HLA-G alleles and their impacts on placental HSV-1 infection in women from southern Brazil.
The Human Leukocyte Antigen G (HLA-G) is an immunoregulatory molecule with a critical role in pregnancy success. HLA-G alleles are associated with differential susceptibility to multiple conditions, including gestational problems, infectious diseases, and viral persistence. Of note, both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can impair HLA-G expression, interfering with HLA-G-associated immunoregulation. On the other hand, the impacts of HLA-G alleles on susceptibility to Herpesviridae infection is a neglected issue. Therefore, this study evaluated HLA-G allele frequencies and their associations with placental Herpesviridae infection in women from southern Brazil. Placenta samples were collected soon after delivery, and detection of viral DNA of HSV-1, HSV-2 and human cytomegalovirus (HCMV) was performed by polymerase chain reaction (PCR). A fragment of HLA-G (exons 2-4) was amplified by PCR, sequenced, and analyzed to allele determination. One hundred and seventy women had their alleles determined. Overall, 25 HLA-G alleles were found, distributed into 56 different genotypes. The most frequent alleles were G* 01:01:01 and G* 01:01:02, found in 37.9 % and 16.5 % of samples, respectively. Among the 170 women, 89 (52.4 %) tested positive for Herpesviridae DNA in the placenta, 55 (32.3 %) tested negative, 3 (1.8 %) were negative for HSV-1 and HSV-2 (with absent HCMV data), and 23 (13.5 %) were undetermined. The G* 01:01:01 allele was significantly associated with an increased risk of placental HSV-1 infection (p = 0.0151; OR=1.837; IC=1.108-3.045). This study describes new information concerning placental HLA-G alleles in women from southern Brazil and helps explain how genetic background can modify susceptibility to placental infections.


Modelling method of inter-building movement for campus-scale occupancy simulation: A case study.
As an important factor in the investigation of building energy consumption, occupant behavior (OB) has been widely studied on the building level. However so far, studies of OB modelling on the district scale remain limited. Indeed, district-scale OB modelling has been facing the challenges from the scarcity of district-scale data, modelling methods, as well as simulation application. This study initiates the extrapolation of occupancy modelling methodology from building level to district scale through proposing modelling methods of inter-building movements. The proposed modelling methods utilize multiple distribution fittings and Bayesian network to upscale the event description methods from inter-zone movement events at the building level to inter-building movement events at the district level. This study provides a framework on the application of the proposed modelling methods for a university campus in the suburbs of Shanghai, taking advantages of data sensing, monitoring and survey techniques. With the collected campus-scale occupancy data, this paper defines five patterns of inter-building movement. One pattern represents the dominated inter-building movement events for one kind of students in their daily campus life. Based on the quantitative descriptions for various inter-building movement events, this study performs the stochastic simulation for the campus district, using Markov chain models. The simulation results are then validated with the campus-scale occupancy measurement data. Furthermore, the impact of inter-building movement modelling methods on building energy demand is evaluated for the library building, taking the deterministic occupancy schedules suggested by current building design standard as a baseline.


Validation of a novel molecular orbital approach (COMPACT) for the prospective safety evaluation of chemicals, by comparison with rodent carcinogenicity and Salmonella mutagenicity data evaluated by the U.S. NCI/NTP.
The molecular dimensions and electronic structures of 100 chemicals of structural diversity have been determined from molecular orbital calculations and molecular mechanics. From these parameters of molecular structure, those chemicals that are likely substrates of cytochromes P4501 and P4502E have been identified by the computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) programme, and their potential toxicity, mutagenicity and carcinogenicity evaluated. The degree of correlation between COMPACT prediction of toxicity and rodent two species life-span carcinogenicity data is estimated to be 92%, and between COMPACT and Salmonella mutagenicity (Ames test) data is 64%. Anomalous rodent carcinogens are rationalized on the basis of biochemical mechanisms of metabolism, genotoxicity and carcinogenicity. Correlation of the Ames test data with rodent carcinogenicity data was 64%, but correlation of COMPACT plus Ames data versus rodent carcinogenicity data provided the highest correlation of 94%.


Evoked potential variation in schizophrenic subgroups.
Unmedicated chronic schizophrenic inpatients and nonpsychotic controls were tested in a paradigm designed to elicit habituated event-related potentials (ERPs) to auditory stimuli. Analysis of Variance of the ERP components recorded at bilateral frontal (F1 and F2) and temporal (T3 and T4) scalp leads revealed significant decreases in N1 component amplitudes in both frontal leads in the schizophrenic subjects. P2 and N2 amplitudes also tended to be smaller at frontal leads in the schizophrenic subjects, but these differences were not found to be statistically significant overall. The schizophrenic subjects were assigned to diagnostic subgroups following administration of the Diagnostic Interview Schedule, the Maine Paranoid Scale, and the Scale for the Assessment of Negative Symptoms. Subjects meeting DSM-III criteria for paranoid schizophrenia were assigned to one subgroup (PS subgroup), and those meeting DSM-III criteria for residual or undifferentiated schizophrenia were assigned to another subgroup (RS subgroup). The Analysis of Variance of the N1 amplitude measures was repeated with subgroup diagnosis as a factor, revealing significant decreases in N1 amplitude in the PS, but not the RS, patients. Patients in the PS subgroup were found to differ significantly from those in the RS subgroup on this ERP measure, as well as from controls. These results suggest that subgroup differences exist within the schizophrenic population that are reflected in differential changes in ERP morphology.


An association between plasma asymmetric dimethylarginine and membrane fluidity of erythrocytes in hypertensive and normotensive men: an electron paramagnetic resonance investigation.
Evidence indicates that increased levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, are associated with increased risk of vascular dysfunction. The present study was performed to assess the possible relationship between plasma ADMA levels and membrane fluidity in hypertensive and normotensive men. Membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes in hypertensive (n = 38) and normotensive (n = 35) men were measured using an electron paramagnetic resonance (EPR) and spin-labeling method. The order parameter (S) for the spin-label agent (5-nitroxide stearate) in the EPR spectra of erythrocyte membranes was significantly higher in hypertensive men than in normotensive men (mean +/- SEM: hypertensive subjects, 0.725 +/- 0.001,n = 38; normotensive subjects, 0.713 +/- 0.001, n = 35, P < .001), indicating that membrane fluidity of erythrocytes was decreased in hypertensive men compared with normotensive men. Plasma NO metabolite (nitrite and nitrate) concentration was lower in hypertensive than in normotensive men. In contrast, plasma ADMA levels were higher in hypertensive than in normotensive men. In the overall analysis of hypertensive and normotensive men, the order parameter (S) of erythrocytes was inversely correlated with plasma NO metabolites (r = -0.36, n = 73, P < .01) and positively correlated with plasma ADMA levels (r = 0.44, n = 73, P < .001), indicating that the reduced membrane fluidity of erythrocytes was associated with decreased NO and increased ADMA levels in plasma. When correlation analysis was performed separately for hypertensive and normotensive men, there was a positive correlation between plasma ADMA levels and the order parameter (S) of erythrocytes in both groups. The results of the present study showed that the plasma ADMA levels were elevated in hypertensive men and associated with lower membrane fluidity of erythrocytes, suggesting that ADMA might have a close correlation with the rheologic behavior of erythrocytes and the microcirculation in hypertension.


Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis.
Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States. Retrospective cohort study. Overall, 9,984 patients in the Optum's Market Clarity database identified by the presence of at least 2 natural language processing-derived IgAN signs and disease and symptoms terms; 813 with linked claims data included in a health care resource utilization/cost subcohort. High-risk proteinuria (≥1 g/d), chronic kidney disease (CKD) stage. Standardized prevalence, health care resource utilization, costs. Descriptive statistics for categorical and continuous variables. Direct standardization for prevalence estimation. Generalized linear models for health care resource utilization/costs, reported as per-patient-per-month (PPPM) costs in 2020 US dollars. The estimated standardized US prevalence of IgAN (2016-2020) was 329.0 per 1,000,000 persons. High-risk proteinuria (≥1 vs <1 g/d) was associated with a higher mean PPPM number of outpatient visits (3.49 vs 1.74; P = 0.01) and pharmacy claims (3.79 vs 2.41; P = 0.01), contributing to higher mean total costs PPPM ($3,732 vs $1,457; P = 0.01). Furthermore, higher CKD stage was also associated with higher health care resource utilization (number of outpatient visits PPPM, number of pharmacy claims PPPM, proportion of patients with inpatient visits and emergency department visits; P < 0.001) and mean total cost PPPM (from $2,111 CKD stage 1 to $10,703 CKD stage 5/kidney failure; P < 0.001). Generalizability outside of the catchment group for the database, missing data/errors inherent in retrospective database studies, relatively small sample size, use of Optum Market Clarity standardized pricing algorithms, exclusion of out-of-pocket costs. Health care resource utilization and costs were higher for IgAN patients with high-risk proteinuria and worsening kidney function. Treatments that reduce proteinuria and slow CKD disease progression may reduce the economic burden associated with IgAN. Immunoglobulin A nephropathy (IgAN) is a rare kidney disease. Over time, the kidneys may leak protein into the urine (proteinuria). IgAN can lead to kidney failure. Because IgAN is rare, it is hard to know how many people have it. This study used electronic health records to estimate the number of patients with IgAN in the United States, describe the characteristics of patients, and understand their treatments and the costs. The number of patients with IgAN increased between 2016 and 2020. The researchers think this is because doctors learned more about IgAN. Patients with severe disease used more health care resources and had higher costs. The authors believe treatments that slow kidney damage may reduce the cost of treating IgAN.


