Race, ethnicity, and gender reporting in North American clinical trials for BCG-unresponsive non-muscle invasive bladder cancer.
The National Institutes of Health (NIH) Revitalization Act of 1993 established guidelines for the inclusion of racial/ethnic minorities and women in clinical research. However, the reporting rate of such patient demographic data in clinical trials for BCG-unresponsive non-muscle invasive bladder cancer is not well characterized. We identified published clinical trials of all phases (I -III) for BCG-unresponsive non-muscle invasive bladder cancer conducted in the US and/or Canada. We calculated the proportion of studies reporting patient gender and race/ethnicity, tabulating these data when present. We compared reported trial participant race, ethnicity and gender with the number of new bladder cancer cases and deaths using the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI) U.S. Cancer Statistics data from 2013 -2017. We identified 27 trials published from 1998 -2021 enrolling a total of 1673 patients. While all trials included data on patient gender (22% women overall), only 40.7% included any data on patient race/ethnicity. Among those that did, trial participants were reported as white (94%), Black (2.1%), Hispanic (0.6%), Asian (0.9%), and Other (2.3%). Racial/ethnic minorities were underrepresented in clinical trials relative to their proportion of new bladder cancer cases and deaths. Most clinical trials that have been conducted for BCG-unresponsive non-muscle invasive bladder cancer do not report data on patient race or ethnicity despite NIH guidelines advocating for inclusion of such data. Racial/ethnic minorities remain underrepresented in these trials relative to the burden of bladder cancer prevalence and mortality faced by these groups.


Strength imbalances and prevention of hamstring injury in professional soccer players: a prospective study.
The relationship between muscle injury and strength disorders remains a matter of controversy. Professional soccer players performed a preseason isokinetic testing aimed at determining whether (1) strength variables could be predictors of subsequent hamstring strain and (2) normalization of strength imbalances could reduce the incidence of hamstring injury. Cohort study (prognosis); Level of evidence, 1. A standardized concentric and eccentric isokinetic assessment was used to identify soccer players with strength imbalances. Subjects were classified among 4 subsets according to the imbalance management content. Recording subsequent hamstring injuries allowed us to define injury frequencies and relative risks between groups. Of 687 players isokinetically tested in preseason, a complete follow-up was obtained in 462 players, for whom 35 hamstring injuries were recorded. The rate of muscle injury was significantly increased in subjects with untreated strength imbalances in comparison with players showing no imbalance in preseason (relative risk = 4.66; 95% confidence interval: 2.01-10.8). The risk of injury remained significantly higher in players with strength imbalances who had subsequent compensating training but no final isokinetic control test than in players without imbalances (relative risk = 2.89; 95% confidence interval: 1.00-8.32). Conversely, normalizing the isokinetic parameters reduced the risk factor for injury to that observed in players without imbalances (relative risk = 1.43; 95% confidence interval: 0.44-4.71). The outcomes showed that isokinetic intervention gives rise to the preseason detection of strength imbalances, a factor that increases the risk of hamstring injury. Restoring a normal strength profile decreases the muscle injury incidence.


An alternative method for production of microalgal biodiesel using novel Bacillus lipase.
In this study, enzymatic interesterification is carried out using encapsulated lipase as biocatalyst with methyl acetate as acyl acceptor in a solvent-free system. Lipase, isolated from a marine bacterial isolate, Bacillus sp.S23 (KF220659.1) was immobilized in sodium alginate beads. This investigation elaborated on the effects of various parameters, namely enzyme loading, temperature, water, molar ratio, reaction time and agitation for interesterification. The study resulted in the following optimal conditions: 1.5 g immobilized lipase, 1:12 molar ratio of oil to methyl acetate, 35 °C, 8 % water, 60 h reaction time, 250 rpm of agitation. With the standardized condition, the maximum conversion efficiency was 95.68 %. The immobilized beads, even after ten cycles of repeated usage showed high stability in the presence of methyl acetate and no loss of lipase activity. The microalgal biodiesel composition was analyzed using gas chromatography. The current study was efficient in using immobilized lipase for the interesterification process, since the method was cost-effective and eco-friendly, no solvent was involved and the enzyme was encapsulated in a natural polymer.


Detection and characterization of antibodies to polymerized human serum albumin (AAA) by ELISA.
Immunodiffusion and passive hemoagglutination with human or sheep red blood cells for the detection of antibodies to polymerized human serum albumin (AAA) in sera of patients with various liver diseases have some deficiencies. A sensitive ELISA method for detection and characterization of AAA is described.


Is intravenous thrombolysis useful in carotid artery dissection with tandem occlusion?
Cervical artery dissection no longer represents an obstacle for performing intravenous (IV) thrombolysis. This treatment can be used safely for patients with cervical artery dissection, but tandem lesions may be related to poor outcome. We report a patient with an occlusive internal carotid artery (ICA) dissection and middle cerebral artery (MCA) embolus, with collateral circulation through the ophthalmic artery and communicating anterior artery. He underwent IV thrombolysis, with subsequent MCA recanalization and good outcome. In cases of tandem lesions in cervical artery dissection with MCA occlusion, IV thrombolysis is indicated despite the presence of ICA occlusion. Due to the presence of collateral circulation and the composition of the embolus, recanalization of MCA might be possible.


Interaction of epoprostenol (PGI2) with vasoconstrictors on diameter of large coronary arteries of the dog.
The platelet release products thromboxane A2 (TxA2) and serotonin (5-HT) might contribute to coronary vasoconstriction in humans. We have examined the effects of a TxA2-like analogue (U46619), 5-HT, and epoprostenol (PGI2) on the left anterior descending coronary artery of the dog. Changes in diameter were measured by sonomicrometry during perfusion of the vessel with blood from a support dog, at constant flow and distal resistance. Intra-arterial infusions of 5-HT (0.01-1 mumol/L) and U46619 (0.003-0.1 mumol/L) reduced external diameter of the artery (about 2.0 mm) by 0.12 mm and 0.16 mm, respectively. Intra-arterial PGI2 (0.01-0.1 mumol/L) increased the diameter of the artery (by 0.08 mm) and reduced blood pressure of the support dog (by 23 mm Hg), but did not significantly (p greater than 0.05) reduce the vasoconstrictor effects of either 5-HT (0.3 mumol/L) or U46619 (0.1 mumol/L) infused simultaneously. Indomethacin (5 mg/kg i.v.) doubled the direct dilator effect of PGI2, and increased the sensitivity of the artery to 5-HT (by 11.5-fold) and to U46619 (by 2.8-fold). After indomethacin infusion, intra-arterial PGI2 (0.1 mumol/L) reduced the constriction induced by continuous infusion of 5-HT or U46619. These data suggest that PGI2 may be of limited usefulness in preventing constriction of large coronary vessels because it causes hypotension. However, endogenous PGI2 produced by the coronary vessels or pericardium may modulate the influence of coronary vasoconstrictors, and these tissues are therefore potential targets for PGI2-releasing drugs.


Motor neuron disease in a patient with a monoclonal IgMk directed against GM1, GD1b, and high-molecular-weight neural-specific glycoproteins.
In a patient with motor neuron disease and benign IgMk monoclonal gammopathy, the M protein reacted with the glycolipids GM1, GD1b, and asialo GM1 and, by immunoblot, with some high-molecular-weight neural-specific glycoproteins. The main reactive bands had an approximate molecular weight of 250 and 400 kd, were most concentrated in the spinal cord, and were also bound by the lectin peanut agglutinin. The presence of the Ga1(beta 1-3)Ga1NAc epitope on these neural-specific glycoproteins may help to explain the selective neurological impairment of the patient.


Development of a validated LC-MS/MS method for determination of doxofylline on rat dried blood spots and urine: application to pharmacokinetics.
A rapid and highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determination of doxofylline on rat dried blood spots and urine was developed and validated. The chromatographic separation was achieved on a reverse phase C18 column (250 mm × 4.6 mm, 5 μm), using 20 mM ammonium acetate (pH adjusted to 3.5 with trifluoroacetic acid) and acetonitrile (75:25 v/v) as a mobile phase at 25 °C. LC-MS detection was performed with selective ion monitoring using target ions at m/z 267 and m/z 195 for doxofylline and caffeine used as internal standard respectively. The calibration curve showed a good linearity in the concentration range of 1-5000 ng/mL. The effect of hematocrit on extraction of doxofylline from DBS was evaluated. The mean recoveries of doxofylline from DBS and urine were 93.46 and 89.86% respectively. The intra and inter-day precisions were less than 4.28% in DBS as well as urine. The limit of detection and quantification were 0.24 and 0.84 ng/mL in DBS and 0.28 and 1.00 ng/mL in urine samples respectively. The method was validated as per ICH guidelines and successfully applied to a pharmacokinetic study of doxofylline in rats.


Immunohistochemical localization of T antigen-like substance in benign hyperplasia and adenocarcinoma of the prostate.
Peanut agglutinin was used in a lectin-anti-lectin immunoperoxidase technique to assess the status of T antigen-like substance in histological sections of benign hyperplasia and adenocarcinoma of the prostate. Of 30 benign lesions 26 (86.7 per cent) had negative staining in the glandular epithelia and 4 showed uneven staining of the epithelial cells in a small proportion of the glands. Additionally, 15 of 30 benign lesions (50 per cent) had positive staining restricted to the basal myoepithelial cells in a variable proportion of the glands. All benign lesions demonstrated the presence of normal cryptic T antigen after neuraminidase digestion. Of 25 adenocarcinomas 14 (56 per cent) were positive and 7 (25 per cent) were negative for T antigen but demonstrated the presence of normal cryptic T antigen after neuraminidase digestion, and 4 (16 per cent) were negative for T and cryptic T antigens. Of 8 grade 1, 9 grade 2 and 8 grade 3 tumors, and 9 tumors from patients with bone metastases 3 (37.5 per cent), 8 (88.9 per cent), 7 (87.5 per cent) and 7 (77.8 per cent), respectively, were positive for T antigen or negative for T and cryptic T antigens. The results show a correlation between the status of T antigen-like substance and tumor grade as well as metastasis in patients with prostatic carcinoma.


