Ultrastructural criteria of cardiomyocyte regeneratory and plastic insufficiency in anthracycline cardiomyopathy.
We analyzed the dynamics of ultrastructural changes in cardiomyocytes in experimental chronic anthracycline cardiomyopathy. Doxorubicin-induced changes in cardiomyocytes were characterized by a specific combination of ultrastructural changes, which can be regarded as markers of the development of regeneratory and plastic insufficiency. These markers include a triad of changes: deformation of the nuclei with reorganization of the nucleolar system; diffuse and small focal lysis of myofibrils (mainly fine filaments); dilatation of agranular sarcoplasmic reticulum and the intermembrane perinuclear space connected to it. The terminal stages of these disorders are degeneration of some cardiomyocytes, their apoptotic death, and resorption by mononuclear cells (processes representing successive stages in the development of regeneratory and plastic insufficiency of the myocardium).


Distal radial epiphyseal displacement after impaired distal ulnar growth.
Impairment of growth of the distal end of the ulna was produced in rabbits by excision of the distal epiphyseal plate. This caused a sequence of changes in the distal radial epiphysis consisting of combined increased chondrogenesis and decreased osteogenesis of the radial two-thirds of the distal epiphysis, and decreased chondrogenesis and increased osteogenesis on the ulnar side. At six to nine days postoperatively, cracks appeared concomitant with tilting of the plate and epiphysis, in the epiphyseal plate or at its metaphyseal junction. An incomplete radial epiphyseal separation occurred, a step-like deformity developed in the metaphysis, and an ulnar deviation developed.


Anaerobic bacteria in uterine infection following first trimester abortion.
Samples of uterine fluid and cervical mucus for bacterial culture were obtained from 23 patients with endometritis following first trimester abortion. Uterine samples were obtained via a sheathed system which minimizes contamination by the cervical flora. A mean of 3.4 isolates were identified in cervical samples as compared to 1.8 in uterine samples. Anaerobic bacteria were found in 57% of the uterine samples and dominated in both uterine and cervical samples. Peptostreptococcus species dominated in cervical samples and Bacteroides species in uterine samples. Significantly more bacterial species were found in uterine samples from patients with a high erythrocyte sedimentation rate. Since no bacteria were found in 39% of uterine samples a possible role of nonmicrobial pyrogenic substances is suggested.


An expression vector tailored for large-scale, high-throughput purification of recombinant proteins.
Production of milligram quantities of numerous proteins for structural and functional studies requires an efficient purification pipeline. We found that the dual tag, his(6)-tag-maltose-binding protein (MBP), intended to facilitate purification and enhance proteins' solubility, disrupted such a pipeline, requiring additional screening and purification steps. Not all proteins rendered soluble by fusion to MBP remained soluble after its proteolytic removal, and in those cases where the protein remained soluble, standard purification protocols failed to remove completely the stoichiometric amount of his(6)-tagged MBP generated by proteolysis. Both liabilities were alleviated by construction of a vector that produces fusion proteins in which MBP, the his(6)-tag and the target protein are separated by highly specific protease cleavage sites in the configuration MBP-site-his(6)-site-protein. In vivo cleavage at the first site by co-expressed protease generated untagged MBP and his(6)-tagged target protein. Proteins not truly rendered soluble by transient association with MBP precipitated, and untagged MBP was easily separated from the his-tagged target protein by conventional protocols. The second protease cleavage site allowed removal of the his(6)-tag.


Myelodysplastic syndrome: diagnostic implications of cytochemical and immunocytochemical studies.
Cytochemical and immunocytochemical studies were performed on bone marrow aspirates from 96 cases of primary myelodysplastic syndrome (MDS), 11 cases of secondary MDS, 22 cases of non-MDS hematologic disorders, and 10 cases of nondiagnostic, apparently normal marrow specimens to determine the practicality and utility of these stains for diagnosing MDS. Cytochemical studies included iron stain, periodic acid-Schiff (PAS), peroxidase, butyrate esterase, chloroacetate esterase, and double esterase stains. Immunocytochemical staining was done with monoclonal antibody HP1-1D, which recognizes the glycoprotein IIb/IIIa complex in megakaryocytes. The iron stain remained most helpful in identifying abnormal ringed sideroblasts, a feature of dyserythropoiesis, and thus in supporting the diagnosis of MDS. The PAS stain was helpful, if positive, in identifying patients with MDS; however, when it was negative, this stain did not help distinguish MDS from non-MDS hematologic disorders. The immunocytochemical stain with HP1-1D monoclonal antibody was also helpful in identifying atypical micromegakaryocytes, indicative of dysmegakaryopoiesis. Other cytochemical abnormalities were infrequently observed and were less specific for the diagnosis of MDS. The combination of two stains--for example, PAS and iron stain or PAS and double esterase--was helpful, however, in excluding MDS, inasmuch as neither the miscellaneous nor the control group stained positively with these combinations.


Triple Emulsion Drops with An Ultrathin Water Layer: High Encapsulation Efficiency and Enhanced Cargo Retention in Microcapsules.
Triple emulsion drops with an ultrathin water layer are developed to achieve high encapsulation efficiency of hydrophobic cargo in a hydrophobic polymeric shell, directly dispersed in water. Furthermore, enhanced retention of volatile hydrophobic cargo is achieved by forming a hydrogel network within this water layer that serves as a physical barrier.


Zonation in the deep benthic megafauna : Application of a general test.
A test based on Maxwell-Boltzman statistics, instead of the formerly suggested but inappropriate Bose-Einstein statistics (Pielou and Routledge, 1976), examines the distribution of the boundaries of species' ranges distributed along a gradient, and indicates whether they are random or clustered (zoned). The test is most useful as a preliminary to the application of more instructive but less statistically rigorous methods such as cluster analysis. The test indicates zonation is marked in the deep benthic megafauna living between 200 and 3000 m, but below 3000 m little zonation may be found.


Tracking organic matter and microbiota dynamics during the stages of lignocellulosic waste composting.
The dynamics of biologically meaningful soluble and polymeric carbon fractions and the combined relationships between physical, chemical and biological parameters during composting of lignocellulosic waste were evaluated. The first thermophilic stage is crucial in determining the further evolution of soluble and polymeric carbon fractions but the dynamics of carbon is still important at the maturation stage. Multivariate data analysis showed that not only are all parameters interrelated but also influence one another's variability. To discern completion of bio-oxidative stage other parameters in addition to temperature should be measured. Evaluation of soluble organic carbon, microbial biomass carbon, pH and inorganic nitrogen can be of great use in detecting the composting stage. This study offers new insights into the mechanisms involved in the biodegradation of organic matter and help to prioritize the parameters that contribute at critical stages of the process.


Impact of rice paddy agriculture on habitat usage of migratory shorebirds at the rice paddy scale in Korea.
Approximately 58 shorebird species, including endangered and threatened species, use various habitats while traveling on their long-distance migratory routes in the East Asian-Australasian Flyway (EAAF). Coastal rice paddies in midwestern Korea, which are located in the EAAF, serve as inland wetlands and provide important stopover sites for long-distance migratory shorebirds. We studied how shorebird population density is affected across periods, time since habitat formation, and field type, at the rice field scale. The shorebirds most frequently observed in rice paddies were, in order, black-tailed godwits (Limosa limosa), common greenshanks (Tringa nebularia), and wood sandpipers (T. glareola). Black-tailed godwits and wood sandpipers were affected by time since formation, field type, and water level, whereas field type affected common greenshanks. We propose that (1) flooding time, (2) shallow water level, (3) harrowed field type, and (4) 5-7 days of management intervals at paddy fields are important factors influencing shorebird species density, although all the factors did not influence common greenshank density. We propose that environmental characteristics derived from field management in rice paddies influence habitat use by migratory shorebirds. These factors need to be considered to systematically protect and manage shorebirds that use rice paddies as stopovers during their migration events.


Critical evaluation of the Credé maneuver: a urodynamic study of 207 patients.
The efficacy of Credé's maneuver to promote voiding was evaluated prospectively in 207 patients with a variety of lower urinary tract disorders. The normal response to Credé's maneuver was a contraction of the external urethral sphincter (the Credé effect), an increase in urethral pressure and maintained closure of the vesical neck. Relaxation of the external urethral sphincter and synchronous opening of the bladder neck during Credé's maneuver were seen in only 4 patients (2 per cent). We conclude that Credé's maneuver is an inefficient method of bladder emptying in the majority of patients and even when voiding is accomplished with Credé's maneuver it usually is grossly inefficient and associated with significant urethral obstruction.


Comparative neurology of the optic tectum in ray-finned fishes: patterns of lamination formed by retinotectal projections.
Retinotectal projections were studied in 33 different species of Actinopterygii, the ray-finned fishes, with horseradish peroxidase and cobalt tracing techniques. The distribution of retinorecipient layers in the contralateral optic tectum was analyzed. In addition, the degree of differentiation of the stratum periventriculare, and the presence of ipsilateral retinotectal projections was examined. Retinofugal fibers are labeled in the stratum opticum (SO), stratum fibrosum et griseum superficiale (SFGS), stratum griseum centrale (SGC), stratum album centrale (SAC) and stratum periventriculare (SPV). Some species lack the projection to the SO, others lack the projection to the SGC, and a third group of fishes lack both projections. Five different patterns of retinorecipient tectal strata are distinguished. These patterns correlate with the species' taxonomic position. Evolutionary trends of tectal lamination and retinotectal innervation are described. The retinotectal projection patterns provide a useful indicator of phylogenetic relationships. Some of our data suggest different relationships between actinopterygian species than hitherto believed.


Effects of a new indole derivative on guinea pig reproduction.
The effect of a new indole derivative, (1,1,3-trimethyl-3-(3'-indolyl)-1,2,3,4-tetra-hydrocyclopent[b]-in dole) denoted 1 related to indomethacin and yeuhchukene 2 were tested on guinea pig reproduction. In mating experiments ten females were given compound 1 p.o. from cycle day 14 and onwards throughout pregnancy. Two groups of ten females each were used as controls. Conception occurred significantly (p less than 0.001) faster in the treatment group. The litter size was significantly (p less than 0.001) smaller after treatment with the indole derivative. Dams and pups did not seem to have been adversely affected by the treatment as judged by their exterior, behavior and survival. The results are suggested to be due to a reduction in the number of ova available for conception (litter size) in combination with improved conditions for ovum implantation and/or a facilitated sperm migration in the female genital tract. These effects are discussed in relation to known effects of arachidonic acid metabolites on reproduction.


