Systematic Analysis of Gene Expression Profiles Controlled by hnRNP Q and hnRNP R, Two Closely Related Human RNA Binding Proteins Implicated in mRNA Processing Mechanisms.
Heteregeneous ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins that take part in all processes that involve mRNA maturation. As a consequence, alterations of their homeostasis may lead to many complex pathological disorders, such as neurodegeneration and cancer. For many of these proteins, however, their exact function and cellular targets are still not very well known. Here, we focused the attention on two hnRNP family members, hnRNP Q and hnRNP R, that we previously found affecting TDP-43 activity both in Drosophila melanogaster and human neuronal cell line. Classification of these two human proteins as paralogs is suported by the high level of sequence homology and by the observation that in fly they correspond to the same protein, namely Syp. We profiled differentially expressed genes from RNA-Seq and generated functional enrichment results after silencing of hnRNP Q and hnRNP R in neuroblastoma SH-SY5Y cell line. Interestingly, despite their high sequence similarity, these two proteins were found to affect different cellular pathways, especially with regards to neurodegeneration, such as PENK, NGR3, RAB26, JAG1, as well as inflammatory response, such as TNF, ICAM1, ICAM5, and TNFRSF9. In conclusion, human hnRNP Q and hnRNP R may be considered potentially important regulators of neuronal homeostasis and their disruption could impair distinct pathways in the central nervous system axis, thus confirming the importance of their conservation during evolution.


Litter quality and inflammatory response are dependent on mating strategy in a reptile.
Maintenance of health and the production of offspring are competing processes that can result in trade-offs. As vertebrates invest substantial resources in their immune system, it is crucial to understand the interactions between immunity and reproductive strategies. In the lizard Zootoca vivipara, females have condition- and context-dependent mating strategies. We predicted that, if the risk of infection is higher for polyandrous females, then polyandrous females should invest more in immune system while monandrous females should invest more in reproduction. In order to test our prediction, we captured 62 gravid females of known age in a natural population; we kept them until parturition to access to their offspring. Then, using microsatellite marker-based paternity analyses within litters, we determine the mating strategy of females (monandrous or polyandrous). Females were also challenged with PHA to estimate their inflammatory response. Our results show that polyandrous females have a higher PHA response than the monandrous females, and that monandrous females produce more males and more juveniles of better body condition than polyandrous females. The relationship between mating behaviour and immune function may have consequences for females and may shape the evolution of mating systems.


The Global Prevalence of Neospora caninum Infection in Sheep and Goats That Had an Abortion and Aborted Fetuses: A Systematic Review and Meta-Analysis.
Neospora caninum (N. caninum) can be a potential factor causing a significant rate of miscarriages in small ruminants (sheep and goats) worldwide. Therefore, the present study aimed to determine the global status of N. caninum in sheep and goats that had an abortion and aborted fetuses. Five English databases (PubMed, ScienceDirect, Web of Science, Scopus, and ProQuest) were searched for relevant scientific articles published from their inception until November 4, 2021. Finally, 21 studies conducted on sheep (1,671 aborted fetuses and 935 abortive sheep) and 10 studies on goats (130 aborted fetuses and 80 abortive goats) were included for the final meta-analysis. A random-effects meta-analysis model was used to estimate the pooled prevalence with 95% confidence intervals (CIs). Moreover, sensitivity analysis, publication bias test, and quality assessment were performed in this study. The pooled prevalence of N. caninum in aborted fetuses of sheep and goats globally was estimated to be 15% (95% CI: 9-21%) and 7% (95% CI: 2-12%) using molecular methods. Besides, the seroprevalence of N. caninum was estimated to be 17% for aborted fetuses of sheep. The overall prevalence rate of N. caninum infection in sheep that had an abortion was 3%. The present results show a relatively high prevalence of N. caninum infection in sheep that had an abortion and aborted fetuses compared to goats. Therefore, further studies using different diagnostic techniques to more accurately estimate the rate of infection in sheep and goats may help provide adequate control measures and strategies to reduce the rate of abortion in sheep and goats and reduce economic damage to the livestock industry. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO; code: CRD42020216694).


Purification and partial characterization of a collagenolytic enzyme from Pseudomonas aeruginosa.
A proteinase from Pseudomonas aeruginosa exhibiting collagenolytic activity was purified 1575-fold with a recovery of 24% by use of chemical and chromatographic technics. The enzyme preparation appeared to be homogeneous when subjected to chromatographic, electrophoretic and ultracentrifugational analyses. A standard state sedimentation coefficient of 2.10 S was calculated and further analyses indicated that the enzyme had a molecular weight of 17 500 and dimerizes under certain conditions to yield an apparent molecular weight of 34 000. In addition to insoluble collagen, the enzyme catalyzed the hydrolysis of congocoll, azocoll, soluble collagen and casein, but did not attack orcein-elastin, azoalbumin, p-toluene eulfonyl-L-arginine methyl ester, benzoyl-L-tyrosine ethyl ester, and the hexapeptide N-benzyloxycarbonyl-glycyl-L-prolyglycylglycyl-L-prolyl-L-alanine. Enzymatic activity against congocoll was 6-fold greater at pH 7.5 in Tris with HCl than in phosphate buffer at the same ionic strength. Cobalt, and to a lesser extent, Zn2+ appeared to activate the enzyme, especially in phosphate buffer. NcCN and p-chloromercuribenzoate did not appreciably inhibit enzyme activity, while (NH4)2 SO4, EDTA and cysteine displayed a significant inhibitory effect under certain conditions.


Abnormal amygdala functional connectivity and deep learning classification in multifrequency bands in autism spectrum disorder: A multisite functional magnetic resonance imaging study.
Previous studies have explored resting-state functional connectivity (rs-FC) of the amygdala in patients with autism spectrum disorder (ASD). However, it remains unclear whether there are frequency-specific FC alterations of the amygdala in ASD and whether FC in specific frequency bands can be used to distinguish patients with ASD from typical controls (TCs). Data from 306 patients with ASD and 314 age-matched and sex-matched TCs were collected from 28 sites in the Autism Brain Imaging Data Exchange database. The bilateral amygdala, defined as the seed regions, was used to perform seed-based FC analyses in the conventional, slow-5, and slow-4 frequency bands at each site. Image-based meta-analyses were used to obtain consistent brain regions across 28 sites in the three frequency bands. By combining generative adversarial networks and deep neural networks, a deep learning approach was applied to distinguish patients with ASD from TCs. The meta-analysis results showed frequency band specificity of FC in ASD, which was reflected in the slow-5 frequency band instead of the conventional and slow-4 frequency bands. The deep learning results showed that, compared with the conventional and slow-4 frequency bands, the slow-5 frequency band exhibited a higher accuracy of 74.73%, precision of 74.58%, recall of 75.05%, and area under the curve of 0.811 to distinguish patients with ASD from TCs. These findings may help us to understand the pathological mechanisms of ASD and provide preliminary guidance for the clinical diagnosis of ASD.


MAP65/Ase1 promote microtubule flexibility.
Microtubules (MTs) are dynamic cytoskeletal elements involved in numerous cellular processes. Although they are highly rigid polymers with a persistence length of 1-8 mm, they may exhibit a curved shape at a scale of few micrometers within cells, depending on their biological functions. However, how MT flexural rigidity in cells is regulated remains poorly understood. Here we ask whether MT-associated proteins (MAPs) could locally control the mechanical properties of MTs. We show that two major cross-linkers of the conserved MAP65/PRC1/Ase1 family drastically decrease MT rigidity. Their MT-binding domain mediates this effect. Remarkably, the softening effect of MAP65 observed on single MTs is maintained when MTs are cross-linked. By reconstituting physical collisions between growing MTs/MT bundles, we further show that the decrease in MT stiffness induced by MAP65 proteins is responsible for the sharp bending deformations observed in cells when they coalign at a steep angle to create bundles. Taken together, these data provide new insights into how MAP65, by modifying MT mechanical properties, may regulate the formation of complex MT arrays.


Congestive Heart Failure and Thyroid Dysfunction: The Role of the Low T3 Syndrome and Therapeutic Aspects.
Both the morbidity and mortality rates from congestive heart failure (CHF) remain elevated despite the medical and non-medical management of the disease, thus suggesting the existence of residual risk factors such as thyroid dysfunction. Particularly, the 15-30% of patients with CHF, especially those with severe ventricular dysfunction, display the so-called low T3 syndrome (LT3S), which seems to negatively affect the cardiovascular prognosis. Only a few clinical trials have been carried out to verify both the safety and the efficacy of thyroid replacement in the LT3S, aiming to ameliorate the prognosis of CHF, and most of the results were controversial. Since the aim of the present review was to briefly overview both the indication and contraindication of triiodothyronine replacement in CHF and LT3S, the authors searched PubMed using the medical subject headings (MeSH) related to the following terms: "congestive heart failure" and "low T3 syndrome" or "euthyroid sick syndrome" or "non-thyroidal sick syndrome". The research study only focused on the narrative and systematic reviews, randomized clinical trials and meta-analysis studies which were conducted before June 2019. Studies conducted in both animal models and humans provided controversial information about the effectiveness and safety of the T3 replacement for improving ventricular dysfunction, particularly in the long-term. Further clinical trials are needed to better explore the role of LT3S in patients with CHF and its consequent therapeutic strategy in this clinical setting.