The Accuracy of Digital Imaging in Diagnosis of Retinopathy of Prematurity in Iran: A Pilot Study.
To evaluate sensitivity and specificity of digital retinal image reading in the diagnosis of referral-warranted retinopathy of prematurity (ROP). Infants referred to the ROP clinic underwent fundus examination through indirect ophthalmoscopy. Fundus photographs were acquired using RetCam (shuttle 2; Clarity medical systems, Pleasanton, CA, USA). Four retinal specialists who were blind to patients' information reviewed the RetCam fundus photographs. By comparing the results of photographs' readings with that of indirect ophthalmoscopy as the gold standard, the sensitivity and specificity of telescreening was determined. A total of 147 treatment-naïve patients met the inclusion criteria and were enrolled in the study. Mean gestational age (GA) was 28.6 ± 2.0 weeks. Digital retinal imaging had sensitivity of 85% and specificity of 35% in detecting referral-warranted ROP in our study. Positive predictive value of digital photography was 80%, and negative predictive value was 43%. Digital photography for diagnosis of ROP may show good potential as a screening modality in developing countries. It can facilitate early diagnosis, prevent unnecessary referrals, and be implemented for investigational purpose. However, the overall study result did not provide evidence to propose digital photography as a substitute for indirect ophthalmoscopy in the diagnosis of ROP.


Quantum dot assisted tracking of the intracellular protein Cyclin E in Xenopus laevis embryos.
Luminescent semiconductor nanocrystals, also known as quantum dots (QD), possess highly desirable optical properties that account for development of a variety of exciting biomedical techniques. These properties include long-term stability, brightness, narrow emission spectra, size tunable properties and resistance to photobleaching. QD have many promising applications in biology and the list is constantly growing. These applications include DNA or protein tagging for in vitro assays, deep-tissue imaging, fluorescence resonance energy transfer (FRET), and studying dynamics of cell surface receptors, among others. Here we explored the potential of QD-mediated labeling for the purpose of tracking an intracellular protein inside live cells. We manufactured dihydrolipoic acid (DHLA)-capped CdSe-ZnS core-shell QD, not available commercially, and coupled them to the cell cycle regulatory protein Cyclin E. We then utilized the QD fluorescence capabilities for visualization of Cyclin E trafficking within cells of Xenopus laevis embryos in real time. These studies provide "proof-of-concept" for this approach by tracking QD-tagged Cyclin E within cells of developing embryos, before and during an important developmental period, the midblastula transition. Importantly, we show that the attachment of QD to Cyclin E did not disrupt its proper intracellular distribution prior to and during the midblastula transition. The fate of the QD after cyclin E degradation following the midblastula transition remains unknown.


Molecular mapping of human hepatocellular carcinoma provides deeper biological insight from genomic data.
DNA microarray analysis of human cancer has resulted in considerable accumulation of global gene profiles. However, extraction and understanding the underlying biology of cancer progression remains a significant challenge. This study applied a novel integrative computational and analytical approach to this challenge in human hepatocellular carcinoma (HCC) with the aim of identifying potential molecular markers or novel therapeutic targets. We analysed 100 HCC tissue samples by human 30K DNA microarray. The gene expression data were uploaded into the network analysis tool, and the biological networks were displayed graphically. We identified several activated 'hotspot' regions harbouring a concentration of upregulated genes. Several 'hotspot' regions revealed integrin and Akt/NF-kappaB signalling. We identified key members linked to these signalling pathways including osteopontin (SPP1), glypican-3 (GPC3), annexin 2 (ANXA2), S100A10 and vimentin (VIM). Our integrative approach should significantly enhance the power of microarray data in identifying novel potential targets in human cancer.


Cloning, expression and characterization of L-asparaginase from Pseudomonas fluorescens for large scale production in E. coli BL21.
L-Asparaginase (E.C. 220.127.116.11) is used as an anti-neoplastic drug in the treatment of acute lymphoblastic leukemia. L-Asparaginase from Pseudomonas fluorescens was cloned and overexpressed in E. coli BL21. The Enzyme was found to be a Fusion protein-asparaginase complex which was given a lysozyme treatment and sonication, and then was purified in a Sepharose 6B column. The enzymatic properties of the recombinant enzyme were studied and the kinetic parameters were determined with kilometre of 109.99 mM and V max of 2.88 µM/min. Recombinant enzyme showed pH optima at 6.3 and temperature optima at 34 °C. Asp gene was successfully cloned into E. coli BL21 which produced high level of asparaginase intracellularly with 85.25 % recovery of enzyme with a specific activity of 0.94 IU/mg protein. The enzyme was a tetramer with molecular weight of approximately 141 kDa.


[Research on motor dysfunction and the role of CTP after traumatic brain injury in rats].
This is a study on the level of molecular biology to clarify the possible mechanism of delayed neural death after traumatic brain injury (TBI) and to probe into the influences of motor function of cytidine triphosphate(CTP) on rats after brain trauma. The model of severe closed traumatic brain injury (TBI) was established according to the method created by Marmarou in 1994. 300 Wistar rats were divided randomly into TBI group (n = 96), CTP treating group and sham operation group, and each of these three groups was divided into 8 subgroups, namely, 3, 6, 12, 24, 48, 72, 168 and 336 hours. At the same time, the rest 12 rats were taken as the normal group for comparison. The CTP treating group after injury were treated with injection of CTP (30 mg/(kg.d)) in peritoneum; the TBI group, the sham operation group and the normal group were treated with normal saline for comparison at the same time and all were killed at each time point. Another 48 rats were divided randomly into 4 groups, namely, brain injury group, CTP treating group, sham operation group and the normal group, and their motor dysfuction was evaluated using Neurological Severity Score (NSS). The methods such as immunohistochemistry, TUNEL and NSS were used to dynamically observe the pathological changes in cortex of rats, the expression of P53 protein and the motor function after TBI. The increased expression of P53 protein and neural apoptosis showed up in cortex and motor dysfunction occurred after TBI. The increased expression of P53 protein may bring about nerve cell apoptosis after TBI. Motor dysfunction is the inevitable outcome of nerve cell apoptosis in cortex. CTP can reduce P53 protein expression and nerve cell apoptosis, and it can improve motor function.


Detection and quantitation of the fetal hemoglobin variant Hb F-Malta-I in adults.
A variant of fetal hemoglobin (Hb F-Malta-I) has been detected and quantitated in adult blood with a sensitive radioimmunoassay employing monospecific antisera. The concentration of Hb-F-Malta-I was 0.002-0.05%, with an average value of 0.011%. The ratio of Hb F-Malta-I/Hb F in adults was about 4.8%, compared to a ratio of about 27% in the newborn. Since the F-Malta-I variant is a product of a mutated Ggamma locus, which is one of the nonallelic structural genes directing the gamma chain synthesis, its presence in blood of adults shows that the synthesis of this gene is not completely suppressed after birth, as was previously suggested.


Pneumatosis intestinalis induced by osimertinib in a patient with lung adenocarcinoma harbouring epidermal growth factor receptor gene mutation with simultaneously detected exon 19 deletion and T790 M point mutation: a case report.
Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene. A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer. Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved.


[Suggestion for the evaluation of roentgen diffractometric urinary calculus analysis results based on the 5th and 6th East German trial].
The evaluation system suggested allows the results of urinary-calculi analysis centres to be compared after estimating the calculus stages present, the distinction between primary and secondary components and the deviation from normal composition. Afterwards the quality of the results of analysis of urinary calculi improved using the standard method.