Association of the polymorphism of DR4 with the risk and severity of lumbar disc degeneration in the Chinese Han population.
Death receptor 4 (DR4), an apoptosis-associated gene, plays an important role in the pathophysiology of lumbar disc degeneration (LDD). The present study aimed to determine whether the C626G polymorphism (rs4871857) of the DR4 gene is associated with the risk and severity of LDD in the Chinese Han population. A total of 296 patients with LDD and 208 healthy controls were enrolled in this study. The grade of disc degeneration was determined according to Schneiderman's classification for MRI. The C626G polymorphism of DR4 was genotyped using polymerase chain reaction and the restriction fragment length polymorphism method. The genotype frequency of the C626G polymorphism was in agreement with the Hardy-Weinberg equilibrium (p = 0.194). The frequencies of the 626CG and GG genotypes were higher among LDD patients compared with normal controls; however, the differences were not significant. Patients with LDD showed significantly higher frequencies of the G allele than normal controls (p = 0.023). Unconditional logistic regression analysis revealed that the G allele was significantly associated with an increased risk of LDD compared with the C allele (p = 0.025; OR 1.958; 95% CI 1.087-3.526). However, no association was found between the different genotypes and the risk of LDD. In addition, the 626CG and GG genotypes, as well as the G allele were associated with higher degenerative grades of LDD compared with the CC genotype and the C allele, respectively (p = 0.005 and p < 0.001, respectively). The C626G polymorphism of DR4 may be associated with the risk and severity of LDD in the Chinese Han population.


Affective instability, childhood trauma and major affective disorders.
Affective instability (AI), childhood trauma, and mental illness are linked, but evidence in affective disorders is limited, despite both AI and childhood trauma being associated with poorer outcomes. Aims were to compare AI levels in bipolar disorder I (BPI) and II (BPII), and major depressive disorder recurrent (MDDR), and to examine the association of AI and childhood trauma within each diagnostic group. AI, measured using the Affective Lability Scale (ALS), was compared between people with DSM-IV BPI (n=923), BPII (n=363) and MDDR (n=207) accounting for confounders and current mood. Regression modelling was used to examine the association between AI and childhood traumas in each diagnostic group. ALS scores in descending order were BPII, BPI, MDDR, and differences between groups were significant (p<0.05). Within the BPI group any childhood abuse (p=0.021), childhood physical abuse (p=0.003) and the death of a close friend in childhood (p=0.002) were significantly associated with higher ALS score but no association was found between childhood trauma and AI in BPII and MDDR. The ALS is a self-report scale and is subject to retrospective recall bias. AI is an important dimension in bipolar disorder independent of current mood state. There is a strong link between childhood traumatic events and AI levels in BPI and this may be one way in which exposure and disorder are linked. Clinical interventions targeting AI in people who have suffered significant childhood trauma could potentially change the clinical course of bipolar disorder.


Overexpression of Shp-2 attenuates apoptosis in neonatal rat cardiac myocytes through the ERK pathway.
During cardiac ischemia and end-stage heart disease, a large number of cardiac cells are apoptotic, and therefore, heart function is impaired. Although the role of Shp-2 in cell survival has been reported, its regulation of cardiac apoptosis is still undetermined. To better understand the potential role of Shp-2 in apoptosis, cell death was determined in serum-depleted cardiomyocytes. Shp-2 was inhibited by NSC87877, and apoptosis, Cyt C release and caspase 3 activation were determined. To evaluate the notion that Shp-2 plays a role in survival stimulation, wild-type and gain-of-function mutant Shp-2 adenoviruses were infected into neonatal cardiomyocytes, and ERK activation was examined. Finally, the MEK inhibitor U0126 was utilized to block the ERK pathway and determine the role of Shp-2 in this pathway. We found that Shp-2 inhibition enhanced apoptosis via regulation of mitochondrial Cyt C release and activation of caspase 3. Overexpression of Shp-2 inhibited apoptosis through activation of ERK. The MEK inhibitor U0126 abolished Shp-2's effect on apoptosis in cardiomyocytes. Our results have revealed that Shp-2 functions as an intracellular inhibitor of apoptosis. These data provide insight into the pathogenesis and the therapeutic strategies of heart diseases.


Sternberg working memory performance following treatment with pramipexole in patients with moderate-to-severe restless legs syndrome.
We recently reported that the P300 amplitude related to the Sternberg working memory (WM) task was significantly lower in drug-naïve severe restless legs syndrome (RLS) patients than controls. Here, we evaluated the effects of pramipexole on the Sternberg WM task performance by event-related potential (ERP) study. Thirteen drug-naïve RLS patients (52.0 ± 9.48 years) were enrolled in the study. Pramipexole was administered over a period of 12 weeks every night 1 h before bedtime. Two ERP studies were carried out: the first was performed just before giving the first dose of pramipexole and the second was conducted at 12-16 weeks after commencement of pramipexole administration. P300 amplitudes and reaction times were compared before and after treatment considering brain regions and memory load as within-subject factors. Clinical and sleep-related variables were correlated with P300 amplitude. After treatment with pramipexole, the International RLS Severity Scale (IRLS) score was significantly decreased. Sleep quality and depression were also significantly improved. Omission error was significantly reduced without significant change of commission error. Reaction time was significantly shortened, regardless of memory load size, following treatment with pramipexole. Parietal P300 amplitude was significantly increased after treatment with pramipexole for all memory load sizes. Increase of frontal P300 amplitude was significantly correlated with improvement of sleep duration, IRLS, Insomnia Severity Index, and Pittsburgh Sleep Quality Index score. Our study suggested that pramipexole improves WM performance in patients with RLS in addition to improving RLS symptoms, sleep disturbance, and depression.


The effect of repeated withdrawal episodes on subsequent withdrawal severity in ethanol-treated rats.
Male rats were given ethanol via an intragastric catheter (8.0-11.0 g/kg per day) for either 8 weeks daily or for four 2-week periods with a 2-week period of no drug treatment intervening between each period of ethanol administration (binge). Older rats were administered ethanol for 2 weeks, to assess the effects of age on ethanol withdrawal as age can alter an animal's sensitivity to ethanol. The presence of physical dependence during withdrawal was assessed on an open field test. Rats that experienced repeated episodes of withdrawal (binge) showed more severe withdrawal signs in successive withdrawal episodes. Older animals showed more severe signs of withdrawal than younger animals after 2 weeks of ethanol treatment. The results of this study lend support to the hypothesis that the experience of withdrawal from ethanol can alter an animal's subsequent response to the drug. Aging appeared to contribute to this effect, but further work is needed to delineate its role.


Protein design: novel metal-binding sites.
In natural proteins, metal ions play a variety of roles, including nucleophilic catalysis, electron transfer and the stabilization of protein structure. The de novo design of metal-binding sites is therefore an attractive means by which to impart proteins with novel properties and activities.


Importance of confirming HER2 overexpression of recurrence lesion in breast cancer patients.
The systemic management of metastatic breast cancer (MBC) is usually based on ER or HER2 status of the primary tumor. However, the hormonal status or the overexpression of human epidermal growth factor 2 (HER2) may change in every metastatic site because of the effects of the long-term treatment of metastatic cancer with endocrine therapy, chemotherapy, or biological agents. The purpose of this study was to investigate the frequency of change in HER2 expression in primary and distant metastatic tumors in breast cancer patients. Another objective of the study was to examine the effect of the clinical therapy on the basis of HER2 expression in a metastatic tumor. In our hospital between 1991 to December 2010, retrospectively, 156 patients had biopsy or surgical resection of their metastatic site. All sample were analyzed pathologically to confirm metastatic disease and, second, to evaluate HER2 status by immunohistochemistry or by FISH. The recurrence lesions were resected from the breast or lymph node (n = 67, local lesion), brain (n = 27), lung (n = 16), liver (n = 20), bone (n = 16), and from the stomach, intestine, ovary, and uterus (n = 10). Loss, increase, or no change in HER2 overexpression was observed in 3, 5, and 92%, respectively. Positive changes of HER2 in metastatic sites were 3 (4%) local lesion, 3 (11%) brain, 1 (7%) lung, 0 (0%) liver, 2 (17%) bone, and 0 (0%) others. In 3 of these 8 patients, trastuzumab was administered. In 2 of 3 patients, trastuzumab achieved long stable disease. The negative conversion rate of HER2 expression in metastatic lesions was 37% in patients treated with trastuzumab and 6% in those not treated with trastuzumab, a significant difference between the two groups (P < 0.05). The results of this study emphasize the significance of confirming HER2 expression in a recurrence lesion. For patients with positive conversion of HER2 status, more treatment options may be available. On the other hand, the rate of loss of HER2 expression was high in patients treated with trastuzumab, suggesting that the results of biopsy may provide an opportunity to reconsider treatment strategies for these patients.


Distribution characteristics and policy-related improvements of PM2.5 and its components in six Chinese cities.
This study presents the distribution characteristics and possible sources of fine particulate matter (PM2.5) and its components, as well as policy-related pollution reduction in the Chinese cities of Jinan, Shijiazhuang (SJZ), Chengdu, Wuxi, Wuhan, and Harbin (HRB). PM2.5 samples were collected using mid-volume samplers during the autumn of 2017 in all six cities. The samples were analyzed to determine the ambient PM2.5 compositions, including the concentrations of water-soluble inorganic ions (WSIIs), carbonaceous aerosols, and elements concentrations. The chemical ratios of organic carbon to elemental carbon and nitrate to sulfate as well as the enrichment factors of elements were calculated to establish the possible sources of PM2.5 in all six cities. The highest PM2.5 concentration was 152 μg/m3 in SJZ, while the lowest concentration was 47 μg/m3 in HRB. During the sampling period in these six cities, the PM2.5 concentrations exceeded the World Health Organization recommended daily average air quality guidelines by 2.4-6.1 times, and WSIIs, carbonaceous aerosols, and elements accounted for 31.8%-61.6%, 9.8%-35.1%, and 0.9%-2.5% of the PM2.5, respectively. In 2013, the Chinese government formulated the Air Pollution Prevention and Control Action Plan (APPCAP) for controlling air pollution, and effective measures have been implemented since then. Compared with previous studies conducted during 2009-2013 before the implementation of the APPCAP, the concentrations of PM2.5 and most of its components decreased to varying degrees, and large changes in the chemical ratios of PM2.5 components were observed. These results indicate that PM2.5 sources vary among these six cities and that China has improved the ambient air quality in these cities through the implementation of air pollution control policies. The APPCAP have achieved considerable results in continuously reducing pollution concentrations, although the air pollution concentrations observed in this study remain high compared with those of other countries.


