Model selection in magnetic resonance imaging measurements of vascular permeability: Gadomer in a 9L model of rat cerebral tumor.
Vasculature in and around the cerebral tumor exhibits a wide range of permeabilities, from normal capillaries with essentially no blood-brain barrier (BBB) leakage to a tumor vasculature that freely passes even such large molecules as albumin. In measuring BBB permeability by magnetic resonance imaging (MRI), various contrast agents, sampling intervals, and contrast distribution models can be selected, each with its effect on the measurement's outcome. Using Gadomer, a large paramagnetic contrast agent, and MRI measures of T(1) over a 25-min period, BBB permeability was estimated in 15 Fischer rats with day-16 9L cerebral gliomas. Three vascular models were developed: (1) impermeable (normal BBB); (2) moderate influx (leakage without efflux); and (3) fast leakage with bidirectional exchange. For data analysis, these form nested models. Model 1 estimates only vascular plasma volume, v(D), Model 2 (the Patlak graphical approach) v(D) and the influx transfer constant K(i). Model 3 estimates v(D), K(i), and the reverse transfer constant, k(b), through which the extravascular distribution space, v(e), is calculated. For this contrast agent and experimental duration, Model 3 proved the best model, yielding the following central tumor means (+/-s.d.; n = 15): v(D) = 0.07 +/- 0.03 for K(i) = 0.0105 +/- 0.005 min(-1) and v(e) = 0.10 +/- 0.04. Model 2 K(i) estimates were approximately 30% of Model 3, but highly correlated (r = 0.80, P < 0.0003). Sizable inhomogeneity in v(D), K(i), and k(b) appeared within each tumor. We conclude that employing nested models enables accurate assessment of transfer constants among areas where BBB permeability, contrast agent distribution volumes, and signal-to-noise vary.


Detection of an HLA-C*01:02:01:01 variant, HLA-C*01:02:43, in a Taiwanese individual.
One nucleotide substitution in codon 126 of HLA-C*01:02:01:01 results in a novel allele, HLA-C*01:02:43.


Transitions in Health Insurance During the Perinatal Period Among Patients With Continuous Insurance Coverage.
Although health insurance continuity is important during the perinatal period to improve birth outcomes and reduce maternal morbidity and mortality, insurance disruptions are common. However, little is known about insurance transitions among insurance types for individuals who remained insured during the perinatal period. To examine insurance transitions for birthing individuals with continuous insurance, including those with Medicaid and Medicaid managed care coverage, before, during, and after pregnancy. This cohort study used January 1, 2014 to December 31, 2018 data from the Massachusetts All-Payer Claims Database. The sample included deliveries from January 1, 2015, to December 31, 2017, to birthing individuals aged 18 to 44 years old with continuous insurance for 12 months before and after delivery. Data were analyzed from November 9, 2021, to September 2, 2022. Insurance type at delivery. The primary outcome was a binary indicator of any transition in insurance type from 12 months before and/or after delivery. The secondary outcomes were measures of any predelivery transition (12 months before delivery month) and any transition during the postpartum period (delivery month to 12 months post partum). Multivariate logit regression models were used to analyze the association of an insurance transition in the perinatal period with insurance type in the delivery month, controlling for age and socioeconomic status based on a 5-digit zip code. The analytic sample included 97 335 deliveries (mean [SD] maternal age at delivery, 30.4 [5.5] years). Of these deliveries, 23.4% (22 794) were insured by Medicaid and 28.1% (27 347) by Medicaid managed care in the delivery month. A total of 37.1% of the sample (36 127) had at least 1 insurance transition during the 12 months before and/or after delivery. In regression-adjusted analyses, those individuals covered by Medicaid and Medicaid managed care at delivery were 47.0 (95% CI, 46.3-47.7) percentage points and 50.1 (95% CI, 49.4-50.8) percentage points, respectively, more likely to have an insurance transition than those covered by private insurance. Those covered by Marketplace plans at delivery had a 33.1% (95% CI, 31.4%-34.8%) regression-adjusted predicted probability of having a postpartum insurance transition. Results of this study showed that insurance transitions during the perinatal period occurred for more than 1 in 3 birthing individuals with continuous insurance and were more common among those with Medicaid or Medicaid managed care at delivery. Further research is needed to examine the role of insurance transitions in health care use and outcomes during the perinatal period.


Cytomegalovirus viremia in solid organ transplantation: does the initial viral load correlate with risk factors and outcomes?
Consistent data for using CMV quantitative PCR (QnPCR) on initial presentation to predict outcomes after solid organ transplantation (SOT) are lacking. Recipients with measurable CMV QnPCR and either CMV-V (asymptomatic viremia) or CMV-D (symptomatic CMV infection) were analyzed over 24 months. Risk factors and outcomes were evaluated in relation to initial QnPCR by regression analysis and time-to-event curves. Twenty-eight recipients were identified: five CMV-V, 23 CMV-D. Patients with CMV-D had a higher median initial QnPCR (230 000 copies/mL) compared with CMV-V (2500 copies/mL; p < 0.05). No patients with CMV-V had an initial QnPCR > 10 000 copies/mL compared with 83% of the CMV-D (p = 0.004). The initial QnPCR was higher (250 000 copies/mL) in patients who did not clear CMV PCR than those who cleared (8000 copies/mL) after 14 d of treatment (p = 0.03). Risk factors and indirect CMV effects were not associated with initial QnPCR. Our results highlight the importance of the initial CMV QnPCR in relation to the development of symptomatic CMV and a slower response to therapy. Alternatively, late asymptomatic viremia and recurrent CMV are associated with lower PCR levels and a low likelihood to progress and result in clinical disease.


Chronic gastrointestinal bleeding caused by a Dieulafoy's lesion in the small intestine: a case report.
Dieulafoy's lesion, first found by Paul Georges Dieulafoy, is an infrequent but important cause of recurrent upper gastrointestinal bleeding. The bleeding is usually severe, but patients rarely present with chronic, occult gastrointestinal bleeding. In this article, we discuss the case of a 68-year-old caucasian man with a history of recurrent hematemesis and chronic anemia with evidence of extravasation of contrast in the lumen of the bowel loop on computed tomography angiography. The patient was taken to the operating room, and a laparotomy procedure was performed. Due to the infrequency of Dieulafoy's lesion compared with other causes of gastrointestinal bleeding, it is often missed in the process of differential diagnosis. In this article, we have demonstrated the importance of this disease and different approaches to the treatment of this lesion, considering the location of the lesion among other factors.


Risk of mature B-cell neoplasms and precursor conditions after joint replacement: A report from the Haematological Malignancy Research Network.
Associations between previous joint replacement and B-cell lymphoid malignancies have been reported, but despite numerous reports, associations with the disease subtypes have received little attention. Using a UK-based register of haematological malignancies and a matched general population-based cohort, joint replacements from linked hospital inpatient records were examined. Cases diagnosed 2009-2015 who were aged 50 years or more were included; 8,013 mature B-cell neoplasms comprising myeloma (n = 1,763), diffuse large B-cell lymphoma (DLBCL, n = 1,676), chronic lymphocytic leukaemia (CLL, n = 1,594), marginal zone lymphoma (MZL, n = 957), follicular lymphoma (FL, n = 725) and classical Hodgkin lymphoma (CHL, n = 255), together with monoclonal gammopathy of uncertain significance (MGUS, n = 2,138) and monoclonal B-cell lymphocytosis (MBL, n = 632). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated relative to 10 age- and sex-matched controls using conditional logistic regression. Having had a joint replacement before diagnosis was associated with myeloma (OR = 1.3, 95% CI 1.1-1.5, p = 0.008) and MGUS (OR = 1.3, 95% CI 1.1-1.5, p < 0.001). Excluding replacements in the year before diagnosis, the MGUS risk remained, elevated where two or more joints were replaced (OR = 1.5, 95% CI 1.2-2.0, p = 0.001), with hip (OR = 1.2, 95% CI 1.0-1.5, p = 0.06) or knee replacements (OR = 1.5, 95% CI 1.2-1.8, p < 0.001). Associations with CHL and two or more replacements (OR = 2.7, 95% CI 1.3-5.6, p = 0.005) or hip replacements (OR = 1.9, 95% CI 1.0-3.4, p = 0.04); and between DLBCL and knee replacements (OR = 1.3, 95% CI 1.0-1.6, p = 0.04) were also observed. Our study reports for the first time a relationship between joint replacements and MGUS; while absolute risks of disease are low and not of major public health concern, these findings warrant further investigation.


Patient demographics, clinicopathologic features, and outcomes in wild-type gastrointestinal stromal tumor: a national cohort analysis.
Wild-type KIT and PDGFRA gastrointestinal stromal tumors (GIST) are rare tumors with limited treatment options. We sought to determine the clinicopathologic features of wild-type GIST and identify factors that influence overall survival (OS) using a large national database. Retrospective evaluation of patients with wild-type GIST in the National Cancer Database (NCDB) was performed. Demographic, clinicopathologic, and treatment data were analyzed. Features associated with OS were investigated using Kaplan-Meier analysis and Cox proportional hazards model. 244 patients with median diagnosis age of 59 years (95% CI 57-63) were identified. The stomach was the most common primary site (57%) followed by the small intestine (35%). Surgical resection was performed on 85% of patients and 53% of patients received systemic therapy. Factors associated with decreased OS on multivariable analysis included small intestine primary (HR 2.72, 95% CI 1.13-6.69, P = 0.026) and > 5 mitoses per 50 HPF (HR 4.77, 95% CI 1.86-13.2, P = 0.001). Wild-type GISTs may be identified in older patients, with most arising in the stomach and small bowel. Surgery remains the principal treatment modality. Small intestine primary site and high mitotic count were associated with abbreviated OS.


Biokinetics in repeated-dosing in vitro drug toxicity studies.
The aim of the EU FP7 Predict-IV project was to improve the predictivity of in vitro assays for unwanted effects of drugs after repeated dosing. The project assessed the added benefit of integrating long-lived in vitro organotypic cell systems with 'omics' technologies and in silico modelling, including systems biology and pharmacokinetic assessments. RPTEC/TERT1 kidney cells, primary rat and human hepatocytes, HepaRG liver cells and 2D and 3D primary brain cultures were dosed daily or every other day for 14 days to a selection of drugs varying in their mechanism of pharmacological action. Since concentration-effect relationships not only depend on the activity of the drug or the sensitivity of the target, but also on the distribution of compounds in the in vitro system, the concentration of a selection of drugs in cells, microtitre plate plastic and medium was measured over time. Results, reviewed in this paper, indicate that lipophilic drugs bind significantly to plastic labware. A few drugs, including less lipophilic drugs, bind to cell-attachment matrices. Chemicals that reach high concentrations in cells, including cyclosporin A and amiodarone, significantly accumulate over time after repeated dosing, partly explaining their increased toxicity after repeated dosing, compared to a single dose.