Prospective assessment of sexual function in women treated for recurrent major depression.
Although multiple factors may influence the sexual function of depressed women over the course of treatment, the independent contributions of these factors are poorly understood. The current study examined the effects of depression, SSRI treatment, and sexual partner availability on women's sexual function. The sexual function of 68 recurrently depressed women was assessed at 3-month intervals over a 1-year course of treatment with interpersonal psychotherapy with or without adjunctive SSRI treatment. Random regression models assessing changes in sexual function were conducted to test the effects of three time-dependent covariates: depression symptom scores, sexual partner availability, and SSRI medication status. Controlling for the other variables, depressive symptoms were associated with decrements in sexual desire, sexual cognition/fantasy, sexual arousal, orgasmic function, and global evaluations of sexual function. SSRI treatment was associated with orgasmic difficulty only. The availability of a sexual partner was associated with increased sexual arousal, orgasmic function, and sexual behavior. Among treatment remitters, patient reports of severe sexual dysfunction did not change over the course of treatment, although mild improvement was observed in patients' global assessment of the quality of their sexual function. This report illustrates the prevalence and persistence of sexual dysfunction in this sample, and highlights the importance of monitoring both pharmacologic and psychosocial variables that can affect the sexual function of recurrently depressed women throughout the course of treatment.


To reverse or not to reverse? A systematic review of autograft polarity on functional outcomes following peripheral nerve repair surgery.
The literature describing the best clinical practice for proximal-distal autograft orientation, otherwise known as nerve graft polarity, is inconsistent. With existing disparities in the peripheral nerve literature, the clinical question remains whether reversing nerve autograft polarity bears an advantage for nerve regeneration. A comprehensive review of the literature using Embase and PubMed databases (1940-June 2015) was performed to retrieve all original articles on the effects of nerve autograft polarity on nerve regeneration and functional recovery following primary repair of peripheral nerve defects. The initial database search yielded 318 titles. Duplicate exclusion, title review and full text review yielded six articles which directly compared nerve autograft polarity. Histological, morphometric, electrophysiological, and behavioral outcomes were reviewed. All retained articles were animal studies, of which none demonstrated significant differences in outcomes between the normal and reversed polarity groups. A reversed graft may ensure that regenerating nerve fibers are not lost at branching points, however this may not translate into improved function. There is insufficient data to suggest that nerve autograft polarity has an impact on nerve regeneration and functional outcomes.


Effect of clonidine, amphetamine, and their combinations on the locomotor activity of CD-1 and C57BL/6 mice.
Clonidine inhibited the exploratory motor activity of C57BL/6 mice non-habituated to the testing conditions. In CD-1 mice clonidine did not depress exploratory activity but did elevate the basal locomotor activity of animals both non-habituated and habituated to testing conditions. Amphetamine increased the locomotor activity of many C57BL/6 mice and conversely inhibited the locomotion of many CD-1 mice. In both strains, amphetamine in doses up to 2 mg/kg was unable to alter effects produced by clonidine. Results suggest that the locomotor activity of C57BL/6 mice is more sensitive than that of CD-1 mice to drugs affecting the central noradrenergic system.


Temperature-Directed Micellar Morphological Transformation Using CABC-Block Copolymers and Its Applications in Encapsulation and Hidden Segment.
A temperature-directed micellar morphological transformation was developed using CABC multi-block copolymers with a hydrophobic block A, a hydrophilic block B, and a thermally responsive block C with a lower critical solution temperature (LCST). The micellar structure was switched from a star (below LCST) to a flower (above LCST). The transition temperature was tunable in a wide range (11-90 °C) by varying the C monomer composition. The large difference in the loading capacity between the star and flower enabled efficient encapsulation and controlled release of external molecules. Unlike conventional systems, the present star-to-flower transformation keeps micellar structures and hence does not liberate polymers but only external molecules selectively. Another application is a hidden functional segment. A functional segment is hidden (shielded) below the LCST and exposed to interact with external molecules or surfaces above the LCST.


Serum miR-181b-5p predicts ascites onset in patients with compensated cirrhosis.
Treatment with non-selective beta-blockers (NSBBs) reduces the risk of ascites, which is the most common decompensating event in cirrhosis. This study aimed to assess the ability of a serum microRNA (miRNA) signature to predict ascites formation and the hemodynamic response to NSBBs in compensated cirrhosis. Serum levels of miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p were analyzed in patients with compensated cirrhosis (N = 105). Hepatic venous pressure gradient (HVPG) was measured at baseline, after intravenous propranolol, and 1 year after randomization to NSBBs (n = 52) or placebo (n = 53) (PREDESCI trial). miRNAs were analyzed at baseline and at 1 year. Nineteen patients (18%) developed ascites, of whom 17 developed ascites after 1 year. miR-181b-5p levels at 1 year, but not at baseline, were higher in patients that developed ascites. The AUC of miR-181b-5p at 1 year to predict ascites was 0.7 (95% CI 0.59-0.78). miR-429 levels were lower at baseline in acute HVPG responders to NSBBs (AUC 0.65; 95% CI, 0.53-0.76), but levels at baseline and at 1 year were not associated with the HVPG response to NSBBs at 1 year. Serum miR-181b-5p is a promising non-invasive biomarker to identify patients with compensated cirrhosis at risk of ascites development. Ascites marks the transition from the compensated to decompensated stage in cirrhosis and indicates a worsening in prognosis. There are currently no easily accessible tools to identify patients with compensated cirrhosis at risk of developing ascites. We evaluated the levels of novel molecules termed microRNAs in the blood of patients with compensated cirrhosis and observed that miR-181b-5p can predict which patients are going to develop ascites.


Ultrafast switching in synthetic antiferromagnet with bilayer rare-earth transition-metal ferrimagnets.
In spintronics, it is important to be able to manipulate magnetization rapidly and reliably. Several methods can control magnetization, such as by applying current pulses or magnetic fields. An applied current can reverse magnetization with nanosecond speed through the spin torque effect. For faster switching, subpicosecond switching with femtoseconds laser pulse has been achieved in amorphous rare-earth transition-metal ferrimagnets. In this study, we employed atomistic simulations to investigate ultrafast switching in a synthetic antiferromagnet with bilayer amorphous FeGd ferrimagnets. Using a two-temperature model, we demonstrated ultrafast switching in this synthetic antiferromagnet without external magnetic fields. Furthermore, we showed that if we initially stabilize a skyrmion in this heterostructure, the ultrafast laser can switch the skyrmion state using the same mechanism. Furthermore, this bilayer design allows the control of each ferrimagnetic layer individually and opens the possibility for a magnetic tunnel junction.


Polyaniline Films as Electrochemical-Proton Pump for Acidification of Thin Layer Samples.
Here, we provide the first experimental evidence of proton release from polyaniline (PANI) films subjected to anodic potentials at environmental pHs. We conducted an extensive characterization of unpolarized/polarized PANI films-synthesized by traditional sequential voltammetric scanning-by using spectroelectrochemistry, synchrotron radiation-X-ray photoelectron spectroscopy, near edge X-ray absorption fine structure, and potentiometric pH sensing in the vicinity of the PANI layer. This new insight enables the utilization of PANI as a proton pump, which is actively tuned through an electrochemical pulse, so as to controllably acidify well-confined thin layer samples. Furthermore, we demonstrate the analytical significance of this system by measuring the alkalinity of artificial and natural water samples by using two faced planar PANI electrodes, one working as a proton source and the other one as pH electrode. Finally, the impact of this approach is 2-fold: (i) all-solid-state electrode materials may be used with devisible consequences in miniaturized and implementable submersible probes, and (ii) rapid determination of alkalinity as compared to traditional approaches together with a versatility in pH adjustment in any kind of sample, among other applications.


Neuronal Soluble Fas Ligand Drives M1-Microglia Polarization after Cerebral Ischemia.
This study explored sFasL expression in neurons and the potential role of neuronal sFasL in modulating the microglial phenotypes. In vivo, middle cerebral artery occlusion (MCAO) was induced in both FasL-mutant (gld) and wild-type (wt) mice. In vitro, primary cortical neuron or microglia or coculture from wt/gld mice was subjected to oxygen glucose deprivation (OGD). sFasL level in the supernatant was evaluated by ELISA. Neuronal-conditioned medium (NCM) or exogenous sFasL was applied to primary microglia with or without FasL neutralizing antibody. Protein expression of JAK2/STAT3 and NF-κB pathways were determined by Western blot. The effect of microglia phenotype from wt/gld mice on the fate of ischemic neurons was further elucidated. In vivo, compared with wild-type mice, M1 markers (CD16, CD32 and iNOS) were attenuated in gld mice after MCAO. In vitro, post-OGD neuron released more sFasL. Both post-OGD NCM and exogenous sFasL could trigger M1-microglial polarization. However, this M1 phenotype shift was partially blocked by utilization of FasL neutralizing antibody or gld NCM. Consistently, JAK2/STAT3 and NF-κB signal pathways were both activated in microglia after exogenous sFasL treatment. Compared with wild-type mice, M1-conditioned medium prepared from gld mice protected neuron against OGD injury. Ischemic neurons release sFasL, which contributes to M1-microglial polarization. The underlying mechanisms may involve the activation of JAK2/STAT3 and NF-κB signaling pathways.