A Case Report of a Giant Tubular Adenoma With a Concurrent Fibroadenoma of the Breast.
Tubular adenomas are rare benign epithelial tumors of the breast. Only a handful of cases have been reported in literature. We describe a very rare case of a giant tubular adenoma with a concurrent fibroadenoma in a young woman.


Higher level practice in nursing: a prerequisite for nurse consultants?
The Prime Minister has stated that he wishes nurse consultant posts to be introduced in the NHS. The UKCC is currently consulting on a framework for recognizing nurses who are working at a higher level of practice, and this work could form the professional standards infrastructure for those seeking a nurse consultant post.


Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on LCAT, PLTP, and CETP in plasma and peripheral lymph in humans.
We have previously shown that intravenous apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) discs increase plasma pre-beta HDL concentration and stimulate reverse cholesterol transport (RCT) in humans. We have now investigated the associated changes in the following 3 HDL components that play key roles in RCT: lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). apoA-I/PC discs (40 mg/kg over 4 hours) were infused into 8 healthy men. Samples of blood and prenodal peripheral lymph were collected for 24 to 48 hours. At 12 hours, plasma LCAT concentration had increased by 0.40+/-0.90 mg/L (+7.8%; mean+/-SD; P<0.05), plasma cholesterol esterification rate by 29.0+/-9.0 nmol/mL per h (+69.5%; P<0.01), plasma CETP concentration by 0.5+/-0.2 mg/L (+29.7%; P<0.01), and plasma PLTP activity by 1.45+/-0.67 micromol/mL per h (+23.9%; P<0.01). In contrast, plasma PLTP concentration had decreased by 4.4+/-2.7 mg/L (-44.8%; P<0.01). The changes in PLTP were accompanied by alterations in the relative proportions of large lipoproteins containing inactive PLTP and small particles containing PLTP of high specific activity. No changes were detected in peripheral lymph. Nascent HDL secretion may induce changes in PLTP, LCAT, and CETP that promote RCT by catalyzing pre-beta HDL production, cholesterol esterification in HDLs, and cholesteryl ester transfer from HDLs to other lipoproteins.


On the informational content of viral DNA.
This paper is concerned primarily with how information is stored in viral DNA. The general problem of defining information content is discussed and a procedure for analysis extended from that of Gatlin (1972) is developed. Long range correlations in base sequences are analyzed for several viral genomes. The relationship of these correlations to the existence of strong codon biases is examined and the consequences discussed.


Melatonin application differentially modulates the enzymes associated with antioxidative machinery and ascorbate-glutathione cycle during arsenate exposure in indica rice varieties.
Arsenic (As) contamination and accumulation in rice is a serious concern causing severe oxidative damage. Melatonin acts as a protective agent in plant defence against multiple abiotic stresses. The mechanism of antioxidant function of melatonin during As stress in rice genotypes is less studied. In this study, hydroponically-grown As-susceptible (Khitish) and As-tolerant (Muktashri) rice cultivars, subjected to 150 µm arsenate stress, were supplemented with exogenously applied melatonin (20 µm) to examine the plant defence mechanism. Melatonin (Mel) increased root and shoot length, fresh and dry weight, chlorophyll a and b content and activated reducing power and free radical scavenging capacity in both rice cultivars. The role of Mel in the sensitive variety appeared to be more prominent with respect to reduced water saturation deficit by reducing endogenous As and H2 O2 accumulation, and enhancing overall antioxidant capacity by imposing reduced requirement of catalase for ROS detoxification, and restoring As-inhibited activity of glutathione-S-transferase, glutathione peroxidase and dehydroascorbate reductase. In contrast, melatonin treatment in the tolerant cultivar required reduced involvement of ascorbate peroxidase to deal with As toxicity, and complemented the stress-mediated inhibition of guaiacol peroxidase activity. Isozyme profiling also established extensive varietal differences with regard to induction of new isoform(s) by Mel during As treatment. This study provides clear insights into mechanistic details of the regulation of antioxidative enzymes by melatonin in contrasting rice genotypes, which may prove helpful in generating As tolerance in susceptible rice varieties grown in marginalized soils, thereby improving crop yield and productivity.


Toxicology observation: nystagmus after marijuana use.
Traditional teaching has held that horizontal-gaze nystagmus is a sign of intoxication by sedatives such as alcohol but not marijuana. This is a case report of an adult male who presents with 3 days of visual disturbance and dizziness following marijuana use. The exam was notable for gaze-evoked nystagmus and ataxia. Lab testing was normal except that urine drug screening was positive for marijuana only. Imaging included computed tomography (CT) and magnetic resonance imaging (MRI) scans of the head. Prior studies showing a negative association of nystagmus with marijuana are reviewed. This case is presented as a possible exception to the generalisation that marijuana is not associated with nystagmus.


Tween 80 assisted washing ciprofloxacin-contaminated soil, and recycled it using active chlorines.
Active chlorines (ACs) can selectively oxidize contaminants with benzene rings to recycle surfactants, which greatly facilitates the resource cycle. This paper firstly utilized Tween 80 to assist in ex-situ washing the ciprofloxacin (CI) contaminated soil, including the solubilization experiment, shake washing and soil column washing, all of which showed that 2 g/L of Tween 80 (TW 80) was the most effective in removing CI. Then electrochemically treated the collected soil washing effluent (SWE) at 10 V with an electrolyte of 20 mM NaCl + 10 mM Na2SO4; Pre-experiments screened the range of electrode spacing, pH and temperature, based on which an orthogonal design Table L9 (34) was designed. Visual analysis and ANOVA were performed on the ciprofloxacin removal efficiency and Tween 80 retention efficiency during the orthogonal experiments in 9 groups, and the results showed that CI was usually degraded within 30 min, and 50% of TW 80 was still present at the end of the experiment, and there was no significant effect of all three factors. LC-MS demonstrated that CI was mainly degraded synergistically by ·OH and ACs, and ·OH effectively reduced the biotoxicity of the SWE, so the mixed electrolyte may be more suitable for the electrochemical recycling system of ACs. This paper conducted the washing remediation study of CI-contaminated soil for the first time, and applied the theory of selective oxidation by ACs on benzene ring to treat the SWE, which provides a new treatment idea for antibiotic-contaminated soil.


Respirator weaning of the newborn: some practical considerations.
Weaning of neonates from assisted ventilation or continous positive pressure breathing is a complex process. Unfortunately, at present we lack sensitive indices to measure the infant's ability to sustain spontaneous breathing. In the absence of such criteria we should rely heavily on clinical findings correlated with available biochemical data. Good clinical acumen and experience is necessary for successful weaning.


Detection of the t(2;5)-associated NPM/ALK fusion cDNA in peripheral blood cells of healthy individuals.
The translocation t(2;5), which leads to the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to the receptor kinase ALK on chromosome 2p23, is found in CD30+ anaplastic large cell lymphomas and some cases of B-cell lymphoma. Hodgkin's disease (HD) is a malignant lymphoma characterized by large multinucleated tumour cells, Hodgkin and Reed-Sternberg (H&RS) cells, surrounded by a dense lymphohistiocytic infiltrate. Our group recently demonstrated NPM/ALK fusion cDNAs by single-cell RT-PCR in < 3% of CD30+ tumour cells in 2/9 cases of HD. To further delineate the relevance of this finding for HD, we studied the occurrence of NPM/ALK fusion genes in peripheral blood cells of healthy donors by RT-PCR. NPM/ALK fusion cDNAs were found by RT-PCR in 14/29 healthy individuals and confirmed by hybridization with a breakpoint-specific oligonucleotide. Due to the low rate of NPM/ALK-positive cells in the peripheral blood of positive individuals, an assignment to a defined cellular subpopulation was not possible. We conclude that NPM/ALK fusion genes are present in peripheral blood cells of healthy donors. After t(14;18) and t(9;22), t(2;5) represents the third example of tumour-associated translocation products in blood cells of apparently healthy donors. The implications of this finding are discussed.


Isolation and characterization of two groups of novel marine bacteria producing violacein.
Thirteen strains of novel marine bacteria producing a purple pigment were isolated from the Pacific coast of Japan. They were divided into two groups based on their 16S ribosomal RNA gene sequences, and both groups of bacteria belonged to the genus Pseudoalteromonas. The UV-visible spectrum of the pigment was identical to those of violacein, a pigment produced by several species of bacteria including Chromobacterium violaceum, an opportunistic pathogen. Further analysis of the chemical structure of the pigment by mass spectroscopy and nuclear magnetic resonance spectroscopy showed that the pigment was violacein. The high purity of violacein in the crude extract enabled us to employ simple and nonpolluting procedures to purify the pigment. Isolated bacteria may be useful as a C. violaceum substitute for the safe production of violacein.


Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.
Novel oral poliovirus vaccine type 2 (nOPV2) was used to control an outbreak of type 2 circulating vaccine derived poliovirus (cVDPV2) in Tajikistan, in 2021. We measured seroconversion and seroprevalence of type 2 polio antibodies in children who were reported to have received two doses of nOPV2 in outbreak response campaigns. In this community serosurvey, children born after Jan 1, 2016 were enrolled from seven districts in Tajikistan. Dried blood spot cards were collected before nOPV2 campaigns and after the first and second rounds of the campaigns and were sent to the Centers for Disease Control and Prevention (Atlanta, GA, USA) for microneutralisation assay to determine presence of polio antibodies. The primary endpoint was to assess change in seroprevalence and seroconversion against poliovirus serotype 2 after one and two doses of nOPV2. 228 (97%) of 236 enrolled children were included in the analysis. The type 2 antibody seroprevalence was 26% (53/204; 95% CI 20 to 33) before nOPV2, 77% (161/210; 70 to 82) after one dose of nOPV2, and 83% (174/209; 77 to 88) after two doses of nOPV2. The increase in seroprevalence was statistically significant between baseline and after one nOPV2 dose (51 percentage points [42 to 59], p<0·0001), but not between the first and second doses (6 percentage points [-2 to 15], p=0·12). Seroconversion from the first nOPV2 dose, 67% (89/132; 59 to 75), was significantly greater than that from the second nOPV2 dose, 44% (20/45; 30 to 60; χ2 p=0·010). Total seroconversion after two nOPV2 doses was 77% (101/132; 68 to 83). Our study demonstrated strong immune responses following nOPV2 outbreak response campaigns in Tajikistan. Our results support previous clinical trial data on the generation of poliovirus type 2 immunity by nOPV2 and provide evidence that nOPV2 can be appropriate for the cVDPV2 outbreak response. The licensure and WHO prequalification of nOPV2 should be accelerated to facilitate wider use of the vaccine. World Health Organization, Centers for Disease Control and Prevention, and Rotary International.