Limiting total mixed ration availability alters eating and rumination patterns of lactating dairy cows.
The objective of this study was to investigate the effect of restricting total mixed ration (TMR) eating time with or without supplemental long hay offered on diurnal total intake, rumination, and rumen pH patterns in mid-lactation dairy cows. Eight multiparous Holstein cows were used in a replicated 4 × 4 Latin square design study with 21-d periods. The basal diet was the same for all 4 treatments with or without additional long grass hay (the same hay used in the TMR). For cows on limited-time TMR, diets were taken away at 1500 h (5 h before evening milking and feeding), and dry matter intake (DMI), ruminating, and rumen pH were monitored and summarized every 10 m for 7 d in each period. With restricted feeding, cows changed DMI patterns by consuming a large meal after feed was reinstated, resulting in lower DMI. Ruminating patterns closely mirrored intake patterns, as could be expected. Rumen pH was not different between groups but resulted in different diurnal patterns due to differences in eating and rumination patterns between the groups. Limiting feed availability can be used to change eating and rumination patterns, resulting in different rumen pH patterns.


Care of newborns born to mothers with COVID-19 infection; a review of existing evidence.
The novel Coronavirus disease 2019 (COVID-19) pandemic is already wreaking havoc on families and communities' welfare. It is critical to discuss newborn care of infected mothers with COVID-19 based on the latest international guidelines and national guidelines of countries with the highest incidence of COVID-19 cases. We discuss how to care for a newborn of a suspected or infected mother with COVID-19 using existing evidence. As of 16 April 2020, we reviewed articles and guidelines related to COVID-19 in the reproductive health field, mother, and newborn health. Our review yielded in 10 categories (i) the risk of diagnostic procedures in suspected mothers on fetus/infant health, (ii) the risk of intrauterine or postpartum transmission to the fetus/infant, (iii) appropriate method and delivery time in women with confirmed COVID-19, (iv) umbilical cord clamping and skin to skin contact, (v) clinical manifestations of infected infants, (vi) confirmation of infection in a suspected neonate/infant, (vii) instructions for infant's care and how to feed her/him, (viii) bathing the baby, (ix) the criteria of discharging baby from the hospital, (x) the impact of isolation on the maternal mental health. Our findings showed that the possibility of intrauterine or perinatal transmission of COVID-19 is still questionable and ambiguous. However, what has been agreed upon in the existing texts and guidelines is that the close contact of mother and infant after birth can transmit the virus to the baby through droplets or micro-droplets. Based on our findings, it is recommended to separate the baby from the mother with confirmed (or suspected) COVID-19 infection for at least 2 weeks. Since the motivation and stable situation of mothers allow breastfeeding during the isolation, infected mothers should be taught about breast expression skills, common breast problems, the symptoms of their baby's infection, and the principles of personal hygiene to protect the infant against COVID-19 infection.


Triaging women with ovarian masses for surgery: observational diagnostic study to compare RCOG guidelines with an International Ovarian Tumour Analysis (IOTA) group protocol.
To compare guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG) based on the Risk of Malignancy Index (RMI) with a protocol based on logistic regression model LR2 developed by the International Ovarian Tumour Analysis (IOTA) group for triaging women with an ovarian mass as low, moderate, or high risk of malignancy. Observational diagnostic study conducted between 2005 and 2007 at 21 oncology referral centres, referral centres for ultrasonography and general hospitals. In all, 1938 women undergoing surgery for an ovarian mass. RCOG guidelines use the RMI to triage women as low (RMI < 25), moderate (25-250), or high (above >250) risk. The IOTA protocol uses LR2s estimated probability of malignancy (<0.05 indicates low risk, ≥ 0.05 but <0.25 moderate risk, and ≥ 0.25 high risk). Percentages of benign, borderline and invasive tumours classified as low, moderate or high risk. The IOTA and RCOG protocols classified 71.1% and 62.1% of benign tumours as low risk, respectively (difference 9.0; 95% CI 6.2-11.9, P < 0.0001). Of invasive tumours, 88.6% and 73.6% were labelled high risk (difference 15.0; 10.6-19.4, P < 0.0001), and 3.0% and 5.2% were labelled low risk (difference -2.2; -4.6 to 0.2, P = 0.07) respectively by each protocol. Similar results were found after stratification for menopausal status. The IOTA protocol was more accurate for triage than the RCOG protocol. The IOTA protocol would avoid major surgery for more women with benign tumours while still appropriately referring more women with an invasive tumour to a gynaecological oncologist.


[Instrumentation and evaluation of the pharmacopoeia test of color].
Instrumental investigation of colorimetric matching fluids of the Hungarian Pharmacopoeia has been carried out. It has been established that by means of the internationally accepted CIELAB parameters the samples can be well characterized and comparative tests can be precisely accomplished.


Evolution of a chimeric aspartate kinase for L-lysine production using a synthetic RNA device.
Aspartate kinase (AK) is a key enzyme involved in catalyzing the first step of the aspartate-derived amino acid biosynthesis, including L-lysine and L-threonine, which is regulated by the end-metabolites through feedback inhibition. In order to accumulate the end-metabolites in the host, the feedback inhibition of AK has to be released. In this study, a chimeric aspartate kinase, which is composed of the N-terminal catalytic region from Bacillus subtilis AKII and the C-terminal region from Thermus thermophilus, was evolved through random mutagenesis and then screened using a high-throughput synthetic RNA device which comprises of an L-lysine-sensing riboswitch and a selection module. Of three evolved aspartate kinases, the best mutant BT3 showed 160 % increased in vitro activity compared to the wild-type enzyme. Recombinant Escherichia coli harboring BT3 produced 674 mg/L L-lysine in batch cultivation, similar to that produced by the strain harboring the typical commercial widely used feedback resistant aspartate kinase AKC (fbr) from E. coli. The results suggested that this strategy can be extended for screening of other key enzymes involved in lysine biosynthesis pathways.


Videotaped experiments to drop safety behaviors and self-focused attention for patients with social anxiety disorder: do they change subjective and objective evaluations of anxiety and performance?
Safety behavior (SB) and self-focused attention (SFA) have been posited as important maintenance factors in the cognitive model of social anxiety disorder (SAD). The present study reports the results of experiments to drop SB and SFA among clinically diagnosed patients with SAD employing their own idiosyncratic anxiety-provoking situations. The ratings for observable anxiety, belief in feared outcome and overall performance were better for role plays without SB and SFA than for role plays with them. The degree of drop in SFA predicted drop in observable anxiety and belief in feared outcome. Dropping SB and SFA, however, was unable to completely correct the cognitive distortion because the subjective ratings were still significantly worse than the objective ratings.


Quantitation of antigen-presenting cell MHC class II/peptide complexes necessary for T-cell stimulation.
The number of specific complexes formed between peptide and the class II major histocompatibility complex (MHC) molecules expressed by an antigen-presenting cell (APC) after exposure to protein antigens is unknown, as is the number that activates T cells. Presentation of foreign peptides by APC takes place when many class II molecules may be occupied by autologous peptides. We have now estimated the number of specific peptide/class II complexes per APC by quantitative immunoprecipitation of I-Ak after pulsing the APC with stimulatory levels of a radioactive immunogenic peptide derived from hen egg-white lysozyme protein. T cells were activated by APC that expressed as few as 210-340 specific peptide/class II complexes (0.1% of the I-Ak molecules). These figures were confirmed using anti-CD3 antibody bound to latex beads as an alternative activating ligand. This low number explains the simultaneous presentation of multiple foreign antigens, even in the face of peptide competition.


Olax subscorpioidea prevented scopolamine-induced memory impairment through the prevention of oxido-inflammatory damage and modulation of cholinergic transmission.
Olax subscorpioidea oliv. is a shrub plant of the Olacaceae family with reported usage in ethnomedicine as a nootropic agent for the management of Alzheimer's-like dementia. The aim of this study is to investigate the nootropic potential of methanol extract of Olax subscorpioidea (MEOS) in scopolamine-induced Alzheimer's-like dementia. Thirty male mice, assigned into six groups (n = 8), were used for this study. Group, I received distilled water, group II received scopolamine (1 mg/kg, i.p.), groups iii-v received 25, 50, and 100 mg/kg, p.o. of MEOS and scopolamine (1 mg/kg/i.p.), and group vi received donepezil 5 mg/kg, p.o.and scopolamine (1 mg/kg, i.p.). The animals were pre-treated with MEOS and Donepezil for 14 days, and scopolamine from the 8th to 14th day. Followed by cognitive, oxidative stress, neuroinflammation, and histology assessments. 100 mg/kg MEOS significantly reduced transfer latency and increased discrimination index in the elevated plus maze and novel object recognition test cognitive assessments. 100 mg/kg MEOS, significantly reduced oxidative stress, protect endogenous antioxidants, suppressed neuroinflammation, and acetylcholinesterase (ACHE) activity. The histomorphometry study of the hippocampus revealed that MEOS prevented extensive pyknosis, karyolysis, chromatolysis, and loss of hippocampal neurons that accompanied scopolamine treatment. MEOS protected against Alzheimer's-like dementia via the suppression of neuroinflammation and oxidative stress associated with scopolamine-induced amnesic behavior.


Crohn's disease and ulcerative colitis are associated with different lipid profile disorders: a nationwide population-based study.
The relationships between lipid profiles and IBD remain elusive. To determine the association of IBD with serum lipid profiles. A nationwide population-based study was performed using claims data from the Korean National Healthcare Insurance service. A total of 9 706 026 subjects undergoing medical check-ups in 2009 were enrolled and followed up until 2016. Individuals who developed Crohn's disease (CD) or ulcerative colitis (UC) were identified during follow-up. Adjusted hazard ratio (aHR) by age, sex, body mass index, cigarette smoking, alcohol drinking, exercise, income and underlying comorbidities was calculated to define the impact of serum lipid profiles on developing IBD. During a median follow-up of 7.3 years, IBD was detected in 7,058 (0.07%) individuals. Compared with the highest quartile of serum total cholesterol (TC) levels, lower TC levels were associated with higher incidence of CD (aHR: Q1, 2.52; Q2, 1.52; Q3, 1.27), but not UC. Lower serum LDL-C levels were associated with higher incidence of CD (aHR: Q1, 1.92; Q2, 1.47; Q3, 1.22), but not UC. Moreover, lower serum HDL-C levels were associated with higher incidence of CD (aHR: Q1, 2.49; Q2, 1.90; Q3, 1.43), but not UC. In contrast, lower serum triglyceride levels were associated with higher incidence of UC (aHR: Q1, 1.22; Q2, 1.19; Q3, 1.19), but not CD. Low serum TC, LDL-C and HDL-C levels were associated with CD. Low serum triglyceride levels were related to UC.