Additive manufacturing of geopolymers with hierarchical porosity for highly efficient removal of Cs.
Geopolymers (GPs) have emerged as promising adsorbents for wastewater treatment due to their superior adsorption stability, tunable porosity, high adsorption capacity, and low-energy production. Despite their great promise, developing GPs with well-controlled hierarchical structures and high porosity remains challenging, and the mechanism underlying the ion adsorption process remains elusive. Here we report a cost-effective and universal approach to fabricate Na or K GPs with sophisticated architectures, high porosity, and arbitrary cation species exchange by means of additive manufacturing and a surfactant. The introduction of sodium lauryl sulfate (SLS) enhanced the porosity of the GP adsorbents, yielding NaGP-lattice-10%SLS adsorbent with a high total porosity of 80.8 vol%. Combining static and dynamic adsorption tests, the effects of morphology, surfactant content, and cation species on Cs+ adsorption performance were systemically investigated. With an initial Cs+ concentration of 900 mg/L, the printed NaGP exhibited a maximum Cs+ adsorption capacity of 80.1 mg/g, outperforming other adsorbents reported so far. The quasi-second-order fit of the NaGP adsorbent showed overall higher R2 values than the quasi-first-order fit, indicating that the adsorption process was dominated by ion exchange. Combined with first-principles calculations, we verified that the content of water in the GP sod cages also affected the ion-exchange process between Na+ and Cs+.


The clinical utility of the continuous performance test and objective measures of activity for diagnosing and monitoring ADHD in children: a systematic review.
Attention-deficit hyperactivity disorder (ADHD) is typically diagnosed using clinical observation and subjective informant reports. Once children commence ADHD medication, robust monitoring is required to detect partial or non-responses. The extent to which neuropsychological continuous performance tests (CPTs) and objective measures of activity can clinically aid the assessment and titration process in ADHD is not fully understood. This review describes the current evidence base for the use of CPTs and objectively measured activity to support the diagnostic procedure and medication management for children with ADHD. Four databases (PsycINFO, Medline, Allied and Complementary Medicine (AMED), and PsycARTICLES) were systematically searched to understand the current evidence base for (1) the use of CPTs to aid clinical assessment of ADHD; (2) the use of CPTs to aid medication management; and (3) the clinical utility of objective measures of activity in ADHD. Sixty relevant articles were identified. The search revealed six commercially available CPTs that had been reported on for their clinical use. There were mixed findings with regard to the use of CPTs to assess and manage medication, with contrasting evidence on their ability to support clinical decision-making. There was a strong evidence base for the use of objective measures of activity to aid ADHD/non-ADHD group differentiation, which appears sensitive to medication effects and would also benefit from further research on their clinical utility. The findings suggest that combining CPTs and an objective measure of activity may be particularly useful as a clinical tool and worthy of further pursuit.


Air-soil exchange of mercury from background soils in the United States.
The air-surface exchange of mercury (Hg) was measured, using a dynamic polycarbonate flux chamber, for soils with low or "background" Hg concentrations (<0.1 mg/kg) at eleven locations across the contiguous United States. Sampling locations included agricultural, desert, grassland, mixed and pine forest ecosystems (n=1326 soil flux measurements at 46 individual sites). An overall soil Hg flux of 0.9+/-0.2 ng/m2/h for these background soils was obtained by averaging the means for the different locations. Soil Hg fluxes were significantly lower in dark conditions than in the light for all but the grassland sites. Mean inlet air Hg concentrations were 1.0+/-0.1 ng/m3 in the dark and 1.3+/-0.2 ng/m3 in the light. Soil temperature inside and outside of the chamber, air temperature, relative humidity, and irradiance were measured concurrently with soil Hg flux. Soil-air Hg exchange was weakly predicted by environmental variables (R2 from 0.07 to 0.52). For a single location, flux was better correlated with soil moisture than other measured environmental parameters, suggesting that soil moisture might be an important driver for Hg emissions from background soils. In addition, based on data collected we suggest some quality control measures for use of Tekran 2537A analyzers when measuring low mercury fluxes. Using basic scaling procedures, we roughly estimate that natural emissions from soils in the contiguous U.S. release approximately 100 Mg/yr of Hg to the atmosphere.


Association of an Electronic Health Record Add-on App for Neonatal Bilirubin Management With Physician Efficiency and Care Quality.
The usefulness of electronic health record (EHR) systems could be significantly enhanced by innovative, third-party EHR add-on apps. To evaluate whether an EHR add-on app for neonatal bilirubin management can save clinicians time and improve patient care. This quality improvement study was conducted at the University of Utah Health Well Baby nursery and outpatient clinics and consisted of 4 substudies: (1) time savings were estimated in an experimental task-timing study comparing the time required for physicians to manage newborns' bilirubin levels with and without the add-on app, (2) app use was estimated from app logs, (3) health care use measures and guideline compliance were compared retrospectively before and after the intervention, and (4) clinician-perceived usability was measured through System Usability Scale surveys. The study took place between April 1, 2016, and September 3, 2019. Data analyses were conducted from October 30, 2018, to September 23, 2019. At baseline, clinicians used a manual approach to ensure compliance with an evidence-based clinical guideline for neonatal bilirubin management. To facilitate guideline compliance, an EHR add-on app that automatically retrieves, organizes, and visualizes relevant patient data was developed. The app provides patient-specific assessments and recommendations, including the risk of rebound hyperbilirubinemia following phototherapy based on a predictive model. The add-on app was integrated with the University of Utah Health EHR on April 12, 2017. Clinician time savings, app use, health care use measures, guideline-compliant phototherapy ordering, and perceived usability as measured by the System Usability Scale survey. The survey is composed of 10 statements with responses ranging from 1 (strongly disagree) to 5 (strongly agree). The survey results in a single score ranging from 0 to 100, with ratings described as worst imaginable (mean System Usability Scale score, 12.5), awful (20.3), poor (35.7), okay (50.9), good (71.4), excellent (85.5), and best imaginable (90.9). In 2018, the application was used 20 516 times by clinicians for 91.84% of eligible newborns. Use of the app saved 66 seconds for bilirubin management tasks compared with a commonly used tool (95% CI, 53-79 seconds; P < .001). Following the intervention, health care use rates remained stable, while orders for clinically appropriate phototherapy during hospitalization increased for newborns with bilirubin levels above the guideline-recommended threshold (odds ratio, 1.84; 95% CI, 1.16-2.90; P = .009). Surveys indicated excellent usability (System Usability Scale score, 83.90; 95% CI, 81.49-86.31). Well-designed EHR add-on apps may save clinicians time and improve patient care. If time-saving apps, such as the bilirubin app, were implemented widely across institutions and care domains, the potential association with improved patient care and clinician efficiency could be significant. The University of Utah Health bilirubin app is being prepared for release into EHR app stores as free-to-use software.


Depression mediates impaired glucose tolerance and cognitive dysfunction: A neuromodulatory role of rosiglitazone.
Comorbidity of depression and diabetes is a serious risk factor worsening the complications such as cognitive function and locomotion. Treatment under this condition becomes extremely complicated. Insulin signaling and autophagy pathways are involved in modulation of learning and memory. Rosiglitazone (ROSI) ameliorate cognitive deficit associated with depression and insulin resistance. In the present study, we investigated the effect of ROSI against chronic unpredictable stress (CUS) induced depression as a risk factor for diabetes and behavioral dysfunctions. Adult male Swiss albino mice were exposed to CUS alongside ROSI (5mg/kg/day) treatment for 21days. Thereafter, animals were subjected to different behavioral studies to assess depressive like behavior, cognition and locomotion. The effect of ROSI on insulin signaling, autophagy and apoptosis were evaluated in the hippocampus. CUS resulted in depressive like behavior, cognitive impairment and hypolocomotion associated with oxidative stress, impaired glucose tolerance and hypercorticosteronemia. CUS significantly impaired hippocampal insulin signaling, membrane translocation of glucose transporter type 4 (GLUT4) as well as decreased the expression of autophagy5, autophagy7, B-cell lymphoma 2 and apoptosis inhibitory protein 2. ROSI significantly reduced depressive like behavior, postprandial blood glucose, hypercorticosteronemia, oxidative and inflammatory stress, and apoptosis in stressed mice. Moreover, ROSI treatment effectively improved hippocampal insulin signaling, GLUT4 membrane translocation and cognitive performance in depressed mice. ROSI administration might prove to be effective for neurological disorders associated with depressive like behavior and impaired glucose tolerance.


EEG topogram--an aid in describing EEG to the clinician.
The investigation presents a simple, reliable method to show localized EEG abnormalities in a topographical display. The aim of the study was to find a method which could be used in clinical practice, and which in topographical form could complement the written EEG report with information about degree and localization of an EEG abnormality. The EEG was recorded on a 21-channel polygraph (Siemens-Elema). The source derivation recording technique was used. Besides being displayed as a conventional EEG record, the signals were fed to a small computer that calculated an abnormality feature based on the time domain descriptors activity, mobility and complexity. Obtained values were converted into ink density in topograms by modulating the displacement velocity of the ink jet beam. The dynamic range was chosen so that maximum and minimum densities represented 1.5 and 0.5 times the average for each descriptor. The ink density in the topogram was thus related to the degree of EEG abnormality. The recording procedure followed the ordinary clinical routine except that the conventional EEG display was interrupted several times for a few seconds, on command by the EEG technician, to write out the topogram on the EEG paper. It is concluded that EEG topograms produced on line as part of the EEG examination procedure may greatly enhance EEG information conveyed from the neurophysiologist to the clinician. Furthermore, they permit direct visual comparison with other diagnostic topographic displays such as CT scan.