Effect of estrogen on melatonin synthesis in female peripubertal rats as related to adenylate cyclase activity.
To determine the mechanism for the modulatory effect of estrogen on melatonin synthesis, we evaluated the effects of estrogen on the activity of adenylate cyclase in female Sprague-Dawley rats of peripubertal age. Adenylate cyclase activity was measured in homogenates of pineal glands from rats aged 3 and 10 weeks in the mid-dark and in the mid-light. Ovariectomy was performed and a subcutaneous injection of estradiol benzoate (E2B) was administered daily starting at the age of 6 weeks. A peak in adenylate cyclase activity in the pineal gland was observed in untreated (control) rats with intact ovaries at 4 weeks. Ovariectomy at week 6 led to significant increases in the activity of adenylate cyclase at week 8. At week 10, adenylate cyclase activity resembled that of control animals. The subcutaneous injection of E2B (1.0 microg/day) suppressed the increase in adenylate cyclase activity induced by ovariectomy, similar to the level seen in control rats with intact ovaries. The changes in the mid-light activity of pineal adenylate cyclase resembled that seen at the mid-dark with the value being significantly lower than that observed in the mid-dark. Such changes in the mid-dark activity of adenylate cyclase resembled those observed with N-acetyltransferase (NAT) at the same time, as previously described. Results suggest that estrogen modulates adenylate cyclase activity in the pineal gland of peripubertal female rats. The decline in melatonin synthesis during puberty may be related to an increase in estrogen level. The inhibitory effect of estrogen on melatonin synthesis appeared to be mediated by a change in the norepinephrine-induced stimulation of pineal adenylate cyclase activity.


Evaluation and development of automatic two-dimensional measurements of histomorphometric parameters reflecting trabecular bone connectivity: correlations with dual-energy x-ray absorptiometry and quantitative ultrasound in human calcaneum.
In osteoporosis, bone fragility results from both bone loss and changes in trabecular microarchitecture, which can be quantified by bone histomorphometric parameters. Twenty human calcaneum were collected after necropsy. All measurements were performed at the same anatomical location. Bone histomorphometric parameters were measured on histological slides with an automatic image analyzer. The aims of our study were (1) to develop automatic measurements of four additional parameters reflecting trabecular network connectivity and complexity, i.e., trabecular bone pattern factor (TBPf), Euler number/tissue volume (Euler) according to the three definitions previously reported and to a fourth one established in the laboratory (Euler(strut.cavity)), marrow star volume, and interconnectivity index, and to determine their usefulness in microarchitecture characterization; and (2) to validate these parameters by evaluating their relationship with dual-energy X-ray absorptiometry and quantitative ultrasound (QUS) measurements performed on the same samples. The statistical analysis showed that TBPf and Euler(strut.cavity) appeared to be the most significant connectivity parameters, independently of bone quantity (bone mineral density, apparent density, cancellous bone volume). For QUS, after adjustment for bone quantity, only speed of sound (SOS) was significantly and negatively correlated to Euler(strut.cavity). Broadband ultrasound attenuation depends only on bone quantity. In conclusion, TBPf (a strut analysis parameter extrapolable in three dimensions) and Euler(strut.cavity) (the only bone connectivity parameter reflecting SOS) are two valid bone microarchitecture parameters. These new parameters were significantly correlated to the established trabecular structure parameters: trabecular thickness or trabecular spacing, being weakly correlated with SOS.


Splenic artery ligation in splenic injuries.
The risk of sepsis after splenectomy is well known. This chiefly concerns the surgeon, who should make every effort to save an injured spleen. This may be achieved by not operating on selected cases, by partial resection, or by suturing the splenic ruptures. Another treatment is ligation of the splenic artery, which is simple and effective in controlling even severe bleeding without splenectomy. Five patients have been treated in this way without complications.


Enlightenment about the new Architect-i2000 estradiol (Abbott Laboratories) immunoassay during in vitro fertilization.
We assessed a new estradiol (E2) immunoassay on the Architect-i2000 (Abbott Laboratories) for monitoring ovulation stimulation for IVF-ET and re-establishing clinical cut-off points. The method has been modified to improve E2 measurements especially at normal and low concentrations. E2 was determined for 552 samples, from 83 women, presenting normal follicular status and undergoing 100 cycles of IVF treatment. We assessed the value of this assay for down-regulation of E2 concentration limit using gonadoliberin-releasing hormone agonist (GnRHa), and monitoring of the ovarian hyperstimulation, expected range of E2 per mature follicle prior to the administration of exogenous hCG and day 3 concentration limit. We compared results with our routine method (E2-6II Advia-Centaur; Siemens-Diagnostics) for which decision-making values were known. Considering E2 concentrations obtained with the new Architect-i2000 assay for patients treated with GnRHa for 2 weeks, the cutoff-point for ovarian down-regulation should be set down at 110 pmol/L to maintain 100% of sensitivity. Considering day 3 concentration limit determination, results were not significantly different from those obtained with our routine method. The mean E2 values per mature follicle fell into the range generally expected. E2 determination with the new E2 Architect-i2000 assay could be used to monitor ovulation, in patients undergoing IVF-ET, in combination with transvaginal ultrasound.


Providing Prenatal Care for Patients with Limited Medical Insurance Coverage.
Newer immigrants to the United States, whether undocumented, recent legal immigrants, those here on temporary visas, or migrant workers, are far less likely than native-born residents of the United States to have reliable health insurance. This entire group of patients is then at risk for delayed or absent medical care. Our study focused on what effects a free, quality prenatal care program had upon prenatal care and delivery outcomes for an underinsured population, primarily of immigrant women. With a recent change in Iowa's eligibility criteria for Presumptive Medicaid (referred to as Temporary Medicaid), pregnant patients who have less than a 5-year legal permanent residency status, undocumented status, or out-of-country resident status can receive up to two months of covered antepartum care, whereas previously eligible for coverage for the entirety of their pregnancy. With that reality, several faculty members from the Department of Family Medicine at the University of Iowa started a weekly prenatal care clinic in collaboration with the longstanding Iowa City Free Medical Clinic. This study sought to compare outcomes for patients who utilized only Temporary Medicaid to those who also had access to this prenatal free medical clinic (FMC), as well as to compare outcomes for the FMC program to typical Medicaid patients who had access to full prenatal care. Compared to the Temporary Medicaid-only group, our FMC patients had a significantly greater number of prenatal visits. This increased access of continuity prenatal care led to increased screening for gestational diabetes, receipt of recommended vaccinations, and screening for group B streptococcus. Our effort has shown that expanding prenatal healthcare coverage to this underinsured population can greatly increase the quality of maternity care and reduce the potential for high-risk pregnancies, bettering the care for these pregnant women and their newborns.


Long-Term Clinical Outcomes of Gastric MALT Lymphoma: A Nationwide Multicenter Study in Korea.
Treatment recommendations for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are based on case series and expert opinions. Only a few previous studies have focused on the long-term outcomes of gastric MALT lymphoma, especially according to stage. Patients diagnosed with gastric MALT lymphoma from January 2000 to December 2018 at nine university hospitals in Korea were included. Clinical data of medical history, endoscopic features, histological diagnosis, results of Helicobacter pylori (H. pylori) testing, stage, treatment conditions, and outcomes were collected. A total of 1,163 patients was enrolled, and 97.6% (n=1,038) of patients were diagnosed as stage IE. 10-year overall survival (OS) for the entire population was 99.1% and was better for patients in stage IE compared with patients in stage III/IV (p=0.002). The 10-year OS for H. pylori-positive patients was better than that of H. pylori-negative patients (p=0.022). Multivariate analyses revealed initial stage III/IV as a prognostic factor associated with over-all survival. The majority of gastric MALT lymphoma patients are diagnosed at an early localized stage in Korea. The overall survival rate of gastric MALT lymphoma is excellent and is associated with the initial stage of the disease.


Experimental investigation on the effect of soil solarization incorporating black, silver, and transparent polythene, and straw as mulch, on the microbial population and weed growth.
Soil solarization is a non-chemical method for eliminating crop-threatening weeds and selectively decontaminating soil. The effect of various soil solarization with black, silver, transparent polythene sheet and straw as mulching on the microbial count and weed growth was studied experimentally. The farm investigation comprised six soil solarization treatments: mulching with black, silver, and transparent polyethylene sheets of 25 μm (μ), organic mulch (soybean Straw), weed-free, and control. All six treatments were repeated in four sets in a Randomized Block Design (RBD) plot size of 5.4 m × 4.8 m. Black, silver, and transparent polythene mulches significantly reduced fungal count compared to non-solarized soil. Straw mulch significantly increased soil fungal count. Solarized treatments had much lower bacterial populations than straw mulch, weed-free, and control treatments. Black, silver, straw mulch, and transparent polythene had 18746, 22763, 23999, and 3048 weeds ha-1 at 45 days after transplanting (DAT). The analysis of dry weed weight demonstrated a significantly low weed dry weight of 0.44 t/ha for black polythene (T1) based soil solarization, representing an 86.66% reduction in dry weed biomass. Soil solarization had the lowest weed index (WI), with black polythene mulch (T1) reducing weed competition. Among various soil solarization treatments, black polythene (T1) showed the highest weed control efficiency of 85.84%, indicating its suitability for use in weed control. The results suggest that soil solarization is effective for soil disinfestation and weed control with polyethene mulch and summer heat in central India.


A field study to predict Cd bioaccumulation in a soil-wheat system: Application of a geochemical model.
An accurate model to predict Cd accumulation in crops based on soil properties would facilitate evaluations of soil quality and the potential risk posed by metals. However, given the heterogeneity of soil, such models are difficult to establish on large regional scales. This study for the first time examined the applicability of a multi-surface speciation model (MSM) in predicting Cd accumulation in wheat at a regional field scale, based on 140 soil-wheat paired samples collected from a 205-km2 field. The MSM resulted in a better correlation between Cd accumulation in wheat grain (R2 = 0.75) and roots (R2 = 0.74) than obtained with chemical extraction methods (total Cd in soil, 0.01 M CaCl2, and 0.43 M HNO3). In addition, while the performance of the MSM was comparable to that of a traditional multiple regression model, a parameter-fitting process was not required. The predictive ability of the MSM was further used to assess and predict the soil Cd risk and to develop a soil Cd sensitivity map to better localize areas of greatest sensitivity to Cd contamination. The results showed that the MSM can serve as a useful tool for regional soil risk assessments and thus in the development of soil protection measures.