Frailty trajectories in ICU survivors: A comparison between the clinical frailty scale and the Tilburg frailty Indicator and association with 1 year mortality.
To test the agreement of the Clinical Frailty Scale (CFS) and the Tilburg Frailty Indicator (TFI), their association with 3, 6 months and 1-year mortality and the trajectory of frailty in a mixed population of ICU survivors. This is a prospective, multicenter, longitudinal study on ICU survivors ≥18 years old with an ICU stay >72 h. For each patient, sociodemographic and clinical data were collected. Frailty was assessed during ICU stay and at 3, 6, 12 months after ICU discharge, through both CFS and TFI. 124 patients with a mean age of 66 years old were enrolled. The baseline prevalence of frailty was 15.3% by CFS and 44.4% by TFI. Baseline CFS and TFI correlated but showed low agreement (Cohen's K = 0.23, p < 0.001). Baseline CFS score, but not TFI, was significantly associated to 1 year mortality. Moreover, CFS score during the follow-up was independently associated 1-year mortality (OR = 1.43; 95% CI: 1.18-1.73). CFS and TFI identify different populations of frail ICU survivors. Frail patients before ICU according to CFS have a significantly higher mortality after ICU discharge. The CFS during follow-up is an independent negative prognostic factor of long-term mortality in the ICU population.


The effect of dbcAMP on the lysolecithin induced hemolysis of calf and adult cattle erythrocytes.
The calf erythrocytes have an increased sensitivity against lysolecithin as compared to their adult counterparts. 10(-3)M dbcAMP increases the hemolysis induced by 5 microgram of lysolecithin in 0.15 M NaCl containing 10 mM phosphate buffer (pH 7.4). By increasing the level of phosphate buffer (75 mM) in the incubation mixture, 10(-3)M dbcAMP decreases the hemolysis induced by 5 microgram of lysolecithin. These data suggest a dual effect exerted by dcbAMP: the relatively labilizing or stabilizing effect prevails as a function of exogenous inorganic phosphate level. 10(-6)M dcbAMP also has a relative protective effect against lysolecithin. The combined addition of cAMP (10(-3)) and theophyllin (10(-4)M) does not stabilize the membrane. By increasing the level of lysolecithin to 20 microgram/ml the stabilizing effect of dcbAMP disappears. DbcAMP (10(-3)) as well as cAMP (10(-3)M) and theophyllin (10(-4)M) have a minimum increasing effect on hemolysis in the absence of lysolecithin, too.


Diagnosis of Alternaria disease and leafminer pest on tomato leaves using image processing techniques.
Diseases such as Alternaria and pests such as leafminer threaten tomato as one of the most widely used agricultural products. These pests and diseases first damage the leaves of tomatoes, then the flowers, and finally the fruit. Therefore, the damage to the tomato tree must be controlled in its early stages. It is difficult for farmers to distinguish Alternaria disease from leafminer pest at the early and middle stages of their outbreak on tomato leaves. In the present study, 272 tomato leaf images were prepared from the farm of the Vali-e-Asr University of Rafsanjan, including 100 healthy leaves and 172 infected leaves with both Alternaria and leafminer at the initial stages. The image processing technique, texture, neural networks and adaptive network-based fuzzy inference system (ANFIS) classifiers were used to diagnose Alternaria disease and leafminer pest on this dataset. The results showed that the ANFIS classifier achieved an accuracy of 84.71% when performing an equal error rate, 87.78% in the area under the curve, and 85.23% in 3.26 s on the central processing unit for the segmentation of Alternaria disease and leafminer pest in RGB color space. Also, the accuracy of 90% and 98% were obtained for segmentation and classification on the PlantVillage dataset in YCBCR color space. The present study suggests a high classification accuracy for an intelligent selection of pixel values to train the ANFIS classifier. This classifier has high accuracy and speed, low sensitivity to the light intensity of images, and practical application in diagnosing various diseases and pests on numerous datasets. © 2022 Society of Chemical Industry.


Circadian activity of the endogenous fibrinolytic system in stable coronary artery disease: effects of beta-adrenoreceptor blockers and angiotensin-converting enzyme inhibitors.
To examine circadian changes in the sympathovagal balance, the activity of the renin-angiotensin system and hemostatic variables in patients with stable coronary artery disease, and the effects of beta-adrenoceptor blockade and angiotensin-converting enzyme inhibition. Sympathovagal balance and key components of the fibrinolytic system show circadian variability. The effects of beta-adrenergic blocking agents and angiotensin-converting enzyme inhibitors on these autonomic and hemostatic rhythms are not well defined. Twenty patients with coronary artery disease underwent 24-h Holter monitoring for heart rate variability and blood sampling (6 hourly for 24 hours) after three consecutive treatment phases, (firstly with placebo, then bisoprolol, and finally quinapril). The effects on sympathovagal balance, hemostatic variables and the renin-angiotensin system activity were measured. The fibrinolytic capacity showed marked circadian variation at the end of the placebo phase (p = 0.002), plasminogen activator inhibitor-1 (PAI-1) activity peaking at 06.00 AM when tissue plasminogen activator (tPA) activity was at its nadir. Sympathovagal balance showed a sharp increase at approximately the same time but plasma renin activity did not rise until later in the day. Inspection of the 24-h profiles suggested that bisoprolol reduced sympathovagal balance and the morning peak of PAI-1 activity and antigen, with a small increase in tPA activity, although these changes were not significant. Quinapril produced a substantial rise in renin (p = 0.01) but did not significantly affect either PAI-1 or tPA. Sympathovagal balance was unaffected by quinapril. In patients with stable coronary artery disease, angiotensin-converting enzyme inhibition with quinapril does not affect either sympathovagal balance or the endogenous fibrinolytic system. Our data suggest that the sympathoadrenal system may modify fibrinolytic activity, judged by the response to beta-adrenoreceptor blockade with bisoprolol.


Bone mineral status in children with phenylketonuria under treatment.
Bone mineral status was assessed in 48 children with phenylketonuria (PKU) (20M, 28 F, aged 2.5-17 y). Bone density was measured in the distal third of the right forearm using single photon absorptiometry and was expressed as +/-SD with respect to age- and gender-matched controls. Serum calcium (Ca), magnesium (Mg), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone and 25-hydroxyvitamin D were measured in morning samples. The ratios of urinary Ca/creatinine (UCa/UCr), UP/UCr, UMg/UCr and hydroxyproline (OH-Pr)/UCr were calculated in urine samples collected over a period of 3 h. Patients' data were compared with those of 50 controls (22 M, 28 F, aged 3-15 y). The data showed severe osteopenia (below -2SD) in 22/48 patients. Bone loss was more prominent in patients over 8 y old. Bone density correlated significantly with age (r=-0.56,p < 0.001) and with Phe (r=-0.49, p < 0.007) but did not correlate with the other biochemical indices studied. Comparing PKU children with controls, significantly higher serum calcium and magnesium (p=0.04, p < 0.001, respectively), lower ALP (p=0.01), higher UCa/UCr ratio (p < 0.001), lower UP/UCr (p < 0.001) and lower UOH-Pr/UCr (p < 0.001) were found. Dietary compliance was poor in patients over the age of 8y, as only 3/22 of < or = 8y had mean serum phenylalanine >10mgdl(-1), in contrast to 21/26 in the older group. It is clear from the data that osteopenia is commonly found in PKU patients from early life. The biochemical data indicate a metabolic state of low bone turnover in PKU patients. In conclusion, a better, more restricted diet may correct osteopenia.


Competitive interactions and controlled release of a natural antioxidant from halloysite nanotubes.
Halloysite nanotubes used as potential carrier material for a controlled release stabilizer in polyethylene were thoroughly characterized with several techniques including the measurement of specific surface area, pore volume and surface energy. The high surface energy of the halloysite results in the strong bonding of the additive to the surface. Dissolution experiments carried out with eight different solvents for the determination of the effect of solvent characteristics on the amount of irreversibly bonded quercetin proved that adsorption and dissolution depend on competitive interactions prevailing in the system. Solvents with low polarity dissolve only surplus quercetin adsorbed in multilayers. Polyethylene is a very apolar polymer forming weak interactions with every substance; quercetin dissolves into it from the halloysite surface only above a critical surface coverage. Stabilization experiments confirmed that strong adhesion prevents dissolution and results in limited stabilization efficiency. At larger adsorbed amounts better stability and extended effect were measured indicating dissolution and controlled release.


Uptake of selected antibacterial agents in Mycobacterium avium.
The antibacterial action of 64 drugs against Mycobacterium avium ATCC 15769 was screened in Middlebrook 7H9 liquid medium. The most active drugs were ansamycin, rifampicin, clofazimine, and pristinamycin. The antibacterial action of the selected drugs was confirmed by testing clinical isolates on Middlebrook 7H10 agar medium. The antibacterial actions were not related with the hydrophobicities and molecular weights of the drugs. However, all the active drugs were highly hydrophobic molecules of low polarity. These drugs dissolved into the lipids forming the outer layers of the bacterial envelope and they appeared to interact with the surface amphiphils.


Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160.
The RON receptor tyrosine kinase regulates epithelial cell homeostasis and tumorigenesis by transducing multiple signals through its functional domains. The present study was to determine the significance of the entire C-terminus in RON or its variant RON160-mediated activities related to cell motility and tumorigenesis. Analysis of protein phosphorylation revealed that elimination of the entire C-terminus significantly impairs the ligand-dependent or independent RON or RON160 phosphorylation and dimerization. Phosphorylation of downstream signaling proteins such as Erk1/2, AKT, and p38 MAP kinase was also diminished in cells expressing the C-terminus-free RON or RON160. These dysfunctional activities were accompanied with the inability of truncated RON or RON160 to mediate cytoplasmic beta-catenin accumulation. Functional analysis further demonstrated that truncation of the C-terminus significantly impairs RON or RON160-mediated cell proliferation, morphological changes, and cellular migration. Significantly, oncogenic RON160-mediated tumor growth in athymic nude mice was lost after the deletion of the C-terminus. Thus, the C-terminus is a critical component of the RON receptor. The entire C-terminus is required for RON or RON160-mediated intracellular signaling events leading to various cellular activities.


