, from the European Society of Cardiology and the American College of Cardiology/American Heart Association, published respectively in September and December 2001 included recommendations for patients with preserved left ventricular systolic function and other special populations, including older adults and those at end of life. The purpose of this article is to review the relevance of these two guidelines to heart failure patients living in long-term care facilities. As our population is aging, more heart failure patients are expected to live in long-term care facilities. Appropriate evaluation and management of these patients are essential to improve quality of heart failure care in the coming decades.


Gustatory processing: a dynamic systems approach.
Recent gustatory studies have provided a growing body of evidence that taste processing is dynamic and distributed, and the taste system too complex to be adequately described by traditional feed-forward models of taste coding. Current research demonstrates that neuronal responses throughout the gustatory neuroaxis are broad, variable and temporally structured, as a result of the fact that the taste network is extensive and heavily interconnected, containing modulatory pathways, many of which are reciprocal. Multimodal influences (e.g. olfactory and somatosensory) and effects of internal state (e.g. attention and expectation), shown in both behavioral and neuronal responses to taste stimuli, add further complexity to neural taste responses. Future gustatory research should extend to more brain regions, incorporate more connections, and analyze behaviors and neuronal responses in both time- and state-dependent manners.


Investigating the impact of IoT-Based smart laboratories on students' academic performance in higher education.
The enormous developments in technology have transformed the way we interact with the world around us. Among the extensive yet advanced technological interventions, one of the sophisticated expansions is the appearance of the Internet of Things, a tool for developing connections of physical objects to the virtual world using small-sized sensors and certain internet protocols to lessen human interventions. The domain of education has also adopted these technological services to move from traditional methods to sophisticated and advanced teaching and learning approaches to cope with learning needs and raise quality. This paper intends to conceptualize the impact of integrating IoT in higher education to increase students' academic performance in the engineering domain through the integration of smart laboratories. Several international studies were selected and thoroughly reviewed using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis to build sophisticated insights regarding the topic in terms of its conceptual as well as practical foundations. The key insights gathered through reviewed studies indicate that the Internet of things-based laboratories have significant advantages in uplifting students' academic performance through interaction, motivation, creativity, and practical learning. The integration of the Internet of things in higher educational institutes improves students' academic performance because it allows them to engage in authentic tasks and experience practical and active learning.


How to Manage Heart Failure With Preserved Ejection Fraction: Practical Guidance for Clinicians.
Although patients with heart failure with preserved ejection fraction (HFpEF) (left ventricular ejection fraction ≥50%) comprise nearly half of those with chronic heart failure, evidence-based treatment options for this population have historically been limited. Recently, however, emerging data from prospective, randomized trials enrolling patients with HFpEF have greatly altered the range of pharmacologic options to modify disease progression in selected patients with HFpEF. In the context of this evolving landscape, clinicians are increasingly in need of practical guidance regarding the best approach to management of this growing population. In this review, the authors build on the recently published heart failure guidelines by integrating contemporary data from recent randomized trials to provide a contemporary framework for diagnosis and evidence-based treatment of patients with HFpEF. Where gaps in knowledge persist, the authors provide "best available" data from post hoc analyses of clinical trials or data from observational studies to guide management until more definitive studies are available.


ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma.
Treatment outcome for hepatocellular carcinoma (HCC) is related to tumor burden and liver function. Grading systems assessing liver function need validation in different clinical settings. To evaluate drug-eluting embolic transarterial chemoembolization (DEE-TACE) in Child-Pugh A HCC with respect to albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (P-ALBI) grade. Forty-nine patients with Child-Pugh class A, diagnosed with HCC and allocated to DEE-TACE treatment, were retrospectively analyzed regarding tumor and treatment characteristics, radiological response (mRECIST) one month post treatment, overall survival (OS), and adverse events (AEs; CTCAE, grades ≥3) with respect to ALBI and P-ALBI grade. There were 21 ALBI 1 patients, 29 P-ALBI 1 patients, and 19 patients were both ALBI and P-ALBI 1. Objective response rate was 74% with no statistically significant difference for ALBI (1 vs. 2; P = 0.08), or P-ALBI (1 vs. 2; P = 0.49). OS was 14.8 months (range = 1.7-62.0; ALBI 1 vs. 2: P = 0.08; P-ALBI 1 vs. 2: P = 0.003). OS in responders with ALBI 1 and 2 was 28.9 vs.10.2 months ( P = 0.02), and P-ALBI 1 and 2 was 26.7 vs. 8.6 months ( P < 0.001). In multivariate analyses, both ALBI 2 (HR = 2.4, P = 0.02) and P-ALBI 2 (HR = 3.3, P < 0.01) were negative prognostic factors for survival. There were 15 AEs in 13 patients, with hepatic failure only occurring in ALBI 2 and P-ALBI 2 patients. P-ALBI grade 1 and 2 differentiated survival in Child-Pugh A patients treated with DEE-TACE. Both grading systems can differentiate survival in patients responding to treatment.