Posttransplantation acute tubular necrosis: risk factors and implications for graft survival.
Previous studies aimed at identifying the causes, risk factors, and outcome of kidney transplant recipients with delayed graft function (DGF) have yielded controversial results. We retrospectively analyzed the causes and risk factors for DGF in 263 cadaveric kidney transplantations from November 1988 to March 1997 in one center. Causes of DGF were assessed by postoperative graft evolution and graft biopsy. Univariate and multivariate analysis were used to investigate the risk factors for DGF induced by acute tubular necrosis (ATN). Seventy-six patients (29%) had DGF, which was caused by ATN in 70 patients (92.1%) and acute rejection (AR) in 6 patients (7.9%). Therefore, we focused on risk factors and consequences for ATN-induced DGF. In monofactorial analysis, ATN was significantly associated with greater weight and presence of an atheromatous disease in both donor and recipient. Other risk factors for ATN were older age of donor, recipient American Society of Anesthesiology (ASA) physical status category IV, cold ischemia time (CIT), and transplantation using the right kidney. The multivariate analysis showed that donor and recipient weight, donor age, transplantation using the right kidney, preservation in Eurocollins solution, ASA score, and CIT were associated with ATN. The incidence of rejection and renal function were not different at 3 months or 1 and 5 years. ATN is the main cause of DGF in kidney transplant recipients. ATN is caused by donor and recipient vascular background, grafting the right kidney, and CIT. ATN does not appear to have an adverse effect on long-term kidney function.


Urothelial neoplasm of the bladder in childhood and adolescence: a rare disease.
Bladder tumors are rare in children and adolescents. For this reason, the diagnosis is sometimes delayed in pediatric patients. We aimed to describe the diagnosis, treatment, and follow-up methods of bladder urothelial neoplasms in children and adolescents. We carried out a retrospective multicenter study involving patients who were treated between 2008 and 2014. Eleven patients aged younger than 18 years were enrolled in the study. In all the patients, a bladder tumor was diagnosed using ultrasonography and was treated through transurethral resection of the bladder (TURBT). Nine of the 11 patients (82%) were admitted with gross hematuria. The average delay in diagnosis was 3 months (range, 0-16 months) until the ultrasonographic diagnosis was performed from the first episodes of macroscopic hematuria. A single exophytic tumor (1-4cm) was present in each patient. The pathology of all patients was reported as superficial urothelial neoplasm: two with papilloma, one with papillary urothelial neoplasm of low malignant potential (PUNLMP), four with low grade pTa, and four with low grade pT1. No recurrence was observed during regular cystoscopic and ultrasonographic follow-up. Regardless of the presence of hematuria, bladder tumors in children are usually not considered because urothelial carcinoma in this population is extremely rare, which causes a delay in diagnosis. Fortunately, the disease has a good prognosis and recurrences are infrequent. Cystoscopy may be unnecessary in the follow-up of children with bladder tumors. We believe that ultrasonography is sufficient in follow-up.


Assessment of the fructanolytic activities in the rumen bacterium Treponema saccharophilum strain S.
To characterize the fructose polymer degrading enzymes of rumen bacterium Treponema saccharophilum strain S. Conventional methods were used to examine bacterial growth and enzyme activities. Electrophoretic zymogram under native conditions, and thin layer chromatography, were applied to identify and characterize the enzymes. Treponema saccharophilum utilized Timothy grass fructan, inulin and sucrose but not free fructose. Timothy grass fructan was degraded at a significantly higher rate than sucrose and inulin. Two fructanolytic enzymes were found in the soluble, and one in the membrane fraction of bacterial cell extract. The first degraded each mentioned carbohydrate to monosaccharides. The second released oligosaccharides only from Timothy grass fructan. The bacterium T. saccharophilum strain S is capable of synthesizing non-specific beta-fructofuranosidases and 2,6-beta-D-fructan fructanohydrolase. The enzymes are of constitutive character. It has been stated for the first time that the 2,6-beta-D-fructan fructanohydrolase is synthesized by the rumen bacterium T. saccharophilum. This organism appears to be responsible for grass fructan degradation in the rumen.


Anti-HIV-1 activities of compounds isolated from the medicinal plant Rhus chinensis.
Previously, we reported that the petroleum ether fraction, RC-1, and EtOAc fraction, RC-2, of the medicinal plant Rhus chinensis showed potent anti-HIV-1 activities. To address anti-HIV-1 constituents of RC-1 and RC-2, 17 compounds were isolated. Anti-HIV-1 activities and possible action mechanisms of these compounds were investigated. The syncytial formation induced by HIV-1 was determined under the inverted microscope, cellular toxicity and protection assay were assessed by MTT method, reduction of p24 antigen expression level and RT activity were measured by ELISA, and inhibition of recombinant HIV-1 PR was monitored by the fluorescent signal. The compounds 1 and 13 inhibited HIV-1-induced syncytium formation potently with TI value of 42.31 and 19.07, respectively. Compounds 4, 5, 6, 9 and 10 were less potent with TI value of 8.94, 8.22, 4.14, 5.11 and 5.34, respectively. Compound 1, a benzofuranone-type compound, previously reported as a novel anti-HIV-1 agent, might target late-steps of HIV-1 life cycle. Compound 13 inhibited HIV-1 replication with EC(50) of 7.16mug/ml and might target at/before integration step. These compounds might contribute to anti-HIV-1 activities extracts of the medicinal plant Rhus chinensis.


Comparison of genomic-enabled cross selection criteria for the improvement of inbred line breeding populations.
A crucial step in inbred plant breeding is the choice of mating design to derive high-performing inbred varieties while also maintaining a competitive breeding population to secure sufficient genetic gain in future generations. In practice, the mating design usually relies on crosses involving the best parental inbred lines to ensure high mean progeny performance. This excludes crosses involving lower performing but more complementary parents in terms of favorable alleles. We predicted the ability of crosses to produce putative outstanding progenies (high mean and high variance progeny distribution) using genomic prediction models. This study compared the benefits and drawbacks of 7 genomic cross selection criteria (CSC) in terms of genetic gain for 1 trait and genetic diversity in the next generation. Six CSC were already published, and we propose an improved CSC that can estimate the proportion of progeny above a threshold defined for the whole mating plan. We simulated mating designs optimized using different CSC. The 835 elite parents came from a real breeding program and were evaluated between 2000 and 2016. We applied constraints on parental contributions and genetic similarities between selected parents according to usual breeder practices. Our results showed that CSC based on progeny variance estimation increased the genetic value of superior progenies by up to 5% in the next generation compared to CSC based on the progeny mean estimation (i.e. parental genetic values) alone. It also increased the genetic gain (up to 4%) and/or maintained more genetic diversity at QTLs (up to 4% more genic variance when the marker effects were perfectly estimated).


Upstaging by para-aortic lymph node dissection in patients with locally advanced cervical cancer: A systematic review and meta-analysis.
Accurate staging of para-aortic nodal status in cervical cancer is of great importance for individualizing treatment and impacting outcomes. Three-dimensional imaging (i.e. PET, CT, MRI) may miss para-aortic lymph node (PALN) metastases. The aim of this study was to systematically review and meta-analyze the proportion of upstaging by PALN dissection in patients with locally advanced cervical cancer without suspicious PALNs on imaging. PubMed/MEDLINE and Embase were systematically searched. The analysis included diagnostic studies that reported on 3D imaging and pre-therapeutic surgical assessment of PALN status in patients with cervical cancer. An overall pooled upstaging rate was calculated using a random-effects model. The search identified 16 eligible studies including 18 cohorts with a total of 1530 patients. Pooling of 12 cohorts demonstrated an upstaging rate of 12% (95% confidence interval [CI] 10-15%) by PALN dissection after negative PET or PET-CT. Pooling of 6 cohorts demonstrated a pooled upstaging rate of 11% (95% CI: 8-16%) by PALN dissection after negative MRI or CT. No significant heterogeneity in upstaging proportions across cohorts was observed (I2 = 0% and 27%, respectively). In 7 cohorts including only patients with pelvic nodal metastases on imaging (but no suspicion of PALN involvement) a pooled upstaging rate by PALN dissection of 21% (95% CI: 17-26%) was found (I2 = 0%). This meta-analysis demonstrates that in case of no suspicious PALN on PET-CT or MRI, PALN dissection still identifies lymph node metastases in a considerable amount of patients with locally advanced cervical cancer and especially in those patients with confirmed pelvic nodal metastases.


Increased glycosidic bond stabilities in 4-C-hydroxymethyl linked disaccharides.
Three new hydroxymethyl-linked non-natural disaccharide analogues, containing an additional methylene group in between the glycosidic linkage, were synthesized by utilizing 4-C-hydroxymethyl-α-d-glucopyranoside as the glycosyl donor. A kinetic study was undertaken to assess the hydrolytic stabilities of these new disaccharide analogues toward acid-catalyzed hydrolysis, at 60°C and 70°C. The studies showed that the disaccharide analogues were stable, by an order of magnitude, than naturally-occurring disaccharides, such as, cellobiose, lactose, and maltose. The first order rate constants were lower than that of methyl glycosides and the trend of hydrolysis rate constants followed that of naturally-occurring disaccharides. α-Anomer showed faster hydrolysis than the β-anomer and the presence of axial hydroxyl group also led to faster hydrolysis among the disaccharide analogues. Energy minimized structures, derived through molecular modeling, showed that dihedral angles around the glycosidic bond in disaccharide analogues were nearly similar to that of naturally-occurring disaccharides.


PHLDA1 (TDAG51) is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma.
Morphoeic basal cell carcinoma (BCC) and desmoplastic trichoepithelioma can often be difficult to differentiate on routine sections and few reliable immunohistochemical markers are currently available. Recent cDNA microarray studies revealed the pleckstrin homology-like domain, family A, member 1 protein (PHLDA1) as a highly reliable marker of the hair follicle stem cells. Given the differentiation of trichoepithelioma along the follicular lineage and the proposed role of PHLDA1 as a follicular stem cell marker, we examined the staining pattern of PHLDA1 in the desmoplastic variant of trichoepithelioma and in its differential diagnostic conundrum, morphoeic BCC. To describe the expression pattern of PHLDA1 in morphoeic BCC and desmoplastic trichoepithelioma. Evaluation of the staining pattern for PHLDA1 was performed using standard immunohistochemical techniques. For comparison reasons, we analysed staining for PHLDA1 in normal skin structures with particular reference to the hair follicle. With the exception of one case, all 16 desmoplastic trichoepitheliomas were immunoreactive with more than 80% of the cells stained, whereas all 14 morphoeic BCCs were PHLDA1-negative with the exception of ulcerated tumours. In the latter, the tumour islands close to the ulcer were PHLDA1-positive whereas the deeper located tumour portions remained immunonegative. PHLDA 1 was prominently expressed in the hair follicle bulge of terminal and vellus hair follicles. The hair follicle bulge marker PHLDA1 differentiates between desmoplastic trichoepitheliomas and nonulcerated examples of morphoeic BCCs. We suggest incorporating PHLDA1 in the diagnostic work-up of difficult to differentiate basaloid tumours.