New approach in patients with polycystic ovaries, lessons for everyone.
In vitro maturation is a safe and simple procedure for both the clinician and the patient. The discrepancy between the early clinical results and today's pregnancy rates (PR) of 30% is primarily due to the following modification of the original protocol recently reported by several groups: Priming with FSH and hCG, timing oocyte collection from follicles larger than 12 mm in diameter, and using blastocyst transfer. Furthermore, the endometrial priming should start 2 days before oocyte pick-up. This provides a PR of 40% per ET.


Serum cholesterol levels in Puerto Rican volunteer blood donors.
The blood samples of four hundred and fifty eight healthy volunteer blood donors were analyzed to determine their serum lipid profile. Based on these lipoprotein analyses, it was concluded that approximately 12% of the sampled population was in a high risk group for coronary heart disease.


Rates of forgetting in normal ageing: a comparison with dementia.
This paper examines the effect of normal ageing on the forgetting rate of visuo-spatial material in a sample of 74 subjects, aged between 16 and 83. It finds that normal ageing produces a mild acquisition deficit as well as a significant increase in the forgetting rate; and it demonstrates that the relatively rapid rate of forgetting in the elderly cannot be accounted for by differences in the initial level of acquisition. The present result is contrasted with that obtained in studies of dementia and the Korsakoff syndrome, which have demonstrated a profound acquisition deficit but a normal forgetting rate once initial learning has been accomplished. Possible explanations of these differing patterns of results are briefly considered.


Genetic Diversity Analysis of South and East Asian Duck Populations Using Highly Polymorphic Microsatellite Markers.
Native duck populations have lower productivity, and have not been developed as much as commercials duck breeds. However, native ducks have more importance in terms of genetic diversity and potentially valuable economic traits. For this reason, population discriminable genetic markers are needed for conservation and development of native ducks. In this study, 24 highly polymorphic microsatellite (MS) markers were investigated using commercial ducks and native East and South Asian ducks. The average polymorphic information content (PIC) value for all MS markers was 0.584, indicating high discrimination power. All populations were discriminated using 14 highly polymorphic MS markers by genetic distance and phylogenetic analysis. The results indicated that there were close genetic relationships among populations. In the structure analysis, East Asian ducks shared more haplotypes with commercial ducks than South Asian ducks, and they had more independent haplotypes than others did. These results will provide useful information for genetic diversity studies in ducks and for the development of duck traceability systems in the market.


Dual-recognition detection of Staphylococcus aureus using vancomycin-functionalized magnetic beads as concentration carriers.
Vancomycin, which has a strong antibacterial effect to Gram-positive bacteria, was adopted as one molecular recognition agent for bacterial detection. Magnetic beads (MBs) were functionalized with this antibiotic to effectively concentrate Staphylococcus aureus (S. aureus). In addition, alkaline phosphatase (ALP)-tagged rabbit immunoglobulin G (ALP-IgG) was used as the second recognition agent to improve the specificity based on the binding between the Fc region of rabbit IgG and protein A in the cell wall of S. aureus. MBs-concentrated sandwich complex of vancomycin/S. aureus/ALP-IgG was formed with a one-step incubation protocol. Then ALP chemiluminescent reaction was triggered by injecting substrate solution to quantitate S. aureus. Based on the sandwich molecular recognition mechanism and MBs concentration, an ultrasensitive, specific and rapid method was developed for S. aureus detection. The linear range for S. aureus detection was 12-1.2 × 10(6)CFU mL(-1), with a very low detection limit of 3.3 CFU mL(-1). The whole detection process could be completed in 75 min. Other Gram-positive bacteria and Gram-negative bacteria, including Escherichia coli, Salmonella, Pseudomonas aeruginosa, Micrococcus luteus, Bacillus cereus and Bacillus subtilis, showed negligible interference to S. aureus detection. This method was successfully used to quantitate S. aureus in lake water, milk, human urine and human saliva with acceptable recoveries ranging from 70.0% to 116.7%.


Association between PIK3CA activating mutations and outcomes in early-stage invasive lobular breast carcinoma treated with adjuvant systemic therapy.
The aim of the study was to evaluate the independent prognostic role of PIK3CA activating mutations and an association between PIK3CA activating mutations and efficacy of adjuvant endocrine therapy (ET) in patients with operable invasive lobular carcinoma (ILC). A single institution study of patients with early-stage ILC treated between 2003 and 2008 was performed. Clinicopathological parameters, systemic therapy exposure and outcomes (distant metastasis-free survival [DMFS] and overall survival [OS]) were collected based on presence or absence of PIK3CA activating mutation in the primary tumor determined using a quantitative polymerase chain reaction (PCR)-based assay. An association between PIK3CA mutation status and prognosis in all patient cohort was analyzed by Kaplan-Meier survival analysis, whereas an association between PIK3CA mutation and ET was analyzed in estrogen receptors (ER) and/or progesterone receptors (PR)-positive group of our patients by the Cox proportional hazards model. Median age at diagnosis of all patients was 62.8 years and median follow-up time was 10.8 years. Among 365 patients, PIK3CA activating mutations were identified in 45%. PIK3CA activating mutations were not associated with differential DMFS and OS (p = 0.36 and p = 0.42, respectively). In patients with PIK3CA mutation each year of tamoxifen (TAM) or aromatase inhibitor (AI) decreased the risk of death by 27% and 21% in comparison to no ET, respectively. The type and duration of ET did not have significant impact on DMFS, however longer duration of ET had a favourable impact on OS. PIK3CA activating mutations are not associated with an impact on DMFS and OS in early-stage ILC. Patients with PIK3CA mutation had a statistically significantly decreased risk of death irrespective of whether they received TAM or an AI.


N-terminal pro-brain natriuretic peptide could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.
N-terminal pro-brain natriuretic peptide (NT-proBNP), which is a useful biomarker of chronic heart failure, has been shown to be a strong predictor of cardiovascular mortality. The aim of this study was to evaluate the relationships between NT-proBNP and markers of subclinical atherosclerosis in patients with type 2 diabetes. Relationships of NT-proBNP to pulse wave velocity (PWV) or ankle-brachial index (ABI) as well as to various parameters, including body mass index, blood pressure, serum lipid concentration, serum uric acid concentration, and glycemic control (hemoglobin A1c), age, hemoglobin, serum creatinine concentration, severity of diabetic nephropathy or retinopathy, current treatment of diabetes, cardiothoracic ratio on chest radiograph, presence of left ventricular hypertrophy and/or ST-T changes evaluated by electrocardiograph, smoking status and presence of cardiovascular disease were investigated in 323 consecutive patients with type 2 diabetes. Log (NT-proBNP) correlated positively with PWV (r = 0.283, p < 0.0001) and correlated negatively with ABI (r = -0.144, p = 0.0094). Multiple regression analysis demonstrated that age (β = 0.200, p = 0.0033), systolic blood pressure (β = 0.246, p < 0.0001), total cholesterol (β = -0.135, p = 0.0326), uric acid (β = 0.133, p = 0.0462), creatinine (β = -0.184, p = 0.0122), smoking status (β = -0.129, p = 0.0499) and log (NT-proBNP) (β = 0.177, p = 0.0149) were independently correlated with PWV and that systolic blood pressure (β = -0.145, p = 0.0310), log triglyceride (β = -0.151, p = 0.0397) and log (NT-proBNP) (β = -0.207, p = 0.0094) were independently correlated with ABI. In conclusion, NT-proBNP could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.


Superparasitism in Cotesia glomerata does not benefit the host plant by reduction of herbivory caused by Pieris brassicae.
Superparasitism occurs in Cotesia glomerata L. (Hymenoptera: Braconidae), a gregarious endoparasitoid of Pieris spp. (Lepidoptera: Pieridae). The responses of Pieris brassicae L. larvae to superparasitism were examined in order to elucidate the ecological significance of this behaviour. Models of tritrophic interactions often imply that attraction of herbivore natural enemies by the plant constitutes a defence. Parasitoid attack on herbivores is assumed to result in a reduction in herbivory and or an increase in plant fitness. Coupled with the active involvement of the plant in producing signals, this can be seen as an indirect mediation of wound induced defence. The results show that superparasitism of P. brassicae by the parasitoid C. glomerata reduced survivorship but increased food consumption and weight growth in P. brassicae larvae. The duration of host larval development was found prolonged as the number of oviposition increased and superparasitized larvae (three to five time parasitized) grew slower than unparasitized larvae or larvae parasitized one or two times.


The proportion of influenza vaccination in Ontario, Canada in 2007/2008 compared with other provinces.
In 2000, Ontario, Canada introduced a universal influenza immunization program (UIIP) to provide free vaccines to its residents, whose ages are six months or older. The current study sought to measure the effect of the UIIP on influenza vaccination uptake in Ontario compared with other provinces combined. Data from the 2007/2008 Canadian Community Health Survey (cycle 4.1) were used in the analyses. Logistic regression analyses were conducted to estimate the odds ratios for influenza vaccination 2007/2008 associated with province of residence (Ontario versus other provinces combined) and other factors including chronic disease status, age, gender, household income, smoking status, having a medical doctor, and self-perceived health status. Living in Ontario was positively associated with having an influenza vaccine during the 2007/2008 season [odds ratio (OR) 1.50, 95% confidence interval (CI) 1.45-1.55]. Increased age (OR 6.13, 95% CI 5.77-6.51), a positive chronic disease status (OR 1.70, 95% CI 1.63-1.77) and having a regular medical doctor (OR 1.95, 95% CI 1.85-2.07) also demonstrated a positive relationship with influenza vaccination in 2007/2008. A stratified analysis by province of residence suggested that having a chronic disease, old age and high income had less impact on the likelihood of receiving a vaccine in Ontario than other provinces. The results of this study may help to inform the development of strategies to increase vaccination coverage in Canada.


