Efficacy and safety of anti-interleukin-5 therapy in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized, controlled trials.
Anti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear. A literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation. A total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n = 865; benralizumab, n = 1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86-0.97, I2 = 0%). In addition, no significant differences in the changes in SGRQ scores and FEV1 from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, -0.86, 95% CI, -1.92 - 0.19, I2 = 0%; FEV1, mean difference, 0.01, 95% CI, -0.01 - 0.03, I2 = 0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99-1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72-1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85-1.01) when compared with the placebo. Anti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.


Efficacy and safety of an oral formulation of cetirizine and prolonged-release pseudoephedrine versus budesonide nasal spray in the management of nasal congestion in allergic rhinitis.
The aim of this study was to compare the decongestant properties and tolerability of oral cetirizine and pseudoephedrine in a prolonged release form with those of nasal (aqueous spray) budesonide. Thirty-six individuals experiencing allergic rhinitis to house dustmites (HDM) participated in a study according to a randomized, crossover, two-period, two-treatment design with at least a 2-week washout period between treatments. In each period of 4 consecutive days, medications were taken twice daily. On day 1, immediately after the first intake of medication, individuals were exposed to HDM extract in the Vienna Challenge Chamber (VCC) for 5 hours. The primary efficacy parameter was nasal congestion, assessed by active anterior rhinomanometry and rating of nasal cavity photos. Rhinomanometry and nasal cavity photos both indicated that cetirizine/pseudoephedrine efficacy was statistically superior to budesonide in the management of nasal congestion during VCC sessions. The efficacy of cetirizine/pseudoephedrine was similar to that of budesonide from the end of day 1 up to day 4 when individuals were exposed to their natural environment post exposure to the aeroallergens. This study confirms the efficacy of cetirizine/pseudoephedrine and budesonide in the management of nasal congestion associated with allergic rhinitis. Both medications were well-tolerated. Cetirizine/pseudoephedrine was more effective than budesonide during HDM exposure, whereas budesonide became as effective as cetirizine/pseudoephedrine several hours post exposure to the allergens.


Indoor formaldehyde concentrations in urban China: Preliminary study of some important influencing factors.
The Huai River and Qingling Mountain divide (H-Q) divide China into north and south with respect to public policies for building construction and operation practises. China's building energy efficiency standard mandates that air exchange rates be 0.5h-1 north of the H-Q divide and 1h-1 south of the divide. China's heating policy allows space heating systems only north of the H-Q divide. Consequently, indoor temperature and humidity differ considerably between north and south. A theoretical model using indoor temperature, humidity, and air change rate was developed to predict indoor formaldehyde concentrations. Data for 39 cities were obtained from 42 studies. There was good agreement between the literature and modelling in a theoretical reference room. The United States Environmental Protection Agency (U.S.EPA) model was applied to estimate cancer risk from formaldehyde exposure indoors. The median indoor formaldehyde concentration for renovation ever from 2002 to 2015 in Chinese cities was 125μg/m3, which is higher than the WHO threshold, 100μg/m3. The median indoor formaldehyde concentrations in the north were higher than in the south (0.5 times higher for dwellings renovated within the past year and 0.2 times higher for renovation ever), driven by the much higher northern winter concentrations (40-1320%). The U.S.EPA model predicts that the lifetime formaldehyde related cancer risk for people living north of the H-Q divide is 1.2 times greater than for people living south. This can be partly explained by greater indoor exposure to formaldehyde for Chinese living north of the H-Q divide.


Heartworm (Dirofilaria immitis) infection in a leopard (Panthera pardus pardus) housed in a zoological park in north-eastern Italy.
Canine heartworm (cHW) disease is now recognised as potential cause of serious disease in cats and other felids, especially in endemic areas. In March 2009, a 23-years-old male African leopard (Panthera pardus pardus) housed in a zoological park located in the Province of Padova (Veneto Region), a cHW endemic area of the north-eastern Italy, died and was immediately necropsied. A cloth completely occluding the pyloric lumen was considered the presumptive cause of death. During necropsy, six nematodes (4 males and 2 females) were found within the right ventricle of the heart and the pulmonary artery. Diagnosis of HW (Dirofilaria immitis) infection was carried out by morphological features of adult worms and microfilariae, and then confirmed by detection of circulating HW antigens using a commercial SNAP kit (IDEXX Laboratories inc., USA). D. immitis infection was also confirmed by PCR amplification of the 5S ribosomal spacer region, performed on worm fragments and microfilaraemic blood samples obtained from the right ventricle of the heart. A glomerulonephritis of immuno-mediated origin and most likely associated with the HW infection is also reported. HW chemoprophylaxis and annual serological testing on wild felids housed outdoors in endemic cHW disease areas are recommended. This is the first diagnosis of D. immitis infection in an exotic felid in Italy.


Stakeholder position paper: dairy producer.
Bacterial antimicrobial resistance is a problem common to both animal and public health. An important public policy issue is to develop and implement prudent use practices where antimicrobials are used. As policy develops, there are questions regarding the use of antimicrobials in animal agriculture and whether these uses constitute prudent use. A series of papers assessing the risk to the public health from agricultural use of antimicrobials have consistently concluded that risk estimation is hampered by the lack of data that describe the amount, types, and uses of antimicrobials in animal agriculture. The absence of information has spurred efforts to develop a framework to collect these data. However, the reasons and benefit of collecting these data should be carefully defined. The dairy industry, contrasted to other major animal commodities, is not focused on meat production but on milk production. Milk production is constrained by disease and antimicrobial treatment is a common management tool, but unlike many other animal agricultural systems where the value and safety of the product is measured in the future; the value of milk is zero when an antimicrobial is used in a lactating cow and milk must be discarded because of residues. While there are exceptions, e.g. non-lactating cow therapy, this difference results in antimicrobials being used sporadically and directed at therapy rather than prophylactic uses. In the dairy industry, antimicrobial use data and its consequences may exist in sufficient detail or could be estimated from existing datasets without the expense of additional surveys. Finally, the main food product milk is mainly pasteurized and all shipments of milk from the farm to the processing plant are tested for the presence of antimicrobials. This makes the likelihood of farm-origin antimicrobials or bacteria appearing in finished product very low. This suggests that the use and quantity of antimicrobials in the dairy system has little impact on public health. This does not imply that the dairy industry does not have a significant role in developing guidelines for appropriate and careful application of antimicrobials, but the effort and cost to collect additional data should be used to fund efforts that improve our diagnostic and managerial skills. These data would change the use of antimicrobials by decreasing the rates of disease and ultimately decreasing prophylactic, metaphylactic and therapeutic use of antimicrobial. These studies and outcome are as important to the dairy industry as to public health.


Posttransplant renal artery stenosis--outpatient intraarterial DSA versus color aided duplex Doppler sonography.
A prospective trial was conducted to assess the accuracy of color aided duplex Doppler (CADD) sonography to rule out transplant renal artery stenosis (TRAS) and to determine feasibility and safety of intraarterial digital subtraction angiography (DSA) in hypertensive renal allograft recipients on an outpatient basis. All patients were hypertensive (n = 18, mean age: 42 +/- 11 years) and underwent CADD and an i.a. DSA with 4F catheters. There was a 4 hour rest post DSA. Duplex Doppler measurements of maximum velocity were obtained. Absolute values of > or = 100 cm/s were considered indicative to suspect TRAS. DSA revealed severe TRAS in 4 patients (22%). The stenoses were located near the iliorenal anastomosis (n = 2) and at the bifurcation of the renal artery (n = 2). Duplex Doppler classified twelve (67%) renal artery pedicles normal (maximum velocity: 79 +/- 23 cm/s). TRAS was suspected in 6 patients with a maximum velocity of 159 +/- 48 cm/s (P < 0.01). False positive CADD diagnoses were due to tortuous graft vessels and a postbiopsy arteriovenous fistula. Sensitivity of CADD was 100%, specificity 86%. There were no DSA related complications. No impairment of graft function occurred. CADD allows renal angiography to be reserved to clarify an inconclusive ultrasound study and for definite diagnosis of angiomorphology and lesion classification. Intraarterial DSA of renal grafts in outpatients may be performed without an increased risk of procedure-related complications.


Making carbon-nitrogen bonds in biological and chemical synthesis.
The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable in nature.


Oxygen consumption and force development in turtle and trout cardiac muscle during acidosis and high extracellular potassium.
Relative to species such as rainbow trout, freshwater turtle shows a high tolerance to challenges involving acidosis and increases in extracellular K+. Therefore, the effects of acidosis or high K+ on twitch force and oxygen consumption were examined in ventricular ring preparations from these two species. The oxygen consumption associated with force development was estimated by net oxygen consumption (oxygen consumption during twitch force development minus that during rest). For turtle, elevation of CO2 from 2% (pH 7.7) to 12% (pH 6.9) in the gas equilibrating the muscle bath decreased twitch force by 20% without any effects on oxygen consumption. Decreasing pH from 7.7 to 6.9 with 22 mM lactic acid had similar effects. For trout, CO2-induced acidosis decreased twitch force by approximately 60%. Furthermore, force development became energetically less efficient as it fell disproportionately more than net oxygen consumption. This was not observed for lactic acidosis. For trout but not for turtle, acidosis resulted in an increase in oxygen consumption during rest. An increase in extracellular K+ from 2.5 mM to 10 mM depressed force and oxygen consumption proportionately for both species. Adrenaline (10 microM) increased twitch force for both species and oxygen consumption for trout; it attenuated the effects of high extracellular K+. Neither adrenaline nor high K+ influenced the ratio of force to net oxygen consumption. As opposed to high extracellular K+, acidosis appears to increase the energetic cost of contractility, particularly for the trout heart.


Fibrocellular tissue response after percutaneous transluminal coronary angioplasty. An immunocytochemical analysis of the cellular composition.
Restenosis after initial, successful percutaneous transluminal coronary angioplasty (PTCA) is due to fibrocellular proliferation. The present study focused on the nature of fibrocellular tissue in humans by use of immunocytochemical techniques. Four hearts (five coronary arteries) were investigated; time lapse between PTCA and death varied between 20 days (two arteries) and 1 year 7 months. Proliferating cells stained positive with smooth muscle cell-specific monoclonal antibodies. Cells from early proliferative lesions (20 days) have a phenotypic expression different from cells in "old" lesions. Proliferating cells stained positive with vimentin but were negative with desmin, irrespective of the lesion's age. The findings indicate a change in actin isoform expression of smooth muscle cells while adapting to a pathological state.