Dissociation and reassociation of the bovine pituitary multicatalytic proteinase complex.
The eukaryotic multicatalytic proteinase complex (proteasome) is a high molecular mass enzyme which contains 13-15 nonidentical subunits of similar size (molecular masses of 21-31 kDa), but differing widely in net charge (isoelectric points ranging from 3 to 10). At least four catalytic components termed chymotrypsin-like, trypsin-like, peptidylglutamyl peptide-hydrolyzing, and caseinolytic are associated with the proteinase. The catalytic nature of the components is unknown, since sequences of cloned subunits bear no homology to known proteinases and proteolytically active subunits have not been isolated. Analysis of the relationship between structure and catalytic function would be greatly facilitated if a means for reversibly dissociating and reassociating the proteinase were available. We provide the first evidence of reassembly of dissociated multicatalytic proteinase complex into a functional molecule. Incubation with the organic mercurial, p-chloromercuribenzoic acid disrupts in a concentration-dependent manner the quaternary structure of the enzyme, leading to formation of a heterogeneous population of subunits. Dissociation of the complex coincides with progressive loss of chymotrypsin-like, trypsin-like, and peptidylglutamyl peptide hydrolyzing activities. The caseinolytic activity of the residual undissociated enzyme is markedly activated. Exposure of the dissociated enzyme to dithiothreitol restores the catalytic profile and reassociates the enzyme. Evidence for catalytically active subcomplexes was not obtained indicating that structural integrity may be necessary for expression of all defined activities.


Erectile Function and Sexual Satisfaction: The Importance of Asking About Sexual Desire.
Erectile function, libido, and sexual bother are incompletely correlated: a man may or may not be satisfied for a given level of erectile function; similarly, 2 men may have the same erectile function and different levels of sexual desire. To explore the relationship between erectile function, sexual satisfaction and sexual desire. We examined the Spearman correlation among erectile function (International Index of Erectile Function [IIEF-6]), sexual desire, and sexual bother in 3,944 questionnaires completed by patients after radical prostatectomy as part of routine care. IIEF-6 scores were adjusted if a patient indicated that the reason for not having intercourse was other than lack of ability of confidence (eg, lack of partner). Patient-reported outcome instruments. Median age at surgery and preoperative IIEF-6 were 63 years and 26, respectively. Among questionnaires completed after surgery, there was moderate correlation among the IIEF-6 score and both sexual desire (Spearman rho: 0.41) and sexual bother (Spearman rho: 0.30). In men who reported high or moderate bother relating to sexual function, there was a narrow distribution of erectile function scores, with most men reporting poor function (median IIEF-6: 6, interquartile range 3, 11). For men who reported small or no problem with sexual function, the distribution of erectile function scores was wide, and particularly bimodal as a function of sexual desire. Among patients with high desire, the correlation between sexual bother and erectile function was 0.61 (ie, the poorer is your function, the greater you are bothered), whereas it was -0.081 among patients with low desire, meaning that some men are not bothered by poor erections. We provided useful insights to help physicians during sexual counselling after surgery for prostate cancer. The study included a large number of patients and provides evidence for implementation of patient-reported outcome insturments. Limitations include the retrospective nature of our data. Sexual desire helps explain the moderate correlation between erectile function and sexual bother. Sexual desire and bother questions should be incorporated in patient-reported outcome instruments for male sexual function. Bravi CA, Tin A, Montorsi F, et al. Erectile Function and Sexual Satisfaction: The Importance of Asking About Sexual Desire. J Sex Med 2020;17:349-352.