Assessing the Consumer Food Environment in Restaurants by Neighbourhood Distress Level across Saskatoon, Saskatchewan.
To assess the consumer food environment in restaurants in Saskatoon, using the Nutrition Environment Measures Survey for Restaurants (NEMS-R), to examine differences by neighbourhood distress level and to reflect on the need for further refinement of the assessment of restaurant consumer food environments. Neighbourhoods were classified as low, middle, or high distress level based on the socioeconomic indicators (income, employment, and education) in the Material Deprivation Index. Differences in restaurant consumer food environments, indicated by mean NEMS-R total and sub-scores, were examined by various restaurant categories and by varying neighbourhood distress levels. Chain coffee shops and pita and sandwich restaurants had higher NEMS-R totals and "Healthy Entrées" sub-scores; however, burger and chicken restaurants and pizza restaurants had more barriers to healthful eating. Although restaurants in lower distress level neighbourhoods generally rated healthier (higher NEMS-R scores), only a few measures (such as "Facilitators" and "Barriers") significantly differed by neighbourhood distress level. The findings highlight the importance of developing interventions to improve restaurant consumer food environments, especially in neighbourhoods with higher distress levels. The results suggest that reliable measures of the consumer food environment could be developed beginning with what can be measured by NEMS-R.


Effect of acrylamide on neurotransmitter metabolism and neuropeptide levels in several brain regions and upon circulating hormones.
The effect of acute and subchronic acrylamide treatment on levels of dopamine, serotonin, and their metabolites was determined in several brain regions of the rat. Concentrations of several neuropeptides and circulating hormones were also measured. Both a single and repeated doses of acrylamide resulted in elevated levels of 5-hydroxyindolacetic acid in all regions studied (frontal cortex, striatum, hippocampus, brain stem, and hypothalamus). Changes in regional content of other monoamines were much less pronounced. Turnover studies following pargyline blockage of monoamine oxidase, suggested results were due to increased rates of serotonin turnover in acrylamide-treated rats. Changes in neuropeptide levels were only detected in the hypothalamus where a single acrylamide treatment caused elevated levels of beta-endorphin and substance P, and in frontal cortex where met-enkephalin levels were higher after repeated acrylamide injection. Such repeated injection caused a major depression in plasma levels of testosterone and prolactin.


Effect of compression by elastic bandages on pain and function in individuals with knee osteoarthritis: protocol of a randomised controlled clinical trial.
Although compression is used to control pain in knee osteoarthritis (KOA), its clinical application is poorly supported, and there is a lack of scientific evidence to support its clinical use. As a low-cost and accessible protocol, compression using elastic bands could be a non-pharmacological intervention to reduce pain and improve physical function in individuals with KOA. This study aims to evaluate the effects of compression on pain and function in individuals with KOA. A randomised controlled clinical trial will be conducted. Individuals with KOA (n=90; both sexes; between 40 and 75 years old) will be allocated to three groups (n=30/group): compression (compression by the elastic bandage on the affected knee, once a day for 20 min, on four consecutive days); sham (same protocol, but the elastic band is placed around the affected knee without compression) and control (no intervention). The individuals in the three groups will be evaluated 1 day before the first intervention, 1 day after the last intervention, and at the 12th and 24th weeks after the end of the intervention. Pain intensity by the Visual Analogue Scale and pain scale from Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) will be the primary outcomes. The secondary variables will be physical function assessed by the WOMAC questionnaire and physical tests (step test; 30 s sit and stand test; 40 m accelerated walk test). The Global Rating of Change Scale (GRC) will also be applied to quantify the volunteers' perceived change. The project was approved by the Human Research Ethics Committee of the Federal University of São Carlos, São Paulo, Brazil (3955692). The results will be published in peer-reviewed journals. NCT04724902.


Leveraging Artificial Intelligence and Synthetic Data Derivatives for Spine Surgery Research.
Retrospective cohort study. Leveraging electronic health records (EHRs) for spine surgery research is impeded by concerns regarding patient privacy and data ownership. Synthetic data derivatives may help overcome these limitations. This study's objective was to validate the use of synthetic data for spine surgery research. Data came from the EHR from 15 hospitals. Patients that underwent anterior cervical or posterior lumbar fusion (2010-2020) were included. Real data were obtained from the EHR. Synthetic data was generated to simulate the properties of the real data, without maintaining a one-to-one correspondence with real patients. Within each cohort, ability to predict 30-day readmissions and 30-day complications was evaluated using logistic regression and extreme gradient boosting machines (XGBoost). We identified 9,072 real and 9,088 synthetic cervical fusion patients. Descriptive characteristics were nearly identical between the 2 datasets. When predicting readmission, models built using real and synthetic data both had c-statistics of .69-.71 using logistic regression and XGBoost. Among 12,111 real and 12,126 synthetic lumbar fusion patients, descriptive characteristics were nearly the same for most variables. Using logistic regression and XGBoost to predict readmission, discrimination was similar with models built using real and synthetic data (c-statistics .66-.69). When predicting complications, models derived using real and synthetic data showed similar discrimination in both cohorts. Despite some differences, the most influential predictors were similar in the real and synthetic datasets. Synthetic data replicate most descriptive and predictive properties of real data, and therefore may expand EHR research in spine surgery.


Correction to: Toward clinically usable CAD for lung cancer screening with computed tomography.
The original version of this article, published on 24 July 2014, unfortunately contained a mistake. In section "Discussion," a sentence was worded incorrectly.


Rapid synthesis of cyclopropane-dipeptide analogues.
The synthesis of cyclopropane-substituted nitrile-dipeptides is reported. The straightforward transformation of the nitrile function into an amide or methylketone function leads to dipeptide analogues of potentially interesting pharmacologic profile.


miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA.
MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.


Arterial response to mild balloon injury in the normal rabbit: evidence for low proliferation rate in the adventitia.
The role of constrictive remodeling, spasm and proliferation (particularly in the adventitia) in the genesis of chronic lumen narrowing after balloon injury remains under debate. This study analyzed the time course of these components following mild injury in normal arteries. Iliac injury was induced by balloon overstretch in 32 rabbits, sacrificed at timed intervals from day 3 to 28. Angiographic response to nitrates, morphometric, immunohistochemical and biochemical analysis were performed at each time point. Quantitative angiography showed a decrease in lumen diameter and no change in response to nitrates over time. On morphometric analysis, remodeling was usually constrictive, appeared as early as day 3 and was responsible for 69+/-14% of the histologic lumen area stenosis at day 28. Constrictive remodeling was correlated negatively to intimal hyperplasia (r= 0.51, P< 0.002) and positively to the lumen area stenosis (r= 0.92, P< 0.0001). Macrophages (labeled by anti-RAM 11 antibodies) were very rare at all time points. Immunohistochemistry identified a high rate of proliferating smooth muscle cells in the media (13+/-7%) and intima (49+/-8%) at day 7, which decreased rapidly. Proliferating cells in the adventitia were rare (3+/-2% at day 7). The number of proliferating cells was time-dependent (r= 0.82, P< 0.0001) and related to cyclin A mRNA measured by reverse transcription-polymerase chain reaction (r= 0.84, P< 0.0001). In this model, luminal loss was mainly caused by constrictive remodeling rather than intimal hyperplasia. Constrictive remodeling appeared early and was not time-dependent. Macrophages, spasm and adventitial proliferation did not contribute to this constrictive remodeling.


Techniques, challenges and future prospects for cell-based meat.
In response to a growing population and rising food demand, the food industry has come up with a wide array of alterations, innovations, and possibilities for making meat in vitro. In addition to revolutionizing the meat industry, this advancement also has profound effects on the environment, health, and welfare of animals. Thus, rather than using slaughtered animals, animal cells are employed to generate cell-based meat, with the cells' proliferation and differentiation taking place in the culture environment. The primary goal of this paper is to examine the overall mechanism and numerous approaches involved in the creation of cell-based meat. It also covers upcoming issues like technical, consumer, and regulatory issues, environmental concerns, the economy, cost of the product, health and safety concerns, and ethical, religious, and societal taboos. Finally, it assesses the future prospects of cell-based meat production.


Resolution of chiral cannabinoids on amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase: effects of structural features and mobile phase additives.
The separation of six pairs of chiral cannabinoids was achieved using a dimethylphenylcarbamate derivative of amylose, immobilized on silica gel (ChiralPak AD, Daicel), using 2-propanol and ethanol as the modifiers of n-hexane in the mobile phase. Good separation was achieved for most of the solutes in both solvent systems under various conditions. The chromatographic parameters of various cannabinoids in the two solvent systems were determined. The pairs differ from each other in small structural features such as the degree of saturation, position of a double bond and closure of a pyran ring. Therefore, a comparative study could give some clues regarding the mechanism of discrimination between the enantiomeric pairs on the chiral stationary phase. Preliminary measurements of limit of determination showed that it was possible to assess 99.9% enantiomeric purity of the cannabinoids, owing to the high efficiency of the separation. Enantiomers of two monoterpenes, used as intermediates or as starting materials in the chiral synthesis of cannabinoids, were also separated, hence the described procedure is capable of assessing whether the chiral centres in the molecules were sustained throughout the synthetic procedures.