Combination of affinity depletion of abundant proteins and reversed-phase fractionation in proteomic analysis of human plasma/serum.
The tremendous complexity of the serum and plasma proteome presents extreme analytical challenges in comprehensive analysis due to the wide dynamic range of protein concentrations. Therefore, robust sample preparation methods remain one of the important steps in the proteome characterization workflow. We present the results on a new column for the specific depletion of 14 high-abundant proteins from human serum and plasma and the subsequent reversed-phase fractionation of the flow-through proteins. Analysis of tryptic peptides was accomplished with microfluidic HPLC-Chip/MS system. Results indicate that high-abundant protein depletion combined with RP fractionation of plasma showed an improved dynamic range for proteomic analysis and enabled the identification of low-abundant plasma proteins.


A New Conjugated Polymer that Enables the Integration of Photovoltaic and Light-Emitting Functions in One Device.
Exploring the intriguing bifunctional nature of organic semiconductors and investigating the feasibility of fabricating bifunctional devices are of great significance in realizing various applications with one device. Here, the design of a new wide-bandgap polymer named PBQx-TCl (optical bandgap of 2.05 eV) is reported, and its applications in photovoltaic and light-emitting devices are studied. By fabricating devices with nonfullerene acceptors BTA3 and BTP-eC9, it is shown that the devices exhibit a high power conversion efficiency (PCE) of 18.0% under air mass 1.5G illumination conditions and an outstanding PCE of 28.5% for a 1 cm2 device and 26.0% for a 10 cm2 device under illumination from a 1000 lux light-emitting diode. In addition, the PBQx-TCl:BTA3-based device also demonstrates a moderate organic light-emitting diode performance with an electroluminescence external quantum efficiency approaching 0.2% and a broad emission range of 630-1000 nm. These results suggest that the polymer PBQx-TCl-based devices exhibit outstanding photovoltaic performance and potential light-emitting functions.


Correction to: Characteristics and Outcomes of Patients Undergoing Debridement of Pancreatic Necrosis.
There is an author's name misspelled in the published paper, Shyam Varadarajula should be Shyam Varadarajulu.


Salivary gland hypofunction in KK-Ay type 2 diabetic mice.
Hypofunction of different organs in the body is associated with diabetes, including in the oral cavity. Diabetes is often associated with xerostomia, but the underlying mechanism is not well characterized. Thus, the mechanisms underlying diabetes-induced xerostomia were investigated in this study in KK-A y mice as an experimental model of type 2 diabetes. The mechanisms involved in diabetes-induced xerostomia were investigated using the ex vivo glandular perfusion technique, histological analysis, and immunohistochemical and intracellular signaling analyses. Ex vivo submandibular gland secretions from KK-Ay mice decreased by 30% following stimulation with 0.3 μmol/L carbachol (CCh), a cholinergic agonist. Acinar cell weight was comparable between KK-Ay and control mice, whereas duct cell weight was significantly greater in KK-Ay mice. Concentrations of Na+ and Cl- in the secreted saliva decreased significantly in KK-Ay mice, supporting the finding of increased ductal tissue in KK-Ay mice. Immunohistochemistry revealed no significant differences between KK-Ay and control mice in terms of the expression of Cl- and water channels, Na+ -K+ -2Cl- cotransporters, and membrane proteins critical for fluid secretion. Cellular signaling analysis revealed that the increase in [Ca2+ ]i in response to 0.3 μmol/L CCh was reduced by 30% in KK-Ay mice, although there was no significant difference in the thapsigargin (1.0 μmol/L)-induced increase in store-depleted calcium between KK-Ay and control mice. These results demonstrate that submandibular fluid secretion is diminished in KK-Ay mice because of a diminished increase in [Ca2+ ]i . Duct cell weight increased in KK-Ay mice, possibly leading to increased ion reabsorption and thus decreased Na+ and Cl- concentrations in the secreted saliva.


Loneliness in older chinese adults: a risk factor for elder mistreatment.
To examine loneliness as a risk factor for elder mistreatment in an urban, community-dwelling Chinese population. Cross-sectional descriptive study. Major urban medical center in NanJing, China. Four hundred twelve subjects aged 60 and older who presented to the general medical clinic. The mean age of the participants was 70, and 34% were female. Mean education level was 8.5 years of schooling. Loneliness was assessed using validated instruments, and direct questions were asked regarding mistreatment experienced by older adults. Elder mistreatment was found in 35.2% of the participants. After adjusting for confounding factors, feeling of often lacking companionship (odds ratio (OR)=4.06; 95% confidence interval (CI)=1.49-11.10) and feeling of sometimes being left out in life (OR=1.69; 95% CI=1.01-2.84) were positively associated with the risk of mistreatment. Risk of mistreatment was also correlated with higher total loneliness scores (OR=2.74; 95% CI=1.19-6.26). Loneliness appeared to be a risk factor associated with elder mistreatment in this older Chinese population. Further prospective studies are needed to confirm this finding. An exploration of Chinese culture and tradition may yield insight into shaping a prevention framework for mistreatment of older Chinese people.


The prolonged disease state of infertility is associated with embryonic epigenetic dysregulation.
To evaluate the epigenetic consequence of a prolonged disease state of infertility in euploid blastocysts. Methylome analysis as well as targeted imprinted methylation and expression analysis on individual human euploid blastocysts examined in association with duration of patient infertility and time to live birth. Research study. One hundred four surplus cryopreserved euploid blastocysts of transferrable-quality were donated with informed patient consent and grouped based on time to pregnancy (TTP). None MAIN OUTCOME MEASURE(S): The Methyl Maxi-Seq platform (Zymo Research) was used to determine genome-wide methylation, while targeted methylation and expression analyses were performed by pyrosequencing and quantitative real-time polymerase chain reaction, respectively. Statistical analyses used Student's t test, 1-way ANOVA, Fisher's exact test, and pairwise-fixed reallocation randomization test, where appropriate. The methylome analysis of individual blastocysts revealed significant alterations at 6,609 CpG sites associated with prolonged infertility (≥60 months) compared with those of fertile controls (0 months). Significant CpG alterations were localized to numerous imprinting control regions and imprinted genes, and several signaling pathways were highly represented among genes that were differentially methylated. Targeted imprinting methylation analysis uncovered significant hypomethylation at KvDMR and MEST imprinting control regions, with significant decreases in the gene expression levels upon extended TTP (≥36 months) compared to minimal TTP (≤24 months). The prolonged disease state of infertility correlates with an altered methylome in euploid blastocysts, with particular emphasis on genomic imprinting regulation, compared with assisted reproductive technologies alone.


Transcutaneous vagus nerve stimulation in patients with attention-deficit/hyperactivity disorder: A viable option?
Individuals with attention-deficit/hyperactivity disorder (ADHD) suffer from a range of cognitive and behavioral problems that severely impair their educational and occupational attainment. ADHD symptoms have been linked to structural and functional changes within and between different brain regions, particularly the prefrontal cortex. At the system level, reduced availability of the neurotransmitters dopamine (DA) and norepinephrine (NE) but also γ-aminobutyric acid (GABA) have been repeatedly demonstrated. Recently, non-invasive brain stimulation (NIBS) techniques have been explored as treatment alternatives to alter dysfunctional activation patterns in specified brain areas or networks. In the current paper, we introduce transcutaneous vagus nerve stimulation (tVNS) as a systemic approach to directly affect NE and GABA neurotransmission. TVNS is a non-drug intervention with low risk and proven efficacy in improving cognitive particularly executive functions. It is easy to apply and therefore well-suited to provide home-based or mobile treatment options allowing a significant increase in treatment intensity and providing easier access to medical care for individuals who are unable to regularly visit a clinician. We describe in detail the underlying mechanisms of tVNS and current fields of application and discuss its potential as an adjuvant treatment for ADHD.


Understanding the psychosocial determinants of Italian parents' intentions not to vaccinate their children: an extended theory of planned behaviour model.
This study aimed to identify the psychosocial factors involved in Italian parents' intentions not to vaccinate their children. For this purpose, we used an extended version of the Theory of Planned Behaviour, which included both proximal and distal factors influencing intention not to vaccinate children. Participants included 447 Italian parents, each completed an online questionnaire, which measured intention not to vaccinate children, attitude toward not vaccinating, subjective norms, perceived behavioural control, anticipated regret, negative attitude toward vaccines, risk perception, trust in healthcare institutions, trust in science and religious morality. Results showed that attitude toward not vaccinating was strongly associated with intention not to vaccinate children. Furthermore, attitude toward not vaccinating was associated with negative attitude toward vaccines, which in turn was affected by all the distal factors considered (risk perception, trust in healthcare institutions, trust in science, religious morality). Finally, negative attitude toward vaccines fully mediated the effect of the distal factors on attitude toward not vaccinating children. These findings provide support for the validity of the proposed extended TPB model in explaining parents' intention not to vaccinate children. Theoretical and practical implications, in terms of understanding and promoting vaccination behaviour, are discussed.


Transmission Immunoelectron Microscopy of Herpes Simplex Virus-1-Infected Dorsal Root Ganglia Neurons Sectioned in Growth Plane.
Transmission immunoelectron microscopy allows for the ultrastructural detection and localization of herpes simplex virus-1 (HSV-1) particles and viral proteins within the infected cell and their relation to the cell cytoskeleton, cellular proteins, vesicles, membranes, and organelles. For the successful application of immunoelectron microscopy, preservation of cell ultrastructure and of epitope antigenicity is essential during sample preparation. This chapter describes the use of chemical fixation followed by rapid cooling of HSV-1 infected sensory neurons in the presence of sucrose as a cryoprotectant to achieve optimal preservation of cell morphology and the use of freeze substitution and resin polymerization at low temperatures for preservation of protein antigenicity. In order to examine HSV-1 infection in the specialized compartments of the neurons (cell body, axons, and growth cones), neurons cultured on plastic coverslips are flat embedded prior to resin polymerization. Overall, this method allows for the ultrathin sectioning and immunogold labeling of the neurons and their axons in growth plane.