Resonant modes and musical ratios in otoacoustic emissions.
The ratios between frequency components of evoked otoacoustic emissions (OAE) were investigated for 100 ears. The signals were decomposed by means of an adaptive approximation method into basic waveforms coming from a very large and redundant dictionary of Gabor functions. The high time-frequency resolution of the method and the parametric representation of the waveforms allowed for an estimation of the frequency ratios of the basic components. A repetitive occurrence of the "fifths", "fourths" and octaves connected with the Pythagorean temperament was found. The octaves containing "fifths" were identified. This kind of sequences in OAE tend to appear in the same form for tonal stimulations of different frequencies and for broadband stimuli. The significance of the results was confirmed by comparison to Monte Carlo simulations of the null hypothesis of random distribution of frequency modes. These findings support the resonance theory of hearing, which binds musical ratios with the geometrical spacing of outer hair cells in the cochlea.


Anatomical element localization by EDXS in Grevillea exul var. exul under nickel stress.
Grevillea exul var. exul, an endemic serpentinic Proteaceae of New Caledonia, was chosen to study the spatial distribution of Ni because this species supports strong content of metals, which can allow important absorptions thus detectable by microanalysis. Fine transversal sections of axenic G. exul var. exul plants grown during 15 days on nickel sulphate medium were examined by EDXS microanalysis. It showed that in Ni treated plants, Ni was concentrated mostly in the phloem compared to the xylem and the epidermis, either in roots or in the basal part of the stems and was mostly in the epidermis in the upper part of the stems and not detectable in the leaves. This metal took the place of P and K in the treated plants whereas the localization of these macroelements was quite uniform in control sections. We assume that a mechanism of phloem loading is implicated to restrict Ni accumulation in G. exul var. exul.


Differential Diagnosis of Bipolar II Disorder and Borderline Personality Disorder.
Differentiating bipolar (BP) disorders (in particular BP II) from borderline personality disorder (BPD) is a common diagnostic dilemma. We sought to critically examine recent studies that considered clinical differences between BP II and BPD, which might advance their delineation. Recent studies focused on differentiating biological parameters-genetics, epigenetics, diurnal rhythms, structural and functional neuroimaging-with indicative differences not yet sufficient to guide diagnosis. Key differentiating factors include family history, developmental antecedents, illness course, phenomenological differences in mood states, personality style and relationship factors. Less differentiating factors include impulsivity, neuropsychological profiles, gender distribution, comorbidity and treatment response. This review details parameters offering differentiation of BP II from BPD and should assist in resolving a frequent diagnostic dilemma. Future studies should specifically examine the BP II subtype directly with BPD, which would aid in sharpening the distinction between the disorders.


Biodegradation and flushing of MBT wastes.
Mechanical-biological treatment (MBT) processes are increasingly being adopted as a means of diverting biodegradable municipal waste (BMW) from landfill, for example to comply with the EU Landfill Directive. However, there is considerable uncertainty concerning the residual pollution potential of such wastes. This paper presents the results of laboratory experiments on two different MBT waste residues, carried out to investigate the remaining potential for the generation of greenhouse gases and the flushing of contaminants from these materials when landfilled. The potential for gas generation was found to be between 8% and 20% of that for raw MSW. Pretreatment of the waste reduced the potential for the release of organic carbon, ammoniacal nitrogen, and heavy metal contents into the leachate; and reduced the residual carbon remaining in the waste after final degradation from ∼320g/kg dry matter for raw MSW to between 183 and 195g/kg dry matter for the MBT wastes.


Erythropoietin and other blood-boosting methods.
Dating back to the earliest Olympics, athletes have been searching for a performance edge. Recombinant human erythropoietin was made commercially available in 1987 to treat various diseases associated with anemia. Within a few years, elite endurance athletes capitalized on its potential as an undetectable performance-enhancing agent. Although antidoping agencies have developed a test to detect its use, there are pitfalls. More importantly, athletes continue to add more sophisticated doping practices to their armamentarium, challenging regulatory agencies, putting their health at great risk, and tainting the spirit of fair competition.


Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2.
The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2. A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months. HbA1c improved in both treatment arms (pioglitazone: 7.52 +/- 0.85% to 6.71 +/- 0.89%, p < .0001; glimepiride: 7.44 +/- 0.89% to 6.83 +/- 0.85%, p < .0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 +/- 4.05 to 3.85 +/- 1.92, p < .0001) and remained unchanged in the glimepiride group. The microvascular response to heat significantly improved in both treatment groups (pioglitazone 48.5 [15.2; 91.8] to 88.8 [57.6; 124.1] arbitrary units [AU], p < .0001; glimepiride 53.7 [14.1; 91.9] to 87.9 [52.9, 131.0] AU, p < .0001, median [lower and upper quartile]). Endothelial function as measured with the acetylcholine response improved in the pioglitazone group (38.5 [22.2; 68.0] to 60.2 [36.9; 82.8], p = .0427) and remained unchanged in the glimepiride group. Improving metabolic control has beneficial effects in microvascular function in type 2 diabetic patients. Treatment of type 2 diabetic patients with pioglitazone exerts additional effects on endothelial function beyond metabolic control.


Protocolized Intervention for Children and Adolescents With Phagophobia.
We aimed to prospectively evaluate the effectiveness of a protocolized shaping intervention in children with phagophobia, which occurs when an aversive oral experience causes fear of swallowing and can result in restricted oral intake and weight loss. Twenty-one children (12 males) diagnosed with phagophobia (mean age 8.5 years) underwent initial medical workup and a pediatric psychologist driven shaping protocol. The outpatient protocol involved graduated food exposure with anxiety reduction strategies to eliminate anxiety and expand participants' diet. The participants completed an average of 6 treatment sessions. Post-treatment, there was a significant increase in weight, total number of foods consumed, and number of foods consumed across food groups and texture. Additionally, self-reported subjective units of distress were low for all participants throughout treatment. We conclude that after appropriate medical workup behavioral treatment is safe and efficacious in children with phagophobia and returns children to premorbid functioning and diet.


Female perspective. Interview by Sue Learner.
The problems women with diabetes encounter can be reduced through support from diabetes specialist nurses.


The effect of norflurazon on protein composition and chlorophyll organization in pigment-protein complex of photosystem II.
The pyridazinone-type herbicide norflurazon SAN 9789 inhibiting the biosynthesis of long-chain carotenoids results in significant decrease in PS II core complexes and content of light-harvesting complex (LHC) polypeptides in the 29.5-21 kDa region. The Chl a forms at 668, 676, and 690 nm that belong to LHC and antenna part of PS I disappear completely after treatment. The intensity of the Chl b form at 648 nm is sharply decreased in treated seedlings grown under 30 or 100 lx light intensity. The bands of carotenoid absorption at 421, 448 (Chl a), 452, 480, 492, 496 (beta-carotene), and 508 nm also disappear. The band shift from 740 to 720 nm and decrease in its intensity relative to the 687 nm emission peak in the low-temperature fluorescence spectrum (77 K) suggests a disturbance of energy transfer from LHC to the Chl a form at 710-712 nm.


Hybrid Chitosan-TiO2 Nanocomposite Impregnated in Type A-2186 Maxillofacial Silicone Subjected to Different Accelerated Aging Conditions: An Evaluation of Color Stability.
This study explores the impact of the incorporation of a chitosan-TiO2 nanocomposite on the color stability of pigmented room-temperature vulcanization maxillofacial silicone under various accelerated aging conditions. Five hundred disk-shaped specimens were formed with type A-2186 silicone elastomer, and they were distributed into groups based on pigment types and nanoparticle treatments. The color difference (ΔE) was assessed using a colorimeter in the CIELAB color system before and after exposure to aging conditions, including UV-accelerated aging and outdoor weathering. ANOVA, Dennett's T3, and Tukey HSD tests revealed significant color alterations across all silicone types, with the most pronounced being in the red-colored 3% chitosan specimens and the least pronounced being in the 2% TiO2 specimens that underwent UV-accelerated aging. Outdoor weathering consistently increased the ΔE values across all categories. This study suggests that while nanoparticles may offer some resistance against accelerated aging, they fall short in adequately defending against UV radiation during outdoor weathering.


Fix it, don't trash it: Ribosome maintenance by chaperone-mediated repair of damaged subunits.
Acute stressors or normal cellular function may result in ribosomal protein damage, which threatens the functional ribosome pool and translation. In this issue, Yang et al.1 show that chaperones can extract damaged ribosomal proteins and replace them with newly synthesized versions to repair mature ribosomes.