A highly sensitive dual-readout assay for perfluorinated compounds based CdTe quantum dots.
Perfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS) are two typical perfluorinated compounds (PFCs) that poss potential ecological toxicity. In this work, a fluorescence and resonance light scattering (RLS) dual-readout strategy for the detection of PFCs at picomole level based on the water-soluble CdTe quantum dots (CdTe QDs) has been proposed. It is found that the CdTe QDs exhibit a quenching in the presence of PFCs and thus serve as useful probes for PFCs. The linear ranges are 0.032-10.0 nM with a limit of detection(LOD) of 32.02 pM for PFOA and 0.044-15.0 nM with a LOD of 43.96 pM for PFOS, respectively. Meanwhile, PFCs can form complexes with CdTe QDs in acid medium, resulting in remarkable RLS signals. The enhanced RLS intensities are in proportion to the concentrations of PFOA and PFOS, respectively. And the linear ranges are 0.048-5.0 nM with a LOD of 47.78 pM for PFOA, and 0.057-5.0 nM with a LOD of 56.72 pM for PFOS, respectively. This dual-mode detection increases the reliability of the measurement. The proposed method is simple, sensitive and cost-effective, with potential applications in environmental monitoring and assessment.


Difficulties in diagnosing group o human immunodeficiency virus type 1 acute primary infection.
We report a rare case of acute human immunodeficiency virus (HIV) type 1 group O infection in a French Caucasian woman. Her sexual partner was secondarily diagnosed with HIV infection, and transmission was confirmed by phylogenetic analysis. The unequal performance of many of the serologic and molecular assays commercially available leads to delays in diagnosis and affects patient management.


Evidence for group A-related M protein genes in human but not animal-associated group G streptococcal pathogens.
Group G streptococci have on their surface antiphagocytic M protein-like antigens. To determine if these organisms have genes similar to the M protein genes of Streptococcus pyogenes (group A), DNA from independent group G isolates of human and animal origin were tested for homology to probes representing sequences encoding the carboxy-terminus and leader peptide of the type 12 M protein (M12) of group A streptococci. All eight human-associated group G strains tested had DNA homologous to the carboxy-terminal probe. Six of these strains also had DNA that hybridized with the leader peptide probe. Using probes representing the group A M12 gene (emm12) and adjacent 5' sequences, we found that one of these strains, known to produce an M12 antigen, had a nearly complete duplication of the group A emm12 gene, differing only in 0.26 kb of sequence at the 5' end. The other human-associated strains did not hybridize with emm12-specific sequences. None of the group G strains had homology to 5' proximal sequences thought to be associated with group A emm12 regulation, but all the human-associated strains had DNA homology to a 1.5 kb DNA segment which mapped 2.5 kb upstream of the emm12 gene in group A streptococci. None of the twelve animal-associated strains tested hybridized with any of the probes used in this study. These results suggest that human but not animal-associated group G isolates have group A-related M protein genes. We propose that expression of these genes are critical for infection of the human host and that group A and G shared upstream sequences could encode additional virulence factors.


Startle reactivity in children at risk for migraine.
Numerous studies have shown a higher responsiveness and/or a lack of habituation to sensory stimuli of various modalities in migraine. This study investigated psychophysiological responses to aversive acoustic stimuli in children at risk for migraine. We measured eyeblink responses to acoustic stimuli (40ms bursts of white noise at 102dB) during anticipation of unpleasant stimuli in 74 adolescents (40 females, age 17.6+/-2.9). A mixed effects linear model was applied to test group differences in startle reactivity during baseline, safe and threat conditions among adolescents by maternal and personal history of migraine. The strongest association with migraine vulnerability emerged for baseline startle reactivity, which was significantly elevated in high risk youth with a history of maternal migraine. This group of offspring also had enhanced startle response during the threat condition and the threat-safe difference. Our findings indicate that migraine is associated with a higher acoustic startle responsiveness that is present already in children at risk for developing the disorder. The significant effect of both maternal history of anxiety disorder and migraine on baseline startle indicates that these two diagnostic entities might in part share common pathophysiological mechanisms, and that the anxiety-migraine comorbidity should be considered when investigating each of these disorders.


Practice patterns and outcomes of urgent versus elective ureteroscopy in a statewide surgical collaborative.
Urgent indications for nephrolithiasis treatment include obstruction with intractable pain or renal impairment without untreated infection. Patients and hospitals may benefit from urgent primary ureteroscopy. We aimed to examine variation in urgent ureteroscopy utilization and associated outcomes. Using Reducing Operative Complications from Kidney Stones (ROCKS), we identified all ureteroscopy's between 2016 and 2019. Cases were classified by acuity (elective versus urgent). We assessed practice/urologist variation in urgent ureteroscopy performance. We characterized patients demographic, operative and outcomes data, making bivariate comparisons with elective ureteroscopy to understand implications of urgent surgery. We performed multilevel modeling to understand factors associated with unplanned healthcare encounters after urgent ureteroscopy. 12,859 cases were identified from 33 practices and 204 urologists, 10,854 (84.4%) elective and 2005 (15.6%) urgent. Urgent ureteroscopy was performed on younger patients (53 vs 57, p < 0.001), with higher rates of ureteral stones (72.8% vs 56.8%, p < 0.001). Urgent ureteroscopy rates varied widely by practice (2-70%) and urologist (0-98%). Urgent ureteroscopy had higher stenting rates (77.4% vs 72.5%, p < 0.001), stone free rates (66% vs 58.4%, p < 0.001), and postoperative ED visits (11% vs 7.2%, p < 0.001). There were no differences in intraoperative complications or unplanned hospitalizations. Factors predictive of ED visits in urgent ureteroscopy included concomitant ureteral/renal stone location (OR = 1.53, CI = 1.05-2.23, p = 0.035). In Michigan elective ureteroscopy is performed 5 times more frequently than urgent ureteroscopy with wide variation. Urgent ureteroscopy demonstrated low morbidity. Urgent ureteroscopy produced modestly higher stone free rates with a slightly increased frequency of unscheduled ED visits particularly for ureteral stones.


Triamcinolone acetonide suppresses interleukin-1 beta-mediated increase in vascular endothelial growth factor expression in cultured rat Müller cells.
Intravitreal injection of triamcinolone acetonide (TA) is used for the treatment of diabetic macular edema and other vitreoretinal diseases. Vascular endothelial growth factor (VEGF) plays a key role in regulating vascular permeability associated with macular edema. We investigated the effect of TA on the expression of VEGF mRNA and protein induced by interleukin-1 beta (IL-1b) and hypoxia in cultured rat Müller cells. Müller cells were isolated from removed eyeballs of 40 rats. Total RNA was prepared from Müller cells stimulated by IL-1b or hypoxia, in the absence or presence of TA, and then was subjected to Northern blot analyses. The amount of VEGF protein in the culture medium was measured by enzyme-linked immunosorbent assay (ELISA). The stability of RNA was determined by actinomycin D decay assay. Reporter construct, consisting of the VEGF promoter-luciferase gene, was transiently transfected into Müller cells for luciferase assays. Stimulation of Müller cells by either IL-1b or hypoxia induced VEGF mRNA expression. Pretreatment of cells with TA efficiently suppressed VEGF induction by IL-1b but not by hypoxia. ELISA showed that TA significantly reduced the production of VEGF protein from IL-1b-stimulated cells. RNA decay assays and promoter analysis of the VEGF gene indicated that TA inhibited the IL-1b-mediated increase in VEGF gene expression at the transcriptional level. TA suppressed VEGF expression induced by IL-1b in Müller cells at the transcriptional level. Our data sustained the clinical effect of TA for diabetic macular edema and suggested an important role of TA for the suppression of the VEGF gene expression in ocular tissues.


Exhaled breath condensate MMP-9 level and its relationship wıth asthma severity and interleukin-4/10 levels in children.
Matrix metalloproteases (MMPs) are key mediators in airway remodeling, and MMP- 9 is the main type investigated to discover its implication for the pathogenesis and severity of asthma. To evaluate MMP-9 and its natural tissue inhibitors of metalloproteinases (TIMP-1) levels of exhaled breath condensate (EBC) in children with asthma. We also analyzed any potential relationship between these enzymes and EBC interleukin (IL)-4/10 levels as well as asthma severity. Three study groups were formed: group 1, children with persistent asthma (n = 20); group 2, children with intermittent asthma (n = 10), and group 3, healthy controls (n = 12). Pulmonary functions were measured as forced expiratory volume in 1 second (FEV(1)), peak expiratory flow (PEF), and forced expiratory flow from 25% to 75% of vital capacity values by spirometry, and MMP-9, TIMP-1 and IL-4/10 levels in EBC were analyzed by enzyme-linked immunosorbent assay (ELISA). The MMP-9 levels of EBC were found to be 57.7 ± 17.5, 35.4 ± 11.7, and 30.6 ± 3.7 ng/mL in children belonging to group 1, group 2 and group 3, respectively. Children belonging to group 1 and group 2 showed significantly higher MMP-9 levels of EBC in comparison with the controls (P < .001 and P = .047, respectively). No statistically significant difference was found between groups regarding TIMP-1 levels of EBC. EBC MMP-9 levels were inversely correlated with both FEV(1) and PEF values (r = -0.472, P = .011, and r = -0.571, P = .002, respectively) in children with asthma. Positive correlations were also seen between MMP-9 levels and IL-4/10 levels of EBC (r = 0.419, P = .027 and r = 0.405, P = .032, respectively) in children with asthma. We showed that MMP-9 levels of EBC are elevated in children with asthma and correlated with lung functions and other inflammatory markers such as IL-4/IL10 in EBC.


Drug delivery of Insulin-like growth factor I.
This review starts off outlining the control of Insulin-like growth factor I (IGF-I) kinetics in Nature and by virtue of a complex system of 6 binding proteins controlling half-life and tissue distribution of this strong anabolic peptide. In addition, alternative splicing is known to result in IGF-I variants with modulated properties in vivo and this insight is currently translated into advanced IGF-I variants for therapeutic use. Insights into these natural processes resulted in biomimetic strategies with the ultimate goal to control pharmacokinetics and have recently propelled new developments leading to optimized pharmaceutical performance of this protein in vivo. Aside from parenteral administration routes, IGF-I was successfully delivered across various epithelial barriers from liquid as well as from solid pharmaceutical forms opening novel and more convenient delivery modalities. IGF-I decoration yielded effective targeting upon systemic administration expanding the options for optimally deploying the growth factor for therapy. This review summarizes the exciting biotechnological and pharmaceutical progress seen for IGF-I delivery in recent years and critically discusses outcome in light of translational application for future IGF-I therapeutics.