Improving prenatal detection of congenital hand defects through collaborative goal-directed antenatal care: a case report on symbrachydactyly.
Prenatal ultrasonography for the detection of fetal structural anomaly is an important component of antenatal care. During the assessment, proximal limb deformities are readily diagnosed. Distal limb, especially digit, abnormalities, however, may be difficult to detect, particularly if the ultrasonography is performed in the third trimester, and the deformity is unilateral and isolated. A 24-year-old primigravida booked for antenatal care with a general practitioner had threatened miscarriage at 12 weeks of gestation, and at 34 weeks was referred to an obstetrician for further care and delivery. The growth ultrasonographic examination was normal but at 40 weeks of gestation she developed antepartum haemorrhage of unknown origin. She had a caesarean delivery and a female baby with "rudimentary" left fingers ("isolated symbrachydactyly") was delivered. The parents were counselled and they declined further assessment of the baby by a hand surgeon and a clinical geneticist. At 3 years of age, the baby had normal development and "is using her hand even without fingers," according to the mother. Collaborative goal-directed antenatal care that involves different categories of healthcare professionals, but particularly a certified sonologist who performs fetal anomaly ultrasonography, is essential for the detection of congenital hand defects. Adequate counselling is essential for the satisfaction of the baby's family.


Curettage as first surgery for bone giant cell tumor : adequate surgery is more important than oncology training or surgical management by high volume specialized teams.
We reviewed the files of 203 patients with extremities GCTB treated with curettage as first surgery from 1990 to 2013. Median follow-up was 84.2 months. We evaluated whether the years of practice and training in orthopaedic oncology are associated with local recurrences, function and complications after curettage as first surgery for giant cell tumour of bone (GCTB). Local recurrences were not significantly different between orthopaedic oncology trained and non-trained orthopaedic surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. Function was not significantly different between orthopaedic oncology trained and non-trained surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. The only important univariate and multivariate predictor for local recurrence was PMMA adjuvant. Complications were not significantly different between orthopaedic oncology trained and non-trained orthopaedic surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. Curettage may be effectively performed as first surgery for GCTB by early-career (< 10 years of practice) non-trained orthopaedic oncology orthopaedic surgeons. PMMA adjuvant is recommended after appropriate curettage.


A rapid and sensitive procedure for the simultaneous analysis of beta-phenylethylamine and tranylcypromine in rat brain using trichloroacetylation and gas chromatography.
Aqueous trichloracetylation followed by electron-capture gas chromatography has been employed for the rapid, sensitive and simultaneous analysis of the endogenous trace amine beta-phenylethylamine and the anti-depressant tranylcypromine.


Prey Status Affects Paralysis Investment in the Ponerine Ant Harpegnathos venator.
The paralysis behavior of some ponerine ants when foraging may be important for food storage and colony development. However, how workers invest in paralysis under different prey circumstances is often overlooked. Here, we report the prey-foraging behavior and paralysis behavior of Harpegnathos venator under different food supply conditions. Solitary hunting was the main foraging mode of H. venator, with occasional simple collective hunting. Nymphal cockroaches with high activity were the most attractive to H. venator. In the experiment, we found that the stings of H. venator completely paralyzed the cockroaches. The stinging time was significantly longer at a higher prey activity level and for larger cockroaches. In addition, there was no significant difference in the stinging time of H. venator for different prey densities. The results showed that the longer similar cockroaches were stung, the longer it took for them to revive and move. These results are helpful for further understanding the behavioral mechanism underlying the food storage of live prey by predatory insects.


Combining sequence data from multiple studies: Impact of analysis strategies on rare variant calling and association results.
Individual sequencing studies often have limited sample sizes and so limited power to detect trait associations with rare variants. A common strategy is to aggregate data from multiple studies. For studying rare variants, jointly calling all samples together is the gold standard strategy but can be difficult to implement due to privacy restrictions and computational burden. Here, we compare joint calling to the alternative of single-study calling in terms of variant detection sensitivity and genotype accuracy as a function of sequencing coverage and assess their impact on downstream association analysis. To do so, we analyze deep-coverage (~82×) exome and low-coverage (~5×) genome sequence data on 2,250 individuals from the Genetics of Type 2 Diabetes study jointly and separately within five geographic cohorts. For rare single nucleotide variants (SNVs): (a) ≥97% of discovered SNVs are found by both calling strategies; (b) nonreference concordance with a set of highly accurate genotypes is ≥99% for both calling strategies; (c) meta-analysis has similar power to joint analysis in deep-coverage sequence data but can be less powerful in low-coverage sequence data. Given similar data processing and quality control steps, we recommend single-study calling as a viable alternative to joint calling for analyzing SNVs of all minor allele frequency in deep-coverage data.


Agreement between patients and physicians on scores of inflammatory bowel disease activity and burden assessed on a telemonitoring platform.
Telemonitoring is increasingly used in the management of IBD patients. We investigated the agreement between patients and physicians on scores of disease activity and burden. Consecutive outpatients at one IBD clinic were recruited between February and December 2021. Enrolled patients completed a questionnaire for disease activity (Harvey-Bradshaw Index [HBI] for Crohn's disease or Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis) and a test of disease burden (Pictorial Representation of Illness and Self Measure [PRISM]). They did the tests within 5 days of an outpatient visit, working independently on IBD Tool, a new web-based telemonitoring application. Concomitantly, the senior and junior physicians who examined them completed the same tests. The agreement was tested for every pair of scores. Five hundred and sixty patients (289 Crohn's disease; 271 ulcerative colitis) completed disease questionnaires on IBD Tool (in total, 742 times). By Spearman's correlation, the agreement was substantial both for HBI (rho 0.685-0.837) and SCCAI (rho 0.694-0.888) for comparisons between patients, junior and senior physicians. The agreement was moderate-to-substantial for PRISM (rho 0.406-0.725) for the same comparisons. The correlation between disease activity (HBI/SCCAI) and PRISM scores was substantial for senior (rho 0.757-0.788) or junior (rho 0.746-0.753) physicians and moderate for patients (rho 0.458-0.486). The median PRISM score difference was 2.3-1.6 points lower between patients and senior-junior physicians. Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease impact. The inclusion of disease burden scoring in telemonitoring platforms provides important information for the management of IBD patients.Study highlightsWhat IS known•Continuous response to treatments and patient-reported outcomes became an essential goal for IBD patient management.•The use of tele-monitoring and eHealth technologies allows for regular disease assessments and for managing more efficiently IBD patients; disease questionnaires and tests are key to support eHealth tools.What is new here•Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease burden, while agreement among junior and senior physicians was substantial for both.•PRISM performs as well for ulcerative colitis as for Crohn's patients.•The inclusion of disease burden tests might add to eHealth platforms valuable information, complemental to disease activity questionnaires.


Influence of early feeding style on adiposity at 6 years of age.
In a previous study we found that a vigorous infant feeding style measured in the laboratory at 2 and 4 weeks of age predicted the degree of adiposity at 1 and 2 years of age. A follow-up of this cohort of infants at 3 and 6 years of age is now reported. Factors predicting adiposity, measured by body mass index at 3 years of age, were pressure of suckling, with high-pressure sucking (denoting a vigorous feeding style) associated with greater adiposity, and time of introduction of solid food, with delayed introduction of solid food or breast-feeding longer than 5 months, or both, being associated with greater adiposity. Predictive factors at 6 years of age were adiposity at birth, with greater adiposity at birth predicting greater fatness at 6 years, parental education, with less education associated with fatness, and a prolonged period of breast-feeding with delayed introduction of solid food. These factors accounted for 40.4% of the variance in adiposity at 3 years of age and 31.2% at 6 years. The effects of social learning on body mass index, indicated by parental educational level, appear to strengthen over time, whereas the effects of the vigorous feeding style wane.


Genetic localization of diuron- and mucidin-resistant mutants relative to a group of loci of the mitochondrial DNA controlling coenzyme QH2-cytochrome c reductase in Saccharomyces cerevisiae.
Diuron-resistance, DIU (Colson et al., 1977), antimycin-resistance, ANA (Michaelis, 1976; Burger et al., 1976), funiculosin-resistance, FUN (Pratje and Michaelis, 1977; Burger et al., 1977) and mucidin-resistance, MUC (Subik et al., 1977) are each coded by a pair of genetic loci on the mit DNA of S. cerevisiae. In the present paper, these respiratiory-competent, drug-resistant loci are localized relative to respiratory-deficient BOX mutants deficient in coenzyme QH2-cytochrome c reductase (Kotylak and Slonimski, 1976, 1977) using deletion and recombination mapping. Three drug-resistant loci possessing distinct mutated allelic forms are distinguished. DIU1 is allelic or closely linked to ANA2, FUN1 and BOX1; DIU2 is allelic or closely linked to ANA1, MUC1 and BOX4/5; MUC2 is allelic to BOX6. The high recombinant frequencies observed between the three loci (13% on the average for 33 various combinations analyzed) suggest the existence of either three genes coding for three distinct polypeptides or of a single gene coding for a single polypeptide but subdivided into three easily separable segments. The resistance of the respiratory-chain observed in vitro in the drug-resistant mutants and the allelism relationships between respiratory-competent, drug-resistant loci and coQH2-cyt c reductase deficient, BOX, loci strongly suggest that each of the three drug-resistant loci codes for a structural gene-product which is essential for the normal coQH2-cyt c reductase activity and is obviously a good candidate for a gene product of the drug-resistant loci mapped in this paper. Polypeptide length modifications of cytochrome b were observed in mutants deficient in the coQH2-cyt c red and localized at the BOX1, BOX4 and BOX6 genetic loci (Claisse et al., 1977, 1978) which are precisely the loci allelic to drug resistant mutants as shown in the present work. Taken together these two sets of data provide a strong evidence in favor of the idea that there exist three non contiguous segments of the mitochondrial DNA sequence which code for a single polypeptide sequence of cytochrome b. In each segment mutations which modify the polypeptide sequence can occur leading to the loss (BOX mutants) or to a modification (drug resistant mutants) of the enzyme activity.