A case of giant axonal neuropathy showing focal aggregation and hypophosphorylation of intermediate filaments.
We report here the clinicopathological features of a typical case of giant axonal neuropathy (GAN). Scanning electron microscopy of the hair of this case revealed an extraordinarily irregular cuticle. Focal accumulation of intermediate filaments in axons, Schwann cells, muscle fibers and skin fibroblasts were also found under an electron microscopy. When examined immunocytochemically, muscle fibers exhibited local disruption of the filamentous network in the subsarcolemmal space and in the central cytoplasm accompanied by focal accumulation of desmin. The intracellular network of vimentin was also disrupted, exhibiting global accumulation in some of the cultured skin fibroblasts. Decreased interneurofilament spacing was found in enlarged axons, suggesting the presence of hypophosphorylation of neurofilaments in this patient. These findings suggest general disorganization, abnormal distribution and possible defective phosphorylation of intermediate filaments in GAN.


MplK, a natural variant of the thrombopoietin receptor with a truncated cytoplasmic domain, binds thrombopoietin but does not interfere with thrombopoietin-mediated cell growth.
Interaction of thrombopoietin (TPO) with its receptor c-Mpl is responsible for the formation of megakaryocytes and platelets. In humans, there are two major c-mpl molecules, MplP and MplK, which are generated by alternative splicing. In contrast to MplP, MplK has none of the intracellular sequences required for typical signal transduction but instead has a unique 27 amino acid sequence that is coded by intron 10. We tested to determine if MplK exerts a negative effect on TPO Mpl signal transduction by interfering with the normal homodimerization of MplP. A cassette coding for MplK cDNA was introduced into parental and MplP-expressing BaF3 cells and TPO-mediated cell growth studied. Cells expressing MplK alone did not respond to TPO compared to cells that expressed MplP. When MplK was coexpressed with MplP on the cell surface of BaF3, no modification in cell growth was observed when compared to those expressing MplP alone. To determine if the normal homodimerization process was negatively influenced, two genetically engineered variants of c-Mpl, one lacking the box1 sequence and the other containing only the first nine amino acids of the intracellular domain, were introduced into MplP-expressing cells. In contrast to MplK, these mutants had a dominant negative effect on TPO-mediated cell growth. MplK does not influence TPO-mediated growth of Mpl-expressing cells. Our data suggest that the absence of a dominant negative effect of MplK most probably is due to the inability of MplK to dimerize with the MplP receptor.


Preferential prescribing and utilization trends of diabetes medications among patients with renal impairment: Emerging role of linagliptin and other dipeptidyl peptidase 4 inhibitors.
Although many newer diabetes medications have become available in the last decade, most have not been widely studied in populations with chronic kidney disease under routine care. Linagliptin, a recently marketed dipeptidyl peptidase 4 (DPP-4) inhibitor, is the only agent in the U.S. that does not require dose adjustment in patients with diabetes mellitus type 2 (T2DM) and renal impairment. We sought to describe baseline kidney function and other key characteristics among patients with diabetes mellitus type 2 (T2DM) initiating linagliptin and other diabetes medications, and to explore prescribing patterns among T2DM patients with moderate to severe renal impairment before and after the launch of linagliptin. Using a population-based cohort study design nested in a large U.S. commercial healthcare dataset linked to laboratory values, we described characteristics of T2DM patients initiating linagliptin and other diabetes medications between May 2011 (launch of linagliptin) and September 2015. We also explored prescribing trends among T2DM patients with moderate to severe renal impairment (ICD-9 diagnosis code 585.3x-6x) who initiated linagliptin and other diabetes medications between January 2006 to September 2015 (before and after the launch of linagliptin). We identified 1,174,476 T2DM patients initiating a diabetes medication (28,900 linagliptin initiators) between 05/2011-09/2015. We also identified 100,847 T2DM patients with moderate to severe renal impairment initiating a diabetes agent between 01/2006-09/2015. Among patients initiating newer diabetes medications between 05/2011-09/2015, those initiating linagliptin had the highest prevalence of moderate to severe renal impairment, suggesting preferential prescribing in routine care. DPP-4 inhibitors overall were among the most frequently chosen agents among T2DM patients with moderate to severe renal impairment between 01/2006-09/2015. Further investigation of the safety and effectiveness of DPP-4 inhibitors in routine care of T2DM patients with renal impairment is needed to either corroborate or discourage current prescribing patterns.


Incidence and outcomes of surgical site infection following emergency laparotomy during the COVID-19 pandemic in a low resource setting: A retrospective cohort.
Surgical site infection (SSI) is the commonest form of hospital acquired infection in sub-Saharan Africa, associated with increased morbidity and mortality. This study was aimed at determining the incidence and outcomes of surgical site infection following emergency laparotomy during the COVID -19 pandemic in a low resource setting. This was a retrospective single Centre cohort of patients that had emergency laparotomy between July 2021-June 2022 (COVID period) and July 2018-June 2019 (pre-COVID period). Analysis was done using SPSS version 22 in which SSI rates were compared between the two periods using the chi squared test. Mortality, re-operation rates and length of hospital stay were also compared. Of the 453 patient files included in analysis, 244 (53.9%) were for the COVID period, while 209 (46.1%) were for the pre COVID period. The incidence of SSI was insignificantly higher in the COVID period (17.6% versus 16.7%; P = 0.901). Mortality was also insignificantly higher in the SSI group (3.8% versus 3.5%; P = 0.745). Presence of surgical site infection increased the risk for re-operation (P < 0.001) and prolonged hospital stay (P < 0.001). Since the incidence and outcomes of surgical site infection appear not to have changed following the pandemic, the same measures that were previously used to prevent SSI could still be effective even during the pandemic if followed appropriately and combined with the COVID specific peri-operative care recommendations.


On the sensitivity of a marine dispersion model to parameters describing the transfers of radionuclides between the liquid and solid phases.
The sensitivity of a marine dispersion model for non-conservative radionuclides, previously developed and validated for the English Channel, to parameters describing the exchanges between the liquid and solid phases (suspended matter and bottom sediments) has been studied using a Monte Carlo method. A probability distribution is assigned to each parameter. They are sampled to obtain a set of model parameters and a model run is carried out. This process is repeated to obtain a distribution of model outputs. Partial correlation coefficients are calculated to assess the relative influence of each parameter on model output. Errors are also assigned to model results. Three situations are studied: an instantaneous release of radionuclides, a continuous release and the case of a contaminated sediment behaving as a long-term source of radionuclides. Calculations have also been carried out for two radionuclides with different geochemical behaviour: (137)Cs and (239,240)Pu. The results indicate that all parameters are relevant, depending on the phase we are interested in obtaining the result and on the source term (instantaneous, continuous or due to sediments). However, parameters that are, in general, more influential are kinetic rates, mixing depth in the sediment and mean radius of suspended and sediment particles. This suggests that including several particle sizes in future radionuclide dispersion models could lead to an improvement in model results. Differences have also been found with respect to the relevance of some parameters depending on the geochemical behaviour of the radionuclide.


Effect of increased intake of concentrates and sodium butyrate supplementation on reticulorumen macroanatomy and reticulorumen fermentation in growing rams.
Increased ruminal butyrate production is considered to have mostly positive impacts on rumen macro- and microanatomy and its functions. However, excessive ruminal butyrate production may also affect the rumen negatively. Forty-two growing rams were allocated into six treatments and fed a diet with low (22.5% of diet DM; LOW) or high (60% of diet DM; HIGH) inclusion of concentrates in combination with no, low (1.6% of diet DM) or high (3.2% of diet DM) sodium butyrate (SB) supplementation to obtain low or high reticuloruminal (RR) pH with different concentrations of butyrate. Both absolute (L/day) and relative (% of BW) water intake increased linearly with increasing dose of SB (P ≤ 0.02). The RR fluid pH was lower for HIGH compared to LOW treatments (P < 0.01) but was not affected by SB supplementation (P = 0.35). Total short-chain fatty acid concentration, propionate and valerate concentrations in the RR fluid were higher for HIGH compared to LOW treatments (P ≤ 0.01), but were not affected by SB supplementation (P ≥ 0.22). Reticuloruminal butyrate was higher for HIGH compared to LOW treatments and increased linearly with increasing dose of SB (P < 0.01). High concentrate inclusion in the diet (P < 0.01) decreased and SB supplementation tended to (P = 0.10) decrease fibrolytic activity in the RR. Increasing doses of SB linearly decreased acetate, isovalerate and NH3-N concentrations in RR fluid, and RR digesta DM weight (g DM/kg BW; P ≤ 0.02). Relative RR and rumen tissue weights (g/kg BW) were higher for LOW compared to HIGH (P ≤ 0.03) treatments but were not affected by SB inclusion in the diet (P ≥ 0.35). Also, there was no impact of concentrates or SB inclusion in the diet on ruminal epithelium DM weight (mg/cm2), either in the ventral or dorsal sac of the rumen (P ≥ 0.14). Under conditions of the current study, SB supplementation in the diet decreased RR digesta DM concentration and weight, acetate, isovalerate and NH3-N concentration in the RR fluid, and tended to reduce fibrolytic activity in the RR. At least part of this response could be due to increased intake of water, and consequently passage of digesta from the RR to lower regions of the gastrointestinal tract.


GORD symptoms in lung transplantation: how efficient is the reflux symptom index questionnaire compared to the esophageal impedance test?
As Gastroesophageal reflux disease (GORD) affects long-term survival in lung transplant recipients, the aim of this observational prospective study was to analyze the efficacy of The Reflux Symptom Index Questionnaire (RSI) compared to the esophageal impedance test. Both esophageal impedance studies and RSI questionnaire were routinely performed in all patients who had completed rehabilitation following lung transplantation from June 2013 till March 2014. RSI generates a score of between zero and forty-five, taking into account any symptoms within four wk of the questionnaire. Our analysis considered RSI score cut-offs of 10 and 13 indicating significance of reflux. Out of 84 patients, 50 (59.5%) had evidence of GORD detected by impedance studies, whereas only 33 (39.2%) and 22 (26.2%) had RSI >10 and 13, respectively. An elevated RSI was not found to be associated with positive impedance studies using a score of either 10 or 13 (p = 0.127 and p = 0.142, respectively); 32.1% (n = 27) and 40.5% (n = 34) were found to have negative RSI and positive impedance test using 10 or 13 as cut-off, respectively. RSI Score is an unreliable predictor of GORD among lung transplant recipients. The authors therefore recommend the routine use of impedance testing in post-transplant patients.


LOGIT: a program for dose-response analysis.
We describe a FORTRAN computer program for fitting the logistic distribution function: (formula: see text) Where x represents dose or time, to dose-response data. The program determines both weighted least squares and maximum likelihood estimates for the parameters alpha and beta. It also calculates the standard errors of alpha and beta under both estimation methods, as well as the median lethal dose (LD50) and its standard error. Dose--response curves found by both fitting methods can be plotted as well as the 95% confidence bands for these lines.