Heart conditioned medium elicits post-lesion muscarinic receptor recovery in vivo.
Intraseptal administration of heart conditioned medium (HCM) stimulates the growth of injured cholinergic fibers into iris implants placed in the anterodorsal hippocampus. The aims of the present report were to monitor muscarinic cholinergic receptor concentrations during denervation and central innervation of the peripheral tissue targets, and to evaluate the effect of HCM on these changes. For 0, 4, 8, 16 and 28 days after mechanical injury to septohippocampal axons, animals received either intraseptal injections of HCM or control vehicle. Binding of [3H]quinuclidinylbenzilate ([3H]QNB) within iris implants was used as an index of cholinergic muscarinic receptor concentration. The results indicate that within the iris implants: (1) a dramatic drop in the number of muscarinic receptors is observed 4 days after denervation; (2) under control conditions, central cholinergic innervation is not associated with muscarinic receptor recovery; and (3) after administration of HCM, muscarinic receptor levels begin to increase within two weeks and approach the pre-lesion endogenous concentration following 28 days of treatment. These results support the hypothesis that trophic factors may facilitate the restoration of effective, appropriate connections between nerve fibers and their targets.


Cost-Utility Analysis of VEGF Inhibitors for Treating Neovascular Age-Related Macular Degeneration.
To perform 11- and 2-year health care sector (ophthalmic) and societal cost perspective reference case, cost-utility analyses comparing bevacizumab, ranibizumab, and aflibercept monotherapies for neovascular age-related macular degeneration (NVAMD). Cost-utility analysis. The authors performed 11-year and 2-year ophthalmic and societal cost perspective, cost-utility analyses comparing bevacizumab, ranibizumab, and aflibercept monotherapies for neovascular age-related macular degeneration (NVAMD). We employed patient utilities, bilateral outcomes, 2018 U.S. dollars, vision-related mortality, a Medicare fee schedule, and CATT (Comparison of Age-Related Macular Degeneration Treatments) study and VIEW (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD) trial. Cochrane data were also used. Center for Value-Based Medicine. Patient/study population: patients with NVAMD. Cost-utility analyses using published data. Data-modeled 10-year vision outcomes were modeled forward to year 11. These included cost-utility ratios (CURs), costs, and quality-adjusted life-years (QALYs) gained. $100,00/QALY was considered the US cost-effectiveness upper limit. Bevacizumab and ranibizumab each conferred an 11-year, 1.339 QALY gain versus observation. Aflibercept conferred a 1.380 QALY gain. Aflibercept conferred greater QALY gain for less cost than ranibizumab but was not cost-effective compared to bevacizumab ($1,151,451/QALY incremental CUR). The average ophthalmic cost perspective CUR for bevacizumab was $11,033/QALY, $79,600/QALY for ranibizumab, and $44,801/QALY for aflibercept. Eleven-year therapies saved a 1.0 year-of-life loss without treatment from the 11.0-year life expectancy. Early treatment was 138%-149% more cost-effective than late treatment. Two-year therapy prevented a 1-month-of-life loss, and revealed bevacizumab, ranibizumab, and aflibercept conferred 0.141, 0.141, and 0.164 QALY gains, respectively, with corresponding average CURs of $40,371/QALY, $335,726/QALY, and $168,006/QALY, respectively. From an ophthalmic (medical) cost perspective, bevacizumab, ranibizumab, and aflibercept NVAMD monotherapies were all cost-effective over 11 years, with bevacizumab 6.21× more cost-effective than ranibizumab and 3.06× more cost-effective than aflibercept. Two-year modeling revealed bevacizumab was cost-effective, whereas ranibizumab and aflibercept were not. Early treatment was critical for obtaining optimal vision and cost-effectiveness, as is long-term follow-up and adherence to treatment.


Engineered arylsulfatase A with increased activity, stability and brain delivery for therapy of metachromatic leukodystrophy.
A deficiency of human arylsulfatase A (hASA) causes metachromatic leukodystrophy (MLD), a lysosomal storage disease characterized by sulfatide accumulation and central nervous system (CNS) demyelination. Efficacy of enzyme replacement therapy (ERT) is increased by genetic engineering of hASA to elevate its activity and transfer across the blood-brain barrier (BBB), respectively. To further improve the enzyme's bioavailability in the CNS, we mutated a cathepsin cleavage hot spot and obtained hASAs with substantially increased half-lives. We then combined the superstabilizing exchange E424A with the activity-promoting triple substitution M202V/T286L/R291N and the ApoEII-tag for BBB transfer in a trimodal modified neoenzyme called SuPerTurbo-ASA. Compared with wild-type hASA, half-life, activity, and M6P-independent uptake were increased more than 7-fold, about 3-fold, and more than 100-fold, respectively. ERT of an MLD-mouse model with immune tolerance to wild-type hASA did not induce antibody formation, indicating absence of novel epitopes. Compared with wild-type hASA, SuPerTurbo-ASA was 8- and 12-fold more efficient in diminishing sulfatide storage of brain and spinal cord. In both tissues, storage was reduced by ∼60%, roughly doubling clearance achieved with a 65-fold higher cumulative dose of wild-type hASA previously. Due to its enhanced therapeutic potential, SuPerTurbo-ASA might be a decisive advancement for ERT and gene therapy of MLD.


Indications for early plasma transfusion and its optimal use following trauma.
This study aimed to evaluate the effect of plasma transfusion before urgent hemostasis initiation on in-hospital mortality in hemodynamically unstable patients with severe trauma. This retrospective observational study of patients admitted to hospital between January 2011 and January 2019 grouped patients according to whether plasma transfusion was initiated before (Before group) or after (After group) hemostasis initiation. Patients with severe trauma who were unable to wait for plasma transfusion and had started hemostasis before the plasma infusion were excluded. We used multivariable logistic regression analysis to determine the effect of plasma transfusion before the initiation of urgent hemostasis on in-hospital mortality. We included 47 and 73 patients in the Before and After groups, respectively. Blunt trauma was more common, and the D-dimer levels and Injury Severity Score were significantly higher in the Before group than in the After group (median D-dimer, 57.5 versus 38.1 μg/mL; P = 0.040; median Injury Severity Score, 50 versus 34; P < 0.001). Plasma given before hemostasis initiation was associated with significantly lower in-hospital mortality (adjusted odds ratio, 0.27; 95% confidence interval, 0.078-0.900; P = 0.033) in contrast with the total plasma volume given in the first 6 or 24 h. Plasma transfusion before hemostasis initiation could be an important factor for improving outcomes in hemodynamically unstable patients with blunt trauma, high D-dimer levels, or a high Injury Severity Score.


Recommendations for research and public policy in gambling studies.
The purpose of this article is to respond to and expand on the ideas presented by Father McGowan in The Ethics of Gambling Research: An Agenda for Mature Analysis. We provide specific recommendations for future research and public policy in the field of gambling studies. We suggest that key conceptual definitions--such as, problem, compulsive, and pathological gambling--should be clarified, established, and distinguished from one another before gambling research is conducted. Proper methodological procedures are recommended, where power analyses, pilot studies, and representative samples are appropriately conducted and analyzed. Retrospective and Prospective studies are considered and differentiated while Discrete Time Event History Analysis--namely, Life Tables Analysis and Discrete Time Logistic Regression--are proposed.


The clinical features and prognosis of infective endocarditis in the elderly from 2007 to 2016 in a tertiary hospital in China.
Infective endocarditis (IE) especially in the elderly is a serious disease, with a worse prognosis. A retrospective cohort study was conducted. A total of 405 patients with definite IE were divided into three groups: 205 patients under 50 years old, 141 patients between 50 and 64 years old and 59 patients over 65 years old. For older patients, clinical symptoms such as fever, anemia, and heart murmur were as common as the younger patients. IE in old patients had more frequent nosocomial origin (P = 0.007) and tended to be more frequent with bad oral hygiene (p = 0.008). The most frequent isolated pathogens in the old groups was streptococci and coagulase-negative staphylococci. The old patients had a lower operation rate (40.7% vs 58.9% vs 62.4%, P = 0.012) and higher in-hospital mortality (20.3% vs 10.6% vs 8.8%, P = 0.044) compared with the younger patients. Surgical treatment was a significant predictor of one-year mortality even after adjusting for the confounders (HR = 2.45, 95% CI 1.027-10.598, P = 0.009). The one-year survival rate was higher for older patients with surgical intervention than those without (95.8% vs 68.6%, P = 0.007). Older patients with IE presented with more comorbidities, bad oral hygiene, more nosocomial origin and a more severe prognosis than younger patients. Streptococci was the most frequent micro-organisms in this group. Surgery were underused in old patients and those with surgical treatment had better prognosis.


Efficacy of extracorporeal shockwave therapy for knee osteoarthritis: a randomized controlled trial.
Extracorporeal shockwave therapy (ESWT) has been widely used for pain relief and treatment of musculoskeletal disorders. We aimed to assess ESWT for knee osteoarthritis (OA) over 12 wk by comparison with placebo treatment. We randomized 70 patients to receive placebo (n = 36) or ESWT (n = 34). For ESWT, patients received 4000 pulses of shockwave at 0.25 mJ/mm(2) weekly for 4 wk. In the placebo group, patients received shockwave at 0 mJ/mm(2) in the same area. The effect on OA was assessed by pain on a visual analog scale and disability on the Lequesne index, Western Ontario and McMaster University Osteoarthritis Index, and patient perception of the clinical severity of OA. Evaluation was performed at baseline and after 1, 4, and 12 wk. We found no adverse events during and after ESWT. ESWT was more effective than placebo in reducing pain on movement at each period (P < 0.01). The mean visual analog scale score with ESWT was 3.83 at 12 wk versus 7.56 at baseline (P < 0.01). The Lequesne index and the Western Ontario and McMaster University Osteoarthritis Index score were reduced with ESWT. Moreover, patient perception of clinical severity of OA was significantly greater with ESWT than that with placebo (P < 0.01). ESWT is effective in reducing pain and improving knee function, with better results than placebo during the 12-wk treatment. However, further pilot studies are needed to determine whether ESWT should be recommended at an early or later stage of OA or combined with conventional therapies.


Primary Cutaneous Coccidioidomycosis in an Italian Nun Working in South America and Review of Published Literature.
Coccidioidomycosis is a systemic disease caused by the dimorphic fungus Coccidioides, endemic in parts of the Southwestern USA and Central and South America. Two species, Coccidioides immitis and Coccidioides posadasii, were differentiated. Primary cutaneous coccidioidomycosis (PCC) has been reported rarely. An unusual case of PCC characterized by a persistent solitary lesion diagnosed in Italy in an immunocompetent Italian nun living in Argentina is described. The isolate was identified by sequence analysis as C. posadasii. Antibody screening was negative. A total of 39 cases of PCC have been reported in the literature. Infections occurred as a consequence of traumatic implantation in a natural setting in endemic areas or of accidental inoculation in laboratory workers. Importance of accurate investigation of travel history and of occupational hazards to laboratory workers is outlined.