Enhanced biomass productivity of Arthrospira platensis using zeolitic imidazolate framework-8 as carbon dioxide adsorbents.
In order to improve CO2 diffusion in algae solution and conversion into dissolved HCO3-, zeolitic imidazolate framework-8 (ZIF-8) with zinc cores as unsaturated metal sites was first used as CO2 adsorbents. Flue gas CO2 from coal-chemical industry can be adsorbed and can be made available throughout cultivation to promote biomass productivity of Arthrospira platensis. The ZIF-8 adsorbent with particle size of 719 nm performed the largest pore area of 351.8 m2/g, which promoted CO2 conversion into HCO3- by 72.9% compared to control condition without ZIF-8. The increased HCO3- concentration enhanced thylakoid membrane proportion in cell cross-sectional area by 1.3 times to 78.3%, which resulted in enhancement of photosynthesis in A. platensis cells. Relative electron transport rate increased by 9.4% accordingly, which was attributed to the improvement of chlorophyll a concentration by 110%. The biomass productivity using ZIF-8 adsorbent with particle size of 719 nm markedly increased by 64.0%.


Distinguishing between benign and malignant breast lesions using diffusion weighted imaging and intravoxel incoherent motion: A systematic review and meta-analysis.
We sought to evaluate the diagnostic performance of diffusion weighted imaging (DWI) and intravoxel incoherent motion (IVIM) for distinguishing between benign and malignant breast tumors by performing a meta-analysis. We comprehensively searched the electronic databases PubMed and Embase from January 2000 to April 2020 for studies in English. Studies were included if they reported the sensitivity and specificity for identifying benign and malignant breast lesions using DWI or IVIM. Studies were reviewed according to QUADAS-2. The data inhomogeneity and publication bias were also assessed. In order to explore the influence of different field strengths and different b values on diagnostic efficiency, we conducted subgroup analysis. We analyzed 79 studies, which included a total of 6294 patients with 4091 malignant lesions and 2793 benign lesions. Overall, the pooled sensitivity and specificity of ADC for detecting malignant breast tumors were 0.87 (0.86-0.88) and 0.80 (0.78-0.81), respectively. The PLR was 5.09 (4.16-6.24); the NLR was 0.15 (0.13-0.18); and the DOR was 38.95 (28.87-52.54). The AUC value was 0.9297. The highest performing parameter for IVIM was tissue diffusivity (D), and the pooled sensitivity and specificity was 0.85 (0.82-0.88) and 0.87(0.83-0.90), respectively; the PLR was 5.65 (3.91-8.18); the NLR was 0.17 (0.12-0.26); and the DOR was 38.44 (23.57-62.69). The AUC value was 0.9265. Most of parameters demonstrated considerable statistically significant heterogeneity (P < 0.05, I2>50 %) except the pooled DOR, PLR of D and the pooled DOR and NLR of D*. Our meta-analysis indicated that DWI and IVIM had high sensitivity and specificity in the differential diagnosis of breast lesions; and compared with DWI, IVIM could not further increase the diagnostic performance. There was no significant difference in diagnostic accuracy.


Active taurocholic acid flux through hepatoma cells increases the cellular pool of unesterified cholesterol derived from lipoproteins.
The effect of bile acid flux on the fate of lipoprotein-derived cholesterol was studied in bile acid-transporting McNtcp.18 hepatoma cells. The intracellular unesterified cholesterol (UC) concentration rose when McNtcp.18 cells grown in the presence of either high density lipoproteins (HDL) or low density lipoproteins (LDL) were incubated with taurocholic acid (TCA). This effect was more pronounced when the exogenous source of cholesterol was HDL. The presence of TCA in the culture medium of McNtcp.18 cells had no discernible effect on the uptake of cholesteryl esters (CE) from either lipoprotein. TCA treatment of cells preincubated with either lipoprotein did not affect cholesterol synthesis but antagonized the stimulation of cholesterol esterification in cells that were incubated with LDL. The CE concentration in cells treated with TCA was decreased, relative to cells not incubated with TCA, suggesting that cellular CE stores were also hydrolyzed. The TCA treatment reduced the amount of total cholesterol released into the medium by the lipoprotein-treated cells, which was coincident with the reduction in the amount of apolipoprotein B in the culture medium. However, the proportion of UC released into the medium by the lipoprotein-treated cells was increased in cells capable of active bile acid transport. The results indicate that active bile acid flux through hepatoma cells increases the cellular pool of UC derived from lipoproteins. The UC released by the cells into the culture medium under this condition may represent cholesterol destined for direct biliary secretion.


Anti-neutrophil cytoplasmic antibodies and anti-endothelial cell antibodies.
Anti-neutrophil cytosolic antibodies (ANCA) and anti-endothelial cell antibodies (AECA) have been identified in a wide variety of disorders, but their pathophysiological role remains unclear. ANCA appear to be particularly associated with various forms of vasculitis including Wegener's granulomatosis. Kawasaki disease and microscopic polyarteritis. Cytoplasmic staining (cANCA) on indirect immunofluorescence is associated with extrarenal disease and a perinuclear pattern (pANCA) with renal limited disease. The cANCA antigen appears to be proteinase 3 and that for pANCA myeloperoxidase. AECA have been detected in systemic lupus erythematosus, scleroderma and dermatomyositis but are also found in systemic vasculitis, Kawasaki disease, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura and renal allograft recipients at the time of rejection. Their presence appears to be correlated with disease activity and they may be directed against epitopes on as yet unidentified infective agents that precipitate some of the diseases in which they are found that cross-react with antigenic sites exposed on endothelial cells. Measurement of these antibodies has a diagnostic role, facilitates monitoring of disease activity and may prove valuable in understanding the pathogenesis of the diseases in which they are found.


Size-dependent axial instability of microtubules surrounded by cytoplasm of a living cell based on nonlocal strain gradient elasticity theory.
Microtubules including tubulin heterodimers arranging in a parallel shape of cylindrical hollow plays an important role in the mechanical stiffness of a living cell. In the present study, the nonlocal strain gradient theory of elasticity including simultaneously the both nonlocality and strain gradient size dependency is put to use within the framework of a refined orthotropic shell theory with hyperbolic distribution of shear deformation to analyze the size-dependent buckling and postbuckling characteristics of microtubules embedded in cytoplasm under axial compressive load. The non-classical governing differential equations are deduced via boundary layer theory of shell buckling incorporating the nonlinear prebuckling deformation and microtubule-cytoplasm interaction in the living cell environment. Finally, with the aid of a two-stepped perturbation solution methodology, the explicit analytical expressions for nonlocal strain gradient stability paths of axially loaded microtubules are achieved. It is illustrated that by taking the nonlocal size effect into consideration, the critical buckling load of microtubule and its maximum deflection associated with the minimum postbuckling load decreases, while the strain gradient size dependency causes to increase them.


Predictors of weaning failure in case of VA ECMO implantation.
The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for the treatment of refractory cardiogenic shock has increased significantly. Nevertheless, early weaning may be advisable to reduce the potential for severe complications. Only a few studies focusing on ECMO weaning predictors are currently available. Our objective was to evaluate factors that may help predict failure during VA ECMO weaning. We included 57 patients on VA ECMO support previously considered suitable for weaning based on specific criteria. Clinical, haemato-chemical and echocardiographic assessment was considered before and after a "weaning test" (ECMO flow < 2 L/min for at least 60 min). ECMO removal was left to the discretion of the medical team blinded to the results. Weaning failure was defined as a patient who died or required a new VA ECMO, heart transplant or LVAD 30 days after ECMO removal. Thirty-six patients (63.2%) were successfully weaned off VA ECMO, of whom 31 (54.4%) after the first weaning test. In case of first test failure, 3 out of 7 patients could be weaned after a 2nd test and 3 out of 4 patients after a 3rd test. Pre-existing ischemic heart disease (OR 9.6 [1.1-83]), pre-test left ventricular ejection fraction (LVEF) ≤ 25% and/or post-test LVEF ≤ 40% (OR 11 [0.98-115]), post-test systolic blood pressure ≤ 120 mmHg (OR 33 [3-385]), or length of ECMO support > 7 days (OR 24 [2-269]) were predictors of weaning failure. The VA ECMO weaning test failed in less than 40% of patients considered suitable for weaning. Clinical and echocardiographic criteria, which are easily accessible by a non-expert intensivist, may help increase the probability of successful weaning.


Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice.
Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AAA, no safe and efficient pharmacotherapies exist for patients. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs, making it an ideal target for delivering drugs to the AAA site. In this research, we conjugated nanoparticles with an elastin antibody that only targets degraded elastin while sparing healthy elastin. After induction of aneurysm by 4-week infusion of angiotensin II (Ang II), two biweekly intravenous injections of pentagalloyl glucose (PGG)-loaded nanoparticles conjugated with elastin antibody delivered the drug to the aneurysm site. We show that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastic lamina, and improve the mechanical properties of the aorta at the AAA site. Therefore, simple iv therapy of PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to reverse disease progression and return the aorta to normal homeostasis.


PD-1/PD-L1 immune checkpoints: Tumor vs atherosclerotic progression.
Immunotherapy has become one of the most attraction cancer therapy strategies. The PD-1/PD-L1 pathway plays key roles in immune responses and autoimmunity by regulating T cell activity. Overactivation of this pathway dampens T cell and immune function, which allows tumor cells immune escape. Antibody or inhibitors of PD-1/PD-L1 immune targets have been implicated in clinic anti-cancer therapy and gain great clinic outcoming for their high efficiency. However, recent studies showed that the PD-1/PD-L1 immunotherapy in some tumor patients was found to accelerate T cell-driven inflammatory and the progression of atherosclerotic lesions. This article reviews the research progression of PD-1/PD-L1 in tumors and atherosclerosis, and the possible mechanisms of anti-PD-1/PD-L1 immunotherapy increasing the risk of atherosclerotic lesions.