Physiologically based pharmacokinetic model for the renal clearance of phenolsulfonphthalein and the interaction with probenecid and salicyluric acid in the dog.
Plasma kinetics and renal excretion of intravenous phenolsulfonphthalein (PSP, 1.0 g), with and without concomitant administration of probenecid or salicyluric acid (SUA), were studied in the Beagle dog. Pharmacokinetic analysis revealed that tubular secretion is the predominant route of excretion, and that secretion is inhibited by probenecid and SUA. A physiologically based kidney model was developed that incorporates the functional characteristics of the kidney that determine the excretion of PSP, i.e., renal plasma flow, urine flow, nonlinear protein binding, glomerular filtration, tubular secretion, and tubular accumulation. The model enabled an accurate description and analysis of the measured plasma levels and renal excretion rates. The interaction with probenecid and SUA could be adequately described with the model by inhibition of the carrier-mediated uptake of PSP into the proximal tubular cells. However, both compounds clearly differed in their inhibitory action. Whereas probenecid showed simple competitive inhibition, for SUA a considerably more complex interaction (two-site competitive system) had to be taken into consideration. Especially in the interaction experiments, only satisfactory fits to the model were obtained when secretion was assumed to be dependent on unbound PSP concentrations. Model calculations showed that in the control experiments tubular secretion was accompanied by a pronounced accumulation of PSP within the proximal tubular cells, which was clearly diminished in presence of probenecid or SUA. The predicted accumulation ratios were in good agreement with previous studies.


Distinctive proliferative phase differences in gene expression in human myometrium and leiomyomata.
To gain a comprehensive view of the gene expression and regulation involved in uterine leiomyomata and matched normal myometrium using oligonucleotide microarray-based hybridization analysis. Retrospective analyses of tissue obtained in a prospective randomized clinical study. Academic institution. Seven patients with leiomyomata scheduled for surgery during the proliferative phase. Seven paired samples of leiomyomata and adjacent myometrium were obtained from patients undergoing hysterectomy. The total RNA extracted from leiomyomata and myometrium was used for gene expression profiling of 6800 human genes using high-density oligonucleotide microarrays. In addition, reverse transcriptase-semiquantitative polymerase chain reaction and immunohistochemistry were used to validate tumor-specific gene expression. A comparison of expression patterns in each paired sample revealed 68 genes significantly up- or down-regulated in each paired tissue sample, of which 23 genes showed increased expression and 45 showed decreased expression in leiomyomata compared with normal myometrium. Cluster analysis supported the relevance of these candidate genes for distinguishing between normal myometrium and leiomyomata biologic activity. Expression profiling of uterine leiomyomata using high-density oligonucleotide microarrays yields signature patterns that reflect the distinctive differences between normal human myometrium and leiomyomata during the proliferative phase. These observations suggest that a number of genes are involved in the tumorigenesis of leiomyomata.


Explaining Children's Life Outcomes: Parental Socioeconomic Status, Intelligence and Neurocognitive Factors in a Dynamic Life Cycle Model.
The goal of the present paper is to introduce a dynamic life cycle model that explains the reproduction of wealth and health over generations by introducing knowledge from cognitive neuroscience into the existing knowledge from the socioeconomic literature. The socioeconomic literature successfully identified the major role of socioeconomic status of parents, both as a direct and indirect effect, in the shaping and intergenerational reproduction of wealth and health. Furthermore, the importance of cognitive abilities as actor in this process has been widely studied in socioeconomic literature. A third factor that has been identified by the socioeconomic discipline is the so-called non-cognitive capabilities. This category, however, lacks a clear definition and seems to be a catchall for a collection of factors. Within the repository of these non-cognitive capabilities the construct of executive functions is an interesting and important contribution from cognitive neuroscience. The multidimensional construct of executive functioning or cognitive control (i.e. planning and formulation of objectives) and monitoring processes (i.e. influences the execution of these goals) is a valuable addition to a framework on reproduction of wealth and health over generations, because executive functions are sensitive to training. Merging insights of the socioeconomic literature and cognitive neuroscience in a life cycle model opens the opportunity of educational initiatives with regard to executive functions to break the intergenerational reproduction of poverty and deprivation.


Comparison of the phytotoxic activity of the phytotoxin destruxin B and four natural analogs.
A quantitative bioassay utilizing staining of plant cell suspension cultures of Sinapis alba was employed to establish a structure-phytotoxic activity correlation among destruxin B, homodestruxin B, and desmethyldestruxin B, toxins produced by Alternaria brassicae (Berk.) Sacc., the causative agent of Alternaria blackspot of brassicas. In addition, the phytotoxicity of destruxin B, homodestruxin B, and their respective metabolites hydroxydestruxin B and hydroxyhomodestruxin B were tested on resistant and susceptible plant species utilizing in planta leaf assays and leaf uptake of toxin solutions. Overall, the results obtained from punctured leaf and cell staining assays indicated that homodestruxin B (EC(50) 3x10(-4) M) was the most toxic of the five compounds, followed by destruxin B (EC(50) 5x10(-4) M), and desmethyldestruxin B (EC(50)&z.Gt;5x10(-4) M). On the other hand, the hydroxylated destruxins (hydroxydestruxin B EC(50)&z.Gt;5x10(-4) M) were significantly less phytotoxic than the parent toxins.


[Deinococcus radiodurans RecX and Escherichia coli RecX Proteins Are Able to Replace Each Other in vivo and in vitro].
A plasmid carrying the Deinococcus radiodurans recXgene under the control of a lactose promoter decreases the Escherichia coli cell resistance to UV irradiation and γ irradiation and also influences the conjugational recombination process. The D. radiodurans. RecX protein functions in the Escherichia coli cells similarly to the E. coli RecX protein. Isolated and purified D. radiodurans RecX and E. coli RecX proteins are able to replace each other interacting with the E. coli RecA and D. radiodurans RecA proteins in vitro. Data obtained demonstrated that regulatory interaction of RecA and RecX proteins preserves a high degree of conservatism despite all the differences in the recombination reparation system between E. coli and D. radiodurans.


Simultaneous bilateral fluorescein angiography of the retina and the iris in central retinal vein occlusion.
Twenty-two patients with a recently developed C.R.V.O. (central retinal vein occlusion) (symptoms: less than four weeks) are discussed. A delay in A.R.C.T. (arm to retina circulation time) in the affected eye was found in two patients with an ischaemic type of C.R.V.O. and in 3 patients with a non-ischaemic type of C.R.V.O. No side difference could be demonstrated in A.I.C.T. (arm to iris circulation time). Leakage of radial iris vessels on fluorescein angiography was found in 6 out of 7 patients with an ischaemic type of C.R.V.O. and in 2 out of 15 patients with a non-ischaemic type of C.R.V.O. Radial iris vessel leakage may be a helpful prognostic sign in C.R.V.O.


Gamma amino butyric acid (GABA) levels in hypophyseal stalk plasma of rats.
To determine the possible physiologic contribution of GABA to the tonic hypothalamic inhibition of adenohypophyseal prolactin secretion, we compared GABA levels in hypophyseal stalk plasma with those found in the peripheral circulation. Hypophyseal stalk blood was collected via a parapharyngeal approach from 8 urethane anesthetized diestrus rats. Peripheral blood was collected simultaneously from the external jugular vein of the same rat at a rate similar to hypophyseal stalk blood flow. Blood samples resulting from a single 4 hr collection per animal were centrifuged, and the plasma stored frozen before ethanol extraction and assay using a radioreceptor method. GABA levels in hypophyseal stalk plasma (909 +/- 171 pmol/ml; X +/- S.E.M.) were not significantly higher than levels in peripheral plasma (845 +/- 182; p greater than 0.05), indicating little or no secretion of GABA by the median eminence.


Interaction of the sarcin/ricin domain of 23 S ribosomal RNA with proteins L3 and L6.
We investigated interaction of an RNA domain covering the target site of alpha-sarcin and ricin (sarcin/ricin domain) of Escherichia coli 23 S rRNA with ribosomal proteins. RNA fragments comprising residues 2630-2788 (Tox-1) and residues 2640-2774 (Tox-2) of 23 S rRNA were transcribed in vitro and used to analyze the binding proteins by gel shift and filter binding. Protein L6 bound to both Tox-1 (Kd: 0.31 microM) and Tox-2 (Kd: 0.18 microM), and L3 bound only to Tox-1 (Kd: 0.069 microM) in a solution containing 10 mM MgCl2 and 175 mM KCl at 0 degreesC. Footprinting studies were performed using the chemical probe dimethyl sulfate on full-length 23 S rRNA. Binding of L6 protected a single base, A-2757, and strongly enhanced reactivity of C-2752. A direct role of A-2757 in the L6 binding was verified by site-directed mutagenesis; replacements of A-2757 with G and C impaired the L6 binding. On the other hand, binding of L3 protected A-2632, A-2634, A-2635, A-2675, A-2726, A-2733, A-2749, and A-2750. Interestingly, binding of L6 and L3 together protected additional bases A-2657, A-2662, C-2666, and C-2667 in the sarcin/ricin loop, in addition to A-2740, A-2741, A-2748, A-2753, A-2764, A-2765, and A-2766 in the other stem-loop. This appears to be due to cooperative interaction of L3 and L6 with the RNA. The results are discussed with respect to conformational modulation of the sarcin/ricin domain by the protein binding.