Arginine vasopressin response to hypertonicity in hypertension studied by arginine vasopressin assay in unextracted plasma.
To investigate whether plasma osmolality (Posm)-plasma arginine vasopressin (PAVP) response relationships with particular characteristics of sensitivity, gain or response pattern (linear/non-linear) occur more frequently in hypertensive than normotensive subjects. Analysis of Posm-PAVP curves observed in individual normotensive and hypertensive subjects rather than whole groups was considered appropriate for the described objective. A sensitive and precise radioimmunoassay of PAVP in unextracted plasma was developed. Posm was raised in 11 normotensive and 19 hypertensive subjects by infusion of NaCl solution (0.86 mol/l, i.v.), and PAVP assayed at intervals. Best-fitting linear and non-linear equations for the Posm-PAVP relationship were established by computer. The mean rise in osmolality, blood pressure and blood volume was similar in the two groups. Hypertensive subjects showed a tendency towards higher rates of response (pmol AVP/l per mosm per kg) at Posm greater than 290 mosm/kg, leading to a non-linear response pattern compared with the normotensive subjects. The enhanced PAVP responses found in the hypertensive subjects at Posm greater than 290 mosm/kg may reinforce vascular and central nervous pathogenetic mechanisms.


A method for chemical-shift-selective imaging.
Selective suppression of a given resonance in an NMR image can be obtained with a pi/2 pulse whose excitation spectrum is zero at the appropriate chemical shift. The selective pi/2 pulse presented here is composed of two nonselective pi/2 pulses of opposite phase. The two pulses are separated by a short interval which determines the excitation spectrum.


Heel pad thickness: determination by high-resolution ultrasonography.
Heel pad thickness classically is increased in acromegaly and can also be noted in long-term Dilantin therapy. A high-resolution 10-MHz dedicated superficial small parts real-time scanner was used to evaluate heel pad thickness without the use of radiation and without the magnification inherent in the standard procedure, a lateral radiograph of the foot. Fifty-four patients were studied, and it was determined in 10 controls that heel pad thickness averaged 16.6 mm. In 38 diabetics without ulcers of the feet, the heel pad was 17.8 mm. A single treated acromegalic had a heel pad thickness of 21 mm. Ultrasonography offers an effective alternative to radiography in the measurement of heel pad thickness.


Simultaneous quantitative determination of eight triterpenoid monoesters from flowers of 10 varieties of Calendula officinalis L. and characterisation of a new triterpenoid monoester.
Dichloromethane extracts of dried flowers of Calendula officinalis contain eight known bioactive triterpendiol monoesters, namely, faradiol-3-O-palmitate, faradiol-3-O-myristate, faradiol-3-O-laurate, arnidiol-3-O-palmitate, arnidiol-3-O-myristate, arnidiol-3-O-laurate, calenduladiol-3-O-palmitate and calenduladiol-3-O-myristate. These pentacyclic terpenoids have been quantified simultaneously using reversed-phase HPLC with isocratic elution and internal standardisation. Of the 10 varieties of C. officinalis investigated, Calypso Orange Florensis produced the highest amounts of the bioactive monoesters, followed by Fiesta Gitana Gelb and May Orange Florensis. The lipophilic extract from the flowers of Calypso Orange Florensis variety also contained low levels of the newly characterised calenduladiol-3-O-laurate.


Identification of benzamides derivatives of norfloxacin as promising microRNA-21 inhibitors via repressing its transcription.
MicroRNA-21 is a carcinogenic microRNA, whose overexpression arises in a variety of tumor tissues. Hence, microRNA-21 a prospective target for cancer treatment, and regulation of microRNA-21 by small molecule inhibitors is deemed as a promising approach for tumor therapy. In this work, to discover potent microRNA-21 inhibitor, series of 4-(N-norfloxacin-acyl)aminobenzamides were designed and synthesized, and their inhibitory effects were appraised by utilizing dual luciferase reporter assays. The results indicated that compound A7 was the most efficient microRNA-21 small molecule inhibitor. What's more, A7 suppressed the migration of Hela cells and the colony formation of Hela and HCT-116 cells as well as promoted apoptosis of Hela cells. In the mechanism study, results of RT-qPCR certified that A7 could reduce the level of mature microRNA-21 via disrupting its expression at the transcriptional level of its primary form "pri-miR-21", which was distinct from most previous inhibitors directly binding with pre-miR-21. Noticeably, Western blotting and RT-qPCR uncovered A7 could upregulate the expression PTEN, EGR1 and SLIT2, which are the downstream functional targets of microRNA-21. These findings demonstrated that A7 was a promising microRNA-21 small molecule inhibitor and 4-(N-norfloxacin-acyl) aminobenzamide can serve as a new scaffold for discovery of potent microRNA-21 inhibitor.


Investigating the specificity of real-time PCR assays using synthetic oligonucleotides.
Potato spindle tuber viroid (PSTVd) causes damaging diseases of solanaceous crops and is a quarantine pathogen in the European Union. Previously a one-tube real-time RT-PCR assay based on TaqMan chemistry was developed and shown to be ideally suited to PSTVd detection. However, since it was impossible to trace infected plant material for every published PSTVd sequence reported, in silico predictions were made about assay specificity based on the positions of nucleotide polymorphisms within the published viroid sequences and the regions of the primers and probe. The predictions could not be verified due to the absence of viroid material. This paper describes work investigating the detection of these sequence variants by designing synthetic oligonucleotides to sequences from the database and testing them with a real-time PCR assay. The results show that all PSTVd sequence variants are detected, and that the closely related Mexican papita viroid is also detected, although with a lower efficiency. The paper gives indications as to what effect nucleotide changes at different positions within primers and probes might do and should aid in the testing of future assays, although it is difficult to draw fixed rules about the possible effect changes may have.


Desipramine-induced increase in efflux of endogenous dopamine from rat hypothalamus in vitro: mechanism and specificity.
In vitro exposure of minced rat hypothalamus to desipramine (DMI) resulted in a significant elevation of the net efflux of endogenous norepinephrine (NE) and dopamine (DA) at a drug concentration as low as 10 nM. The net efflux of epinephrine was increased only by a 1000-fold greater concentration of desipramine. The increase in efflux of DA was not secondary to changes in the efflux of NE since nisoxetine elevated the efflux of NE but not of DA and the removal of calcium from the incubation medium blocked the effect of desipramine on the efflux of DA but not of NE. Elimination of calcium did not alter the "spontaneous" hypothalamic efflux of catecholamine. In contrast, desipramine did not affect the net efflux of either DA or NE from the olfactory tubercle or striatum at concentrations of less than 100 microM. At this concentration, the efflux of DA was significantly increased only in the striatum, while the efflux of NE was reduced in the striatum but increased in the olfactory tubercle. Again, in contrast to the hypothalmus, the removal of calcium from the medium markedly reduced "spontaneous" efflux of catecholamine and the desipramine induced efflux of NE, but not the increase in striatal DA efflux produced by desipramine. The results indicate that marked regional differences exist in brain in the ability of desipramine or calcium removal to alter the efflux of both endogenous DA and NE, and suggest that hypothalamic DA and NE neurons are uniquely sensitive to the effects of desipramine.


Modulating effects of bodyweight unloading on the lower limb nociceptive withdrawal reflex during symmetrical stance.
To investigate the effects of bodyweight unloading on the excitability of the nociceptive withdrawal reflex (NWR) and of its receptive fields organisation during quiet stance in humans. The NWR was elicited in 14 volunteers by electrical stimulation of the sole of the foot at mid-forefoot, arch, and heel points. Participants stood upright and wore a whole-body harness connected via a rope to a pulley. Data were recorded at 0%, 10%, 25% and 40% of the bodyweight unloading. The root mean square of the EMG activity was measured bilaterally from several lower limb muscles. Kinematics of ankle, knee, and hip were measured bilaterally using goniometers. Two-way ANOVA for repeated measures revealed higher reflex sizes at higher degrees of unloading in the tibialis anterior, soleus, and biceps femoris muscles and in the kinematics of the knee joint of the ipsilateral limb. No interaction between stimulation site and unloading was revealed. Unloading induced a generalised enhancement of NWR excitability without modifying the reflex receptive field organisation. Our study indicates that bodyweight unloading in general enhances the NWR excitability and suggests that only load-related afferent inputs in concert with joint movements may modify the modular organisation of the NWR.


Polycystic ovary syndrome: abnormalities and management with pulsatile gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs.
Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The administration of a gonadotropin-releasing hormone analog for 4 to 8 weeks before the initiation of pulsatile gonadotropin-releasing hormone ovulation induction can temporarily correct endocrine abnormalities of polycystic ovary syndrome, such as excessive luteinizing hormone and androgen secretion, and improve ovulatory and pregnancy rates in these patients. For optimal results, this pretreatment should probably be repeated before each pulsatile gonadotropin-releasing hormone ovulation induction cycle. Obesity is associated with a lower success rate, and spontaneous abortion remains a prominent complication in polycystic ovary syndrome even after gonadotropin-releasing hormone analog suppression. With this regimen the risks of ovarian hyperstimulation and multiple pregnancy are virtually abolished. Thus, pulsatile gonadotropin-releasing hormone appears to be highly effective and safe for ovulation induction in patients with polycystic ovary syndrome also, provided that this treatment is preceded by pituitary-ovarian suppression with a gonadotropin-releasing hormone analog.


Insulin resistance estimated by estimated glucose disposal rate predicts outcomes in acute ischemic stroke patients.
Estimated glucose disposal rate (eGDR), a simple and noninvasive measure of insulin resistance, has been proven to be an independent risk factor for first-time stroke and all-cause mortality. In this study, we aimed to investigate the associations between eGDR and the stroke outcome in patients with first-time acute ischemic stroke (AIS). We included first-time AIS patients with available data on eGDR in the China National Stroke Registry III (CNSR-III), and divided the subjects into lower eGDR group (eGDR ≤ 6 mg/kg/min) and higher eGDR group (eGDR > 6 mg/kg/min). The primary outcome was excellent functional outcome (modified Rankin Scale score 0-1) at 3 months. Secondary outcomes included stroke recurrence and favorable functional outcome (modified Rankin Scale score 0-2) at 3 months, and functional outcome and combined vascular event at one year. Univariate and multivariate analyses were performed to evaluate the association between eGDR and outcomes. A total of 6,271 patients with AIS were included in this study. The median values of eGDR in lower and higher eGDR group were 5.0 mg/kg/min (interquartile range, 4.2-5.6) and 7.6 mg/kg/min (interquartile range, 6.8-9.6), respectively. Patients with higher eGDR were significantly associated with higher incidence of excellent functional outcome (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.45; P < 0.01) at 3 months and favorable (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.93; P < 0.01) and excellent (adjusted odds ratio, 1.28; 95% confidence interval, 1.08-1.51; P < 0.01) functional outcome at one year. However, there was no significant difference in stroke recurrence between these two groups at 3 months (adjusted odds ratio, 0.81; 95% confidence interval, 0.61-1.06; P = 0.12) and one year (adjusted odds ratio, 0.91; 95% confidence interval, 0.73-1.14; P = 0.41). eGDR is a predictor of functional outcome in patients with AIS, independent of traditional cardiovascular predictors.