A non-covalent strategy combining cationic lipids and CPPs to enhance the delivery of splice correcting oligonucleotides.
Modulation of pre-mRNA splicing by steric-block oligonucleotides constitutes a promising strategy for the treatment of many diseases, but requires efficient delivery to cell nuclei. In the present study, we evaluated the efficacy of a non-covalent strategy that combines a cell penetrating peptide with a lipoplex-based formulation to mediate the delivery of splice-switching oligonucleotides. The splice correcting ability of these new formulations was assessed using splice-switching oligonucleotides targeted towards the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc/705 splice correction model. Importantly, the optimal splice correcting activity was exhibited by the formulation containing both lipid and peptide components, the order of component addition in these formulations being crucial for their efficacy. Our results demonstrate that the inclusion of cationic liposomes in the formulation provides the ability to improve release from endocytic vesicles, a barrier that severely limits the efficiency of oligonucleotide delivery by cell penetrating peptides. On the other hand, cell penetrating peptides potentiate the cellular uptake and delivery of the oligonucleotides by the lipoplexes. Moreover, when combining cell penetrating peptides with the lipoplex formulations, a significant reduction in the amount of required cationic lipid could be achieved, while maintaining or even enhancing biological activity.


Construction of N-Boc-2-Alkylaminoquinazolin-4(3H)-Ones via a Three-Component, One-Pot Protocol Mediated by Copper(II) Chloride that Spares Enantiomeric Purity.
Chiral 2-alkylquinazolinones are key synthetic intermediates, but their preparation in high optical purity is challenging. Thus, a multicomponent procedure integrating anthranilic acids, N-Boc-amino acids, and amines in the presence of methanesulfonyl chloride, N-methylimidazole, and copper(II) chloride was developed to mildly afford N-Boc-2-alkylaminoquinazolin-4(3H)-ones with excellent preservation of enantiomeric purity (>99% ee). Copper(II) chloride was essential to retaining enantiopurity, and reaction component structural changes were well tolerated, resulting in an efficient, all-in-one procedure that promotes sequential coupling, lactonization, aminolysis, and cyclization in good yields. The method was applied to the rapid assembly of four key intermediates used in the synthesis of high profile quinazolinones, including several PI3K inhibitor drugs.


Intestinal water transport.
The current knowledge of the physiology of the transport of sodium and water across the intestinal epithelium is summarized. A brief review of its hormonal and nervous control is also given.


Effect of a home program of hip abductor exercises on knee joint loading, strength, function, and pain in people with knee osteoarthritis: a clinical trial.
Hip abductor muscle weakness may result in impaired frontal-plane pelvic control during gait, leading to greater medial compartment loading in people with knee osteoarthritis (OA). This study investigated the effect of an 8-week home strengthening program for the hip abductor muscles on knee joint loading (measured by the external knee adduction moment during gait), strength (force-generating capacity), and function and pain in individuals with medial knee OA. The study design was a nonequivalent, pretest-posttest, control group design. Testing was conducted in a motor performance laboratory. An a priori sample size calculation was performed. Forty participants with knee OA were matched for age and sex with a control group of participants without knee OA. Participants with knee OA completed a home hip abductor strengthening program. Three-dimensional gait analysis was performed to obtain peak knee adduction moments in the first 50% of the stance phase. Isokinetic concentric strength of the hip abductor muscles was measured using an isokinetic dynamometer. The Five-Times-Sit-to-Stand Test was used to evaluate functional performance. Knee pain was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire. Following the intervention, the OA group demonstrated significant improvement in hip abductor strength, but not in the knee adduction moment. Functional performance on the sit-to-stand test improved in the OA group compared with the control group. The OA group reported decreased knee pain after the intervention. Gait strategies that may have affected the knee adduction moment, including lateral trunk lean, were not evaluated in this study. Hip abductor strengthening did not reduce knee joint loading but did improve function and reduce pain in a group with medial knee OA.


Slurry phase bioremediation of PAHs in industrial landfill samples at laboratory scale.
The effect of Tween 80 and selected bacteria additions on the bioremediation of PAH contaminated landfill soil (70.38mgkg(-1)) was evaluated in a slurry phase bioreactor. A phenanthrene-degrading consortium was selected by enrichment cultures and used as autochthonous inoculum. The Tween 80 addition increased the aqueous concentration of both high and low molecular weight PAHs. In the experiment with Tween 80 and inoculum addition, added microorganisms improved (>90%) the biodegradation of two- and three-ring PAHs as well as of the four-ring PAHs pyrene and fluoranthene. Biodegradation of the higher molecular weight PAHs was about 30% in experiments with Tween 80 addition, with and without inoculum addition.


Sample preparation for structural and functional analyses of the STRA6 receptor for retinol-binding protein.
STRA6 (stimulated by retinoic acid 6) is a 75kDa polytopic transmembrane protein that facilitates cellular retinol uptake from retinol-binding protein (RBP). Structural characterization of STRA6 from Danio rerio purified in detergent and reconstituted in amphipol A8-35 was achieved by single-particle cryo-electron microscopy (cryo-EM). This provided the first high-resolution snapshot of this protein, showing a novel topology of a tightly assembled homodimer, and an unexpected physiological association with calmodulin in addition to insights into its potential mechanism of function. Specifically, a large hydrophobic cavity in the center of STRA6 linked to the known site of interaction with RBP suggested a route of retinol entry into the cell by diffusion into the membrane through a lateral opening of the cavity directly into the bilayer. Moreover, the capability to produce pure and homogeneous protein has allowed previously unattainable functional characterization of STRA6 in a reconstituted system. Here, we describe detailed methods for Danio rerio STRA6 expression in insect cells, purification in detergent and reconstitution in amphipol for structural characterization by cryo-EM. Furthermore, we show reconstitution of the protein in liposomes for an in vitro proteoliposome-based assay of STRA6-mediated retinol uptake. Finally, we present methods and preliminary cryo-EM data for STRA6 incorporated in lipid-filled nanodiscs, a close to native milieu to study membrane protein structure and function.


Functional ligand directed assembly and electronic structure of Sn18-oxo wheel nanoclusters.
A bilayer hexagonal wheel Sn18-oxo cluster, as the largest tin-oxo wheel to date, was successfully constructed by structural directing of organic ligands. Moreover, the ligands show important effects on the electronic structure and third-order nonlinear optical properties of the Sn18-oxo wheel, which is demonstrated by detailed theoretical calculations.


Dose response relationship of methotrexate in combination with cisplatin in murine bladder cancer.
Methotrexate (MTX) has activity in transitional cell carcinoma (TCC) in man and some have suggested an advantage of high-dose methotrexate versus the standard dose in controlling tumor growth and prolonging survival. MBT-2, a poorly differentiated TCC induced by the carcinogen FANFT, is both grossly and histologically similar to human TCC and has been used as an animal model. One hundred twenty C3H/HE female mice were injected in the hind limb with 7.5 X 10(4) MBT-2 tumor cells. When palpable tumors developed in all animals, therapy was initiated. Animals were randomized into a control group and nine treatment groups as follows: cisplatin (DDP), MTX32 mg, MTX50 mg, MTX80 mg, DDP + MTX32, MTX50 + Leucovorin, MTX80 + Leucovorin, DDP + MTX50 + Leucovorin, DDP + MTX80 + Leucovorin. The combination of MTX50 mg with Leucovorin + DDP and DDP alone were the two most effective regimens in controlling tumor growth and prolonging survival. No statistically significant difference was observed between the group treated by high-dose MTX alone and those treated by low-dose MTX. No toxicity was observed even when high doses of MTX were used.


Prevalence of chronic disease and insurance coverage among refugees in the United States.
Little is known about the health status of refugees beyond the immediate post-arrival period in the US. Using data from the 2003 New Immigrant Survey, a nationally representative survey of immigrants who had recently become legal permanent residents, we determined the prevalence of chronic conditions and health insurance coverage among adult refugees who had lived in the US for at least 1 year (n = 490). We compared their health status with that of other immigrants (n = 3,715) using multivariable logistic regression. The median duration of US residency was 5.6 and 8.0 years among refugees and other immigrants, respectively. Refugees were more likely than other immigrants to report at least one chronic condition (24.7 vs. 15.6 %, P < 0.001). After adjusting for sociodemographic differences, the odds of the following conditions remained significantly higher among refugees: arthritis (adjusted odds ratio [AOR] = 1.67, 95 % confidence interval [CI] = 1.07, 2.61), heart disease (AOR = 2.49, 95 % CI = 1.30, 4.74), stroke (AOR = 5.87, 95 % CI = 1.27, 27.25), activity-limitation due to pain (AOR = 1.96, 95 % CI = 1.31, 2.93), and any chronic condition (AOR = 1.37, 95 % CI = 1.03, 1.81). Although similar percentages of refugees (49.0 %) and other immigrants (47.4 %) were uninsured, 46.5 % of refugees with chronic conditions lacked health insurance. Refugees have a high burden of chronic disease and would benefit from expanded insurance coverage for adults with preexisting conditions.


The toxic effects of pentachlorophenol on rat Sertoli cells in vitro.
Pentachlorophenol (PCP) is the most toxic contaminant of chlorophenols (CPs). Due to improper disposal, PCP has become an environmental pollutant and is now considered to be ubiquitous. Previous studies about the influences of PCP on reproductive function were mostly focused on experiments in vivo. The aim of our present study was to estimate the toxic effects of PCP on cultured Sertoli cells from Sprague-Dawley rats. The viability of Sertoli cells was detected and morphological examination was performed followed by flow cytometric assay to evaluate its toxic effects. The 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that the toxic effects of PCP on cultured Sertoli cells were dose- and time-dependent. By flow cytometric assay, it was found that the number of dead Sertoli cells increased with the increase of exposed PCP levels. The results indicated that PCP had direct and dose-dependent cytotoxic effects on Sertoli cells in vitro.


Sources of error in bone mineral density estimates from quantitative CT.
Bone mineral density (BMD) estimates from quantitative computed tomography (QCT) have proven useful for opportunistic screening of osteoporosis, treatment monitoring, and bone strength measurement. These estimates are subject to bias and variance from a variety of sources related to the imaging equipment, methods applied in the estimation procedure, and the patients themselves. In this article, we review the literature to describe the sources and sizes of error in spine and hip BMD estimates from single-energy QCT that can result from factors related to the scanner, imaging techniques, imaging subject, calibration phantom, and calibration approach. We also describe the baseline variance that can be expected based on repeatability and reproducibility studies. Though reproducible BMD estimates may be achievable with QCT, a thorough understanding of the potential sources of error and their size relative to the diagnostic task is essential to their appropriate and meaningful interpretation.