Type 2 diabetes affects arsenic metabolism via transporters in arsenic trioxide treated acute promyelocytic leukemia patients.
Our study aimed to explore whether type 2 diabetes (T2DM) can affect arsenic metabolism in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide. We found that compared with non-diabetic APL patients, the concentrations of arsenic metabolites in APL patients with T2DM increased significantly and positively correlated with blood glucose (P < 0.05). Meanwhile, APL patients with T2DM were more prone to liver injury and QTc interval prolongation due to altered arsenic methylation capacity. Then we cultured HEK293T cells at different glucose concentrations, and the results showed that the cells with high glucose had higher concentrations of arsenic metabolites compared to other cells. Meanwhile, the high glucose significantly increased the mRNA and protein expression levels of the arsenic uptake transporter AQP7 in HEK293T cells. Overall, our study demonstrated that T2DM can lead to elevated concentrations of arsenic metabolites in APL patients by increasing AQP7 expression.


Impact of social disadvantage on cerebral palsy severity.
To investigate the impact of socio-economic disadvantage on indicators of cerebral palsy (CP) severity - motor impairment, intellectual disability, and the presence of severe comorbidities - in children with CP in Australia. Data from the Australian Cerebral Palsy Register were analysed. Socio-economic disadvantage was assessed using maternal age, maternal country of birth, and a measure of neighbourhood socio-economic status (SES) at the time of the child's birth. Descriptive bivariate analysis, trend analysis, risk ratios, and mediation analysis were undertaken to examine the impact of disadvantage on the indicators of CP severity. A socio-economic gradient was demonstrated with an increasing proportion of children with non-ambulant status, at least moderate intellectual disability, and the presence of severe comorbidities (having epilepsy, functional blindness, bilateral deafness, and/or no verbal communication) with decreasing neighbourhood SES, adolescent motherhood, and maternal minority ethnicity. In Australia, socio-economic disadvantage at birth impacts adversely on CP severity at age 5 years. By identifying that socio-economically disadvantaged children with CP are at greater risk of more severe functional outcomes, we can inform targeted interventions at the family and neighbourhood level to reduce these inequities for children with CP. Socio-economic disadvantage is associated with increased severity of cerebral palsy functional outcomes. This encompasses low neighbourhood socio-economic status, adolescent motherhood, and maternal minority ethnicity.


[Invasive squamous cell carcinoma of the uterine cervix three years after cryosurgical treatment of a benign ectopy (author's transl)].
Report on a 33 years old para 4, who developed invasive squamous cell carcinoma of the cervix three years after cryosurgery for a large ectopy of the ectocervix. The carcinoma developed under an intact layer of normal superficial epithelium. The pap smears were negative at yearly intervals until a positive smear was obtained from a small iodinenegative area. Cases following cryosurgery appear to require careful follow-ups.


Cases from the aerospace medicine residents' teaching file. Case #55. Symmetrical peripheral edema in a 33-year-old Army aviator.
Initial presentation, evaluation, differential diagnosis, and aeromedical disposition of a 33-year-old aviator with tropical sprue is discussed. This unusual case was unique in that the applicable flight regulations do not address tropical sprue.


Carbon dots as light converter for plant photosynthesis: Augmenting light coverage and quantum yield effect.
Carbon dots (CDs) with gradient-changed quantum yield (QY) were prepared by regulating the graphitic N and hydroxyl group contents. Then, the QY effect of CDs on plant photosynthesis was studied using chloroplasts and rice plants. After incubation for 2 h in the dark, CDs entered into the chloroplasts and converted ultraviolet radiation to photosynthetically active radiation. By this mechanism, CD1:0.2 (300 μg·mL-1) with a moderate QY of 46.42% significantly increased the photosynthetic activity of chloroplast (200 μg·mL-1) to reduce DCPIP and ferricyanide by 43.77% and 25.45%, respectively. After spraying on rice seedlings, CD1:0.2 (300 μg·mL-1) was evenly distributed in the leaves and resulted in maximum increases in the electron transport rate and photosynthetic efficiency of photosystem II by 29.81% and 29.88%, respectively. Furthermore, CD1:0.2 significantly increased the chlorophyll content and RuBisCO carboxylase activity of rice by 64.53% and 23.39%, respectively. Consequently, significant increases were observed in the growth of CD1:0.2-treated rice, including 18.99%, 64.31%, and 61.79% increases in shoot length, dry weights of shoot and root. These findings contribute to the exploitation of solar energy and agricultural production using CDs in the future.