Brief Report: T-Cell Receptor α Repertoire Diversity at Birth After in utero Exposure to HIV Integrase Strand-Transfer Inhibitors.
Effectiveness of anti-HIV in the prevention of perinatal transmission has been established. Assessing the tolerance of drug exposure during pregnancy is of the utmost importance given the number of children exposed. HIV integrase and the recombinase-activating gene enzyme involved in the establishment of the T-lymphocyte repertoire show structural similarity. The inhibition of recombinase-activating (RAG) gene by anti-integrases is observed in vitro, in a variable way according to the molecules. Here, we show that in utero exposure to raltegravir did not alter the T-lymphocyte repertoire of 12 newborns. These reassuring data merit verification for other anti-integrases. ( ClinicalTrial.org NCT04024150).


Barriers to adoption of laparoscopic cholecystectomy in a county hospital in Guatemala.
Despite international efforts to increase performance of laparoscopic cholecystectomy (LC) in rural Guatemala, the vast majority of cholecystectomies are still performed via the open cholecystectomy (OC) approach. Our goal was to explore barriers to the adoption of LC in Guatemala as well as possible mechanisms to overcome them. We reviewed 9402 cholecystectomies performed over 14 years by surgeons at the Hospital Nacional de San Benito (HNSB) in El Peten, Guatemala, with either an open or a laparoscopic approach. We conducted personal interviews with all the surgeons who perform cholecystectomies at HNSB to determine current practice and barriers to adopting LC. Overall, seven general surgeons were interviewed who regularly perform cholecystectomy. Of the total number of cholecystectomies reviewed, 8440 (90%) were open and 962 (10%) were laparoscopic. The mean number of cholecystectomies performed per surgeon was 1341.1 ± 1244.9, with OC at 1205.7 ± 1194.9, and LC at 137.4 ± 188.0. Lack of formal training in laparoscopy was identified in 57% of surgeons. Lack of government funds to implement a laparoscopic program was noted by 71% of surgeons (29% felt there was insufficient ancillary staff, 29% poor allocation of hospital funding to purchase laparoscopic equipment/training). Lack of sufficient laparoscopic equipment was identified by 71% of surgeons. Ninety percent of cholecystectomies performed by surgeons at HNSB continue to be OC. The major limitation is the lack of funding to provide sufficient equipment or ancillary staff. The majority of surgeons preferred to perform LC if these problems could be addressed.


Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis.
Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown. Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs). We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42-0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40-0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79-1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34-0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size. Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.


Microfluidics guided by deep learning for cancer immunotherapy screening.
Immunocyte infiltration and cytotoxicity play critical roles in both inflammation and immunotherapy. However, current cancer immunotherapy screening methods overlook the capacity of the T cells to penetrate the tumor stroma, thereby significantly limiting the development of effective treatments for solid tumors. Here, we present an automated high-throughput microfluidic platform for simultaneous tracking of the dynamics of T cell infiltration and cytotoxicity within the 3D tumor cultures with a tunable stromal makeup. By recourse to a clinical tumor-infiltrating lymphocyte (TIL) score analyzer, which is based on a clinical data-driven deep learning method, our platform can evaluate the efficacy of each treatment based on the scoring of T cell infiltration patterns. By screening a drug library using this technology, we identified an epigenetic drug (lysine-specific histone demethylase 1 inhibitor, LSD1i) that effectively promoted T cell tumor infiltration and enhanced treatment efficacy in combination with an immune checkpoint inhibitor (anti-PD1) in vivo. We demonstrated an automated system and strategy for screening immunocyte-solid tumor interactions, enabling the discovery of immuno- and combination therapies.


Negative feedback of corticosterone on the pituitary-adrenal axis is maintained after inhibition of serotonin synthesis with parachlorophenylalanine.
The role of the serotonergic transmission on the negative feedback of corticosterone on the pituitary-adrenal (PA) axis was studied in adult male rats. Animals were given p-chlorophenylalanine (PCPA) and 24 h later were administered corticosterone, 2 h before being subjected to 20 min of noise stress. The main results were as follows: First, PCPA administration increased resting levels of both corticotropin (ACTH) and corticosterone but did not alter PA response to noise stress; second, ACTH response to stress was eliminated in rats given PCPA; third, corticosterone reduced ACTH levels in nonstressed rats only and this effect was maintained after PCPA administration. Taken together, the present results suggest a mediator role for serotonin in the noise-stress-induced PA hormone release but no role in the negative feedback of corticosterone on the PA axis.


LPO and antioxidant defense in the stomach of albino rats injected with angiotensin II and enalapril maleate.
The effects of components of angiotensin II system on LPO and antioxidant defense in the stomach of adult albino rats were studied using biochemical and chemiluminescent methods. Five intraperitoneal injections of angiotensin II in a dose of 100 micro/kg activated LPO and inhibited antioxidant processes in the studied tissues. Oral therapy with enalapril maleate (inhibitor of angiotensin-converting enzyme) in a daily dose of 10 mg/kg for 2 weeks normalized stress-activated LPO processes in gastric tissue.


Adaptive changes in NAD+ metabolism in ultraviolet light-irradiated murine lymphoma cells.
We have determined the ability of UV254nm-irradiated murine lymphoma cells to adapt their NAD+ metabolism to the increased NAD+ consumption for the poly ADP-ribosylation of chromatin proteins. Two murine lymphoma sublines with differential UV-sensitivity and poly(ADP-ribose) turnover were used as a model system. The first subline, designated LY-R is UV254nm-sensitive and tumorigenic in DBA/2 mice. The second subline, LY-S is UV254nm-resistant and nontumorigenic. Following treatment of these cells with 2 mM benzamide, an inhibitor of the NAD(+)-utilizing enzyme poly(ADP-ribose) polymerase, NAD+ levels slowly increased up to about 160% of control levels after 3 hours. When benzamide was added to these cultures 20 min after UV254nm irradiation, a dramatic transient increase of NAD+ levels was observed within 4 min in LY-R cells and more moderately in LY-S cells. At later times after UV254nm irradiation, the NAD+ levels increased in both sublines reaching up to 200% of the concentrations prior to benzamide treatment. These results demonstrate an adaptative response of NAD+ metabolism to UV254nm irradiation. In parallel, we observed a differential repartitioning of ADP-ribosyl residues between the NAD+ and poly(ADP-ribose) pools of LY-R and LY-S cells that correlates with the differential UV sensitivity of these cells.


Results of penetrating keratoplasty with cataract extraction and intraocular lens implantation in Fuchs' dystrophy.
Combined procedure was performed in 25 eyes and triple procedure in 32 eyes of Fuchs' dystrophy. Pre-operative visual acuity was 20/100 or less in 63.2% of eyes. The graft was clear in 76% of combined procedure and in 97% of triple procedure eyes. Post-operative visual acuity of 20/40 or better was obtained in 57.9% of eyes. The common cause of graft failure was allograft reaction. The other causes attributable to visual failure were opacification of posterior capsule, secondary glaucoma, macular degeneration and pre-existing glaucomatous cupping. Intraocular lens insertion at the time of surgery helps in rapid visual rehabilitation.


Carotid plaque histology using real-time ultrasonography. Clinical and therapeutic implications.
To evaluate the ability of ultrasonographic imaging to detect plaque hemorrhage in carotid atheroma, a study was undertaken that compared pathologic findings to preoperative ultrasonographic findings. Ultrasonography identified two plaque categories based on the heterogeneous and homogeneous echo patterns of the lesions studied. Heterogeneous lesions accounted for 91 percent of intraplaque hemorrhages (30 of 33) and 100 percent of ulcerated lesions (15 of 15). In 41 of 50 specimens (82 percent), ultrasonography correctly identified the presence or absence of plaque hemorrhage. False-negative studies (3 of 50) were due to the minute foci of remote hemorrhages. False-positive studies (6 of 50) resulted from plaques that contained large amounts of lipid or cholesterol. Preoperative ultrasound carotid imaging can be used to detect the histologic characteristics of plaque. Since recent clinicopathologic studies have implicated intraplaque hemorrhage and ulceration in symptomatic carotid disease, this information may be of value in choosing therapy, especially for the asymptomatic patient.


Existence of PAF receptors in human platelets and human lung tissue but not in the human myocardium.
The aim of this study was to investigate whether platelet-activating factor (PAF), PAF receptors, and PAF receptor-mediated effects in the human myocardium play a role in cardiac depression during anaphylaxis or septic shock. The effects of PAF, the biologically inactive derivative lyso-PAF, and the specific PAF antagonist WEB 2086 were studied in human myocardial tissue, in human coronary arteries, in human platelets, and in human lung tissue. PAF (C16-PAF, C18-PAF; 0.000001 to 1 mumol/L) had no effect on isometric force of contraction of electrically driven right atrial trabeculae (patients undergoing aortocoronary bypass surgery) and left ventricular papillary muscle strips (mitral valve replacement). PAF (0.2 mumol/L) did not influence the concentration-response curve of either the beta-adrenoceptor agonist isoprenaline (ISO, 0.0001 to 1 mumol/L) or the m-cholinoceptor agonist carbachol (CARB, 0.0001 to 10 mumol/L). The effectiveness (ISO +4.7 +/- 0.7 mN, PAF + ISO + 4.3 +/- 0.44 mN, CARB -2.7 +/- 1.06 mN; PAF + CARB -2.6 +/- 0.52 mN) and the potency--as indicated by the EC50 values--of both isoprenaline and carbachol were identical with and without pretreatment with PAF (0.2 mumol/L). PAF at concentrations of 0.000001 to 10 mumol/L exerted no effect on force of contraction either precontracted (prostaglandin F2 alpha, 0.3 mumol/L) or unprecontracted in human coronary artery rings. Histamine (0.01 to 100 mumol/L) and noradrenaline (0.001 to 30 mumol/L) initiated concentration-dependent contraction in human coronary artery rings (EC50: histamine, 1.86 mumol/L; noradrenaline, 0.69 mumol/L). At lower concentrations (PAF, 0.01 mumol/L) PAF produced complete aggregation of human platelets. In human platelet membranes and lung membranes, 3H-WEB 2086 exhibited saturable high-affinity binding (KD 14.4 nmol/L and 14.3 nmol/L). The maximal binding capacity was 292 fmol/mg protein and 268 fmol/mg protein, respectively. In displacement experiments PAF (0.01 to 10000 nmol/L) and WEB 2086 (0.01 to 10000 nmol/L), but not lyso-PAF, completely displaced 3H-WEB 2086 from its binding sites on human and lung membranes. In contrast, neither in left ventricular membranes nor in right atrial membranes was specific binding of 3H-WEB 2086 observed. These results suggest that there are neither specific PAF receptors nor direct PAF-mediated actions in human myocardial tissue or human coronary artery rings. The effects of PAF on myocardial function may be due to the activation of mediators (e.g., histamine).