Which traumatic spinal injury creates which degree of instability? A systematic quantitative review.
Traumatic spinal injuries often require surgical fixation. Specific three-dimensional degrees of instability after spinal injury, which represent criteria for optimum treatment concepts, however, are still not well investigated. The aim of this review therefore was to summarize and quantify multiplanar instability increases due to spinal injury from experimental studies. Systematic review. A systematic review of the literature was performed using keyword-based search on PubMed and Web of Science databases in order to detect all in vitro studies investigating the destabilizing effect of simulated and provoked traumatic injury in human spine specimens. Together with the experimental designs, the instability parameters range of motion, neutral zone and translation were extracted from the studies and evaluated regarding type and level of injury. A total of 59 studies was included in this review, of which 43 studies investigated the effect of cervical spine injury. Range of motion increase, which was reported in 58 studies, was generally lower compared to the neutral zone increase, given in 37 studies, despite of injury type and level. Instability increases were highest in flexion/extension for most injury types, while axial rotation was predominantly affected after cervical unilateral dislocation injury and lateral bending solely after odontoid fracture. Whiplash injuries and wedge fractures were found to increase instability equally in all motion planes. Specific traumatic spinal injuries produce characteristic but complex three-dimensional degrees of instability, which depend on the type, level, and morphology of the injury. Future studies should expand research on the cervicothoracic, thoracic, and lumbosacral spine and should additionally investigate the destabilizing effects of the injury morphology as well as concomitant rib cage injuries in case of thoracic spinal injuries. Moreover, neutral zone and translation should be measured in addition to the range of motion, while mechanical injury simulation should be preferred to resection or transection of structures to ensure high comparability with the clinical situation.


A further evaluation of the cognitive deficits associated with restless legs syndrome (RLS).
Restless legs syndrome (RLS) is a common sensorimotor disorder that peaks in severity during the night and comes on with rest. As a result, this condition often results in significant chronic sleep loss, especially for those with severe disease. Chronic partial sleep restriction has been associated with conditions such as depression, anxiety, chronic pain, and decline in cognitive function. Furthermore, studies have found that RLS patients suffer from these conditions more than their unaffected peers. Thus, the morbidity rate associated with RLS has often been attributed to the chronic sleep loss that frequently accompanies this condition. However, no study has specifically compared RLS sufferers to otherwise normal sleep-restricted controls in order to assess disease morbidity independent of its sleep deprivation effects. In this study, we compared the cognitive function of RLS patients who were off treatment to sleep-restricted control subjects. A novel chronic partial sleep-restriction protocol that utilized a 14-day combined inpatient and outpatient design was implemented in order to test the differences in cognitive functioning between RLS patients and sleep-restricted controls. The brief cognitive battery included instruments assessing general intelligence and global executive function in order to control for baseline cognitive function between the groups, and then the effects of sleep loss were assessed using prefrontal lobe-specific tasks. The final sample consisted of 16 RLS (11 male and 5 female) and 13 sleep-restricted control subjects (7 male and 6 female). In order to examine the differences in cognitive functioning between sleep-restricted controls and RLS subjects, independent samples t-tests were conducted. RLS subjects performed significantly better on both the Letter Fluency (t=2.13, p<0.05) and Category Fluency (t=2.42, p<0.05) than sleep-restricted controls. RLS subjects performed better than the sleep-restricted controls on two tasks that are particularly sensitive to sleep loss. Although previous studies suggest that sleep deprivation may impact the cognitive function of those with RLS, our data suggests that RLS subjects may show a relative degree of sleep loss adaptation. Future investigations that more closely match the sleep loss pattern of RLS subjects to controls are warranted in order to explore these potential traits further.


Occurrence and risk assessment of typical PPCPs and biodegradation pathway of ribavirin in wastewater treatment plants.
A large number of pharmaceuticals and personal care products (PPCPs) persist in wastewater, and the consumption of PPCPs for COVID-19 control and prevention has sharply increased during the pandemic. This study investigated the occurrence, removal efficiency, and risk assessment of six typical PPCPs commonly used in China in two wastewater treatment plants (WWTPs). Ribavirin (RBV) is an effective pharmaceutical for severely ill patients with COVID-19, and the possible biodegradation pathway of RBV by activated sludge was discovered. The experimental results showed that PPCPs were detected in two WWTPs with a detection rate of 100% and concentrations ranging between 612 and 2323 ng L-1. The detection frequency and concentrations of RBV were substantially higher, with a maximum concentration of 314 ng L-1. Relatively high pollution loads were found for the following PPCPs from influent: ibuprofen > ranitidine hydrochloride > RBV > ampicillin sodium > clozapine > sulfamethoxazole. The removal efficiency of PPCPs was closely related to adsorption and biodegradation in activated sludge, and the moving bed biofilm reactor (MBBR) had a higher removal capacity than the anoxic-anaerobic-anoxic-oxic (AAAO) process. The removal efficiencies of sulfamethoxazole, ampicillin sodium, ibuprofen, and clozapine ranged from 92.21% to 97.86% in MBBR process and were relatively low, from 61.82% to 97.62% in AAAO process, and the removal of RBV and ranitidine hydrochloride were lower than 42.96% in both MBBR and AAAO processes. The discrepancy in removal efficiency is caused by temperature, hydrophilicity, and hydrophobicity of the compound, and acidity and alkalinity. The transformation products of RBV in activated sludge were detected and identified, and the biodegradation process of RBV could be speculated as follows: first breaks into TCONH2 and an oxygen-containing five-membered heterocyclic ring under the nucleosidase reaction, and then TCONH2 is finally formed into TCOOH through amide hydrolysis. Aquatic ecological risks based on risk quotient (RQ) assessment showed that PPCPs had high and medium risks in the influent, and the RQ values were all reduced after MBBR and AAAO treatment. Ranitidine hydrochloride and clozapine still showed high and medium risks in the effluent, respectively, and thus presented potential risks to the aquatic ecosystem.


Return of interdigestive motor complex after abdominal surgery. End of postoperative ileus?
Gastrointestinal mechanical activity was studied in 13 patients after different surgical procedures in a fasted and fed state and after pharmacological stimulation. Mechanical activity was recorded by means of a multi-pressure sensor probe placed intraoperatively into the jejunum. Abdominal surgery abolished normal motility only for a short period of time. The time for the reappearance of regular recurring activity fronts varied with the type of the surgical procedure from 3 hr after cholecystectomy to the sixth postoperative day after colon resection. The fed pattern occurred after the first postoperative interdigestive motor complex in all experiments. Stimulation was observed with ceruletide, which induced contractile activity in the small intestine during postoperative ileus. No coordinated caudad propagating activity was observed. The postoperative interdigestive motor complex did not correlate in time with the first passage of flatus and stool in our patients. Thus, the restoration of motility in the small intestine did not coincide with the clinical relief from the so-called "physiological" postoperative ileus.


Prevalence of Sarcocystis infection and other intestinal parasitisms in dogs from a humane shelter in Ohio.
Fecal specimens from 500 stray dogs in Columbus, Oh, were examined for evidence of intestinal parasitisms. Prevalences (%) of coccidia were: Sarcocystis sp, 1.8; Isospora canis, 1.8; and Isospora ohioensis, 3.6. Prevalences (%) of helminths were: Toxocara canis, 19.2; Toxascaris leonina, 10.2; Trichuris sp, 42.2; Capillaria sp; 1.0; Ancylostoma sp, 60.8; Uncinaria sp, 2.4; and Taenia sp, 7.4.


Methods for rearing Syngaster lepidus and Jarra phoracantha (Hymenoptera: Braconidae), larval parasitoids of the phloem-colonizing longhorned beetles Phoracantha semipunctata and P. recurva (Coleoptera: Cerambycidae).
Two species of cerambycid beetles that attack eucalypts, Phoracantha semipunctata (Fabricius) and P. recurva Newman, have been accidentally introduced from Australia into most regions of the world in which their hosts have been planted. The beetles cause extensive mortality in plantations and landscape plantings of the trees. Management programmes have focused on integration of silvicultural practices, host plant resistance and biological control. To rear and release natural enemies of the larval stages of the beetles in California, mass rearing protocols for continuous production of two species of parasitoids have been developed. The methods described represent the first long-term and large-scale techniques for mass rearing parasitoids of any wood-boring cerambycid species. In addition to providing large numbers of parasitoids for releases, the mass rearing effort has also provided large numbers of parasitoids for fundamental studies of their biology and behaviour.


The health economics of allergen immunotherapy.
In contrast to symptomatic drug treatment, which only temporarily relieves allergy symptoms, allergen-specific immunotherapy (SIT) has the potential to alter the course of allergic disease, thereby reducing the need for long-term treatment, the progression of allergic rhinitis (AR) to asthma, and the development of new allergies. The clinical benefits of SIT have been shown to persist for an additional 3 to 12 years after discontinuation of a 2.5- to 5.0-year treatment. It therefore stands to reason that the clinical benefits of SIT also extend to economic benefits. A growing number of studies have evaluated the economic benefits of SIT in patients with AR and/or asthma. The authors critically examine each of these studies published from 1995 to present.


Doppler assessment of patients with twin-to-twin transfusion syndrome and survival following fetoscopic laser surgery.
To investigate fetal-survival rates following laser surgery for twin-to-twin transfusion syndrome (TTTS) and the impact of Doppler analysis. The present retrospective single-center study included data from patients with pregnancies exhibiting TTTS treated with fetoscopic laser surgery between January 1, 2007, and December 31, 2016. Perinatal outcomes were examined and variables were compared between the donor and recipient fetuses that survived and died, respectively. There were 86 pregnancies exhibiting TTTS treated with fetoscopic laser surgery included in the study. The median length of pregnancy at the time of surgery was 21.1 weeks. Both twin fetuses and at least one fetus survived in 61 (71%) and 73 (85%) pregnancies, respectively. Among recipient fetuses, ductus venosus a-wave anomalies (P=0.026), shorter cervical length (P=0.044), and a greater than 25% discrepancy in the estimated weight of the twin fetuses (P=0.045) were associated with reduced survival. Among pregnancies exhibiting TTTS, laser surgery was associated with significant dual-fetus survival. Preoperative ductus venosus anomalies were associated with lower survival among recipient fetuses, and 1-week postsurgical ultrasonography data demonstrated lower survival among recipient fetuses with persistent anomalous ductus venosus compared with normalized ductus venosus.