Midland Health Board staff and impact of cuts.
An analysis of the 2,719 staff of the Midland Health Board at 31 December, 1988 was made, on the basis of work done. This showed that 7.4% of the staff were engaged on administrative work. The pay cost of the administrative staff was 5.2% of total remuneration and 3.3% of all direct payments made by the health board. Between January, 1986 and the end of 1988, staff numbers were reduced by 293 (9.7%). Of these, 189 (64.5%) were catering, housekeeping and maintenance staff. In the same period medical staff increased by 5 (3.3%), paramedicals increased by 11 (10.4%) and administrators were reduced by 12 (4.2%).


Further evidence for acquired undescended testicle in the UK and its incompatibility with current recommendations in the Hall Report.
The 4th edition of the Hall Report [Hall DMB. Health for all children. Oxford: Oxford University Press; 2003. p. 167] does not expect undiagnosed undescended testicles at the age of 5 years or subsequently to be seen if its advice for diagnosis is carried out. We examine whether that recommendation can be relied upon. A retrospective audit was performed of 228 boys who underwent orchidopexy between January 1992 and December 2003 at the County Hospital Hereford, UK. During that time, 10,048 boys were born at the hospital. Child health records, hospital records and some GP records were used. A total of 103 boys (45%) were treated before their 5th birthday and 125 (55%) were treated after the age of 5; 93 orchidopexies were performed as a result of diagnosis made at birth or 6 weeks, but 83 were undertaken in boys documented as having scrotally placed testes both at birth and 6 weeks. A further 21 had documentation for scrotal testes either at birth (14) or at 6 weeks (7) but not both. The records of the remaining 31 are either missing or did not yield the information required largely because the Parent Held Child Record was introduced after their time. The literature was reviewed, and the results found to concur with those of other papers, in particular with a recent study from The Netherlands, which led to a new classification of undescended testis drawing attention to 'acquired undescended testicle'. The progressive nature of this entity was seen from review of the case notes. The natural history of acquired undescended testis means that recommendations as set out in the Hall Report "that no further check after six weeks need be made if the testes are 'well down' at that stage" cannot be successful, and all concerned in childhood surveillance will need to be aware of this and remain vigilant at least until puberty. Perhaps a prospective study following the Netherlands design should be undertaken in this country.


Radioiodinated anti-hepatocellular carcinoma (HCC) ferritin. Targeting therapy, tumor imaging and anti-antibody response in HCC patients with hepatic arterial infusion.
Radioimmunoimaging and radioimmunotherapy with radioiodinated anti-(hepatocellular carcinoma ferritin) antibody (131I- or 125I-FtAb) have been applied in patients with primary liver cancer. A total of 41 patients with surgically unresectable hepatocellular carcinoma (HCC) and receiving hepatic artery ligation and cannulation during exploratory laparotomy were treated with this regimen by intrahepatic arterial infusion. Compared with the control group, a decline of serum alpha-fetoprotein (65.7% versus 42.9%) and shrinkage of tumor (68.3% versus 33.9%) were observed in the treated group, and a higher second-look resection rate (31.7% versus 5.1%) and longer survival (1-year: 61.0% versus 37.3%, 3-year: 25.0% versus 6.9%) resulted. The administration of antibody through a hepatic arterial catheter (n = 16) was compared with intravenous injection (n = 17) in terms of the tumor-imaging sensitivity in 33 patients with liver cancer. The results indicated that hepatic arterial infusion was superior to intravenous injection. The sensitivity 7 days after the administration was 100% in the i.a. group and 76.5% in the i.v. group, the uptake ratio of tumor to liver being 1.74 +/- 0.57 in the former and 1.34 +/- 0.29 in the latter. Furthermore, intrahepatic arterial infusion revealed a lower anti-antibody detection rate than intravenous injection (0/14 versus 4/11).


Impact of COPD exacerbations on osteoporosis assessed by chest CT scan.
COPD pathology involves not only the lungs but also extrapulmonary abnormalities. Osteoporosis is one of the most important abnormalities because it may cause vertebral compression fractures and deteriorate pulmonary function. COPD patients have many risk factors for osteoporosis, such as low BMI, decreased activity, systemic inflammation, and use of corticosteroids. Some of these factors have been shown to deteriorate with COPD exacerbations. We previously demonstrated the correlation between emphysema and osteoporosis and between emphysema progression and COPD exacerbations. Thus, the hypothesis that exacerbation causes osteoporosis progression in COPD patients was investigated. Forty-two COPD patients not on osteoporosis treatment for over 2 years were recruited. During follow-up, exacerbations had been prospectively recorded. Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and the annual change in BMD was calculated. The change was compared between patients with and without a history of exacerbations. The decrease in thoracic vertebral BMD was greater in patients with than in those without a history of exacerbations (median ΔBMD mg/ml·year: -3.78 versus -0.30, p = 0.02). Moreover, multivariate regression analysis showed that exacerbations and baseline PaO₂ were independent predictors of the BMD decrease (R² = 0.20, p = 0.007, and R² = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking status, and airflow limitation. This is the first longitudinal study to demonstrate that COPD exacerbations are independently associated with osteoporosis progression. Osteoporosis progression should be evaluated in COPD patients, especially in those with a history of frequent exacerbations.


Serotonin turnover in individual brain nuclei: evaluation of three methods using liquid chromatography with electrochemical detection.
Liquid chromatography with electrochemical detection and brain microdissection techniques were used to evaluate three methods of studying serotonin turnover in 10 individual brain nuclei. The increase in serotonin (5-HT) and decline in 5-hydroxyindole acetic acid (5-HIAA) after administration of the monoamine oxidase inhibitor, pargyline, as well as the accumulation of 5-hydroxytryptophan (5-HTP) after the L-amino acid decarboxylase inhibitor, m-hydroxybenzylhydrazine, were measured. Serotonin accumulation and 5-HIAA decline could be detected in the n. caudatus, globus pallidus, cortical amygdala, n. interstitialis striae terminalis, n. preopticus medialis, and n. dorsomedialis. Only serotonin accumulation could be accurately assessed in the n. ventromedialis, n. arcuatus, and median eminence. The pattern of increase of serotonin after pargyline varied in different nuclei. There was a linear increase of serotonin over 90 minutes in the caudate, globus pallidus, and ventromedial nucleus and over 60 minutes in the n. preopticus medialis, and cortical amygdala. This contrasted with a maximal increase at 30 minutes in the other nuclei. However, 5-HIAA decline tended to be greatest after 30 minutes in most nuclei. Increases in 5-HTP concentrations after decarboxylase inhibition were not reliably detected in these areas. These results indicate that two nonsteady state methods may be used to evaluate changes in serotonin turnover in selected individual, nonpooled hypothalamic and forebrain nuclei.


Evaluation on Auto-segmentation of the Clinical Target Volume (CTV) for Graves' Ophthalmopathy (GO) with a Fully Convolutional Network (FCN) on CT Images.
CDATA[Purpose: The aim of this study is to evaluate the accuracy and dosimetric effects for auto- segmentation of the CTV for GO in CT images based on FCN. An FCN-8s network architecture for auto-segmentation was built based on Caffe. CT images of 121 patients with GO who have received radiotherapy at the West China Hospital of Sichuan University were randomly selected for training and testing. Two methods were used to segment the CTV of GO: treating the two-part CTV as a whole anatomical region or considering the two parts of CTV as two independent regions. Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD) were used as evaluation criteria. The auto-segmented contours were imported into the original treatment plan to analyse the dosimetric characteristics. The similarity comparison between manual contours and auto-segmental contours showed an average DSC value of up to 0.83. The max HD values for segmenting two parts of CTV separately was a little bit smaller than treating CTV with one label (8.23±2.80 vs. 9.03±2.78). The dosimetric comparison between manual contours and auto-segmental contours showed there was a significant difference (p<0.05) with the lack of dose for auto-segmental CTV. Based on deep learning architecture, the automatic segmentation model for small target areas can carry out auto contouring tasks well. Treating separate parts of one target as different anatomic regions can help to improve the auto-contouring quality. The dosimetric evaluation can provide us with different perspectives for further exploration of automatic sketching tools.


Glycosyl transfer from nucleotide sugars to C85- and C55-polyprenyl and retinyl phosphates by microsomal subfractions and Golgi membranes of rat liver.
The capacity of isolated membrane fractions to catalyse transfer of sugars from sugar nucleotides to alpha-saturated and non-saturated forms of phosphorylated C85 and C55 polyprenols and retinyl phosphate was examined. The amount of endogenous lipid acceptor present for various sugars was also measured. It appears that the types and amounts of polyprenyl phosphates present in rough- and smooth-microsomal fractions and Golgi membranes are different and the individual polyprenyl phosphates exhibit specificity as sugar acceptors.