[Antimutagenic effect of Eleutherococcus extracts on plants treated with ethylmethane sulfonate].
It is established that Eleutherococcus extracts used in weak concentrations decrease the frequency of chromosome mutations induced by ethylmethanesulphonate in onion and barley. As a result the survival rate of plants under conditions of the field experiment increases. It is shown that the fixation of chromosome mutations takes place in the dividing cells of onion roots in the first four hours after treatment with the mutagen. One of the possible mechanisms of defensive Eleutherococcus action (low concentrations) and of mutagenic one (high concentrations) is discussed.


Aggregate Roundness Classification Using a Wire Mesh Method.
Herein, we suggest a wire mesh method to classify the particle shape of large amounts of aggregate. This method is controlled by the tilting angle and opening size of the wire mesh. The more rounded the aggregate particles, the more they roll on the tilted wire mesh. Three different sizes of aggregate: 11-15, 17-32, and 33-51 mm were used for assessing their roundness after classification using the sphericity index into rounded, sub-rounded/sub-angular, and angular. The aggregate particles with different sphericities were colored differently and then used for classification via the wire mesh method. The opening sizes of the wire mesh were 6, 11, and 17 mm and its frame was 0.5 m wide and 1.8 m long. The ratio of aggregate size to mesh-opening size was between 0.6 and 8.5. The wire mesh was inclined at various angles of 10°, 15°, 20°, 25°, and 30° to evaluate the rolling degree of the aggregates. The aggregates were rolled and remained on the wire mesh between 0.0-0.6, 0.6-1.2, and 1.2-1.8 m depending on their sphericity. A tilting angle of 25° was the most suitable angle for classifying aggregate size ranging from 11-15 mm, while the most suitable angle for aggregate sizes of 17-32 and 33-51 mm was 20°. The best ratio for the average aggregate size to mesh-opening size for aggregate roundness classification was 2.


Role of Cardiovascular Magnetic Resonance in Ischemic Cardiomyopathy.
Ischemic heart disease is the most common cause of cardiovascular morbidity and mortality. Cardiac magnetic resonance (CMR) improves on other noninvasive modalities in detection, assessment, and prognostication of ischemic heart disease. The incorporation of CMR in clinical trials allows for smaller patient samples without the sacrifice of power needed to demonstrate clinical efficacy. CMR can accurately quantify infarct acuity, size, and complications; guide therapy; and prognosticate recovery. Timing of revascularization remains the holy grail of ischemic heart disease, and viability assessment using CMR may be the missing link needed to help reduce morbidity and mortality associated with the disease.


Sustained low-grade inflammation in young participants with childhood onset type 1 diabetes: The Norwegian atherosclerosis and childhood diabetes (ACD) study.
Persons with type 1 diabetes (T1D) have increased mortality from cardiovascular disease. Early inflammation is important in the development of atherosclerosis. We aimed to evaluate the extent of inflammation and difference in mean over a five-year period in young persons with T1D compared to healthy controls. The Norwegian Atherosclerosis and Childhood Diabetes (ACD) study is a prospective population-based cohort study on atherosclerosis development in childhood-onset T1D compared to healthy controls, with follow-ups every fifth year. The original study cohort consisted of 314 children with T1D on intensive insulin treatment and 120 healthy controls of similar age. Circulating levels of VCAM-1, TNA-α, P-selectin, E-selectin, CRP, IL-6, IL-18, MCP-1, MMP-9 and TIMP-1 were measured by ELISAs at baseline and at the five-year follow-up. The group with T1D had mean age 13.7 (SD = 2.8) years, disease duration 5.6 (SD = 3.4) years and HbA1c 68 (SD = 13.1) mmol/mol at baseline. Levels of almost all inflammatory markers were significantly increased in the group with T1D compared to controls, and significant mean-difference between the two groups over the five-year period was observed in four markers: IL-18, P-selectin, E-selectin and TIMP-1. The early low-grade inflammation present in young individuals with T1D five years after diagnosis is sustained at ten-year disease duration, with moderate changes for most markers of inflammation over time. The evolving inflammatory profile indicates an accelerated chain of events in the progression of early atheromatosis in T1D.


Context matters: the structure of task goals affects accuracy in multiple-target visual search.
Career visual searchers such as radiologists and airport security screeners strive to conduct accurate visual searches, but despite extensive training, errors still occur. A key difference between searches in radiology and airport security is the structure of the search task: Radiologists typically scan a certain number of medical images (fixed objective), and airport security screeners typically search X-rays for a specified time period (fixed duration). Might these structural differences affect accuracy? We compared performance on a search task administered either under constraints that approximated radiology or airport security. Some displays contained more than one target because the presence of multiple targets is an established source of errors for career searchers, and accuracy for additional targets tends to be especially sensitive to contextual conditions. Results indicate that participants searching within the fixed objective framework produced more multiple-target search errors; thus, adopting a fixed duration framework could improve accuracy for career searchers.


Type D personality and metabolic syndrome among Finnish female municipal workers.
Type D personality is a combination of high negative affectivity (NA) and high social inhibition (SI). This personality trait is suspected to impair cardiovascular patients' recovery. The 2016 European Guidelines on cardiovascular disease prevention in clinical practice recommend screening of psychosocial risk factors as Type D personality. The aim of this study was to assess the relationship between Type D personality and Metabolic syndrome (MetS) in working-age female population. Six hundred thirty-four female employees with mean age of 48 ± 10 years were evaluated. Type D personality and its components (NA) and (SI) were screened with DS14 questionnaire. The definition of MetS was based on measurements done by trained medical staff. We investigated the relationship between Mets and Type D personality, NA and SI using the logistic regression models adjusting for age, education years, leisure-time physical activity, smoking, alcohol use and depressive symptoms. The prevalence of Type D personality was 10.6% (n = 67) [95% CI: 8.3 to 13.2] and MetS 34.7% (n = 220). Type D personality or its subcomponents were not associated with MetS. Women with Type D personality had significantly worse quality of sleep and lower LTPA. They were also more often unsatisfied with their economic situation, they had more often depressive symptoms and psychiatric disorders than non-D type persons. There were no differences in risk factors for cardiovascular diseases. Screening for Type D personality among working- age, reasonably healthy female population seems not to be practical method for finding persons with risk for cardiovascular disease.


Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer.
To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed. Median follow-up was 8.0 years (0.9-12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ≥4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up. Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.


[Differential sonographic and computer tomographic diagnosis of angiomyolipoma].
3 angiomyolipomas were found in 8,500 CT examinations of the abdomen. The diagnosis was established preoperatively by both computed tomography and sonography. The densitometrically negative density values that are considered to be principal signs in computed tomography, must however be refuted by us. In all cases under investigation we found density values above 40 HU.


Formation of disinfection byproducts during chlorination of mixed nitrogenous compounds in swimming pools.
Disinfection byproducts (DBPs) in swimming pool waters are receiving increasing attention because of their toxicity and widespread occurrence. Current studies rarely investigate the formation of DBPs from typical precursors in swimming pools under mixed exposure. They also rarely investigate the formation of carbonaceous DBPs (C-DBPs) and nitrogenous DBPs (N-DBPs) simultaneously. In this study, the formation of C-DBPs and N-DBPs were investigated during chlorination of mixed precursors (i.e., tryptophan, urea, creatinine, and ammonia). The effects of precursors and operation parameters were also investigated. Among the four precursors, tryptophan had the highest DBP formation potential. Urea and ammonia restrained the formation of C-DBPs but promoted the formation of more toxic N-DBPs. C-DBP yields were significantly higher than N-DBP yields under all experimental conditions. Longer reaction time and higher chlorine dosage promoted the formation of C-DBPs, while higher temperature decreased the concentration of N-DBPs. The presence of bromide not only improved the sum yields of DBPs, but also shifted chlorinated DBPs to brominated species.


Antiproliferative effect of calcitriol on human prostatic cancer cell lines: unrelated to the expression of major histocompatibility complex antigens or intercellular adhesion molecule-1 (ICAM-1).
In addition to its role in calcium and phosphorus metabolism, calcitriol (1,25-dihydroxyvitamin D3; 1,25-D3) demonstrates multiple effects on cell proliferation/differentiation by expressing major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1). It has recently been reported that 1,25-D3 inhibits the growth of prostatic cancer (PCa) cells. In this study we examined the effect of 1,25-D3 on both the growth and expression of HLA-ABC, HLA-DR and ICAM-1 antigens in PCa cells. Four human PCa cell lines (PC-3, PPC-1, ALVA-41 and ALVA-101) were examined. The cell numbers were enumerated, and the effects of interferon-y (IFN-gamma) and 1,25-D3 on the expression of HLA-ABC, HLA-DR and ICAM-1 were quantitated by flow cytometry. A dose-dependent antiproliferative effect of 1,25-D3 was found in all PCa cells lines except ALVA-41.1,25-D3 was approximately 10 times as potent as its analogue 24,25-dihydroxyvitamin D3 in inhibiting the growth of PC-3 cells. Also, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-D3 receptor, indicating that the antiproliferative effect may require a receptor-ligand interaction. HLA-ABC was expressed in PC-3, ALVA-41 and ALVA-101, but not in PPC-1 cells, while HLA-DR was not expressed on any of the tested cells. IFN-gammacould enhance or induce HLA-ABC but not HLA-DR expression in the tested cells. ICAM-1 was expressed in all cells and slightly upregulated by IFN-gamma. In this study 1,25-D3 had an antiproliferative effect on 3 of the 4 examined PCa cell lines.