Evidence for basic fibroblast growth factor receptors in cultured immature Leydig cells.
Previous studies have shown that basic fibroblast growth factor (bFGF) can modulate basal and luteinizing hormone/human chorionic gonadotropin (LH/hCG)-stimulated Leydig cell functions. It has not been ascertained whether these actions are due to direct or indirect effects on Leydig cells. To resolve this question, a multi-step procedure was used to isolate highly-purified Leydig cells from immature rats. 125I-bFGF binding studies were performed on cultured cells. Scatchard analysis of the data indicated a single binding site with an apparent Kd of 82 pM and a binding capacity of approximately 2800 sites per cell. Both bFGF and acidic FGF similarly were effective in displacing 125I-bFGF, suggesting that the receptor binds both bFGF and aFGF. However, neither hCG, follicle-stimulating hormone (FSH), insulin, insulin-like growth factor-1 (IGF-1), prolactin, platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) were effective competitors. When binding studies were conducted on cultured testicular interstitial cellular fractions that are normally discarded during Leydig cell purification, bFGF receptors were identified in these fractions. These results demonstrate that bFGF can have direct effects on Leydig cells through specific receptors; however, because other interstitial cell type(s) also have bFGF receptors, they stress the importance of using highly purified cells when evaluating bFGF actions on Leydig cells.


A novel role of IL-17A in contributing to the impaired suppressive function of Tregs in psoriasis.
Regulatory T cells (Tregs) are crucial in maintaining T cell homeostasis and preventing autoimmune responses. Deficiencies in the suppressive function of Tregs contribute to the pathogenesis of various autoimmune diseases, such as psoriasis. However, whether IL-17A upregulation in psoriatic patients contributes to Treg dysfunction is unknown. To explore the effect and underlying mechanism of IL-17A on the suppressive function of Tregs and to evaluate the restoration of the suppressive function of Tregs in psoriasis during anti-IL-17A (secukinumab) treatment. In vitro suppression assays were performed with or without the addition of IL-17A to the coculture system. The release of inhibitory cytokines, including IL-10 and TGF-β, was assessed by qRT-PCR and flow cytometry. RNA-sequencing was conducted to characterize the cellular responses of Tregs. IL-17A signaling activation was analyzed by flow cytometry and immunofluorescence. Blood samples were collected from three psoriasis patients before and after secukinumab treatment. IL-17A blocked the suppressive function of Tregs, possibly by inhibiting the release of TGF-β and promoting the production of IFN-γ. Moreover, IL-17A activated the NF-κB signaling pathway in Tregs. Inhibition of the NF-κB pathway blocked IL-17A-induced upregulation of IFN-γ without affecting the secretion of TGF-β by Tregs. Clinical treatment in psoriasis with secukinumab restored the suppressive function and increased production of TGF-β in Tregs of psoriasis. Our study implies a crucial role of IL-17A in mediating the dysfunction of the Treg suppressive function in psoriasis. Secukinumab, which neutralizes IL-17A signaling, restored the suppressive function of Tregs to exert its antipsoriatic effect.


Diterpenoids from the pericarp of Platycladus orientalis.
Eight labdane-type diterpenes, 7beta,13S-dihydroxylabda-8(17),14-dien-19-oic acid (1), 12R,15-dihydroxylabda-8(17),13E-dien-19-oic acid (3c), 12R,15-dihydroxylabda-8(17),13Z-dien-19-oic acid (3d), 12R,13R,14S-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4a), 12S,13S,14R-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4b), 15-hydroxy-12-oxolabda-8(17),13E-dien-19-oic acid (5), 14R,15-dihydroxylabda-8(17),12Z-dien-19-oic acid (7a) and 14S,15-dihydroxylabda-8(17),12Z-dien-19-oic acid (7b), along with 20 known diterpenoids, were isolated from the pericarp of Platycladus orientalis. Their structures were unambiguously elucidated by NMR spectroscopic and single crystal X-ray diffraction analyses, as well as via chemical correlation conversion. NMR spectroscopic data of known isomers 8c and 8d were reported as a supplement to existing data.


Evaluation of air quality in Chengdu, Sichuan Basin, China: are China's air quality standards sufficient yet?
Air quality evaluation is important in order to inform the public about the risk level of air pollution to human health. To better assess air quality, China released its new national ambient air quality standards (NAAQS-2012) and the new method to classify air quality level (AQL) in 2012. In this study, we examined the performance of China's NAAQS-2012 and AQL classification method through applying them, the World Health Organization (WHO) guidelines, and the US AQL classification method to evaluate air quality in Chengdu, the largest city in southwestern China. The results show that annual mean concentrations of PM₁₀, PM₂.₅, SO₂, NO₂, and O₃ at the seven urban sites were in the ranges of 138-161, 87-98, 18-32, 54-70, and 42-57 μg/m(3), respectively, and the annual mean concentrations of CO were in the range of 1.09-1.28 mg/m(3). Chengdu is located in one of the four largest regions affected by haze in China, and PM₁₀ and PM₂.₅ were the top air pollutants, with annual concentrations over 2 times of their standards in NAAQS-2012 and over 7 times of the WHO guidelines. Annual mean concentrations of the pollutants were much lower at the background site (LYS) than at the urban sites, but the annual mean concentrations of PM₁₀ and PM₂.₅ at LYS were 3.5 and 5.7 times of the WHO guidelines, respectively. These suggest that severe air pollution in Chengdu was largely associated with local emissions but also related to regional air pollution. The compliance rates of PM₁₀ , PM₂.₅, SO₂, and O₃ met China's NAAQS-2012 standards four times more frequently than they met the WHO guidelines, as NAAQS-2012 uses the loosest interim target (IT) standards of WHO for these four pollutants. Air pollution in Chengdu was estimated and stated to be less severe using China's classification than using the US classification, as China uses weaker concentration breakpoints and benign descriptions of AQL. Furthermore, China's AQL classification method does not capture the cumulative effects of multiple pollutants, and the risk assessment is mainly based on the exposure-response relationship between air pollutant and human health quantified in the North America and West Europe; these can bring some uncertainties into evaluating the risk to human health in China. In summary, although China greatly improved its NAAQS and AQL classification method in 2012, further improvements are still needed.


Tris(tetra-butyl-ammonium) tris-(nitrato-κO,O')tetra-kis-(thio-cyanato-κN)thorium(IV).
The title compound, (C(16)H(36)N)(3)[Th(NCS)(4)(NO(3))(3)], was obtained from the reaction of Th(NO(3))(4)·5H(2)O with (Bu(4)N)(NCS). The Th(IV) atom is in a ten-coordinate environment of irregular geometry, being bound to the N atoms of the four thio-cyanate ions and to three bidentate nitrate ions. The average Th-N and Th-O bond lengths are 2.481 (10) and 2.57 (3) Å, respectively.


Aging-associated alterations in contractility of rat mesenteric lymphatic vessels.
To evaluate the age-related changes in pumping of mesenteric lymphatic vessels in 9- and 24-month-old male Fisher-344 rats. Lymphatic diameters, contraction amplitude, contraction frequency, and fractional pump flow were determined in isolated MLV before and after l-NAME application. The data demonstrate a severe weakening of the lymphatic pump in aged MLV including diminished lymphatic contraction amplitude, contraction frequency, and as a result, lymphatic pump activity. The data also suggest that the imposed flow gradient-generated shear-dependent relaxation does not exist in aged rat MLV, and the sensitivity of both adult and aged MLV to such shear cannot be eliminated by nitric oxide (NO) synthases blockade. These data provide new evidence of lymphatic regional heterogeneity for both adult and aged MLV. In MLV, a constant interplay between the tonic and phasic components of the myogenic response and the shear-dependent release of NO predominantly determine the level of contractile activity; the existence of another shear-dependent, but NO-independent regulatory mechanism is probably present. Aging remarkably weakens MLV contractility, which would predispose this lymphatic network to lower total lymph flow in resting conditions and limit the ability to respond to an edemagenic challenge in the elderly.


Modelling conditional distributions in bivariate survival.
Conditional distributions for bivariate survival can be obtained via a model for the joint distribution, or, as has sometimes been suggested, by modelling the conditioned variable directly, with the conditioning variable included as a covariate. A quantitative comparison of estimated covariate effects and predictive distributions under the two approaches is given. The results are illustrated in a novel frailty application.


Risk factors related to recurrence in inguinal hernia repair: a retrospective analysis.
The aim of this study was to analyze and evaluate the long-term recurrence rate and risk factors for inguinal hernia recurrence in patients treated by the Shouldice suture repair. A total of 293 hernias treated by Shouldice suture technique in 1992 were studied retrospectively. After a 10-year follow-up, 15 potential risk factors for recurrence were assessed in 142 patients undergoing 171 Shouldice repairs. Recurrent hernias showed a significantly higher (22.0%) recurrence rate than primary inguinal hernias (7.7%). Furthermore, an age of more than 50 years, smoking, and the presence of two or more similarly affected relatives were found to be independent risk factors for recurrence. The present study underlines the importance of patient-related risk factors for the development of a recurrent inguinal hernia. Patients at risk should preoperatively be identified in order to improve treatment by, for example, the application of mesh techniques.