Behavioral state-specific inhibitory postsynaptic potentials impinge on cat lumbar motoneurons during active sleep.
High-gain intracellular records were obtained from lumbar motoneurons in intact, undrugged cats during naturally occurring states of wakefulness, quiet sleep, and active sleep. Spontaneous, discrete, inhibitory postsynaptic potentials (IPSPs) were found to impinge on lumbar motoneurons during all states of sleep and wakefulness. IPSPs which occurred during wakefulness and quiet sleep were of relatively low amplitude and had a low frequency of occurrence. During the state of active sleep there occurred a great increase in inhibitory input. This was the result of the appearance of large-amplitude IPSPs and of an increase in the frequency of low-amplitude IPSPs which were indistinguishable from those recorded during wakefulness and quiet sleep. In addition to a difference in amplitude, the time course of the large IPSPs recorded during active sleep further differentiated them from the smaller IPSPs recorded during wakefulness, quiet sleep, and active sleep; i.e., their rise-time and half-width were of longer duration and their rate-of-rise was significantly faster. We suggest that the large, active sleep-specific IPSPs reflect the activity of a group of inhibitory interneurons which are inactive during wakefulness and quiet sleep and which discharge during active sleep. These as yet unidentified interneurons would then serve as the last link in the brain stem-spinal cord inhibitory system which is responsible for producing muscle atonia during the state of active sleep.


A comparison of developmental social-pragmatic and naturalistic behavioral interventions on language use and social engagement in children with autism.
Developmental social-pragmatic and naturalistic behavioral interventions share a number of features, but they differ in their use of facilitative strategies and direct elicitation of child language. In this study, the authors investigated whether these approaches produce different language and social outcomes in young children with autism. The authors used an ABACAD design to compare the effects of a developmental social-pragmatic, naturalistic behavioral, and combined intervention on language type and function and social engagement in 5 children with autism. Milieu teaching and the combined intervention produced higher rates of language targets than did responsive interaction. An analysis of the type and function of language targets suggested that differences between conditions were driven primarily by prompted-and, to a lesser extent, spontaneous-requests. Social engagement ratings were higher during each intervention than at baseline, but differences between treatment conditions were not consistent across children. For children with autism, naturalistic interventions that use direct elicitation of child language lead to greater short-term gains in the use of expressive language targets-in particular, prompted requests-than interventions that use facilitative strategies only. All 3 naturalistic language interventions can promote social engagement. For some children, the combined use of direct elicitation and responsiveness-based strategies may enhance treatment response.


Pine oil cleaner ingestion.
We report the cases of 22 patients who were hospitalized for pine oil cleaner ingestion. The toxic manifestations most commonly observed were mucous membrane and gastrointestinal irritation. Ataxia, which did not occur in adults, was a frequent presenting sign of intoxication in children. Fifty-nine percent of patients who ingested only pine oil cleaner developed central nervous system depression, and three of these developed coma. Three of five children and three of 17 adults developed acute hydrocarbon pneumonitis. Unlike aspiration pneumonitis, which follows petroleum distillate ingestion, chemical pneumonitis from pine oil cleaner may occur from gastrointestinal absorption of pine oil and deposition in lung tissue. However, recovery from pneumonitis in our patients was typically rapid and complete. Only two adults developed secondary bacterial pneumonia; no patient died. Ingestion of pine oil cleaner was rarely life threatening; most patients needed only gastrointestinal decontamination and minimal supportive care.


Seasonal variation in crassulacean acid metabolism in Dudleya blochmanae (Crassulaceae).
Plants of Dudleya blochmanae were studied over a growing season (December-June) in their native habitat on the central California coast. During the season soil water potential fluctuatdd widely, becoming unmeasurably negative (<-5.0 MPa) by early May. In contrast, leaf water potential did not fluctuate greatly with the most negative value of-0.56 MPa occurring in June. The leaves exhibited nocturnal accumulation of titratable acidity at all sampling periods, with the greatest magnitudes of accumulation occurring late in the growing season. The fruits also exhibited nocturnal accumulation of titratable acidity. The biomass δ13C values of all organs were most negative in December and least negative in June. The findings confirmed earlier suggestions that there may be biologically important differences in carbon isotope content among the various organs of a single plant of D. blochmanae. The water potential of thephotosynthetic organs was highly correlated (r2=0.84) with the biomas δ13C value. A greenhouse study demonstrated that the fruits exhibit an, apical dominance with regard to maintenance of plant water potential during drought.


Personalized Medicine and Infectious Disease Management.
A recent study identified pathogen factors associated with an increased mortality risk in Staphylococcus aureus bacteremia, using predictive modelling and a combination of genotypic, phenotypic, and clinical data. This study conceptually validates the benefit of personalized medicine and highlights the potential use of whole genome sequencing in infectious disease management.


The effect of low- and high-penetration light on localized cancer therapy.
The design of a delivery system allowing targeted and controlled drug release has been considered one of the main strategies used to provide individualized cancer therapy, to improve survival statistics, and to enhance quality-of-life. External stimuli including low- and high-penetration light have been shown to have the ability to turn drug delivery on and off in a non-invasive remotely-controlled fashion. The success of this approach has been closely related to the development of a variety of drug delivery systems - from photosensitive liposomes to gold nanocages - and relies on multiple mechanisms of drug release activation. In this review, we make reference to the two extremes of the light spectrum and their potential as triggers for the delivery of antitumor drugs, along with the most recent achievements in preclinical trials and the challenges to an efficient translation of this technology to the clinical setting.


Deletion of 19q13 reveals clinical overlap with Dubowitz syndrome.
Dubowitz syndrome is a presumed autosomal recessive disorder characterized by multiple congenital abnormalities: microcephaly, learning and developmental delay, growth failure, and a predisposition to allergies and eczema. There have been more than 150 individuals reported to have this diagnosis, but no unifying genetic alteration has been identified indicating genetic heterogeneity. We report on a pair of monozygotic twins diagnosed clinically with Dubowitz syndrome by Professor Dubowitz over 30 years ago and identified to have a de novo heterozygous 3.2-Mb deletion at 19q13.11q13.12. Exome sequencing did not identify either a putative pathogenic variant on the trans allele supporting recessive inheritance or any other causative sequence variants. Comparison of the phenotype in our cases shows considerable overlap with the 19q13.11 microdeletion syndrome, suggesting that a subset of individuals diagnosed with Dubowitz syndrome may be due to deletions at 19q13. Our finding further reinforces the genetic and phenotypic heterogeneity of Dubowitz syndrome.


A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse.
As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.


Museum Genomics Confirms that the Lord Howe Island Stick Insect Survived Extinction.
The Lord Howe Island stick insect, Dryococelus australis, was once common on the island but was driven to extinction after the arrival of ship rats in the early 20th century [1, 2]. It was thought to be extinct for decades, until a tiny population of similar-looking stick insects was discovered 20 km away, on the islet of Ball's Pyramid, in 2001 [2]. Individuals from this population are currently being reared in Australia and elsewhere in the world, with the eventual goal of recolonizing Lord Howe Island [3]. Recent surveys of the wild population on Ball's Pyramid suggest that it is among the world's rarest species. However, there are significant morphological differences between Ball's Pyramid and museum specimens, and there has never been a genetic confirmation of the rediscovered population's species identity. Because Dryococelus is monotypic, there are also no known extant relatives for comparison. Using shotgun genomic data from the Ball's Pyramid population, we assembled a draft genome and the complete mitochondrial genome. We found that the genome is massive, over 4 Gb in size, and is most likely hexaploid. We re-sequenced mitochondrial genomes from historic museum specimens collected on Lord Howe Island before the extinction event. Sequence divergence between the two populations is less than 1% and is within the range of intraspecific differences between the museum specimens, suggesting that they are conspecific and that D. australis has successfully evaded extinction so far. This work highlights the importance of museum collections for taxonomic validation in the context of ongoing conservation efforts.


A morphometric study of invasion and metastasis in human colorectal carcinoma.
The cell nuclei within primary and nodal secondaries of colorectal carcinomas were analysed morphometrically in order to identify a primary subpopulation with similar characteristics to cells involved in lymphatic metastasis. No significant difference in nuclear area was seen between cell populations of the primary and secondary. However, a regional variation in mean nuclear area was present, suggesting a relationship between cells at the invasion front and in early nodal metastasis. This subpopulation differed from the cell populations of the primary and more advanced secondaries. These results are consistent with the existence of a morphometrically identifiable metastatic subpopulation within the invasion front of colorectal carcinoma.


Surgical challenges and outcomes of rhegmatogenous retinal detachment in albinism.
To report the outcomes and surgical difficulties during rhegmatogenous retinal detachment (RRD) repair in patients with albinism. Retrospective analysis of 10 eyes of 9 patients with albinism that underwent RRD repair was performed. Collected data included demographic details, preoperative examination details, surgical procedure, surgical difficulties, anatomical, and visual outcomes. Outcome measures were retinal reattachment and visual acuity at the last follow-up. Mean preoperative best-corrected visual acuity (BCVA) was logMAR (Logarithm of the Minimum Angle of Resolution) 2.15 (range 0.9-3.0) with preoperative localization of causative break in six eyes. One eye had proliferative vitreoretinopathy grade C1 preoperatively. Four eyes underwent scleral buckling (SB) and six underwent 20G pars plana vitrectomy (PPV) with silicone oil injection. Intraoperative complication as iatrogenic retinal break occurred in four eyes. For retinopexy during vitrectomy, endolaser delivery was possible in three out of six eyes, whereas three eyes had cryopexy. The mean follow-up was 12 months in SB group (range 1-12; median 12 months) and 5.33 months (range 1-12; median 3 months) in PPV group. Among vitrectomized eye, two eyes had recurrence at 3 months with oil in situ. Rest of the eyes had attached retina at last follow-up. Mean BCVA at last follow-up was logMAR -1.46 (range 0.7-2.0) with mean improvement of -0.57 logMAR. Identification of break, induction of posterior vitreous detachment, and endolaser delivery may be difficult during RRD repair in patients with albinism. The incidence of PVR appeared less in these eyes. Both SB and PPV were efficacious and appear to be good surgical techniques for use in this patient population.