Chemotherapy reduces PARP1 in cancers of the ovary: implications for future clinical trials involving PARP inhibitors.
PARP inhibitors have shown promising clinical results in cancer patients carrying BRCA1/2 mutations. Their clinical efficacy could logically be influenced by PARP1 protein levels in patient tumors. We screened three cohorts of patients with ovarian cancer, totaling 313 samples, and evaluated PARP1 protein expression by immunohistochemistry with further validation by western blotting. We observed that up to 60 % of tumors showed little PARP1 protein expression. In serous ovarian tumors, comparing intratumoral PARP1 expression between chemo-naïve and post-chemotherapy patients revealed a decrease in intratumoral PARP1 following chemotherapy in all three cohorts (immunohistochemistry: p < 0.001, n = 239; western blot: p = 0.012, n = 74). The findings were further confirmed in a selection of matched samples from the same patients before and after chemotherapy. Our data suggest that patients should be screened for PARP1 expression prior to therapy with PARP inhibitors. Further, the observed reduction of intratumoral PARP1 post-chemotherapy suggests that treating chemo-naïve patients with PARP inhibitors prior to the administration of chemotherapy, or concurrently, might increase the responsiveness to PARP1 inhibition. Thus, a change in the timing of PARP inhibitor administration may be warranted for future clinical trials.


Amelioration of age-related neurochemical and behavioral deficits by 3,4-diaminopyridine.
Alterations of the cholinergic system may be responsible for age-related changes in behavior. The in vitro calcium dependent release of acetylcholine and tight rope test performance decline in parallel during senescence. 3,4-Diaminopyridine, which enhances calcium influx by nerve terminals, diminishes these age-related alterations. In aged mice (30 month old), 3,4-diaminopyridine increases the calcium dependent release of acetylcholine (260%) and improves tight rope test performance (428%). These results support the hypothesis that alterations in calcium homeostasis underlie some of the cholinergic and behavioral deficits that accompany senescence.


Development of SSR markers and construction of a linkage map in jute.
Jute is an important natural fibre crop, which is only second to cotton in its importance at the global level. It is mostly grown in Indian subcontinent and has been recently used for the development of genomics resources.We recently initiated a programme to develop simple sequence repeat markers and reported a set of 2469 SSR that were developed using four SSR-enriched libraries (Mir et al. 2009). In this communication, we report an additional set of 607 novel SSR in 393 SSR containing sequences. However, primers could be designed for only 417 potentially useful SSR. Polymorphism survey was carried out for 374 primer pairs using two parental genotypes (JRO 524 and PPO4) of a mapping population developed for fibre fineness; only 66 SSR were polymorphic. Owing to a low level of polymorphism between the parental genotypes and a high degree of segregation distortion in recombinant inbred lines, genotypic data of only 53 polymorphic SSR on the mapping population consisting of 120 RIL could be used for the construction of a linkage map; 36 SSR loci were mapped on six linkage groups that covered a total genetic distance of 784.3 cM. Hopefully, this map will be enriched with more SSR loci in future and will prove useful for identification of quantitative trait loci/genes for molecular breeding involving improvement of fibre fineness and other related traits in jute.


Increased thrombogenicity is associated with revascularization outcomes in patients with chronic limb-threatening ischemia.
Clinically driven target lesion revascularization (CD-TLR) frequently occurs after endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). The total thrombus-formation analysis system (T-TAS) can quantitatively evaluate thrombogenicity. Therefore, we aimed to elucidate the association of the T-TAS parameters with CD-TLR. We analyzed 34 patients with CLTI and 62 patients without CLTI who had undergone EVT. Blood samples collected on the day of EVT were used in the T-TAS to compute the thrombus formation area under the curve for the first 10 minutes for the platelet chip tested at a flow rate of 24 μL/min (PL24-AUC10) and area under the curve for the first 30 minutes for the atheroma chip tested at a flow rate of 10 μL/min (AR10-AUC30). After EVT, clinical follow-up was performed, and the presence of CD-TLR was assessed. During the follow-up period (median, 574 days), 10 patients (29%) in the CLTI group and 11 (18%) in the non-CLTI group had required CD-TLR. In the CLTI group, the patients with CD-TLR had had a higher AR10-AUC30 vs those without (median, 1694 [interquartile range, 1657-1799] vs median, 1561 [interquartile range, 1412-1697]; P = .01). In contrast, the PL24-AUC10 showed no significant differences when stratified by CD-TLR in either group. For the CLTI patients, multivariable Cox regression analysis using propensity score matching revealed that the AR10-AUC30 was an independent predictor of CD-TLR even after adjusting for baseline demographics, lesion characteristics, and anticoagulant use (hazard ratio, 2.04; 95% confidence interval, 1.18-3.88; P = .01; per 100-unit increase). In contrast, for those without CLTI, neither the AR10-AUC30 nor the PL24-AUC10 was significantly associated with CD-TLR. Receiver operating characteristics curve analysis identified an AR10-AUC30 level of 1646 as an optimal cutoff value to predict for CD-TLR (AUC, 0.85; sensitivity, 0.93; specificity, 0.56). For patients with CLTI, but not for those without CLTI, the AR10-AUC30 showed potential to predict for CD-TLR. This finding suggests that hypercoagulability might play a predominant role in the progression of CLTI and that anticoagulant therapy might be useful in preventing revascularization.


23,25-Dihydroxyvitamin D3 is liberated as a major vitamin D3 metabolite in human urine after treatment with β-glucuronidase: Quantitative comparison with 24,25-dihydroxyvitamin D3 by LC/MS/MS.
The complete understanding of the excretion of surplus 25-hydroxyvitamin D3 [25(OH)D3] in humans remains to be accomplished. In our previous study, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] 24-glucuronide was identified as a major urinary vitamin D3 metabolite, while the glucuronide of 23,25-dihydroxyvitamin D3 [23,25(OH)2D3] is another metabolite of interest but has not been sufficiently evaluated. Although the quantitative analysis of 24,25(OH)2D3 liberated in urine by the treatment with β-glucuronidase (GUS) has been conducted, no information was provided about the amount of the glucuronidated 23,25(OH)2D3 in the urine. In this study, we first developed and validated a liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS)-based method for the simultaneous quantification of 23,25(OH)2D3 and 24,25(OH)2D3 liberated in urine by GUS. The analysis of the urine samples revealed that the amount of 23,25(OH)2D3 was almost as much as that of 24,25(OH)2D3, in contrast to the fact that the plasma concentration of 23,25(OH)2D3 was much lower than that of 24,25(OH)2D3. These results strongly suggested that 23,25(OH)2D3 is more susceptible to glucuronidation and more promptly excreted into urine than 24,25(OH)2D3. Furthermore, the amount ratios of 23,25(OH)2D3 to 24,25(OH)2D3 in the urine samples did not markedly vary during the day (morning/evening) and even by a week-long vitamin D3 supplementation (1000 IU/body/day). We concluded that the C-23 hydroxylation plays a crucial role in the urinary excretion of surplus 25(OH)D3.


Mechanical Dentistry: George Derby, An Unknown Artist, and Rube Goldberg.
For more than a century, at least, tooth extraction by ingenious mechanical contraptions has piqued the interest and imagination of illustrators, especially cartoonists. George Derby, an unknown British talent, and Ruben Garrett Lucius "Rube" Goldberg all dabbled in oral surgical mechanical humor.


Draft Genome Sequences of Dickeya sp. Isolates B16 (NIB Z 2098) and S1 (NIB Z 2099) Causing Soft Rot of Phalaenopsis Orchids.
The genus Dickeya contains bacteria causing soft rot of economically important crops and ornamental plants. Here, we report the draft genome sequences of two Dickeya sp. isolates from rotted leaves of Phalaenopsis orchids.


The use of hydrous iron (III) oxides for the removal of hydrogen sulphide in aqueous systems.
The potential for iron (hydr)oxides to remove dissolved hydrogen sulphide from seawater has been examined under flow-through conditions. Ferrihydrite (a hydrous iron (III) oxide) was stabilised by precipitation onto zeolite pellets, and rates of sulphide removal were determined under laboratory conditions at pH 8.5. Sulphide removal kinetics were dependent on the initial sulphide concentration, substrate mass and flow rate. The experimental data suggest that these parameters can be optimised to result in the rapid and effective removal of hydrogen sulphide. The results from laboratory experiments compared favourably with sulphide removal kinetics determined in a series of experiments performed online in a recirculating mariculture production system. However, the presence in solution of ligands such as phosphate may also significantly affect reaction rates; a 50% reduction in sulphide removal rate for substrate removed from an online system was partly attributed to phosphate adsorption. The formation of a more crystalline, less reactive iron (hydr)oxide in recharged substrate was the likely result of FeS oxidation, which may also have contributed to the observed reduction in sulphide removal rates. Ferrihydrite-coated zeolite would appear to provide an efficient, low-cost method for sulphide removal, which is particularly suited to relatively small-scale aqueous flow-through systems. The reaction of iron (hydr)oxides with dissolved sulphide is also accompanied by a distinct colour change due to the formation of black FeS(s) which, under appropriate conditions, may be used as a rapid indicator of sulphidic conditions.


Burkitt's lymphoma: a pericardial presentation.
Described herein is a case of childhood Burkitt's lymphoma initially presenting as a pericardial effusion. A cytological diagnosis was made from a Wright's-Giemsa stained cytospin preparation. Supporting diagnostic evidence was provided by immunological surface marker analysis and electron microscopy. To our knowledge, Burkitt's lymphoma has not hitherto been diagnosed initially from the morphology of cells in pericardial fluid.


Abiotic fate of tolylfluanid and dichlofluanid in natural waters.
To prevent the growth of unwanted organisms on ship hulls, antifouling paints, containing biocides such as tolylfluanid (N-[dichlor(fluor)methyl]sulfanyl-N-(dimethylsulfamoyl)-4-methylaniline) and dichlofluanid (N-(dichlorfluormethylthio)-N',N'-dimethyl-N-phenylsulfamid), are applied. There are concerns over their occurrence and fate in the marine environment due to long-term immersion in water. In the present study, the hydrolysis and photolysis of these compounds were investigated. Results showed that tolylfluanid and dichlofluanid hydrolyzed completely to their respective hydrolysis products DMST (N,N-dimethyl-N'-p-tolylsulfamide) and DMSA (N,N-dimethyl-N'-phenylsulfamide) in coastal water within 24 h. Furthermore, the transformation of tolylfluanid and dichlofluanid under natural sunlight was determined in selected marine waters (coastal water and sea water) in comparison to deionized water. The experiments revealed that photodegradation rates of DMST and DMSA in coastal water were higher than in sea water or deionized water. The indirect phototransformation of the hydrolysis products with selected reactive species (triplet state organic matter, singlet oxygen, and hydroxyl radicals) showed that DMST and DMSA mainly display triplet reactivity. The measured half-lives of the hydrolysis products in natural waters were 2.7 and 23 days, with DMST being considerably faster transformed than DMSA. However, several direct and indirect photoproducts have been newly identified and measured. DMS (N,N-dimethylsulfamide), was identified as the major phototransformation product in natural waters. It is generated by indirect photodegradation processes and exhibits potential persistence in the environment.