Precise Score Validation in Buenos Aires 1 Registry.
The PRECISE-DAPT score predicts the bleeding risk in patients treated with dual antiplatelet treatment after PCI. We asess the prediction power of the score in patients suffering from non-ST elevation acute coronary syndromes. Our cohort included 862 patients from Buenos Aires 1 registry. The PRECISE-DAPT score was calculated upon admission and the follow up period was 15 months. The score as a continuous variable had low to moderate ability to predict bleeding events BARC 2, 3 or 5 (c-statistics 0.58 [95% CI, 0.52-0.61]); moderate at BARC 3 or 5 (c-statistics 0.72 [95% CI, 0.64-0.78]), and poor for MACE (c-statistics 0.49 [95% CI, 0,45-0.51]). PRECISE-DAPT score as a dichotomous variable (≥25, n= 210 [24%]) was associated with very high risk of bleeding (HR 2.1) and ischemic events (HR 1.9, 95% CI 1.8-2.1). As conclusion, PRECISE-DAPT score ≥25 was able to identify a subgroup of patients with high bleeding, and thrombotic events.


Lived experience of having type 2 diabetes: A phenomenological research in three villages in rural Northern Saudi Arabia.
The study was aimed to explore the lived experience among patients with type-2 diabetes living in rural settings. A qualitative phenomenological study design was used in this study. First, the patients' reactions were a mixture of denial and shock regarding their diagnosis of diabetes. Second, they faced challenges of having debilitating disease. Third, all were Muslims, and their faith led them to accept their disease as their destiny from Allah. Fourth, they psychologically accepted the disease to gain the physical acceptance of their condition. Finally, the participants demonstrated a degree of adaptation. The study findings suggested that type-2 diabetes is viewed as a matter of destiny. Although participants in the current study revealed natural feelings of shock and denial towards their illnesses in the early stages; however, they soon became more familiar with their disease and expressed a feeling of acceptance and adaptation, especially during Ramadan.


A decision analysis of allogeneic hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission who have an HLA-matched sibling donor.
Clinical studies using genetic randomization cannot accurately answer whether adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) who have a human leukocyte antigen (HLA)-matched sibling should undergo allogeneic hematopoietic stem cell transplantation (HSCT) or chemotherapy in first remission, as, in these studies, patients without a sibling donor undergo alternative donor transplantation or chemotherapy alone after a relapse. Therefore, we performed a decision analysis to identify the optimal strategy in this setting. Transition probabilities and utilities were estimated from prospective studies of the Japan Adult Leukemia Study Group, the database of the Japan Society for Hematopoietic Cell Transplantation and the literature. The primary outcome measure was the 10-year survival probability with or without quality of life (QOL) adjustments. Subgroup analyses were performed according to risk stratification on the basis of white blood cell count and cytogenetics, and according to age stratification. In analyses without QOL adjustments, allogeneic HSCT in first remission was superior in the whole population (48.3 vs 32.6%) and in all subgroups. With QOL adjustments, a similar tendency was conserved (44.9 vs 31.7% in the whole population). To improve the probability of long-term survival, allogeneic HSCT in first remission is recommended for patients who have an HLA-matched sibling.


[Long-term oral administration of etoposide in the treatment of patients with advanced non-small-cell carcinoma of the lung. The second phase of a clinical study].
Over the period from May 1989 to May 1992 thirty-four patients with advanced non-small cell lung cancer (NSCLC) were treated with prolonged administration of oral etoposide. Etoposide was administered in a dose of 50 mg/m2 a day for 21 days. Nine (26%) patients partially responded to the treatment that lasted 2-7 months (median 5 months). Median survival time was 6 months, and 1-year survival was 32%. The most common toxic events were alopecia and myelosuppression. No patient died of treatment-related toxicity. Results of this study demonstrate moderate efficiency of the prolonged administration of oral etoposide to patients with advanced NSCLC.


Association of State Medicaid Expansion Status With Hypertensive Disorders of Pregnancy in a Singleton First Live Birth.
Incidence of hypertensive disorders of pregnancy is increasing in the United States. Early detection is important to prevent adverse maternal and offspring outcomes. This ecological study evaluated changes in rates of hypertensive disorders of pregnancy among states that expanded Medicaid compared with states that did not expand Medicaid. A quasi-experimental analysis using difference-in-differences models compared changes in rates of hypertensive disorders of pregnancy in Medicaid expansion states relative to non-Medicaid expansion states from 2012 to 2019. Maternal data from singleton first live births to individuals aged 20 to 39 years were obtained from the National Center for Health Statistics. Outcomes of interest included age-adjusted rates of de novo hypertension in pregnancy (gestational hypertension or preeclampsia) and prepregnancy hypertension. Data from 7 764 965 individuals with a singleton first live birth were analyzed from 17 states and Washington, DC that expanded Medicaid and 15 states that did not. Rates of de novo hypertension in pregnancy increased over the study period in both expansion (54.34 [95% CI, 48.25-60.43] to 74.87 [95% CI, 71.20-78.55] per 1000 births) and nonexpansion states (68.32 [95% CI, 61.02-75.62] to 84.79 [95% CI, 80.67-88.91] per 1000 births). In adjusted difference-in-differences analyses, expansion status was associated with a greater increase in rates of de novo hypertension in pregnancy (difference-in-differences coefficient, +8.18 [95% CI, 4.00-12.36] per 1000 live births) but a decline in rates of de novo hypertension in pregnancy complicated by low birth weight (-7.20 [95% CI, -13.71 to -0.70] per 1000 births with hypertensive disorders of pregnancy). In adjusted difference-in-differences analyses, there were no significant changes in rates of prepregnancy hypertension in expansion relative to nonexpansion states (+1.13 [95% CI, -0.09 to +2.35] per 1000 live births). Between 2012 and 2019, states that expanded Medicaid had a significantly greater increase in rates of de novo hypertension, with some evidence of better outcomes among those with de novo hypertension diagnosed in pregnancy.


Anti-HIV/SIV activity of icariin and its metabolite anhydroicaritin mainly involve reverse transcriptase.
AIDS, a serious fatal disease caused by the human immunodeficiency virus (HIV), is an epidemic disease for which no effective vaccine has been established. The current therapeutic interventions for AIDS have limited efficacy because they are unable to clear HIV infections and the continuous occurrence of resistant HIV strains. Therefore, the exploitation of new drugs to prevent the spread of AIDS remains a high priority. In this study, the effects of icariin and its metabolite anhydroicaritin on SIV/HIV replication were investigated. In CEM × 174 cells and PBMC cells, both icariin and anhydroicaritin can significantly inhibit HIV-1 or SIVmac251 replication. Furthermore, molecular docking studies revealed that icariin and anhydroicaritin can act on both HIV reverse transcriptase and protease but could not bind to integrase. Reverse transcriptase and protease inhibition biological assays showed that both icariin and anhydroicaritin could significantly inhibit only HIV reverse transcriptase. In summary, the two compounds can significantly inhibit HIV/SIV in vitro and their targets may be mainly involved with HIV reverse transcriptase.


Detection of microbial contamination based on uracil-selective synthetic receptors.
The here presented work is focused on the development of a method for detection of microbial contamination of food based on uracil-selective synthetic receptors. Because uracil may serve as an indicator of bacterial contamination, its selective and on-site detection may prevent spreading of foodborne diseases. The synthetic receptors were created by molecular imprinting. Molecularly imprinted polymers for selective uracil isolation were prepared by a non-covalent imprinting method using dopamine as a functional monomer. Detection of isolated uracil was performed by capillary electrophoresis with absorption detection (λ - 260 nm). The conditions of preparation of molecularly imprinted polymers, their binding properties, adsorption kinetics and selectivity were investigated in detail. Furthermore, the prepared polymer materials were used for selective isolation and detection of uracil from complex samples as tomato products by miniaturized electrophoretic system suggesting the potential of in situ analysis of real samples.


Ontogenetic changes in citrate synthase and lactate dehydrogenase activity in the jumping muscle of the American locust (Schistocerca americana).
Intraspecific studies have repeatedly shown that muscle-specific oxidative enzyme activities scale negatively with body mass while muscle-specific glycolytic enzyme activities scale positively. However, most of these studies have not included juveniles. In this study, we examined how citrate synthase (CS, EC 188.8.131.52) and lactate dehydrogenase (LDH; EC 184.108.40.206) activity in the jumping muscle of Schistocerca americana grasshoppers varied with ontogeny across a 40-fold increase in body size. In contrast to the pattern observed when adult conspecifics are compared, we show that jumping muscle CS activity increased more than 2-fold from 2nd instars to adults, while jumping muscle LDH activity increased more than 5-fold. The increased LDH activity in older grasshoppers supports previous data that older grasshoppers have a reduced jumping endurance. The increased CS activity with age may help older grasshoppers efficiently produce aerobic ATP to bend cuticular springs for energy storage before a jump or alternatively recover from anaerobic metabolism after jumping. Metabolic changes in S. americana jumping muscle are similar to other developing taxa and highlight the importance of including juveniles within intraspecific studies. When compared to adults, juvenile locomotion may have increased selection pressure because of both greater energetic demands during growth and higher predation rates.


The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults.
The aim of this study was to examine the effects of birth order and parental age on the risk of type 1 and type 2 diabetes among Finnish individuals aged 15-39 years. Data on all cases of type 1 diabetes (n = 1,345) and type 2 diabetes (n = 1,072), diagnosed between 1992 and 1996, were collected from four sources: standardised national reports from diabetes nurses, the National Hospital Discharge Register, the Drug Prescription Register and the Drug Reimbursement Register. Information on matched controls and the family members of all study subjects were obtained from the National Population Registry. The odds ratios (ORs) for both types of diabetes were estimated using a conditional logistic regression model. There was a U-shaped relationship between maternal age and the risk of type 2 diabetes in the offspring: the risk was higher in children born to young and old mothers compared with children born to mothers aged around 30 years. The children born second (OR 0.76, 95% CI 0.62-0.94), third (OR 0.73, 95% CI 0.55-0.95), or fourth (OR 0.66, 95% CI 0.47-0.94) had a lower risk of type 2 diabetes than the first-born children. Maternal age, paternal age, and birth order did not have an effect on the risk of type 1 diabetes in the individuals aged 15-39 years at the time of diagnosis. Maternal age and birth order are both associated with the risk of early-onset type 2 diabetes. However, part of these associations may be due to low birthweight. In this study neither parental age nor birth order showed a significant association with the risk of type 1 diabetes diagnosed after 15 years of age.