Defective proboscis extension response (DPR), a member of the Ig superfamily required for the gustatory response to salt.
Gustatory stimuli, such as sugar, induce a behavioral response in Drosophila that involves extension of the proboscis and consumption of the sugar-containing solution. Addition of salt to the sugar solution inhibits this behavioral response. However, the mechanisms and gene products involved in the salt aversion response have not been described. Here, we report the identification of a locus, defective proboscis extension response (dpr), that is required for salt aversion. dpr was expressed in a subset of primary neurons in the gustatory organs and encoded a protein with two Ig-like domains, a single putative transmembrane domain, and a short region C terminal to the transmembrane segment. In addition, DPR defines a large previously unknown group of > or =20 highly related Ig-containing proteins.


Comparative evaluation of whole blood versus plasma for quantitative detection of cytomegalovirus using an automated system.
Peripheral blood samples were separated into aliquots of whole blood and plasma and tested using an automated PCR system. More positive results were obtained from plasma (43), compared to whole blood (34). Plasma results did not correlate well with those in whole blood and tended to produce higher viral loads.


Striatal dopamine transporter imaging in Parkinson's disease drug-naïve patients: focus on sexual dysfunction.
Dopamine is involved in sexual behavior, but dopaminergic imaging studies establishing the relationship between nigrostriatal dopaminergic degeneration and sexual dysfunction (SD) in Parkinson's disease (PD) are lacking. We retrospectively analyzed clinical and 123I-FP-CIT SPECT data of 43 drug-naïve PD patients. Based on the sexual function domain of the Non-Motor Symptoms Scale (NMSS), we identified 23 patients with sexual concerns (WSC), reporting a score ≥ 2 due to hyposexuality, and 20 patients without sexual concerns (NoSC). Dopamine transporter (DAT) uptake was assessed through semi-quantitative analysis in the most and least affected putamen (maP, laP), and most and least affected caudate (maC, laC). Total putamen-to-caudate ratio and total striatal binding ratio (tSBR) were also quantified. WSC and NoSC had similar demographic and disease-related characteristics. WSC displayed lower uptake values in maC (p = 0.016), maP (p = 0.004), laC (p = 0.019), laP (p = 0.009), and tSBR (p = 0.006). Pearson correlation analysis revealed, in the WSC group, moderate inverse correlations between the log-transformed SD scores and the uptake in maP (r = - 0.473, p = 0.023), maC (r = - 0.428, p = 0.042), laP (r = -0.437, p = 0.037), and tSBR (r = - 0.460, p = 0.027). After controlling in a two-way ANCOVA model for age and sex, between-group differences,between WSC and NoSC remained statistically significant only for dopaminergic denervation in maP [F(1,38) = 7.478, p = 0.009)], laP [F(1,38) = 4.684, p = 0.037)], and tSBR [F(1,38) = 5.069, p = 0.030]. To the best of our knowledge, this is the first study reporting the relationship between the severity of SD and specific patterns of nigrostriatal dopaminergic denervation (especially involving both putamina) in newly diagnosed drug-naïve PD patients.


Pythium glomeratum, a new species isolated from agricultural soil taken in north-eastern France, its ITS region and its comparison with related species.
Pythium glomeratum sp. nov. is described here. It was isolated from soil samples taken in the northern France in 1992, was wrongly identified as Pythium heterothallicum and was kept aside. Recently, the ITS region of the rDNA of this oomycete was amplified and sequenced. The differences between the sequence and a more detailed study of the morphological characters of these two species, revealed that both are related but different species. P. glomeratum is characterized by the presence of branched antheridia that wrap around the oogonia, aplerotic to almost plerotic oospores, and the lack of zoosporangia and zoospores. Taxonomical description of this new species, its comparison with related oomycetes, polymerase chain reaction (PCR) amplification of the internal transcribed region (spacers ITS1, ITS2, and the gene 5.8S) of its ribosomal nuclear DNA and the nucleotide sequence of this region are given here.


The fate of mesenchymal stem cells is greatly influenced by the surface chemistry of silica nanoparticles in 3D hydrogel-based culture systems.
Polymeric hydrogel-based 3D scaffolds are well-known structures, being used for cultivation and differentiation of stem cells. However, scalable systems that provide a native-like microenvironment with suitable biological and physical properties are still needed. Incorporation of nanomaterials into the polymeric systems is expected to influence the physical properties of the structure but also the stem cells fate. Here, alginate/gelatin hydrogel beads incorporated with mesoporous silica nanoparticles (MSNs) (average diameter 80.9 ± 10 nm) and various surface chemistries were prepared. Human adipose-derived mesenchymal stem cells (hASCs) were subsequently encapsulated into the alginate/gelatin/silica hydrogels. Incorporation of amine- and carboxyl-functionalized MSNs (A-MSNs and C-MSNs) significantly enhances the stability of the hydrogel beads. In addition, the expression levels of Nanog and OCT4 imply that the incorporation of A-MSNs into the alginate/gelatin beads significantly improves the proliferation and the stemness of encapsulated hASCs. Importantly, our findings show that the presence of A-MSNs slightly suppresses in vivo inflammation. In contrast, the results of marker gene expression analyses indicate that cultivation of hASCs in alginate beads incorporated with C-MSNs (10% w/w) leads to a heterogeneously differentiated population of the cells, i.e., osteocytes, chondrocytes, and adipocytes, which is not appropriate for both cell culture and differentiation applications.


Selective deletion of endothelial mineralocorticoid receptor protects from vascular dysfunction in sodium-restricted female mice.
Recent evidence by our laboratory demonstrates that women and female mice endogenously express higher endothelial mineralocorticoid receptor (ECMR) than males. Mounting clinical evidence also indicates that aldosterone production is higher in pathological conditions in females compared to males. However, the role for increased activation of ECMR by aldosterone in the absence of a comorbid condition is yet to be explored. The current study hypothesized that increased ECMR activation induced by elevated aldosterone production predisposes healthy female mice to endothelial dysfunction. Vascular reactivity was assessed in aortic rings from wild-type (WT) and ECMR KO (KO) mice fed either a normal salt (NSD, 0.4% NaCl) or sodium-restricted diet (SRD, 0.05% NaCl) for 28 days. SRD elevated plasma aldosterone levels as well as adrenal CYP11B2 and angiotensin II type 1 receptor (AT1R) expressions in female, but not male, WT mice. In baseline conditions (NSD), endothelial function, assessed by vascular relaxation to acetylcholine, was higher while vascular contractility to phenylephrine, serotonin, and KCl lower in female than male WT mice. SRD impaired endothelial function and increased vascular contractility in female, but not male, WT mice effectively ablating the baseline sex differences. NOS inhibition with LNAME ablated endothelial relaxation to a higher extent in male than female mice on NSD and ablated differences in acetylcholine relaxation responses between NSD- and SRD-fed females, indicating a role for NO in SRD-mediated endothelial function. In association, SRD significantly reduced vascular NOX4 expression in female, but not male, mice. Lastly, selective deletion of ECMR protected female mice from SRD-mediated endothelial dysfunction and increased vascular contractility. Collectively, these data indicate that female mice develop aldosterone-induced endothelial dysfunction via endothelial MR-mediated reductions in NO bioavailability. In addition, these data support a role for ECMR to promote vascular contractility in female mice in response to sodium restriction.


Numerical modeling investigations of colloid facilitated chromium migration considering variable-density flow during the coastal groundwater table fluctuation.
Fluctuation of the groundwater table in the coastal zone influences the migration of colloids in vadose zone, which can further carry contaminants to transport. To capture the variable-density water flow and the migration processes, this study developed a colloid-facilitated migration model by adjusting the adsorption coefficient and considering the relationship between colloid and salinity based on the experimental observations. This model was further applied to explore the effects of freshwater and seawater fluctuations on the migration and transformation of colloids and Cr in coastal vadose zones. The greater the hydraulic conductivity of the saturated aquifer was, the more Cr were discharged into the ocean by submarine groundwater discharge. Furthermore, the increase in the freshwater fluctuation amplitude expanded the pollution ranges of colloidal Cr and dissolved Cr. The rise of the seawater fluctuation amplitude had a more obvious reduction effect on the total solid retained Cr in the contaminant source, compared with that of the freshwater fluctuation. As the seawater fluctuation amplitude increased from 0.1 m to 0.8 m, the ratio of total solid retained Cr reduction in the contaminant source to the initial value increased from 1.8 % to 7.8 %. The results obtained from this study deepens our understanding of how colloids and contaminants migrate across a coastal area from vadose zone induced by the groundwater table fluctuation.