Maintenance Treatment with Opium Tincture: A Preliminary Qualitative Study of the Factors Related to Treatment entry.
The current preliminary study aimed to explore the reasons that a group of opiate-dependent patients reported for entry into opium tincture treatment (OTT). Through examinations of 52 qualitative focus group interviews with patients from six OTT centers and 10 health providers (in key informant interviews) in Tehran, this study highlights the factors that participants reported as the reasons associated with entry into OTT. Quantitative data including demographic data and details of drug use were analyzed by using SPSS.v.18.0. Qualitative data was analyzed by using Atlas-ti software. 86.5% of patients were male and 13.5% were female. The median age of patients was 39 yr. The most frequently reasons associated with entry into OTT included methadone misconceptions including dissatisfaction with taking methadone as a chemical medication, methadone dependence, and long duration of MMT. The other reasons included the recommendation of other people in treatment and OT-related characteristics and expectations including the herbal compound of OT, treating opiate craving and withdrawal symptoms, and improving general health. The study findings preliminarily showed the reasons associated with entry into OTT in a sample of treatment seekers. Longitudinal studies with more representative samples and follow-up stages are required to evaluate the clinical effectiveness of OTT as a maintenance treatment in comparison with methadone and buprenorphine. Patient-centered program and policy implications are discussed.


A data retrieval system for the eye clinic. I. Clinical aspects.
The use of a data retrieval system for patients' ophthalmic records is described. Input is by using simple forms and output is in batch. The system is adaptable for on-line use as soon as a terminal is established in the clinic. To date there are over 6000 patients on file, of whom about one half have no other form of ophthalmic medical record.


Outcomes of liver transplantation in children with Langerhans cell histiocytosis: Experience from a quaternary care center.
Langerhans cell histiocytosis (LCH) is a rare but important cause of end-stage liver disease in children. Conventional chemotherapeutic agents that are otherwise the standard-of-care in LCH may be counterproductive in patients with hepatic decompensation. Furthermore, the precise role of liver transplantation (LT) in the management of LCH remains unclear. Review of a prospectively collected database (January 2014 to December 2020) of children with liver disease was performed. All clinical details of patients with LCH managed at our center were collected and data analyzed. Based on the outcomes, a management algorithm was proposed. Of the eight (five male) patients referred to our unit, six (75%) underwent LT (four and two for compensated and decompensated cirrhosis, respectively). Median age at diagnosis of LCH was 25 (range: 9-48) months. Two patients, who had previously completed LCH-specific chemotherapy, underwent upfront LT for compensated cirrhosis. Other two patients with compensated cirrhosis showed evidence of active disease. They underwent LT following completion of chemotherapy. Two children with decompensated cirrhosis also had evidence of active disease and were started on modified chemotherapy Both of them had progression of liver disease while on chemotherapy. Hence, an urgent LT was performed which was followed by completion of chemotherapy in these patients. On a median follow-up of 30.5 (10.5-50) months, all post-LT patients were alive with stable graft function and showed no disease recurrence. We demonstrate that an algorithmic approach, along with newer chemotherapeutic agents, results in excellent outcomes in LCH patients with liver involvement. Larger multicentric studies on this rare disease are, however, needed to validate our findings.


A comparison of the portfolio low-carbohydrate diet and the ketogenic diet in overweight and obese women with polycystic ovary syndrome: study protocol for a randomized controlled trial.
Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine disorders among women of fertile age. Women with PCOS manifest clinical symptoms like menstrual dysfunction, hirsutism, insulin resistance, and hyperinsulinemia. As excessive amounts of insulin levels directly increase ovarian production of androgens, hyperinsulinemia and insulin resistance are considered as the pathogenesis factors of PCOS. The portfolio low-carbohydrate diet (PLCD) is a plant-based diet with 40% carbohydrates combined with five cholesterol-lowering foods and nutrients. On the other hand, the ketogenic diet (KD) is a nutritional protocol with 10% carbohydrates. The purpose of this study is to determine whether PLCD or KD is more effective in alleviating PCOS symptoms. Forty-six overweight or obese women diagnosed with PCOS will be randomly stratified to receive either PLCD or KD for 8 weeks. Measures related to anthropometric and body composition, glucose, and insulin level, HOMA-IR, sex hormones, lipid profile, quality of life, dietary intake, physical activity, and Ferriman-Gallwey score of all participants will be accessed before and after the intervention. Since the first line treatment of PCOS is lifestyle adjustment including diet control and exercise, there has not been determined the optimal diet for this population of women yet. Hence, the goal of conducting this study is to determine whether the PLCD or the KD could have more advantageous effects on attenuating PCOS manifestations. The result of this investigation will give us new insight into curing this disease and will provide evidence-based recommendations for prescribing an optimal diet for PCOS women. IRCT20200912048693N3, Trial registered 2022-12-14. https://www.irct.ir/trial/67548.


On the determination of the stereochemistry of semisynthetic natural product analogues using chiroptical spectroscopy: desulfurization of epidithiodioxopiperazine fungal metabolites.
Isolation and semisynthetic modification of the fungal metabolite chaetocin gave access to a desulfurized analogue of this natural product. Detailed chiroptical studies, comparing experimentally obtained optical rotation values, electronic circular dichroism spectra, and vibrational circular dichroism spectra to computationally simulated ones, reveal the desulfurization of chaetocin to unambiguously proceed with retention of configuration. Consideration of the plausible mechanisms for this process highlighted inconsistencies in the stereochemical assignment of related molecules in the literature. This in turn allowed the stereochemical reassignment of the natural product analogue dethiodehydrogliotoxin.


Lack of Cytosolic Carboxypeptidase 1 Leads to Subfertility due to the Reduced Number of Antral Follicles in pcd3J-/- Females.
Females homozygous for the Purkinje cell degeneration mutation (pcd) are fertile, although the success rate is much lower than in the wild type. We performed detailed analysis of reproductive abnormalities of pcd females. The number of oocytes produced following exogenous gonadotropin treatment was much lower in pcd3J-/- females than in pcd3J+/+ females. Furthermore, the estrous cyclicity of pcd3J-/- females according to the appearance of the vagina was almost undetectable comparing to that of the wild type. Histological analyses and follicle counting of 4- and 8-week-old pcd3J-/- ovaries showed an increase in the number of secondary follicles and a decrease in the number of antral follicles, indicating that AGTPBP1/ CCP1 plays an important role in the development of secondary follicles into antral follicles. Consistent with a previous analysis of the pcd cerebellum, pcd3J-/- ovaries also showed a clear increase in the level of polyglutamylation. Gene expression analysis showed that both oocytes and cumulus cells express CCP1. However, Ccp4 and CCP6, which can compensate the function of CCP1, were not expressed in mouse ovaries. Failure of microtubule deglutamylation did not affect the structure and function of the meiotic spindle in properly aligning chromosomes in the center of the nucleus during meiosis in pcd3J-/- females. We also showed that the pituitary-derived growth and reproduction-related endocrine system functions normally in pcd3J-/- mice. The results of this study provide insight into additional functions of CCP1, which cannot be fully explained by the side chain deglutamylation of microtubules alone.


An ecological perspective on marine reserves in prey-predator dynamics.
This paper describes a prey-predator type fishery model with prey dispersal in a two-patch environment, one of which is a free fishing zone and other is a protected zone. The existence of possible steady states, along with their local stability, is discussed. A geometric approach is used to derive the sufficient conditions for global stability of the system at the positive equilibrium. Relative size of the reserve is considered as control in order to study optimal sustainable yield policy. Subsequently, the optimal system is derived and then solved numerically using an iterative method with Runge-Kutta fourth-order scheme. Numerical simulations are carried out to illustrate the importance of marine reserve in fisheries management. It is noted that the marine protected area enables us to protect and restore multi-species ecosystem. The results illustrate that dynamics of the system is extremely interesting if simultaneous effects of a regulatory mechanism like marine reserve is coupled with harvesting effort. It is observed that the migration of the resource, from protected area to unprotected area and vice versa, is playing an important role towards the standing stock assessment in both the areas which ultimately control the harvesting efficiency and enhance the fishing stock up to some extent.