Fatty acid transport through the blood-brain barrier.
Across the cerebral capillaries, the anatomical locus of the blood-brain barrier, the unidirectional influxes of the saturated fatty acids, octanoic and myristic acids, and the unsaturated essential fatty acid, linoleic acid, were measured. Employing an in situ rat brain perfusion technique that allows control of perfusate composition and accurate measurement of perfusate-to-brain fatty acid transport, we found that both [14C]octanoic and [14C]myristic acids were transported through the blood-brain barrier in vivo, in large part, by a specific, probenecid-sensitive transport system. However, the transport of [14C]linoleic acid was not probenecid sensitive. With 0.5 microM fatty acid but no plasma proteins in the perfusate, the permeability-surface area constant was higher for myristic acid (4.8 X 10(-2) X s-1) than for octanoic and linoleic acids (1.5 and 1.2 X 10(-2) X s-1, respectively). Approximately 70, 30, and 25% of the [14C]myristic, [14C]octanoic, or [14C]linoleic acids, respectively, were extracted from the perfusate.


Decision tree classifier based on topological characteristics of subgraph for the mining of protein complexes from large scale PPI networks.
The growing accessibility of large-scale protein interaction data demands extensive research to understand cell organization and its functioning at the network level. Bioinformatics and data mining researchers have extensively studied network clustering to examine the structural and operational features of protein protein interaction (PPI) networks. Clustering PPI networks has proven useful in numerous research over the past two decades for identifying functional modules, understanding the roles of previously unknown proteins, and other purposes. Protein complexes represent one of the essential cellular components for creating biological activities. Inferring protein complexes has been made more accessible by experimental approaches. We offer a novel method that integrates the classification model with local topological data, making it more reliable and efficient. This article describes a decision tree classifier based on topological characteristics of the subgraph for mining protein complexes. The proposed graph-based algorithm is an effective and efficient way to identify protein complexes from large-scale PPI networks. The performance of the proposed algorithm is observed in protein-protein interaction networks of yeast and human in the Database of Interacting Proteins (DIP) and the Biological General Repository for Interaction Datasets (BioGRID) using widely accepted benchmark protein complexes from the comprehensive resource of mammalian protein complexes (CORUM) and the comprehensive catalogue of yeast protein complexes (CYC2008). The outcomes demonstrate that our method can outperform the best-performing supervised, semi-supervised, and unsupervised approaches to detecting protein complexes.


Effect of the microenvironment on the efficiency of singlet oxygen (O2(1 delta g)) production by photosensitizing anti-inflammatory drugs.
The influence of the medium on the quantum yields of singlet oxygen (O2(1 delta g)) production (phi delta) by a series of photosensitizing non-steroidal anti-inflammatory drugs (NSAID) derived from 2-arylpropionic acid (APA) has been investigated. Four-component oil-in-water and water-in-oil microemulsions, based on anionic and cationic surfactants, have been employed as the simplest models to mimic more complex biological environments. phi delta values have been determined by monitoring the singlet oxygen (1O2) luminescence at 1270 nm upon continuous excitation of the drugs under air-equilibrated conditions. Results indicate that phi delta values are highly affected by the medium, being higher in microheterogeneous systems than in (homogeneous) solution. Some of the anti-inflammatory derivatives are very efficient 1O2 sensitizers: e.g., values of apparent phi delta as high as 0.86 (+/- 0.04) and 0.70 (+/- 0.03) have been found for tiaprofenic acid and suprofen, respectively. The location of the drugs in the interfacial region of the microemulsions combined with their high phi delta values suggest that type II reactions may play a significant role in the overall photodynamic process in more complex organized media, such as biological membranes.


'It is easy to find yourself working outside your comfort zone when working with autistic children'.
Wendy Bellis is Assistant Clinical Director and Specialist Paediatric Senior Dental Officer for Camden and Islington Community Dental Service (Whittington Health). She is considered a world renowned voice on autism and paediatric dentistry, and news editor David Westgarth sat down with her to discuss some of the challenges presented by autistic patients.


Inhibition of histone deacetylase activity by valproic acid blocks adipogenesis.
Adipogenesis is dependent on the sequential activation of transcription factors including the CCAAT/enhancer-binding proteins (C/EBP), peroxisome proliferator-activated receptor gamma (PPARgamma), and steroid regulatory element-binding protein (SREBP). We show that the mood stabilizing drug valproic acid (VPA; 0.5-2 mm) inhibits mouse 3T3 L1 and human preadipocyte differentiation, likely through its histone deacetylase (HDAC) inhibitory properties. The HDAC inhibitor trichostatin A (TSA) also inhibited adipogenesis, whereas the VPA analog valpromide, which does not possess HDAC inhibitory effects, did not prevent adipogenesis. Acute or chronic VPA treatment inhibited differentiation yet did not affect mitotic clonal expansion. VPA (1 mm) inhibited PPARgamma induced differentiation but does not activate a PPARgamma reporter gene, suggesting that it is not a PPARgamma ligand. VPA or TSA treatment reduced mRNA and protein levels of PPARgamma and SREBP1a. TSA reduced C/EBPalpha mRNA and protein levels, whereas VPA only produced a decrease in C/EBPalpha protein expression. Overall our results highlight a role for HDAC activity in adipogenesis that can be blocked by treatment with VPA.


Draft Genome Sequence of Truncatella angustata (Anamorph) S358.
The ascomycete Truncatella angustata has a worldwide distribution. Commonly, it is associated with plants as an endophyte, pathogen, or saprotroph. The genome assembly comprises 44.9 Mbp, a G+C content of 49.2%, and 12,353 predicted genes, among them 12 unspecific peroxygenases (EC 220.127.116.11).


A case of interface keratitis following anterior lamellar keratoplasty.
Anterior lamellar keratoplasty (ALK) is indicated in patients with anterior corneal opacities. Benefits over penetrating keratoplasty include quicker visual rehabilitation, less postoperative astigmatism, and preservation of the host endothelium, thus minimizing the chances of graft rejection. A rare complication of lamellar corneal surgery is infectious interface keratitis between the donor and host tissue. We report a case of infectious interface keratitis following automated ALK successfully treated medically and by removal of the ALK disk, eventually having a deep anterior lamellar keratoplasty with good visual recovery.


What is the best way to keep the patient warm during technical rescue? Results from two prospective randomised controlled studies with healthy volunteers.
Accidental hypothermia is a manifest problem during the rescue of entrapped victims and results in different subsequent problems as coagulopathy and wound infection. Different warming methods are available for the preclinicial use. However, their effectiveness has hardly been evaluated. In a first step a survey among German fire brigades was performed with questions about the most used warming methods. In a second step two crossover studies were conducted. In each study two different warming method were compared with forced air warming - which is the most frequently used and highly effective warming method in operation rooms (Study A: halogen floodlight vs. forced air warming; Study B: forced air warming vs. fleece blanket). In both studies healthy volunteers (Study A: 30 volunteers, Study B: 32 volunteers) were sitting 60 min in a cold store. In the first 21 min there was no subject warming. Afterwards the different warming methods were initiated. Every 3 min parameters like skin temperature, core body temperature and cold perception on a 10-point numeric rating scale were recorded. Linear mixed models were fitted for each parameter to check for differences in temperature trajectories and cold perception with regard to the different warming methods. One hundred fifty-one German fire brigades responded to the survey. The most frequently used warming methods were different rescue blankets (gold/silver, wool) and work light (halogen floodlights). Both studies (A and B) showed significantly (p < 0.05) higher values in mean skin temperature, mean body temperature and total body heat for the forced air warming methods compared to halogen floodlight respectively fleece blanket shortly after warming initiation. In contrast, values for the cold perception were significantly lower (less unpleasant cold perception) during the phase the forced air warming methods were used, compared to the fleece blanket or the halogen floodlight was used. Forced air warming methods used under the standardised experimental setting are an effective method to keep patients warm during technical rescue. Halogen floodlight has an insufficient effect on the patient's heat preservation. In healthy subjects, fleece blankets will stop heat loss but will not correct heat that has already been lost. The studies were registered retrospectively on 14/02/2022 on the German Clinical Trials registry (DRKS) with the number DRKS00028079.


Temperature evolution of Trp-cage folding pathways: An analysis by dividing the probability flux field into stream tubes.
Owing to its small size and very fast folding rate, the Trp-cage miniprotein has become a benchmark system to study protein folding. Two folding pathways were found to be characteristic of this protein: pathway I, in which the hydrophobic collapse precedes the formation of α-helix, and pathway II, in which the events occur in the reverse order. At the same time, the relative contribution of these pathways at different temperatures as well as the nature of transition from one pathway to the other remain unclear. To gain insight into this issue, we employ a recently proposed hydrodynamic description of protein folding, in which the process of folding is considered as a motion of a "folding fluid" (Chekmarev et al., Phys. Rev. Lett. 100(1), 018107 2008). Using molecular dynamics simulations, we determine the field of probability fluxes of transitions in a space of collective variables and divide it into stream tubes. Each tube contains a definite fraction of the total folding flow and can be associated with a certain pathway. Specifically, three temperatures were considered, T = 285K, T = 315K, and T = 325K. We have found that as the temperature increases, the contribution of pathway I, which is approximately 90% of the total folding flow at T = 285K, decreases to approximately 10% at T = 325K, i.e., pathway II becomes dominant. At T = 315K, both pathways contribute approximately equally. All these temperatures are found below the calculated melting point, which suggests that the Trp-cage folding mechanism is determined by kinetic factors rather than thermodynamics.