Hindbrain-hernia-related syringomyelia without syringobulbia, complicated by permanent nocturnal central hypoventilation requiring non-invasive ventilation.
In the absence of syringobulbia, hindbrain hernia does not commonly cause permanent respiratory complications. We present two patients who developed permanent central nocturnal hypoventilation following acute deterioration of hindbrain-hernia-related syringomyelia despite successful surgery. Two children (one boy and one girl, aged 7 and 13 years, respectively) presented with acute neurological deterioration. The boy presented with a 6-week history of progressive tiredness and weakness and a short history of respiratory depression. The girl presented with a 2-year history of left hemiparesis and a short history of left hemiplegia and respiratory depression. On magnetic resonance scan, both had hindbrain hernia, hydrocephalus and cervical syringomyelia. Following cranio-vertebral decompression and, later, a ventriculoperitoneal shunt, the syringomyelia remained well controlled in both patients. In contrast, their respiratory depression improved minimally. Repeated multichannel respiratory monitoring revealed a persistently slow sleeping respiratory rate, with nocturnal hypercapnia and hypoxemia, managed successfully by night-time non-invasive ventilation. Neither the boy nor the girl, after 7 and 4 years, respectively, has developed any complications of nocturnal hypoventilation. When awake, both breathe normally. Both children appear to have suffered a permanent impairment of respiratory control, resulting in nocturnal hypoventilation. This is usually seen with brain stem lesions and is unexpected when syringomyelia does not extend above C2, in the absence of syringobulbia. Central nocturnal hypoventilation is postulated to be due to permanent damage of central brain stem pathways controlling the respiratory muscles, due to local pressure at the cranio-cervical junction associated with acute deterioration of the hindbrain herniation. Sudden deterioration of hindbrain hernia and cervical syringomyelia can rarely impair the central mechanisms of respiratory control, with long-term implications on quality of life.


Protein S-100B, neuron-specific enolase (NSE), myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) and blood of neurological patients.
In this study, data about protein S-100B, neuron-specific enolase, myelin basic protein and glial fibrillary acidic protein in cerebrospinal fluid and blood of patients with an acute or chronic progressive neurological disorder with brain damage are reviewed. Especially in disorders with acute brain damage, determination of these proteins in CSF and blood can be helpful to establish structural and/or functional brain damage to determine severity and prognosis of the disease process and to monitor treatment effects.


Regulation of leucine transport and oxidation in peripheral human lymphocytes by glutamine.
In this study we investigated the influence of physiological levels of glutamine, isoleucine, and valine on leucine oxidation and transport by peripheral lymphocytes in an in vitro system. The presence of glutamine in the incubation mixture inhibited leucine oxidation by 61%. This effect was not significantly augmented by addition of isoleucine and valine. Leucine transport revealed a Km of 124 mumol/L and a Vmax of 24 pmol/10(6) cells/30 sec. Glutamine inhibited leucine transport by 63%. The capacity of lymphocytes for leucine transport exceeded the capacity for leucine oxidation by a factor of 7.8 (13.6 +/- 0.6 v 1.74 +/- 0.1 pmol/10(6) cells/30 sec). It is concluded that glutamine is a regulator of leucine transport and oxidation in human peripheral lymphocytes, and the inhibition of leucine oxidation by glutamine is not due to an alteration of leucine transport but reflects an intracellular event.


Laxative prescribing in relation to opioid use and the influence of pharmacy-based intervention.
Opioid-induced constipation is a common problem and can cause serious complications. It is widely advised that laxatives should be started concurrently with opiates, unless there is a clear indication not to do so. This study was undertaken to estimate how often laxatives were started concurrently with opiates and to describe the effect of pharmacy-based interventions to promote the use of laxatives in patients starting opioids. Twenty-six community pharmacies identified all patients who received a first prescription for a strong opioid during January and February of 1998, 1999 or 2000. Pharmacists collected information on patient, drug and prescriber characteristics (age, gender, use of opiates and laxatives). A separate questionnaire was used to collect data on pharmacy-based interventions to promote the simultaneous prescribing of laxatives with the opiates. Overall, 37% of the patients receiving an opioid started taking laxatives within 5 days. The percentage of patients who received laxatives simultaneously with opioids increased from 31% in 1998 to 35% in 1999 and 42% in 2000. In 117 (43%) of the opioid prescriptions, pharmacy-based intervention had taken place before the prescription date. Of these, 48.7% was accompanied by a laxative. Opioid prescriptions (n=152) without a pharmacy based intervention were accompanied in 27.6%. After adjustment for covariates (including time trends), pharmacy-based intervention increased the probability of concomitant laxative use 1.9 [95% CI 1.1-3.3] times. This study shows that the widely used guideline to start a laxative when prescribing an opioid is not always followed in daily practice. In addition, we showed that pharmacy-based intervention contributed to increasing laxative use in patients receiving opioids.