Higher serum uric acid is associated with poorer cognitive performance in healthy middle-aged people: a cross-sectional study.
Age-related cognitive impairment can occur many years before the onset of the clinical symptoms of dementia. Uric acid (UA), a metabolite of purine-rich foods, has been shown to be positively associated with improved cognitive function, but such association remains controversial. Moreover, most of the previous studies investigating the association included elderly participants with memory-related diseases. Therefore, the present study aimed at investigating whether serum UA (sUA) is associated with cognitive performance in healthy middle-aged individuals. We conducted a cross-sectional study on a cohort of middle-aged individuals (40-60 years old) who participated in the Qatar Biobank. The participants had no memory-related diseases, schizophrenia, stroke, or brain damage. They were divided according to sUA level into a normal group (< 360 μmol/L) and a high group (≥ 360 μmol/L), and underwent an assessment of cognitive function using the Cambridge Neuropsychological Test Automated Battery. Two cognitive function domains were assessed: (a) speed of reaction/reaction time and (b) short-term visual memory. The median age of the 931 participants included in the study was 48.0 years (IQR: 44.0, 53.0), of which 47.6% were male. Adjusted multivariable linear regression analyses showed that higher sUA is associated with poorer performance on the visual memory domain of cognitive function (β = - 6.87, 95% CI - 11.65 to - 2.10, P = 0.005), but not on the speed of reaction domain (β = - 55.16, 95% CI - 190.63 to 80.30, P = 0.424). Our findings support previous studies suggesting an inverse association between high sUA levels and cognitive function in elderly and extend the evidence for such a role to middle-aged participants. Further prospective studies are warranted to investigate the relationship between UA and cognition.


The laryngeal mask airway for difficult airway in temporomandibular joint ankylosis--a case report.
Patients with Temporomandibular Joint Ankylosis are among difficult airways and anesthesia and airway management of these patients encounter anesthesiologists with challenge. Herein we report a case of Temporomandibular Joint Ankylosis with difficult ventilation after failed attempts to intubate with fibroptic broncoscopy a disposable Laryngeal Mask Airway reestablishes the ventilation. The case suggests that the disposable Laryngeal Mask Airway may be useful in airway management of patients with a Temporomandibular Joint Ankylosis.


"Circle of caring": a First Nations worldview of child rearing.
For occupational therapy to be meaningful for all families who have a child with a developmental disability, the profession needs to consider and integrate into practice alternative and more inclusive epistemologies. A greater understanding and respect of a First Nations worldview may help reduce the risk of inadvertently perpetuating oppression and assimilation. To describe raising a child with a developmental disability from the perspective of five members of the Lil'wat Nation. Data were obtained from in-depth interviews and analysed using a constant comparative approach. Within the category of family the subcategories identified were extensive support network, intergenerational learning and doing, and influence of the residential school system. Within the category of raising a child the subcategories identified were health and spirituality, causation beliefs, and a sense of knowing. Occupational therapists need to be cognizant of alternative worldviews on child rearing, family, and health that may differ significantly from their own personal and professional beliefs and practices.


Effects of selective breeding on the cholesterolemic responses to dietary saturated fat and cholesterol in baboons.
Positive assortative mating of baboons (Papio sp.) based on elevation of serum cholesterol concentrations in response to a cholesterol- and saturated fat-enriched diet produced 64 progeny (30 high line; 34 low line). When the animals were 3 to 4 years of age, we tested their lipoprotein cholesterol responses to dietary cholesterol and fat in a factorial experiment with two levels of dietary cholesterol (1.7 and less than 0.01 mg/kcal) and two types of fat, coconut oil (P/S 0.1) and corn oil (P/S 3.5), each providing 40% of total calories from fat; we also tested their responses to chow. The high line animals had significantly higher very low density plus low density lipoprotein (VLDL + LDL) and high density lipoprotein (HDL) cholesterol levels on all diets. The effects of dietary cholesterol on VLDL + LDL cholesterol concentrations were greater in high line animals than in low line animals, but dietary cholesterol's effects on HDL cholesterol were similar in both lines. The effects of saturated fat, compared to unsaturated fat, on both VLDL + LDL and HDL cholesterol levels were similar in both lines. Selective breeding produced lines diverging in lipoprotein cholesterol concentrations by acting on several different genetically mediated processes that control serum lipoprotein levels. At least one of these processes involves responsiveness of serum VLDL + LDL cholesterol concentration to dietary cholesterol.


Developmentally supportive care in the newborn intensive care unit: early intervention in the community.
The traditional focus of hospital nurses on the medical concerns of infants and toddlers is expanding to encompass the more global view that integrates the developmental level of each infant/toddler into the nursing care plan. Research on early brain development has supported the focus on developmentally supportive care in the NICU. Nursing support of the early relationship between infant and parent that will influence the infant's future development is part of this process. The integration of developmental care concepts including family-centered care that begins on admission to the NICU may continue into the process of discharge and transition to home. The nurse is in an excellent position to support the family in naming their concerns, their strengths, and the hopes and dreams they have for their infant. Nurses in the NICU, home care, community, and public health increasingly focus on a developmental perspective in their work but will be continually challenged to increase their knowledge and understanding of developmental milestones, neurodevelopmental assessment, and their role in collaborating with the wider world of early intervention. This collaboration includes the health care system, the educational system, and the social service system as equal players. For some nurses, this will be a new experience whereby the responsibility for the child is shared among members of an interdisciplinary team that includes the parents. Nurses are key to providing developmentally supportive care and working collaboratively on behalf of the infants and toddlers and their families.


Real-World Evaluation of Health-Related Quality of Life in Patients With Multiple Myeloma From Germany.
Real-world health-related quality of life (HRQoL) data in patients with multiple myeloma (MM) are scarce. Here, we report HRQoL by line of therapy in adults with MM in clinical practice in Germany. This descriptive, multicenter, observational study included patients receiving all lines of MM therapy or best supportive care (BSC). The primary endpoint was HRQoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 global health status [GHS]) by line of therapy; secondary endpoints included patient/disease characteristics and treatments by line of therapy. Overall, 490 patients were included from 40 centers (mean age 71.0 years, 62% male); 59% had an Eastern Cooperative Oncology Group performance status of 0 or 1% and 35% had undergone stem cell transplantation. First-line therapy included proteasome inhibitors in 81% of patients; subsequent treatments varied. The mean overall GHS/QoL score was 49.5; HRQoL decreased by therapy line (P < .001) and was lowest in those receiving BSC. Functional and symptoms scores worsened with increasing treatment line. The largest HRQoL reduction occurred when patients switched from active treatment to BSC. Compared with those on active treatment, patients in a treatment-free interval generally had better GHS/QoL, functioning, and fewer symptoms (P < .05). GHS/QoL also generally improved and symptoms lessened in those with ≥1 versus <1 year of ongoing treatment (P < .05). Worse GHS/QoL was observed in patients with ≥1 grade 3/4 toxicity versus those with none (P = .012). Eastern Cooperative Oncology Group performance status was the strongest determinant of HRQoL. This real-world study shows that patients with MM have impaired HRQoL and that HRQoL deteriorates with increasing lines of therapy.


Unauthorized Immigration to the United States: Annual Estimates and Components of Change, by State, 1990 to 2010.
We describe a method for producing annual estimates of the unauthorized immigrant population in the United Sates and components of population change, for each state and D.C., for 1990 to 2010. We quantify a sharp drop in the number of unauthorized immigrants arriving since 2000, and we demonstrate the role of departures from the population (emigration, adjustment to legal status, removal by the Department of Homeland Security (DHS), and deaths) in reducing population growth from one million in 2000 to population losses in 2008 and 2009. The number arriving in the U.S. peaked at more than one million in 1999 to 2001, and then declined rapidly through 2009. We provide evidence that population growth stopped after 2007 primarily because entries declined and not because emigration increased during the economic crisis. Our estimates of the total unauthorized immigrant population in the U.S. and in the top ten states are comparable to those produced by DHS and the Pew Hispanic Center. For the remaining states and D.C., our data and methods produce estimates with smaller ranges of sampling error.


Refractive, biometric and corneal topographic parameter changes during 12 months of orthokeratology.
The aim of this study was to monitor refractive, topographic and biometric changes in Singaporean myopic children fitted with orthokeratology over a period of 12 months. Data from 62 myopic eyes from an Asian population corrected with orthokeratology were retrospectively collected from an optometric clinic in Singapore. Anterior segment parameters were analysed with a Pentacam. Axial length was measured using the IOLMaster and refraction was assessed by subjective examination before the treatment and after one night, one week, and one, three, six and 12 months. A logistic regression model was built to evaluate the probability of slower (< 0.10 mm/year) or faster eye growth (≥ 0.10 mm/year). Subjects had a mean age of 12.2 ± 3.9 years (range 5-19 years), and 71 per cent were female. Baseline myopia was -3.95 ± 1.59 D (range -1.50 and -8.75 D). Statistically significant differences were found after 12 months of treatment for refractive error, parameters of the central anterior corneal surface (curvature and elevation) and central corneal thickness. Topographic and thickness changes stabilised after one week of treatment. During 12 months of orthokeratology treatment there was a significant increase of axial length (difference = 0.11 ± 0.18 mm, p < 0.001) while refraction remained stable. Changes in axial length of subjects above 11 years were not statistically significantly independent of the baseline myopia, and in subjects with baseline myopia greater than 4.00 D. Logistic regression showed that each additional year of age and each additional dioptre of baseline myopia decreased the probability of faster axial elongation (odds ratio [OR] = 1.23, 2.19 95% CI; OR = 1.08, 3.47 95% CI, respectively). Corneal parameters in orthokeratology treatment were stable after one week, particularly for myopes under 4.00 D. Axial length did not change significantly in children older than 11 years of age or in subjects with myopia above 4.00 D undergoing orthokeratology treatment.