The role of HLA-DR antigens in PPD-stimulated lymphocyte-monocyte interactions.
Autologous monocytes are required for an optimal lymphocyte proliferative response to purified protein derivate of tuberculin (PPD) in vitro and for a mixed lymphocyte culture induced by alloantigens. In the proliferative response to PPD we found that autologous monocytes could be replaced with HLA-DR-compatible monocytes and partly with HLA-DR semi-identical. In spite of a statistically significant difference between autologous and HLA-DR disparate monocytes in their cooperative capacity with PPD-stimulated lymphocytes, replacement in nearly one third of the cases was possible. These findings were supported by more detailed studies in which increasing numbers of allogenic and autologous monocytes were added to the isolated lymphocytes in the presence of PPD. It is concluded that the serologically defined HLA-DR antigens alone give insufficient information of the restriction elements controlling the PPD-stimulated lymphocyte-monocyte interactions.


Impact of clinical pharmacist's interventions on pharmacotherapy management in elderly patients on polypharmacy with mental health problems including quality of life: A prospective non-randomized study.
Mental health problems (MHPs) are very common in the elderly and can have an important influence on their quality of life (QoL). There is almost no data on the impact of clinical pharmacists' (CPs) interventions on the QoL including elderly patients and MHPs. The main aim of this study was to determinate the impact of (CP's) interventions on the QoL and quality of pharmacotherapy. A prospective non-randomized pre-post study was designed which included residents of a nursing home aged 65 age or more with at least one MHP. Each patient also filled out the EQ-5D questionnaire. The medical review MR included drug-related problems (DRPs) and potentially drug-drug interactions (pDDIs), as well as potentially inappropriate medications (PIMs). After 2 months, the participants were interviewed again. The mean number of medications before the intervention was 12,2 ± 3,1 per patient and decreased to 10,3 ± 3,0 medications per patient (p < 0,05) (n = 24). The total number of PIMs and pDDIs was also reduced and QoL was also significantly higher (p < 0,05). A collaborative care approach with a CP led to a decrease of DRPs, pDDIs, PIMs, the total number of medications and to an improvement in the patients' QoL.


Detection of group and interspecies reactivities of mammalian C-type virus p30 proteins by an enzyme-linked immunosorbent assay (ELISA): enhancement of interspecies reactivity by denaturation.
The applicability of the enzyme immunoassay technique to the detection of group and interspecies determinants of C-type retroviral proteins was tested. For this purpose four groups of C-type retroviruses (MuLV, FeLV, SiSV/GaLV, and BaEV/RD114) were assayed for group-specific and interspecies reactivities of their p30 proteins by an enzyme-linked immunosorbent assay (ELISA). We found that the ELISA can detect group-specific as well as interspecies determinants with sensitivity and reproducibility in purified p30 proteins, disrupted viruses, and cell extracts if an anti-p30 interspecies antiserum is used. If monospecific antisera against MuLV p30, SiSV p30, or BaEV p30 were used, only group-specific reactivities were detected reproducibly, whereas the detectability of interspecies determinants depended on the antisera used and varied even with the same antisera. In assays in which the reactivity of native and denatured p30 proteins was compared the detectability of sodium dodecyl sulphate-denatured MuLV p30 was better than that of native MuLV p30 suggesting that some of the most broadly cross-reactive sequences are localized inside the protein molecule and are freed by the denaturation process. Antisera raised against native and denatured p30 proteins showed identical spectra of reactivity.


Thymopentin prophylactic treatment in patients with recurrent respiratory infections.
Present immunological methods do not regularly detect abnormalities in patients with chronic bronchitis, and no single parameter appears to be closely associated with the clinical findings. Of the many tests performed in the cited studies, the Merieux multitest procedure seems to offer the best findings in further studies, followed by determination of the OKT4/OKT8 ratio. The theoretical background for the use of an immunologic approach to prevent frequent recurrences of infections is discussed in depth, with particular emphasis on the pharmacologic efficacy profile of thymopentin. The safety of this drug is remarkably unproblematic. The present survey of 11 clinical studies shows that thymopentin treatment reduces the incidence of recurrent respiratory tract infections. The most frequently used dosing regimen is 50 mg SC three times a week for 6 weeks, which may be repeated after 3-6 months. The clinical effect appears long-lasting, ie, 3-4 months after discontinuation of treatment.


Physiological and proteomics analyses of Holm oak (Quercus ilex subsp. ballota [Desf.] Samp.) responses to Phytophthora cinnamomi.
Phytophthora cinnamomi is one of the agents that trigger the decline syndrome in Quercus spp., this being a serious threat to Mediterranean Holm oak forest sustainability and reforestation programs. Quercus ilex responses to Phytophthora cinnamomi have been studied in one-year olds seedlings from two Andalucía provenances, assessing the physiological water status and photosynthesis-related parameters. Upon inoculation with mycelium a reduction in water content, chlorophyll fluorescence, stomatal conductance and gas exchange was observed along a 90 days post inoculation period in both provenances. The reduction was higher in the most susceptible (SSA) provenance, than in the most tolerant (PCO), being these typical plant responses to drought stress. Leaf protein profiles were analyzed in non-inoculated and inoculated seedlings from the two provenances by using a 2-DE coupled to MS proteomics strategy. Ninety seven proteins changing in abundance in response to the inoculation were successfully identified after MALDI-TOF-TOF analyses. The largest group of variable identified proteins were chloroplasts ones, and they were involved in the photosynthesis, Calvin cycle and carbohydrate metabolism. It was noted that a general tendency was a decrease in the protein abundance as a consequence of the inoculation, being it less accused in the least susceptible, the Northern provenance (PCO), than in the most susceptible, the Southern provenance (SSA). This trend is clearly manifested in photosynthesis, amino acid metabolism and stress/defence proteins. On the contrary, some proteins related to starch biosynthesis, glycolysis and stress related peroxiredoxin showed an increase upon inoculation. These changes in protein abundance were correlated to the estimated physiological parameters and have been frequently observed in plants subjected to drought stress.


Severity classification of Tenosynovial Giant Cell Tumours on MR imaging.
Current development of novel systemic agents requires identification and monitoring of extensive Tenosynovial Giant Cell Tumours (TGCT). This study defines TGCT extension on MR imaging to classify severity. In part one, six MR parameters were defined by field-experts to assess disease extension on MR images: type of TGCT, articular involvement, cartilage-covered bone invasion, and involvement of muscular/tendinous tissue, ligaments or neurovascular structures. Inter- and intra-rater agreement were calculated using 118 TGCT MR scans. In part two, the previously defined MR parameters were evaluated in 174 consecutive, not previously used, MR-scans. TGCT severity classification was established based on highest to lowest Hazard Ratios (HR) on first recurrence. In part one, all MR parameters showed good inter- and intra-rater agreement (Kappa≥0.66). In part two, cartilage-covered bone invasion and neurovascular involvement were rarely appreciated (<13%) and therefore excluded for additional analyses. Univariate analyses for recurrent disease yielded positive associations for type of TGCT HR12.84(95%CI4.60-35.81), articular involvement HR6.00(95%CI2.14-16.80), muscular/tendinous tissue involvement HR3.50(95%CI1.75-7.01) and ligament-involvement HR4.59(95%CI2.23-9.46). With these, a TGCT severity classification was constructed with four distinct severity-stages. Recurrence free survival at 4 years (log rank p < 0.0001) was 94% in mild localized (n56, 1 recurrence), 88% in severe localized (n31, 3 recurrences), 59% in moderate diffuse (n32, 12 recurrences) and 36% in severe diffuse (n55, 33 recurrences). The proposed TGCT severity classification informs physicians and patients on disease extent and risk for recurrence after surgical treatment. Definition of the most severe subgroup attributes to a universal identification of eligible patients for systemic therapy or trials for novel agents.


The right place at the right time: novel B7 family members regulate effector T cell responses.
Recent identification of novel members of the B7-family of costimulatory ligands has illustrated their importance for costimulation, not only for initiation of adaptive immune responses, but also for regulation of activated effector lymphocytes. Two key features that distinguish these novel molecules from classical B7.1 and B7.2 costimulatory ligands are their broader expression in non-lymphoid tissues and their binding to receptors induced on activated T cells. Whereas B7.1/B7.2-CD28 interactions are important for priming naïve T cells, novel costimulatory interactions appear critical in regulating effector lymphocytes at sites of infection in the periphery.


Integrating Omic Technologies in Alzheimer's Disease.
Scientific advances in biomedical disciplines have allowed us to identify the underlying causes of many diseases with increased comprehension-leading the way towards precision medicine. In this context, unique disease and medical traits pave the way for the development of adapted disease management, drugs and therapies tailored to each patient. Bearing in mind that reductionism, an approach that has dominated biomedical research for many years and has resulted in the identification of definite cellular phenotypes and human diseases which are linked with specific integral molecules, we strongly believe that Alzheimer's Disease, one of the most common neurodegenerative diseases, could not be applied to the model of one disease-one assay-one drug. Regarding the discrete complexities in the molecular pathogenesis combined with the limited knowledge of inherited and sporadic forms of Alzheimer's disease, the great heterogeneity in the clinical development, as well as the plethora of validated biomarkers that have been proposed for early diagnosis or prognosis of the disease, we presume that a radically different way of thinking is in demand for comprehensive explanations of the molecular pathogenesis of the disease. In this article we highlight the most recent advances made in the omics field of systems biology towards a more complete understanding of Alzheimer's disease mechanisms, emphasizing to the paramount emergence of the development of various high-throughput strategies applied to the omics sciences.


Candida albicans in Multispecies Oral Communities; A Keystone Commensal?
The complexity of the oral cavity, in which many hundreds of microbial species interact represents a challenge for modern microbiologists. What are all these species doing there? And why do we accept so many opportunistic pathogens to be part of our health (commensal) microflora? While the role of bacteria are often being studied, the role of fungi in the interactions within the oral cavity are understudied. This is partly because fungi in the oral cavity are generally considered as pathogens and related to diseases. In this chapter we will explore mechanisms of interaction between bacteria and fungi in the oral cavity that are involved in maintenance of oral health. We will argue that fungi in general and C. albicans specifically, should be regarded a keystone commensal in the oral cavity.