Visual discrimination following partial telencephalic ablations in nurse sharks (Ginglymostoma cirratum).
An instrumental conditioning task was used to examine the role of the nurse shark telencephalon in black-white (BW) and horizontal-vertical stripes (HV) discrimination performance. In the first experiment, subjects initially received either bilateral anterior telencephalic control lesions or bilateral posterior telencephalic lesions aimed at destroying the central telencephalic nuclei (CN), which are known to receive direct input from the thalamic visual area. Postoperatively, the sharks were trained first on BW and then on HV. Those with anterior lesions learned both tasks as rapidly as unoperated subjects. Those with posterior lesions exhibited visual discrimination deficits related to the amount of damage to the CN and its connecting pathways. Severe damage resulted in an inability to learn either task but caused no impairments in motivation or general learning ability. In the second experiment, the sharks were first trained on BW and HV and then operated. Suction ablations were used to remove various portions of the CN. Sharks with 10% or less damage to the CN retained the preoperatively acquired discriminations almost perfectly. Those with 11-50% damage had to be retrained on both tasks. Almost total removal of the CN produced behavioral indications of blindness along with an inability to perform above the chance level on BW despite excellent retention of both discriminations over a 28-day period before surgery. It appears, however, that such sharks can still detect light. These results implicate the central telencephalic nuclei in the control of visually guided behavior in sharks.


Stimulation of lipid absorption in young rats by cholesterol: early time changes and effects on pentobarbital sleeping time.
Four groups of young male and female rats were fed a chow diet (O), chow plus 10% corn oil (F), chow plus 1% cholesterol (C), or chow plus 1% cholesterol plus 10% corn oil (CF) for 1, 2, 4 and 8 days. After 2 dats, male F, C and CF rats exhibited a shorter anesthesia period (-20 to -30%) when given pentobarbital. By 4 days, male F and C rats had pentobarbital sleeping times (PB-ST) 20% less than O rats. These effects were additive and CF rats had 40% shorter PB-ST. Reduction of PB-ST by cholesterol and corn oil was similar but slightly less in female rats. Liver lipid content doubled in 4 days in CF rats, and liver cholesterol was 4 times than of O rats. These changes and the increases in metabolism of barbiturate suggested changes in liver microsomal enzyme activities. Serum glutamic oxaloacetic and glutamic pyruvic transaminase, two enzymes reflective of liver damage, did not increase after 8 days on C, F or CF diets. Our results suggest that consumption of an animal sterol and a high lipid diet by laboratory rats, normally consuming a diet low in fat (3-4%), increase the ability of the animal to detoxify a barbiturate. Storage of absorbed dietary cholesterol in the liver may represent a major mechanism for maintaining extra hepatic cholesterol homeostasis.


The switching glare illusion: Appearance and disappearance of glare effect due to figure-ground reversal.
The glare illusion is an illusory perception of brightness enhancement and self-luminosity from a glare pattern, which consists of a central white area and surrounding areas with radial darkening luminance gradients. Here, we report a phenomenon we call "the switching glare illusion." In this phenomenon, observers experience perceptual alternation in which the glare effect repeatedly appears and disappears or attenuates when the multiple glare patterns are arranged in a grid pattern. This perceptual alternation is caused by a figure-ground reversal in the grid pattern. Since such a phenomenon has not been reported for a single glare pattern, this is caused by arranging multiple glare patterns in a grid. This new finding is worthy for further studies for understanding the mechanisms underlying the glare effect and brightness perception.


Factor optimization for phenol removal using activated carbon immobilized with Pseudomonas putida.
Removal efficiency of phenol from aqueous solutions was measured using a suspended culture of Pseudomonas putida (ATCC 3180) or the activated carbon on which the microorganisms were immobilized. Experiments were performed as a function of pH (7-9), temperature (30-36 degrees C), and concentrations of glucose (0.5-0.7 g/l) and ammonium sulfate (0.5-0.7 g/l). The Box-Behnken design was applied in a second-degree quadratic, polynomial regression model to identify the significant effects and the interactions among the above four factors. Based on response curve method the conditions for maximizing phenol removal (initially 0.2 g/l) were recognized as pH 7, temperature 30 degrees C, glucose 0.6 g/l, and ammonium sulfate 0.6 g/l. The inhibition effect of carbon and nitrogen sources beyond a concentration of 0.6 g/l on phenol removal was obvious.


Numerical analysis of predatory potentiality of Toxorhynchites splendens against larval Aedes albopictus in laboratory and semi-field conditions.
Larvae of the elephant mosquitoes, Toxorhynchites spp. (Diptera: Culicidae) are predacious on larvae of other mosquito species and some small aquatic organisms; this predatory behavior can be applied in (mosquito) vector control. The present study examined the feeding behavior of Toxorhynchites splendens on Aedes albopictus in relation to search area [volume of water (X1)] and prey density (X2), prey instars, predatory preference and larvae's functional response on variable prey densities. Experiments were conducted to determine changes in the feeding activity of T. splendens with different search areas and showed that rate of prey consumption was inversely proportional to the search area as evidenced by a negative value of X1 in the regression equation and positively related to prey density. The non-linear polynomial logistic regression estimated a significant linear parameter (P1 < 0) for the functional response analysis suggesting a Type II functional response. Differences in feeding response related to the different combinations of prey instars were statistically not significant (p > 0.05), expressing that all the instars of prey were equally susceptible to the predator. Toxorhynchites splendens preferred to consume Ae. albopictus larvae rather than Tubifex when supplied together as a food source.


Chromosome segregation: spindle mechanics come to life.
Chromosome segregation is a mechanical process, and the spindle generates, and is subject to, mechanical force. A recent study probes how the mechanical architecture of the spindle allows it to maintain mechanical integrity despite these forces.


Genomic instability and vascular aging: a focus on nucleotide excision repair.
Genomic instability is recognized as one of the primary mechanisms that lead to organismal aging. When genomic maintenance systems, such as nucleotide excision repair, are defective, genomic instability is promoted, which causes accelerated aging (progeria). This can be observed in humans as well as in mouse models of progeroid syndromes. The role of genomic instability related to nuclear DNA is currently under investigation with respect to its role in cardiovascular disease, and in particular those cardiovascular diseases that are associated with vascular aging. In this review, we highlight the first findings in this field of research that come from experiments in nucleotide excision repair-defective mouse models and from genetic studies. Possible mechanisms that mediate the consequences of genomic instability at the local vascular and at the systemic level, such as cell senescence, mutations, mitochondrial damage, and sirtuin 1 and IGF-1 decrease, are discussed and important goals for future research are set.


Coordinated induction of two unrelated glucose-regulated protein genes by a calcium ionophore: human BiP/GRP78 and GAPDH.
The induction of human BiP/GRP78 and GAPDH protein genes by the calcium ionophore A23187 was determined. Steady-state levels of mRNA for both the glucose starvation-responsive BiP/GRP78 gene and the glucose-responsive GAPDH gene were dramatically induced in a variety of human cells. There is a homologous palindromatic sequence GCCGTTAACGGC in the active promoter region of the two genes that is known to be required for the induction of mammalian BiP/GRP78 by A23187. The evidence confirms in general the function of this element in the regulation of calcium-associated gene activity.


[Treatment of circumscribed scleroderma in childhood].
17 children suffering from morphea were treated with penicillin and antimalaria drugs. The best effects were observed after the combination of penicillin and antimalaria drugs.


Identification of molecular determinants for the nuclear import of pseudorabies virus UL31.
Herpes simplex virus 1 (HSV-1) UL31 is a multifunctional protein and important for HSV-1 infection. Pseudorabies virus (PRV) UL31 is a late protein homologous to HSV-1 UL31. Previous studies showed that PRV UL31 is predominantly localized to nucleus, however, the molecular determinants for its nuclear import were unclear to date. Here, by utilizing live cells fluorescent microscopy, UL31 fused with enhanced yellow fluorescent protein was transiently expressed in live cells and confirmed to exclusively target to the nucleus in the absence of other viral proteins. Furthermore, the nuclear import of UL31 was found to be dependent on the Ran-, importin α1-, α3-, α5-, α7-, β1-and transportin-1-mediated pathway. Therefore, these results would open up new avenues for depicting the biological functions of UL31 during PRV infection.


Novelty: Nursing scholars' guide for successful publication.
The "pressure" or "passion" to publish is a common reality in academia. All faculty are required to demonstrate that they are engaged in research and that their work is disseminated in reputable journals. However, writing manuscripts is quite challenging; some papers for publication may take days, weeks, months, and even years. This editorial aims to provide the editors' points of view to assist authors in successful acceptance and publication in an international nursing journal.


CAR T-cell therapy in highly aggressive B-cell lymphoma: emerging biological and clinical insights.
Recently, significant progress has been made in identifying novel therapies, beyond conventional immunochemotherapy strategies, with efficacy in B-cell lymphomas. One such approach involves targeting the CD19 antigen on B cells with autologous-derived chimeric antigen receptor (CAR) cells. This strategy is highly effective in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), as evidenced by recent regulatory approvals. Recent reports suggest that this is an effective strategy for high-grade B-cell lymphoma. The biological underpinnings of these entities and how they overlap with each other and DLBCL continue to be areas of intense investigation. Therefore, as more experience with CAR T-cell approaches is examined, it is interesting to consider how both tumor cell-specific and microenvironmental factors that define these highly aggressive subsets influence susceptibility to this approach.