A CMOS neuroelectronic interface based on two-dimensional transistor arrays with monolithically-integrated circuitry.
The ability to monitor and to elicit neural activity with a high spatiotemporal resolution has grown essential for studying the functionality of neuronal networks. Although a variety of microelectrode arrays (MEAs) has been proposed, very few MEAs are integrated with signal-processing circuitry. As a result, the maximum number of electrodes is limited by routing complexity, and the signal-to-noise ratio is degraded by parasitics and noise interference. This paper presents a single-chip neuroelectronic interface integrating oxide-semiconductor field-effect transistors (OSFETs) with signal-processing circuitry. After the chip was fabricated with the standard complementary-metal-oxide-semiconductor (CMOS) process, polygates of specific transistors were etched at die-level to form OSFETs, while metal layers were retained to connect the OSFETs into two-dimensional arrays. The complete removal of polygates was confirmed by high-resolution image scanners, and the reliability of OSFETs was examined by measuring their electrical characteristics. Through a gate oxide of only 7nm thick, each OSFET can record and stimulate neural activity extracellularly by capacitive coupling. The capability of the full chip in neural recording and stimulation was further experimented using the well-characterised escape circuit of the crayfish. Experimental results indicate that the OSFET-based neuroelectronic interface can be used to study neuronal networks as faithfully as conventional electrophysiological tools. Moreover, the proposed simple, die-level fabrication process of the OSFETs underpins the development of various field-effect biosensors on a large scale with on-chip circuitry.


Bariatric surgery and COVID-19 outcomes: a systematic review and meta-analysis.
Obesity and its associated complications have a negative impact on human health. Metabolic and bariatric surgery (MBS) ameliorates a series of clinical manifestations associated with obesity. However, the overall efficacy of MBS on COVID-19 outcomes remains unclear. The objective of this article is to analyze the relationship between MBS and COVID-19 outcomes. A meta-analysis. The PubMed, Embase, Web of Science, and Cochrane Library databases were searched to retrieve the related articles from inception to December 2022. All original articles reporting MBS-confirmed SARS-CoV-2 infection were included. Outcomes including hospital admission, mortality, intensive care unit (ICU) admission, mechanical ventilation utilization, hemodialysis during admission, and hospital stay were selected. Meta-analysis with fixed or random-effect models was used and reported in terms of odds ratios (ORs) or weighted mean differences (WMDs) along with their 95% confidence intervals (CIs). Heterogeneity was assessed with the I2 test. Study quality was assessed using the Newcastle-Ottawa Scale. A total of 10 clinical trials involving the investigation of 150,848 patients undergoing MBS interventions were included. Patients who underwent MBS had a lower risk of hospital admission (OR: .47, 95% CI: .34-.66, I2 = 0%), mortality (OR: .43, 95% CI: .28-.65, I2 = 63.6%), ICU admission (OR: .41, 95% CI: .21-.77, I2 = 0%), and mechanical ventilation (OR: .51, 95% CI: .35-.75, I2 = 56.2%) than those who did not undergo surgery, but MBS did not affect hemodialysis risk or COVID-19 infection rate. In addition, the length of hospital stay for patients with COVID-19 after MBS was significantly reduced (WMD: -1.81, 95% CI: -3.11-.52, I2 = 82.7%). Our findings indicate that MBS is shown to improve COVID-19 outcomes, including hospital admission, mortality, ICU admission, mechanical ventilation, and hospital stay. Patients with obesity who have undergone MBS infected with COVID-19 will have better clinical outcomes than those without MBS.


Cost-effectiveness of immunization strategies for the control of serogroup C meningococcal disease.
This study compares the cost-effectiveness of a control strategy for serogroup C meningococcal disease (CMD) relying on surveillance and implementation of a mass immunization campaign effective 1 year after the beginning of an epidemic with strategies based on routine immunization, using either three doses of serogroup C conjugate vaccine given in early infancy or one dose at 1 year of age. The simulation model is based on 25 birth cohorts followed up to age 24 years, and seven epidemiological scenarios including low and high level endemicity, and one to five epidemics over a 49-year period. Epidemiological and cost data were mainly collected in the province of Quebec, Canada. Results indicate that the most effective strategy is a three-dose routine program, with the least effective strategy being mass immunization. A one-dose routine program is the most cost-effective strategy in most likely scenarios. In a societal perspective with a vaccine purchase price of CDN$ 50 per dose, the average incremental cost of the one-dose strategy would be $ 190,000 per case averted, US$ 23,000 per life-year gained, and US$ 42,000 per QALY gained. If vaccine-induced immunity is waning rapidly, mass immunization or routine vaccination with booster dose(s) would be the best control options.


Abdominal injuries associated with the use of seatbelts.
The mandatory use of seatbelts has become commonplace in Canada, and such legislation was adopted by the province of British Columbia in 1977. This has provided us with an opportunity to study the effects of seatbelt restraints on accident victims, particularly concerning abdominal injuries. Five hundred sixty-two patient charts were reviewed during a 3-year period. Documented use of seatbelts was found in 126 cases. Thirty-six of these patients underwent laparotomy and form the basis of this study. Compared with previously reported figures for blunt abdominal trauma, there was a high incidence of gastrointestinal injuries (67 percent). In addition, associated lumbar spine injuries were found in a large proportion of patients (19 percent, p less than 0.005). We found an increased risk of spinal injury in patients wearing a lap versus a three-point belt.


Bioprosthetic tricuspid valve dysfunction in patients with transvalvular or epicardial pacing leads.
Dysfunction of native tricuspid valves due to transvenous pacing leads is well described. Patients with bioprosthetic tricuspid valve (BTV) who need ventricular pacing are often advised epicardial lead placement to avoid potential damage to the BTV although there are no data to support this. The aim of the study was to assess the frequency of BTV dysfunction in patients with permanent transvenous right ventricular pacemaker lead and compare it to patients with epicardial leads. A retrospective review of patients with BTV with ventricular pacing lead was conducted. Demographics, lead, BTV, and echocardiographic data were collected. Frequency of BTV dysfunction (moderate or severe) regurgitation or stenosis was compared between epicardial and transvalvular lead groups. Forty-six patients with BTV and ventricular pacing lead (20 transvalvular and 26 epicardial leads) were identified. Mean age was 46 years with the majority being female (85%) and with rheumatic heart disease (87%). Both groups were similar in age, sex, and indications for BTV. Mean echocardiographic follow-up was for 5.5 years (±4.1 years). BTV dysfunction was similar between the transvalvular group with six (30%) patients and the epicardial group with five (19.2%) patients. The incidence of BTV dysfunction was greater in patients in sinus rhythm compared to patients in atrial fibrillation (50% vs 10%, P = 0.004). Development of BTV dysfunction is similar in patients with transvalvular ventricular leads and epicardial leads. The incidence of BTV dysfunction was higher in patients with sinus rhythm compared to atrial fibrillation.


Annexin A4 N-terminal peptide inhibits adenylyl cyclase 5 and limits β-adrenoceptor-mediated prolongation of cardiac action potential.
Adenylyl cyclases (AC) are essential for the normal and pathophysiological response of many cells. In cardiomyocytes, the predominant AC isoforms are AC5 and AC6. Specific AC5 inhibition was suggested as an option for the treatment of heart failure potentially advantageous over β-blockers. We previously reported an interaction between the calcium-binding protein annexin A4 (ANXA4) and AC5 in human embryonic kidney 293 (HEK293) cells and an inhibition of cyclic adenosine monophosphate (cAMP) production in cardiomyocytes. Here, we investigated whether ANXA4 is able to differentiate between AC5 and AC6. In transfected HEK293 cells, ANXA4 specifically co-immunoprecipitated with AC5 and not with AC6, via its N-terminal domain. Both ANXA4 and a peptide comprising the ANXA4 N-terminal sequence (A4N1-22 ) decreased the cAMP production in AC5 and not in AC6 expressing cells. In line with ACs inhibition, in myocytes from ANXA4-deficient mice, β-adrenoceptor (βAR) stimulation led to a higher increase of the L-type calcium current (ICaL ) and to an excessive action potential duration (APD) prolongation as compared to wild-type cardiomyocytes. This enhanced response was reversed in the presence of A4N1-22 peptide likely via specific AC5 inhibition. We conclude that via the N-terminal domain ANXA4 inhibits AC5 not AC6, and that A4N1-22 as a specific AC5 inhibitor could serve as a novel therapeutic tool for the treatment of AC5-linked diseases.


Method development for the certification of a ginsenoside calibration solution via liquid chromatography with absorbance and mass spectrometric detection.
The research presented here describes the development of two analytical methods for use in the certification of a ginsenoside calibration solution Standard Reference Material (SRM) 3389 consisting of seven ginsenosides: Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd. The new methods utilized the liquid chromatographic (LC) separation of ginsenoside mixtures with absorbance detection (UV) and mass spectrometry (MS). Ginsenosides Rb3, Rg2, Rg3, Rh1, and Rh2 were evaluated for use as internal standards for LC/MS measurements. The 12 ginsenosides were baseline resolved by gradient elution LC/UV, with an initial mobile phase composition of 22% acetonitrile and 78% water, flow rate of 0.7 mL/min, and column temperature of 25 °C. The work presented here includes a detailed investigation into the optimization of the chromatographic conditions to minimize measurement biases that result from unresolved constituents. Temperature and mobile phase composition are known to play a significant role in column selectivity; however, flow rate is expected to influence primarily the separation efficiency and detection sensitivity. In the current study, column selectivity changed with changes in flow rate and the relative retention of ginsenoside Rg2 and Rh1 changed as the flow rate increased from 0.6 mL/min to 1.0 mL/min.