The public controversies of AIDS in Puerto Rico.
All articles using the word 'AIDS' that have appeared in the five major daily newspapers in Puerto Rico since 1982 were studied to analyze the way in which AIDS has been presented in the daily press. Virtually all of the articles regarding AIDS, at least those pertaining to Puerto Rico, presented controversies. These were of two kinds. Articles regarding prevalence, incidence, and sources of funding were presented as controversies between the two main political parties of the island. They can be considered extensions of other political arguments between the parties. Those regarding risk factors, prevention, and treatment were presented as controversies between representatives of the people, such as union leaders, and government officials. The victims of AIDS, the homosexuals, drug addicts and hemophiliacs, were generally left out of the controversies as participants. The controversies are generally nonmedical and nonscientific, suggesting that the public perceives insufficient interest on the part of medical and political leaders and is expropriating the problem. That the proposed solutions are directed more toward the victims than the causative organims is also characteristics of past epidemics.


Influence of dietary zinc on hepatic collagen and prolyl hydroxylase activity in alcoholic rats.
The effects of dietary zinc on hepatic collagen and prolyl hydroxylase activity in normal and alcoholic rats has been investigated in four groups of pair-fed male Wistar rats given either liquid ethanol or a control diet for 12 wk. Each group of pair-fed animals received a diet with a different zinc concentration (standard diet, 7.6 mg/L; low-zinc diet, 3.4 mg/L; zinc-supplemented diet, 76 mg/L; and zinc-extrasupplemented, 300 mg/L. There were no significant differences in hepatic collagen concentration and prolyl hydroxylase activity between alcoholic and normal rats receiving a standard diet (collagen, 77 +/- 5 and 73 +/- 6 micrograms/mg protein; and prolyl hydroxylase; 37 +/- 26 and 36 +/- 22 cpm/mg protein). Alcoholic rats fed a low-zinc diet showed increased prolyl hydroxylase activity (75 +/- 10 cpm/mg protein, p less than 0.05), although no changes in hepatic collagen (77 +/- 10 micrograms/mg protein) were observed in comparison with rats fed a standard alcoholic diet. By contrast, hepatic collagen was significantly lower in alcoholic rats fed a zinc-supplemented diet (66 +/- 4 and 63 +/- 3 micrograms/mg protein, p less than 0.05 and p less than 0.01, respectively), and hepatic prolyl hydroxylase activity was particularly lower in rats receiving zinc 300 mg/L (18 +/- 20 cpm/mg protein). Similar effects were observed in normal rats. We conclude that dietary zinc influences hepatic prolyl hydroxylase activity and collagen deposition in alcoholic rats, and in consequence, the control of dietary zinc is necessary to assess the effects of alcohol on collagen metabolism in rats.


Alternative glucose uptake mediated by β-catenin/RSK1 axis under stress stimuli in mammalian cells.
Cells adapt to stress conditions by increasing glucose uptake as cytoprotective strategy. The efficiency of glucose uptake is determined by the translocation of glucose transporters (GLUTs) from cytosolic vesicles to cellular membranes in many tissues and cells. GLUT translocation is tightly controlled by the activation of Tre-2/BUB2/CDC16 1 domain family 4 (TBC1D4) via its phosphorylation. The mechanisms of glucose uptake under stress conditions remain to be clarified. In this study, we surprisingly found that glucose uptake is apparently increased for the early response to three stress stimuli, glucose starvation and the exposure to lipopolysaccharide (LPS) or deoxynivalenol (DON). The stress-induced glucose uptake was mainly controlled by the increment of β-catenin level and the activation of RSK1. Mechanistically, β-catenin directly interacted with RSK1 and TBC1D4, acting as the scaffold protein to recruit activated RSK1 to promote the phosphorylation of TBC1D4. In addition, β-catenin was further stabilized due to the inhibition of GSK3β kinase activity which is caused by activated RSK1 phosphorylating GSK3β at Ser9. In general, this triple protein complex consisting of β-catenin, phosphorylated RSK1, and TBC1D4 were increased in the early response to these stress signals, and consequently, further promoted the phosphorylation of TBC1D4 to facilitate the translocation of GLUT4 to the cell membrane. Our study revealed that the β-catenin/RSK1 axis contributed to the increment of glucose uptake for cellular adaption to these stress conditions, shedding new insights into cellular energy utilization under stress.


Simultaneous measurement of H2O concentration and effective absorption optical path length under unknown optical path length condition based on a single spectral line.
Quantitative gas measurement under the condition of unknown optical path length is a challenge in laser absorption spectroscopy technology field. In this paper, we proposed a tunable diode laser absorption spectroscopy line shape analysis (TDLAS-LSA) method for simultaneous measurement of water vapor concentration and effective optical path length (EOPL) under unknown optical path conditions. A single H2O absorption line near 1383.9 nm (7226.02 cm-1) was selected, and its line strength, self-broadening coefficient and temperature-dependence coefficient were measured experimentally to improve the HITRAN databases. The Lorentz broadening and line area were accurately extracted by Hartmann-Tran profile (HTP) fitting, and the gas concentration and EOPL were calculated based on the spectral line shape analysis method. Eight concentrations of water vapor in the range of 146 ppm ∼ 4.39% were measured experimentally, and the maximum average deviation between the TDLAS-LSA method and the commercial sensor was less than 7.1%. Comparing the EOPL with mechanical measurement, the maximum deviation of multiple measurements is less than 5.7%. The results showed that the TDLAS-LSA method can effectively perform gas sensing under unknown optical path conditions, and has great application potential in low-cost, in-situ and multi-parameter simultaneous measurement.


Correlation of right ventricular volume using axial angulated ventriculography to known right ventricular cast volumes in infants and children with congenital heart disease.
To calculate right ventricular (RV) volumes from biplane cineangiography obtained in nonstandard views, regression equations were developed from RV casts of known volume. Volumes were calculated using Simpson's rule from casts ranging from 2 to 42 ml from 25 postmortem specimens with various congenital heart diseases. The casts were divided into 2 groups: group 1 (n = 15) with abnormal or group 2 (n = 10) with normal RV hemodynamic measurements. Biplane cinegrams were taken in the anterolateral, anterior and long axis oblique, hepatoclavicular and sitting up projections. The true volume of each cast was determined from its weight and specific gravity. Excellent correlations were obtained between measured and true volumes (r = 0.92 to 0.96) in all projections, although each projection overestimated the true volume (slope value less than 1). The regression equations obtained from group 1 were not statistically different from those in group 2 in any view. Although the application of different regression equations is required in measuring RV volumes by multiple angulated angiography, these regression equations appear not to be affected by the hemodynamic state of the ventricle. These results are important in assessing RV volume in pediatric patients with congenital heart disease using axial angulated ventriculography.


Some suggestions for teaching about cooperation between social work and general practice. From the Standing Liaison Committee of the Royal College of General Practitioners and the British Association of Social Workers.
This discussion document emphasizes the importance of co-operation between general practitioners and social workers during their training. Sample aims and objectives suitable for trainees in both professions are listed and discussed.


Toxic effects of single animal hormones and their mixtures on the growth of Chlorella vulgaris and Scenedesmus armatus.
In their environments, aquatic organisms are simultaneously exposed to mixtures of several endocrine disrupting compounds, including hormones. However, most of the toxicity studies so far focused on effects of single contaminants. The available information on the potential toxicity of combined hormones on microalgae is extremely limited. For these reasons the aim of this study was to evaluate the individual and mixture effect of estrone (E1), ß-estradiol (E2), estriol (E3), 17-α-ethinylestradiol (EE2), progesterone (PRO), 5-pregnen-3β-ol-20-one (PRE), levonorgestrel (LG) and testosterone (TST) on Chlorella vulgaris and Scenedesmus armatus. Green algae cells were exposed to different concentrations (0.1-100 mg L-1) of hormones for 14 days. Biomass in the form of dry weight and chlorophyll a was examined. The decreasing order of toxicity (based on EC50, 14d) to Chlorella vulgaris and Scenedesmus armatus was: EE2>PRO > E2>PRE > TST > E3>LG > E1 and EE2>PRO > TST > E2>PRE > LG > E1>E3, respectively. Chlorella vulgaris was more sensitive to the effects of hormones than Scenedesmus armatus. Although mixed hormones were more toxic to green algae than single hormones, in the ecosystem mixtures can pose higher ecological risk than single pollutants. Therefore, data on the toxicology of both single and mixed hormones is very valuable for assessment of the possibility of adverse ecological effects caused by these pollutants. Furthermore, these results suggest that environmental exposure to hormone mixtures may cause toxicity levels different to the sum of those of the single hormones and provides a basic understanding of their toxic effect on algae.