Effectiveness and safety of traditional Chinese medicines for non-alcoholic fatty liver disease: Protocol for systematic review and meta-analysis.
Previous reviews indicate that the effect of Traditional Chinese medicines (TCM) on non-alcoholic fatty liver disease (NAFLD) remains uncertainty. The study results published in the past 8 years may change this situation, but there is no updated systematic review. Therefore, we designed this study to systematically evaluate the effectiveness and safety of TCM in the treatment of NAFLD. We will search nine online databases from inception to October 01 2019, and the language will not be restricted on included trials. Randomized controlled trials that included patients with NAFLD receiving TCM therapy versus a control group will be included. Two researcher will perform independently the selection of studies, risk of bias assessment and data extraction. We will use the RevMan V.5.2 software with fixed effects model or random effects model according to the heterogeneity test to conduct the data synthesis. We will present the dichotomous data and the continuous data with risk ratios with 95% CIs and weighted mean differences or standardized mean differences with 95% CIs. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system will be used to evaluate the evidence quality with low risk, unclear risk, and high risk. This study will demonstrate an evidence-based review of TCM for NAFLD. The study will provide clear evidence to assess the effectiveness and side effects of TCM for NAFLD.


Timing and gender determine if acute pain impairs working memory performance.
The effects of pain on memory are complex, and little is known about the vulnerability of working memory (WM) performance when individuals complete a WM test while concurrently experiencing pain. Here, we subjected 78 healthy nonsmoking participants to either acute pain or a control condition while we administered a WM test. In this context, we also tested WM 20 minutes after pain in order to determine if timing of pain affected WM performance, and assessed objective and subjective measures of pain. We hypothesized that pain would impair WM performance during pain. Further, women's WM performance would be impaired more than men. Importantly, there was an interaction between gender and condition, with women exposed to pain experiencing impairments during but not after the cold pressor task. Our data imply that timing and gender are critically important in whether acute pain is costly to WM performance. Our findings have interesting clinical, professional, and educational implications, and understanding the influence of pain could help to improve the interpretation of WM tests in these diverse settings. Results of this study support the growing body of work that attests to the detrimental effect of pain on WM performance. Further, this study provides new evidence that concurrently experiencing cold pressor pain impairs WM in regularly menstruating women and women taking a contraceptive.


IFNT, ISGs, PPARs, RXRs and MUC1 in day 16 embryo and endometrium of repeat-breeder cows, with or without subclinical endometritis.
Interferon-τ (IFNT), IFN stimulated genes (ISG15, CTSL1, RSAD2, SLC2A1, CXCL10, and SLC27A6), Peroxisome proliferator activated receptors (PPARA, D, and G), Retinoic acid receptors (RXRA, B, and G), and Mucin-1 (MUC1) play decisive roles in embryo elongation. The objective was to elucidate expressions of these genes in day 16 embryo [tubular (n = 4) vs. filamentous (n = 4)] and corresponding endometrium [without (n = 4) vs. with subclinical endometritis (SCE; n = 4)] of repeat breeder Holstein cows (2 × 2 factorial design). Results showed that the mRNA abundances (except PPARA and RXRB) were greater (P < 0.05) in filamentous embryo and endometrium without SCE compared with tubular embryo and endometrium with SCE, respectively. Overall, the mRNA abundances (except RSAD2, PPARA and RXRA) in filamentous embryo and corresponding endometrium of cows without SCE were greater (P < 0.05) than tubular embryo and corresponding endometrium of cows with SCE. Proteins IFNT, ISGs, PPARs and RXRs (except RXRB) were greater (P < 0.05) and protein MUC1 was lower (P < 0.01) in filamentous embryo and corresponding endometrium of cows without SCE compared to tubular embryo and corresponding endometrium of cows with SCE. On pairwise comparison, mRNA and protein abundances of MUC1 significantly differed between tubular embryo in uterus with or without SCE, and corresponding endometrium with or without SCE (P < 0.05). In conclusion, the mRNA and protein abundances of IFNT, ISG15, CXCL10, PPARG and MUC1 differed among filamentous and tubular conceptuses, and endometrium with or without SCE of repeat breeder cows on Day 16, indicating that these genes and their downstream signaling cascades play important roles in embryo elongation. Perhaps, interruptions in cross-talk between endometrium and conceptus impaired conceptus elongation in repeat breeder cows with SCE. In addition to disrupted signaling, the tubular conceptus (compared to filamentous conceptus) was unable to downregulate MUC1 (anti-adhesive glycocalyx) in repeat breeder cows with or without SCE, resulting in early embryonic demise.