Integrating Multiple Evidence Sources to Predict Adverse Drug Reactions Based on a Systems Pharmacology Model.
Identifying potential adverse drug reactions (ADRs) is critically important for drug discovery and public health. Here we developed a multiple evidence fusion (MEF) method for the large-scale prediction of drug ADRs that can handle both approved drugs and novel molecules. MEF is based on the similarity reference by collaborative filtering, and integrates multiple similarity measures from various data types, taking advantage of the complementarity in the data. We used MEF to integrate drug-related and ADR-related data from multiple levels, including the network structural data formed by known drug-ADR relationships for predicting likely unknown ADRs. On cross-validation, it obtains high sensitivity and specificity, substantially outperforming existing methods that utilize single or a few data types. We validated our prediction by their overlap with drug-ADR associations that are known in databases. The proposed computational method could be used for complementary hypothesis generation and rapid analysis of potential drug-ADR interactions.


Mechanobiologically optimized Ti-35Nb-2Ta-3Zr improves load transduction and enhances bone remodeling in tilted dental implant therapy.
The tilted implant with immediate function is increasingly used in clinical dental therapy for edentulous and partially edentulous patients with excessive bone resorption and the anatomic limitations in the alveolar ridge. However, peri-implant cervical bone loss can be caused by the stress shielding effect. Herein, inspired by the concept of "materiobiology", the mechanical characteristics of materials were considered along with bone biology for tilted implant design. In this study, a novel Ti-35Nb-2Ta-3Zr alloy (TNTZ) implant with low elastic modulus, high strength and favorable biocompatibility was developed. Then the human alveolar bone environment was mimicked in goat and finite element (FE) models to investigate the mechanical property and the related peri-implant bone remodeling of TNTZ compared to commonly used Ti-6Al-4V (TC4) in tilted implantation under loading condition. Next, a layer-by-layer quantitative correlation of the FE and X-ray Microscopy (XRM) analysis suggested that the TNTZ implant present better mechanobiological characteristics including improved load transduction and increased bone area in the tilted implantation model compared to TC4 implant, especially in the upper 1/3 region of peri-implant bone that is "lower stress". Finally, combining the static and dynamic parameters of bone, it was further verified that TNTZ enhanced bone remodeling in "lower stress" upper 1/3 region. This study demonstrates that TNTZ is a mechanobiological optimized tilted implant material that enhances load transduction and bone remodeling.


Use of blood culture as a nonlethal method for isolating bacteria from fish.
Simple nonlethal blood culture methodology, an alternative to euthanasia for diagnosing systemic bacterial infections in fish, is described. Blood was extracted from the caudal vein of 20 individuals of five fish species, incubated in brain-heart infusion broth, and then plated onto enriched blood agar. Nine of these fish were subsequently euthanized and necropsied for confirmatory tissue cultures. Five species of bacteria were isolated from the blood cultures from nine fish, and the tissue culture results in euthanized, necropsied fish agreed with the blood culture results in all cases. All the fish that were not euthanized survived for 24 hr, although two heavily parasitized fish subsequently died.


Further studies of antibody levels to Herpes simplex virus, cytomegalovirus, measles virus, and adenovirus type 5 in Burkitt's lymphoma patients.
Sera collected from Burkitt's lymphoma (BL) patients before and after tumor manifestation were tested for antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), measles virus (MV) and adenovirus type 5, using the immunofluorescent (IF) techniques in all instances except for MV where complement fixation (CF) was used. It was found that none of these viruses showed higher antibody levels in BL patients than in controls, either before or after the appearance of the tumor. The patients came from the West Nile District of Uganda.


Impact of Racial and Gender Variations in Patients With Out-of-hospital Cardiac Arrest: A Nation-Wide Study.
The overall incidence of Out-of-hospital Cardiac Arrest (OHCA) is decreasing worldwide due to emergency responses, but there are gender and racial differences in the incidence of OHCA, which remain under investigation. Our aim was to identify the incidence, gender, and racial disparities in patients admitted with OHCA. The National Inpatient Sample Database is one of the largest all-payer inpatient database. It was queried to identify patients 18 years or older who were hospitalized with the principal diagnosis of OHCA. There was a total of 85,988 patients who were discharged with a diagnosis classified as OHCA using the ICD-9 code for a period of 2 years. The mean age of the patients who had presented to the hospital with OHCA was 64.3 (±18.5 years). Overall, a greater number of males suffered from OHCA were compared with female population of (48,635 vs 37,366; P < 0.0001). The incidence of OHCA was higher among Caucasians as compared with African Americans (54,812, 63.8% vs 13,787, 16%; P < 0.0001). In-hospital deaths after OHCA were 43,024 (50%). But African Americans had higher mortality than Caucasians after hospitalization for OHCA (adjusted odds ratio, 1.23; 95% confidence interval, 1.18-1.26; P < 0.01). We observed significant differences in gender and racial factors in the patients who were admitted to the hospital with a diagnosis of OHCA based on an analysis of the national inpatient database.


Contrast enhancement of the cochlear aqueduct in MR imaging: its frequency and clinical significance.
There have been no previous reports on contrast enhancement of the cochlear aqueduct in magnetic resonance imaging. The purpose of the present study was to evaluate the frequency and significance of this finding. Thirty-one patients (15 men and 16 women; age range 18-81 years) with otologic symptoms (sudden sensorineural hearing loss, vertigo, or tinnitus) were examined using contrast-enhanced imaging on a 1.5-T MR scanner. The normal ear served as the control. Two radiologists evaluated contrast enhancement in the area of the cochlear aqueduct. Forty-eight of 62 ears (77.4%) showed contrast enhancement of the cochlear aqueduct, but no significant differences in the frequency of contrast enhancement were observed between patients with and patients without vertigo, tinnitus, sensorineural hearing loss, cerebellopontine angle tumors, or a high-riding jugular bulb. In addition, no gender- or age-related differences were noted. Contrast enhancement of the cochlear aqueduct was frequently observed, but the frequency of enhancement in symptomatic ears was not significantly higher than in control ears. The results of this study may prove helpful in avoiding unnecessary examinations and potential diagnostic confusion.


Correction of developmental and intelligence test scores for premature birth.
When using tests of infant development and intelligence in children born prematurely, the subject's age is commonly corrected for the degree of prematurity. However, there is disagreement: first, on whether this correction should ever be applied, and second, at what age to discontinue the adjustment. In a theoretical model, the difference between corrected and uncorrected scores in early infancy was massive and the difference remained clinically important until the age of 8.5 years in children who were born extremely prematurely. The clinical implications of using corrected or uncorrected scores were then evaluated in 174 very low birthweight children without severe sensorineural disabilities and with paired Bayley Mental Development Index (MDI) and Wechsler Preschool and Primary Scales of Intelligence (WPPSI) full scale scores. Failure to correct for prematurity reduced the mean MDI by 12.1 points but reduced the mean WPPSI by only 4.1 points. The disparity between individual MDI and WPPSI scores increased significantly with decreasing gestational age if uncorrected scores were used (P = 0.015) but not if scores were corrected. Using corrected scores, the MDI correctly predicted the WPPSI category in 86.1% of children (P less than 0.001) but in only 54.6% using uncorrected scores (the difference was not significant). It is suggested that a practical solution to the dilemma is to correct test scores for prematurity in the age range 2-8.5 years recognizing that only in extremely immature infants will uncorrected scores be substantially lower than corrected ones at a later age.


Alzheimer Disease and Related Cognitive Impairment in Older Adults: A Narrative Review of Screening, Prevention, and Management for Manual Therapy Providers.
The aim of this narrative review was to review literature relevant to manual therapists about cognitive impairment, together with screening, potential treatment, and prevention modalities. A literature search of AMED (Allied and Complementary Medicine Database), CINAHL (Cumulative Index of Nursing and Allied Health Literature), PubMed, and MEDLINE was conducted with the search terms "cognitive decline," "cognitive impairment," "screening," and "prevention." We reviewed current screening practices, including functional exams, imaging, and laboratory testing. We reviewed current potential preventive measures and treatments being implemented in practice. We selected 49 resources for this narrative summary. The Montreal Cognitive Assessment and Mini-Mental State Exam are recommended screening tools. Imaging and laboratory testing are not recommended in screening for cognitive decline. Promotion of healthy, active living through physical and mental activities may assist with prevention of cognitive decline. Cognitive decline affects a large proportion of the US population. Recognizing signs and symptoms of this condition starts with individuals, caretakers, family members, and health care providers. Health care providers should utilize the most appropriate screening tools to assess the presence of cognitive conditions.


Molecular Orientation-Induced Second-Harmonic Generation: Deciphering Different Contributions Apart.
We demonstrate and explore an all-optical technique for direct monitoring of the orientation dynamics in gas-phase molecular ensembles. The technique termed "MOISH" utilizes the transiently lifted inversion symmetry of polar gas media and provides a sensitive and spatially localized probing of the second-harmonic generation signal that is directly correlated with the orientation of the gas. Our experimental results reveal selective electronic and nuclear dynamical contributions to the overall nonlinear optical signal and decipher them apart using the "reporter gas" approach. "MOISH" provides new crucial means for implementing advanced coherent rotational control via concerted excitation by both terahertz and optical fields.


Attention-related unit activity in the frontal association cortex during a go/no-go visual discrimination task.
Unit activity related to a go/no-go visual discrimination task was studied in four rhesus monkeys. We recorded 272 task-related cells from frontal cortex in a region extending from the midprincipal sulcus to the central sulcus, and medially to the cingulate sulcus. Units located in anterior regions (dorsolateral prefrontal and anterior cingulate cortex) were typically related to both go and no-go trials (designated type II units) and showed similar ("symmetrical") activity in both kinds of trials; some of them also showed prestimulus ("anticipatory") activity. Such units were present but less common in posterior regions (postarcuate and precentral and posterior cingulate cortex). Units in these posterior regions were active predominantly in go trials (designated type I units). Also found posteriorly were "asymmetrical" type II cells whose activity was greater in go trials and occurred later in the trial, around the behavioral response. The anterior symmetrical and anticipatory type II units in the frontal association cortex were similar to such units described earlier in the brain stem reticular formation and may have similar functions in supporting focused and preparatory attention. On the other hand, asymmetrical type II units in the posterior frontal regions may have a role in the initiation of visually guided motor behavior.