Epidemiology of Pseudomonas aeruginosa infection and the role of contamination of the environment in a cystic fibrosis clinic.
In order to identify the possible reservoirs and routes of cross-infection with Pseudomonas aeruginosa, samples from patients, staff, and the environment of a cystic fibrosis centre and two control wards at an infectious disease clinic were collected during a two-week period in 1980. All the Ps. aeruginosa strains were phage and serotyped. Ps. aeruginosa was isolated from 90 (51%) of the cystic fibrosis patients and most belonged to the 0-3/9 complex, characteristic of strains from patients in the centre. Some of the patients were able to spread Ps. aeruginosa into the air and to their hands by coughing, and Ps. aeruginosa in dried sputum could survive for at least one week. Strains of the same epidemiological types as found in the cystic fibrosis patients were isolated from sinks, soap, baths, toys, tables, brushes, cloths, and air in the clinic. In contrast, Ps. aeruginosa of the same epidemiological types were only found in a few of the sinks in one of the control wards where a few cystic fibrosis patients were regularly treated in isolation cubicles. The precautions employed to prevent future cross-infection include segregation of Ps. aeruginosa-infected from non-infected patients in separate wards and arranging for visits on separate days in the out-patients clinic. The survival of cystic fibrosis patients treated in the centre is much longer than those treated outside the centre despite the problems of cross-infection.


Effects of preoptic area lesions on muramyl dipeptide-induced sleep and fever.
Lesions of the preoptic area of rabbits caused hyperthermia, although they did not alter sleep-coupled changes in brain temperature, and reduced slow-wave sleep, rapid eye movement sleep, and amplitudes of electroencephalographic slow waves during slow wave sleep. The direction and magnitude of the muramyl dipeptide-induced responses were similar before and after the lesions, although the baseline values upon which the changes were superimposed had shifted.


The clinicopathological, ultrastructural, genetic features and diagnosis of small cell variant renal oncocytoma.
The small cell variant renal oncocytoma is until now a rarely described and easily misdiagnosed subtype of renal oncocytoma. The tissue morphology, immunohistochemical profile, ultrastructural and molecular characteristics of four cases of small cell variant renal oncocytoma were analyzed and the literature was reviewed. The patients were three women and one man with ages ranging from 51 to 76 years. The size of the tumors ranged from 3 to 8.5 cm in diameter. The follow-up duration ranged from 6 to 58 months. All patients lived uneventfully without tumor recurrence or metastasis. The tumors were grayish yellow to brown, well demarcated, with a central scar or cystic change. Microscopically, the tumor was arranged in lobular structure containing dense small acini or tubular structures, with small cells featuring weak eosinophilic and scant cytoplasm, small round nuclei and inconspicuous nucleoli. No mitotic figures or necrosis were discerned. The immunohistochemical profile of small cell variant of renal oncocytoma is partially consistent with classic oncocytoma, expressing EMA, CK18, CD117 and E-cad. However, MITO and S-100A1 were intensively expressed in classic RO, but neither of them was expressed in small cell variant RO. Ultrastructurally, a small number of organelles was revealed in the tumor cell, including a few mitochondria, lysosomes and microvilli, less than those in the classic oncocytoma. No genetic aberrations were found in all cases regardless of clinicopathological characteristics and tissue types. Small cell variant renal oncocytoma of the kidney is frequently difficult to be differentiated from other benign and malignant small cell tumors with eosinophilic cytoplasm. The immunohistochemical profile, ultrastructural and genetic features of the tumor are integrally presented here for the first time. Acquaintance with the special characteristics of the tumor could facilitate the correct diagnosis of the tumor.


The lag of cerebral hemodynamics with rapidly alternating periodic stimulation: modeling for functional MRI.
A mathematical model that characterizes the response of venous oxygenation to changes in cerebral blood flow (rCBF) and oxygen consumption has been previously presented. We use this model to examine the dampening phenomenon in functional MRI (fMRI) signals with rapidly alternating periodic stimulation bursts. Using a mass balance approach, the equations for an input-output model are derived and solved using Matlab (the Math Works Inc.). Changes in venous oxygenation are related to the results of fMRI experiments using progressively shorter periods of stimulation. An impulse-response function for the model is derived in an attempt to explore the source of the lag in cerebral hemodynamics. Increasing the frequency of stimulation bursts eventually produces a dampening in the fMRI signal. The dampening phenomenon in fMRI signals occurs with stimulation of high frequency on-off alternation. The dynamics of signal dampening, as well as the impulse-response function of a blood oxygen level-dependent model, lend strong indirect support to the hypothesis that blood oxygen level-dependent contrast at the level of the venous blood pool, rather than R1 inflow effects or changes in oxygenation at the level of the capillary bed, underlies the observed signal changes in fMRI.


Luteal phase support post IVF: individualized early stop.
While the need for progesterone-based luteal phase support is well documented, the required treatment duration is not well established, and a practitioners' survey showed a wide range of empiric stopping points. It is suggested that an early stop can be based on assessing endogenous luteal activity on the day of pregnancy test. To examine this approach, data were retrospectively collected on 99 patients with positive pregnancy test and high serum concentrations of oestradiol and progesterone (≥ 1000 pmol/l and ≥ 110 nmol/l, respectively), whose luteal support was stopped, and compared with those of 85 patients who did not meet the above criteria, and so luteal support was continued until gestational week 9. Both groups were comparable in terms of live birth and miscarriage rates. We conclude that in the face of strong endogenous luteal activity, exogenous support can be stopped on pregnancy test day, without affecting pregnancy outcome. Further research is needed to substantiate this finding.


Subcellular localisation of di- and tripeptidases in guinea pig and rat enterocytes.
Enterocytes were isolated from rat and guinea pig jejunum and subcellular fractions were prepared by density gradient centrifugation. Gradient fractions were assayed for principal organelle marker enzymes and for di- and tripeptidases. The hydrolases showed a dual localisation with both brush border and cytosol components. In the rat, approximately equal portions of dipeptidase activities were found in the two fractions but, in the guinea pig, three times more activity were found in the two fractions but, in the guinea pig, three times more activity was found in the soluble than in the brush border fractions. Cytosol components in the rat were markedly inhibited by p-hydroxymercuribenzoate. In both species tripeptidase, leucyl-2-naphthylamidases and gamma-glutamyltransferase activities were found predominantly in the brush border fractions.


Threshold Amsler grid testing in maculopathies.
The Amsler grid is a suprathreshold target and thus may fail to detect relative scotomas. If the grid is viewed through two cross-polarizing filters creating low luminance conditions (threshold Amsler grid testing) the test is far more sensitive. Ten patients with disorders of the macula with normal standard white Amsler grid testing were studied with three other Amsler grid tests. Of the 15 involved eyes, 12 had visual field defects present with threshold Amsler grid testing. Tangent screen examination showed defects in 10 of these 12 eyes. The two red grids used were not as sensitive as the threshold grid. Three eyes had metamorphopsia with the white grid which became the site of a visual field defect with threshold testing. Threshold Amsler grid testing is a rapid and sensitive technique for the evaluation of the central 10 degrees of visual field in patients with maculopathies.


The Immune Fulcrum: Regulatory T Cells Tip the Balance Between Pro- and Anti-inflammatory Outcomes upon Infection.
Regulatory T cells (Tregs) are indispensable for immune homeostasis and the prevention of autoimmunity. In the context of infectious diseases, Tregs are multidimensional. Here, we describe how they may potentiate effector responses by assisting in recruitment of T cells into the infection site to resolve infection, facilitate accelerated antigen-specific memory responses, limit pathology, and contribute to disease resolution and healing, to the great benefit of the host. We also explore the villainous functions of Tregs during infection by reviewing several diseases in which the depletion or reduction in Treg frequency allows for better generation of effector memory, and results in acute resolution of infection, as opposed to chronicity or severe long-term outcomes. We describe findings generated using mouse models of infection as well as experiments performed using human cells and tissues. We propose that Tregs represent an immunologic fulcrum, promoting both pathogen clearance and damage control by preventing excessive destruction of infected tissues though unchecked immune responses.