New considerations on the time-dependence of toxic changes caused by paraquat poisoning.
1. We have studied the effects of the LD50 and LD100 of paraquat on mouse blood triglycerides and on the time-dependence of the blood clotting, the bleeding time, the number of thrombocytes, and the body temperature. 2. The examined components vary rapidly in response to the toxic doses of paraquat. The changes depend on, among others, the amount of paraquat administered. 3. They are suitable for rapid diagnosis and for establishment of the severity of the poisoning.


Inflammatory markers and long-term risk of ischemic heart disease in men A 13-year follow-up of the Quebec Cardiovascular Study.
We tested the hypothesis that elevated plasma interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen concentrations are independent risk factors and interact in increasing the long-term risk of ischemic heart disease (IHD) in men. A total of 1982 IHD-free men from the Quebec Cardiovascular Study were followed over a period of 13 years during which 210 first fatal IHD events and non-fatal myocardial infarctions were recorded. Increased CRP levels (4th versus 1st quartile) were not associated with an increased risk of IHD after adjustment for non-lipid risk factors (age, body mass index, systolic blood pressure, diabetes, smoking and medication use at baseline), lipid risk factors (LDL and HDL cholesterol and triglyceride levels) and for IL-6 and fibrinogen (RR=0.70, 95% CI=0.43-1.13). High plasma IL-6 levels (4th versus 1st quartile) were associated with a 70% greater risk of IHD independent of confounding risk factors and of the other 2 inflammatory markers (RR=1.71, 95% CI=1.07-2.75). The relationship between high fibrinogen levels (4th versus 1st quartile) and IHD risk was borderline significant in multivariate analyses (RR=1.53, 95% CI=0.97-2.43). An inflammation score based on plasma IL-6 and fibrinogen levels improved the IHD risk predictive value of a multivariate model of traditional risk factors (p=0.03). Including plasma CRP levels into the inflammatory score provided no additional predictive value. In conclusion, elevated plasma IL-6 concentrations are more strongly related to IHD risk than CRP and fibrinogen. An inflammation score based on high plasma IL-6 and fibrinogen levels used in combination with traditional risk factors may improve our ability to adequately identify high risk individuals.


The natural history of unexpected Doppler mitral regurgitation.
It is common for patients to be diagnosed as having valvular regurgitation by Doppler echo when no such murmur has been heard by the referring clinician. To test the hypothesis that such patients have clinically unimportant heart disease, the authors evaluated the records of 213 consecutive men in whom mitral regurgitation had been found by pulsed Doppler. In 95 patients (group I) mitral regurgitation was audible, whereas in the other 118, it was not. In 97 patients with inaudible mitral regurgitation there were no structural mitral valve abnormalities by 2D echo. This group of 97 patients (group II) was defined as having unexpected Doppler mitral regurgitation. In group II patients there was a high prevalence of hypertension (50%), congestive heart failure (44%), alcohol abuse (46%), diabetes (27%), coronary artery disease (63%), and atrial fibrillation (13%). The following variables were distributed similarly in groups I and II: survival time, age, presence of congestive heart failure or coronary artery disease, left ventricular short-axis end diastolic and end systolic dimensions, E point septal separation, and the severity of dyssynergy. Atrial fibrillation was more common in group I (p = 0.017), and group I patients had a higher Quetelet's Index (weight/height squared) (p = 0.03). In group II, the factors most closely related to survival were the presence of dyssynergy, of atrial fibrillation, or of congestive heart failure. Although no group II patient had endocarditis or required mitral valve replacement, their survival was markedly decreased compared with people of similar age in the general population. The majority of cardiogenic deaths in group II patients were due to coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)