Patient Experiences After Aborted Cancer Surgery: A Qualitative Study.
Surgical resection is a necessary component of curative-intent treatment for most solid-organ cancers but is occasionally aborted, most often due to occult metastatic disease or unanticipated unresectability. Despite its frequency, little research has been performed on the experiences, care needs, and treatment preferences of patients who experience an aborted cancer surgery. Semistructured interviews of patients who had previously experienced an aborted cancer surgery were conducted, focusing on their recalled experiences and stated preferences. All interviews were audio recorded, transcribed, and coded by two independent researchers by using NVivo 12. An integrative approach to qualitative analysis was used-both inductive and deductive methods-and iteratively identifying themes until saturation was reached. Fifteen patients with an aborted cancer surgery participated in the interviews. Cancer types included pancreatic (n = 9), cholangiocarcinoma (n = 3), hepatocellular carcinoma (n = 1), gallbladder (n = 1), and neuroendocrine (n = 1). The most common reasons for aborting surgery included local tumor unresectability (n = 8) and occult metastatic disease (n = 7). Five subthemes that characterized the patient experience following an aborted cancer surgery emerged, including physical symptoms, emotional responses, impact on social and life factors, coping mechanisms, and support received. This qualitative study characterizes the impact of aborted cancer surgery on multiple domains of quality of life: physical, emotional, social, and existential. These results highlight the importance of developing patient-centered interventions that focus on enhancing quality of life after aborted cancer surgery.


Oral biodrug delivery using cell-penetrating peptide.
During the past few decades, the novel biotherapeutic agents such as peptides and proteins have been contributed to the treatment of several diseases. However, their oral absorption is significantly limited due to their poor delivery through the intestinal mucosa. Therefore, the feasible approaches are needed for improving the oral bioavailability of biodrugs. Recently, cell-penetrating peptides (CPPs) such as HIV-1 Tat, penetratin and oligoarginine are considered as a useful tool for the intracellular delivery of therapeutic macromolecules. Hence, it was expected that the ability of CPPs may be applicable to enhance the absorption of biodrugs through intestinal epithelial membrane. CPPs are likely to become powerful tools for overcoming the low permeability of therapeutic peptides and proteins through the intestinal membrane, the major barrier to their oral delivery. Further advantage of this promising strategy is that this successful intestinal absorption could be achieved by more convenient methodology, coadministration of CPP with drugs via intermolecular interaction among them. Hereafter, the further establishment of delivery system based on CPPs is required to realize the development of the oral forms of therapeutic peptides and proteins. The aim here is to introduce our vision focusing on oral biodrug delivery by the use of CPPs as potential peptide carrier in order to provide new information in the design and development of new oral delivery systems for novel biotherapeutics.


Isolation and Structure Elucidation by LC-DAD-MS and LC-DAD-SPE-NMR of Cyclopeptide Alkaloids from the Roots of Ziziphus oxyphylla and Evaluation of Their Antiplasmodial Activity.
Nine cyclopeptide alkaloids (1-9), of which five (compounds 2, 3, 5, 8, and 9) are described herein for the first time, were isolated from roots of Ziziphus oxyphylla by means of conventional separation methods as well as semipreparative HPLC with DAD and ESIMS detection and LC-DAD-SPE-NMR. Structure elucidation was done by spectroscopic means. Nummularine-R (1), a previously known constituent from this species, was isolated along with its new derivatives O-desmethylnummularine-R (2) and O-desmethylnummularine-R N-oxide (3). In addition, the known compounds hemsine-A (4) and ramosine-A (6), as well as hemsine-A N-oxide (5), were isolated. Moreover, oxyphylline-C (7), a known constituent of Z. oxyphylla stems, was obtained, and two new compounds were identified, oxyphyllines-E (8) and -F (9). Just like oxyphylline-C, oxyphyllines-E and -F belong to the relatively rare class of neutral cyclopeptide alkaloids. The antiplasmodial activity and cytotoxicity of compounds 1, 2, 4, 6, and 9 were evaluated, and the most promising activity was found for O-desmethylnummularine-R (2), which exhibited an IC50 value of 3.2 ± 2.6 μM against Plasmodium falciparum K1, whereas an IC50 value of >64.0 μM was evident for its cytotoxicity against MRC-5 cells.


The course and relations of the left phrenic nerve in the neck.
In the neck, the left phrenic nerve is in a position that corresponds exactly to that of the right phrenic nerve. Both cross and second part of the subclavian arteries. On the left side there is an additional relationship of the nerve to the subclavian artery in the thorax, where it descends in front of the first part of the artery.


Molecular Epidemiology of Rotavirus A Strains Pre- and Post-Vaccine (Rotarix®) Introduction in Mozambique, 2012-2019: Emergence of Genotypes G3P[4] and G3P[8].
Group A rotavirus (RVA) remains the most important etiological agent associated with severe acute diarrhea in children. Rotarix® monovalent vaccine was introduced into Mozambique's Expanded Program on Immunization in September 2015. In the present study, we report the diversity and prevalence of rotavirus genotypes, pre- (2012-2015) and post-vaccine (2016-2019) introduction in Mozambique, among diarrheic children less than five years of age. Genotyping data were analyzed for five sentinel sites for the periods indicated. The primary sentinel site, Mavalane General Hospital (HGM), was analyzed for the period 2012-2019, and for all five sites (country-wide analyses), 2015-2019. During the pre-vaccine period, G9P[8] was the most predominant genotype for both HGM (28.5%) and the country-wide analysis (46.0%). However, in the post-vaccine period, G9P[8] was significantly reduced. Instead, G3P[8] was the most common genotype at HGM, while G1P[8] predominated country-wide. Genotypes G9P[4] and G9P[6] were detected for the first time, and the emergence of G3P[8] and G3P[4] genotypes were observed during the post-vaccine period. The distribution and prevalence of rotavirus genotypes were distinct in pre- and post-vaccination periods, while uncommon genotypes were also detected in the post-vaccine period. These observations support the need for continued country-wide surveillance to monitor changes in strain diversity, due to possible vaccine pressure, and consequently, the effect on vaccine effectiveness.


Ten minutes of 1 mA transcranial direct current stimulation was well tolerated by children and adolescents: Self-reports and resting state EEG analysis.
Transcranial direct current stimulation (tDCS) is a promising and well-tolerated method of non-invasive brain stimulation, by which cortical excitability can be modulated. However, the effects of tDCS on the developing brain are still unknown, and knowledge about its tolerability in children and adolescents is still lacking. Safety and tolerability of tDCS was assessed in children and adolescents by self-reports and spectral characteristics of electroencephalogram (EEG) recordings. Nineteen typically developing children and adolescents aged 11-16 years participated in the study. Anodal and cathodal tDCS as well as sham stimulation were applied for a duration of 10 min over the left primary motor cortex (M1), each with an intensity of 1 mA. Subjects were unable to identify whether they had received active or sham stimulation, and all participants tolerated the stimulation well with a low rate of adverse events in both groups and no serious adverse events. No pathological oscillations, in particular, no markers of epileptiform activity after 1mA tDCS were detected in any of the EEG analyses. In summary, our study demonstrates that tDCS with 1mA intensity over 10 min is well tolerated, and thus may be used as an experimental and treatment method in the pediatric population.


Quantum oscillations in a molecular magnet.
The term 'molecular magnet' generally refers to a molecular entity containing several magnetic ions whose coupled spins generate a collective spin, S (ref. 1). Such complex multi-spin systems provide attractive targets for the study of quantum effects at the mesoscopic scale. In these molecules, the large energy barriers between collective spin states can be crossed by thermal activation or quantum tunnelling, depending on the temperature or an applied magnetic field. There is the hope that these mesoscopic spin states can be harnessed for the realization of quantum bits--'qubits', the basic building blocks of a quantum computer--based on molecular magnets. But strong decoherence must be overcome if the envisaged applications are to become practical. Here we report the observation and analysis of Rabi oscillations (quantum oscillations resulting from the coherent absorption and emission of photons driven by an electromagnetic wave) of a molecular magnet in a hybrid system, in which discrete and well-separated magnetic clusters are embedded in a self-organized non-magnetic environment. Each cluster contains 15 antiferromagnetically coupled S = 1/2 spins, leading to an S = 1/2 collective ground state. When this system is placed into a resonant cavity, the microwave field induces oscillatory transitions between the ground and excited collective spin states, indicative of long-lived quantum coherence. The present observation of quantum oscillations suggests that low-dimension self-organized qubit networks having coherence times of the order of 100 micros (at liquid helium temperatures) are a realistic prospect.


Prevalence of Visible Third Molars in the United States Population: How Many Individuals Have Third Molars?
To determine the prevalence of third molars in the US population and to report the differences in prevalence of visible third molars in the most recent National Health and Nutrition Examination Survey (NHANES) population of 2011 through 2012 by participant, jaw, and demographics. The number of visible third molars in the NHANES data was assessed in nonclinical settings by trained, calibrated dental hygienists by decade of age beginning in the 20- to 29-year-old cohort through the 70- to 79-year-old cohort. Cross-sectional analyses of third molar data were conducted by the authors from the NHANES databases of 2001 through 2002, 2009 through 2010, and 2011 through 2012 to compare data for similarity of outcomes on third molar prevalence in the US population. Outcomes on third molar prevalence also were assessed from the NHANES of 2011 through 2012 by participant, jaw, and demographics: gender, race or ethnicity (Caucasian, African American, other), and education (less than high school, high school graduate, some college, college graduate). Data on the mean number of third molars from NHANES of 2001 through 2002, 2009 through 2010, and 2011 through 2012 were similar. The number of visible third molars in the NHANES of 2011 through 2012 decreased progressively from a mean of 1.48 in the 20- to 29-year-old cohort to 0.81 in the 60- to 69-year-old cohort, No visible third molars were observed in 47% of the 20- to 29-year-old cohort compared with 53% in the 50- to 59-year-old cohort. Participants who were male, non-Caucasian, and had less than a high school education were more likely to have a visible third molar in all age cohorts. No data were collected by NHANES examiners to determine why third molars were absent. Third molar prevalence did not appear to differ in the US population during the first decade of the 21st century. Numbers of visible third molars, prevalent in young adults, decreased progressively through each successive age cohort. Demographic differences exist for prevalence of third molars in the US population.


Sepharose-linked concanavalin A in the purification and characterization of glycoprotein hormones of the bovine pituitary.
Affinity chromatography on concanavalin A-Sepharose is a time saving step in both large and small scale isolations of the bovine pituitary glycoprotein hormones. After ion-exchange chromatography, the final yield of purified lutropin is 40-50% of material in starting concentrates and of purified thyrotropin is approximately 20%. The final products have the same electrophoretic and immunological properties and amino acid compositions as previous preparations. Less than 3% of the immunoreactive lutropin, follitropin and thyrotropin are present as non-glycosylated forms in either crude pituitary extracts or concentrates. Thyrotropin and follitropin elute from the immobilized lectin as a single fraction, whereas lutropin separates into two glycosylated fractions. Gel filtration of both crude extracts and the glycoprotein fractions shows that less than 5% of the immunoreactivity of the hormones is present as material of apparently high molecular weight. Substantial alpha subunit immunoreactivity, however, is in three fractions (as found by others in human pituitary extracts) corresponding to "high molecular weight material" (7%), intact hormones (46%) and free subunit (47%).


Factor reallocation and cost pass-through under the carbon emission trading policy: Evidence from Chinese metal industrial chain.
Piloted in 2013, the Carbon Emission Trading (CET) policy is the most practical tool for emission reduction in China, however, midstream firms increase capital investment to cope with compliance costs, resulting in more expensive intermediate commodities that may hurt export benefits of industrial chain terminal. Based on the A-shared listed firms of Chinese metal industrial chain during 2008-2018, this paper applies the difference-in-difference model to explore the effects of CET on chain reactions of corporate activities. After a set of robustness tests, the results show that midstream firms accelerate capital deepening in response to CET and become more capital-intensive, but gain losses of outputs both in revenue and in quantity, accompanying cost pass-through to downstream firms, which are all contributed by the external pressure imposed by stakeholders and internal incentive from senior managers. Then, affected by price fluctuation in markets of production factors and carbon-intensive commodities, CET increases the cleanliness standards of midstream firms and promote their export benefits immediately, and cost pass-through generates more expensive intermediate products and results in export contraction of downstream firms, but precision machine manufacturing has seen export growth, as their products are more sensitive to technological breakthroughs than material costs.


Hepatectomy and liver regeneration in the results of treatment of colorectal liver metastasis.
Hepatectomy is currently the most reliable treatment modality for colorectal liver metastases (CRLM). This paper describes and discusses the outcomes of initial versus repeat hepatic resection for CRLM. Between January 2008 and December 2018, we retrospectively analyzed the data of 385 patients who underwent initial and repeat hepatic resection for CRLM at a single institution with respect to surgical outcomes and remnant liver regeneration. The remnant liver volume was postoperatively measured via computed tomography on postoperative day 7 and at 1, 2, 5, 12, and 24 months postoperatively. The liver regeneration rate peaked at 1 week postoperatively, and gradually decreased thereafter. Remnant liver volume plateaued around 1-2 months postoperatively, when regeneration was almost complete. There was no difference in the rate of liver volume regeneration during the entire postoperative period between initial and repeat hepatic resection (p = 0.708, 0.511, 0.055, 0.053, 0.102, and 0.110, respectively). After 2 months postoperatively, the laboratory data showed recovery toward near normal levels, and none of the data exhibited significant differences. There were also no significant differences in morbidity rate, mortality rate, overall survival, and recurrence-free survival after hepatic resection (p = 0.488, 0.124, 0.071 and 0.387, respectively). Initial and repeat hepatectomy showed similar outcomes of remnant liver regeneration and short- and long-term prognoses.


Angioendotheliomatosis.
"Angioendotheliomatosis" is a diagnostic term used in histopathology to describe the proliferation of dilated vessels filled with mononuclear cells that have varying degrees of atypia. Either benign or malignant angioendotheliomatosis may exhibit this histologic pattern, and depending on the clinical course, cases are classified as either reactive angioendotheliomatosis or neoplastic angioendotheliomatosis. A case of neoplastic angioendotheliomatosis is presented and the literature reviewed with special attention to the pathogenesis of this condition.


Oncoplastic Surgery: Keeping It Simple With 5 Essential Volume Displacement Techniques for Breast Conservation in a Patient With Moderate- to Large-Sized Breasts.
Oncoplastic surgery is an evolving field in breast surgery combining the strengths of breast surgical oncology with plastic surgery. It provides the surgeon the ability to excise large areas of the breast in the oncologic resection without compromising, and possibly improving, its aesthetic appearance. The purpose of this review is to provide a guide that could help a breast surgeon excise breast cancer in most areas of the breast using 5 oncoplastic techniques. These techniques would be used depending primarily on the location of the cancer in the breast and also on the size of the tumor.


Lu doping nickel oxide thin films using sol-gel spin coated and density functional theory: optoelectronic and magnetic properties.
For the first time, sol-gel spin coating was used to fabricate thin films of NiO doped with lutetium. The films were characterized to determine their crystalline structure, surface morphology, and optical properties as a function of Lu doping concentration. The investigations revealed that the Lu-doped NiO films consisted of nano-polycrystalline particles with a cubic bunsenite structure and (200) preferential orientation. Optical studies indicated that the optical band gap of pure NiO widened with low levels of Lu incorporation before narrowing with higher concentrations. The Urbach energy value for pure NiO initially decreased with 1 at. % Lu-content, from 224 meV to 190 meV, and then continuously increased to 380 meV with more Lu-level. To investigate the effects of Lu doping on the electronics, magnetic, and optical properties of NiO, first-principle computations were performed. The results showed that bulk magnetization underwent significant modifications due to a high hybridization between the Lu-f/d and Ni-d states. This study suggests that NiO doped with lutetium could be used for spin-polarized transport devices and other spin-dependent applications.


The influence of Metolose structure on the free volume and the consequent metoprolol tartrate release of patches.
Matrix-type patches containing Metoprolol tartrate were prepared from two types of Metolose and acrylate polymers. Metolose SM 4000 and Metolose 90SH 100.000SR were applied in different proportions in the patches where the total polymer content was kept constant in each sample. The purpose of the study was to investigate the effect of Metolose structure on the free volume of the patches and the consequent drug release profile. The drug release profiles were characterized by zero-order and first-order models. The results indicate that Metolose, containing hydroxypropyl ether groups and methyl ether groups, enables the formation of H-bonds, thus increasing the free volume holes and the consequent extent and rate of drug release of patches.


HDR syndrome, detected in the neonatal period by newborn hearing screening.
Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. Because HDR syndrome is caused by haploinsufficiency in GATA3, it exhibits variation in the onset and progression of hearing loss. In previous reports, the automated auditory brainstem response (AABR) was considered insufficient to detect sensorineural hearing loss caused by HDR syndrome. We report a case of HDR syndrome whose congenital hearing loss was detected by newborn hearing screening (NHS) using AABR. In this case, HDR syndrome was suspected due to hearing loss, hypocalcemia, and her family history. Genetic testing confirmed the diagnosis of HDR syndrome at 5 months of age. Because the phenotype of hearing loss due to HDR syndrome is variable and includes progressive hearing loss, these cases may not be detected by the HNS. However, most of the previous reports were published before the NHS became common and given the frequency of hearing loss complications in HDR syndrome. We consider that there is a reasonable number of HDR syndrome cases with abnormalities on the NHS. We believe that the NHS may also be useful for early detection of hearing loss due to HDR syndrome.


Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring.
Psoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis. The study was to elucidate the pathogenesis of PV by quantitative proteomic analysis of skin lesion biopsies of PV and healthy tissues with tandem mass tags (TMTs) coupled with liquid chromatography-mass spectrometry (LC-MS)/MS. A total of 4562 differentially expressed proteins (DEPs) between PV lesional tissues (n = 11) and healthy tissues (n = 11) were identified, of which 299 were upregulated and 206 were downregulated using |fold change| > 1.3 as the cutoff threshold. The Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEPs were mainly enriched in the activation of immune cells (drug metabolism pathway, NOD-like pathway, and IL-17 pathway), cell proliferation (ribosomal pathway, DNA replication pathway, and base replication pathway), metabolism-related pathways (fatty acid biosynthesis and metabolism, PPAR pathway, glycerophospholipid metabolism, and cortisol synthesis and breakdown), and glandular secretion (saliva secretion, gastric acid secretion, and pancreatic fluid secretion). Thirteen DEPs that were relatively highly expressed in the drug metabolism pathway were validated with parallel reaction monitoring (PRM), of which MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 were highly expressed in PV, whereas CES1, MAOB, MGST1, and GSTT1 were less expressed in PV. These findings confirmed that these proteins participate in the drug metabolism-other enzyme pathways and play crucial roles in the activation and proliferation of immune cells in the pathogenesis of PV.


Evidence of calpain/cdk5 pathway inhibition by lithium in 3-nitropropionic acid toxicity in vivo and in vitro.
Lithium reduced striatal neurodegeneration induced in rats by 3-nitropropionic acid inhibiting calpain activation. Lithium prevented an increase in cdk5 activity, as shown by the levels of the co-activator p35. Myocite enhancer factor 2 (MEF2), a downstream substrate for cdk5 with pro-survival activity, showed increased phosphorylation. In primary cultures of neurons treated with 3-NP, lithium also reduced protease activity mediated by calpain, cdk5 activation and cellular death. These observations indicate that lithium has a neuroprotective effect. Lithium treatment also reduced the intracellular increase in calcium induced by 3-NP. The finding that lithium mediates the modulation of the calpain/cdk5 pathway further supports its use in the treatment of neurodegenerative diseases.


Combining adoptive NK cell infusion with a dopamine-releasing peptide reduces senescent cells in aged mice.
Aging inducing the development of senescent cells (SNCs) in various tissues is considered as the main cause of the age-related diseases. Senotherapy has become a promising anti-aging therapy. However, the effectivity and side-effect of senolytic agents are still concern. Here, we observed the downregulation of senescence-related genes by adoptive infusion of natural killer (NK) cells in 26 cases in peripheral blood CD3+ T cells. NK cell treatment also significantly decreased levels of senescence markers and senescence-associated secretory phenotypes (SASPs) in three senescent adipose tissues when culturing them together. Interestingly, cytotoxic activity of mouse NK cells against SNCs was significantly enhanced by dopamine in vitro through D1-like receptors. Acein, dopamine-releasing peptide, promoted the adoptive infusion of NK cells in effectively eliminating SNCs in a variety of tissues and reduced local and systemic SASPs in aging mice but Acein alone did not have the senolytic effect. These data demonstrated that adoptive infusion of NK cells is an effective means in removing SNCs, and peptide Acein combined with NK cells further enhances this effect in aging mice.