Risk Factors for Prolonged Intertwin Delivery Interval and Associated Maternal and Second Twin Morbidity.
This work aimed to identify possible risk factors and the morbidity associated with prolonged intertwin delivery interval (IDI). A retrospective cohort study at a single tertiary care center. Women with twin gestations who reached the second stage of labor between January 2010 and December 2019 were included in the study. Demographic and clinical characteristics were compared between short IDI (≤15 minutes) and prolonged IDI (>15 minutes). The primary outcome was the rate of 5-minute Apgar score ≤ 7. A total of 461 women were included; 312 of whom were in the short IDI group and 149 were in the prolonged IDI group. Rates of 5-minute Apgar score ≤ 7 and neonatal acidemia were significantly higher in the prolonged IDI group (3.5 vs. 9.7%, p = 0.008; 4.3 vs. 15.7%, p = 0.01, respectively). Vaginal delivery was less likely to occur in the prolonged IDI group (75.8 vs. 93.3%). Placental abruption and hemoglobin drop ≥ 3 g/dL were more prevalent in the prolonged IDI group (4 vs. 1%, p = 0.03; 39.1 vs. 24.7%, p = 0.01, respectively). In the multivariate analysis, age ≥ 30 years (adjusted odds ratio [aOR]: 1.76, p = 0.01), nulliparity (aOR: 1.66, p = 0.03), and birth weight ratio ≥ 1.2 (aOR: 1.92, p < 0.05) were associated with prolonged IDI. Prolonged IDI is associated with an increased risk for neonatal acidemia and low 5-minute Apgar score, and with an increased rate of cesarean delivery, placental abruption, and hemoglobin drop ≥ 3 g/dL. Advanced maternal age, nulliparity, and twin birth weight ratio ≥ 1.2 are associated with prolonged IDI. · Prolonged was found to be associated with higher neonatal acidemia and lower 5-minute Apgar score.. · Prolonged IDI is also associated with increased rate of cesarean delivery, placental abruption, and blood loss.. · Advanced maternal age, birth weight discordancy, and nulliparity were associated with prolonged IDI..


Everolimus in hormone receptor-positive advanced breast cancer: targeting receptor-based mechanisms of resistance.
Although patients with hormone receptor (HR)-positive breast cancer are successfully treated with endocrine therapy, many tumors go on to develop resistance to these agents. Studies have determined that mechanisms of resistance to endocrine therapy are quite complex and can involve a multitude of signal transduction pathways, either through direct association with the estrogen receptor or through cross-talk with other pathways. Preclinical studies have suggested the therapeutic importance of the mammalian target of rapamycin (mTOR) pathway and that inhibiting this pathway may restore sensitivity to endocrine therapy. The oral mTOR inhibitor everolimus has been extensively studied for breast cancer. Clinical studies suggest that everolimus in combination with endocrine therapy improves progression-free survival and is well tolerated. A combined approach, targeting both mTOR signal transduction and the HR pathways, promises to take clinical research in a new direction for the treatment of HR-positive advanced breast cancer.


Absence of genotoxic effects of metronidazole and two of its urinary metabolites on human lymphocytes in vitro.
The antiprotozoan agent metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) and two of its major human urinary excretion products, 2-methyl-5-nitromidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole were tested for genotoxic activity in human lymphocytes in vitro by analysis of chromosome aberrations, sister-chromatid exchanges and DNA-repair synthesis. The positive control compounds methyl methanesulphonate (MMS) and nitrogen mustard (HN2) showed significant genotoxic activity in these tests. No such activity of metronidazole and its two metabolites was detected in concentrations up to 1000 microgram/ml (5.8 X 10(-3) M). Nor did these 3 compounds influence DNA-repair synthesis induced by MMS and HN2. These results suggest that metronidazole, 2-methyl-5-nitroimidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole have no direct genotoxic effect on human lymphocytes in vitro.


Screening for novel hexanucleotide repeat expansions at ALS- and FTD-associated loci.
To determine whether GGGGCC (G4C2) repeat expansions at loci other than C9orf72 serve as common causes of amyotrophic lateral sclerosis (ALS). We assessed G4C2 repeat number in 28 genes near known ALS and frontotemporal dementia (FTD) loci by repeat-primed PCR coupled with fluorescent fragment analysis in 199 patients with ALS (17 familial, 182 sporadic) and 136 healthy controls. We also obtained blood from patients with ALS4 for evaluation of repeats surrounding the SETX gene locus. C9orf72 expansions were evaluated in parallel. Expansions of G4C2 repeats in C9orf72 explained 8.8% of sporadic and 47% of familial ALS cases analyzed. Repeat variance was observed at one other locus, RGS14, but no large expansions were observed, and repeat sizes were not different between cases and controls. No G4C2 repeat expansions were identified at other ALS or FTD risk loci or in ALS4 cases. G4C2 expansions near known ALS and FTD loci other than C9orf72 are not a common cause of ALS.


[Accelerated senescence of armed conflicts participants suffering from the consequences of war cranial-cerebral trauma and alcoholism].
The matter under studies was the way accelerated senescence of armed conflicts participants with brain injuries depends on alcohol addiction developed after the injuries and on dysfunction of neurohumoral regulation of heart activity. It has been established that the posttraumatic alcohol addiction considerably activates the processes of accelerated senescence and lipid peroxidation connected with it, depresses the system of antioxidant protection and enhances the progress of dysfunctions in neurohumoral regulation of heart activity.


No-Touch Multi-bipolar Radiofrequency Ablation for the Treatment of Subcapsular Hepatocellular Carcinoma ≤ 5 cm Not Puncturable via the Non-tumorous Liver Parenchyma.
The percutaneous ablation of subcapsular hepatocellular carcinoma (S-HCC) may involve a risk of complications such as hemorrhage and tumor seeding, mainly linked to the direct tumor puncture often inevitable with mono-applicator ablation devices. The purpose of this study was to assess the efficacy and safety of no-touch multi-bipolar radiofrequency ablation (NTMBP-RFA) for the treatment of S-HCC ≤ 5 cm not puncturable via the non-tumorous liver parenchyma. Between September 2007 and December 2014, 58 consecutive patients (median age: 63 years [46-86], nine females) with 59 S-HCC ≤ 5 cm (median diameter: 25 mm [10-50 mm]), not puncturable via the non-tumorous liver parenchyma, were treated with NTMBP-RFA. Response and follow-up were assessed by CT or MRI. Complications were graded using the Cardiovascular and Interventional Radiological Society of Europe classification. Overall local tumor progression (OLTP)-free survival was assessed using the Kaplan-Meier method. A Cox proportional model evaluated the factors associated with OLTP. Signs of peritoneal or parietal tumor seeding were noted during follow-up imaging studies. A complete ablation was achieved in 57/58 patients (98.3%) after one (n = 51) or two (n = 6) procedures. Three patients (5.2%) experienced complications (sepsis, cirrhosis decompensation; CIRSE grade 2 or 3). After a median follow-up period of 30.5 months [1-97], no patients had tumor seeding. The 1, 2 and 3-year OLTP-free survival rates were 98%, 94% and 91%, respectively. No factors were associated with OLTP. NTMBP-RFA is a safe and effective treatment for S-HCC not puncturable via the non-tumorous liver parenchyma.


Impact of the novel powered circular stapler on risk of anastomotic leakage in colorectal anastomosis: a propensity score-matched study.
Several risk factors for anastomotic leakage (AL) following colorectal surgery have been described. Improvement in devices for performing anastomosis is a modifiable factor that could reduce AL rates. The aim of this study was to assess the impact of technical improvements in the Echelon Circular™ powered stapler (ECPS) on the left-sided colorectal AL rate compared to current manual circular staplers (MCS). A cohort study was carried out on consecutive patients between January 2017 and February 2020 in whom left-sided stapled colorectal anastomosis above 5 cm from anal verge was performed. The primary end point was the risk of AL depending on the type of circular stapler used. The ECPS cases were matched to MCS cases by propensity score matching to obtain comparable groups of patients. Two hundred seventy-nine patients met the inclusion criteria. A MCS anastomosis was performed in 218 patients and ECPS anastomosis in 61 (21.9%). Overall, AL was observed in 25 (9%) cases. Factors significantly associated with AL were American Society of Anesthesiologists score (p = 0.025) and type of circular stapler used (p = 0.021). After adjusting the cases with propensity score matching (119 cases MCS versus 60 ECPS), AL was observed in 14 (11.8%) patients in MCS group and in 1 (1.7%) patient in the ECPS group (p = 0.022). AL in the MCS group required reoperation in seven cases (5.8%), the remaining seven patients were treated conservatively. The patient in the ECSP group required an urgent Hartmann's procedure CONCLUSIONS: The ECPS device could have a positive impact by reducing AL rates in left-sided colorectal anastomosis. Multicenter controlled trials are needed for stronger evidence to change practice.


Clinical Characteristics, Quality of Life, and Risk Factors of Amputation Stump Skin Disease and Stump Fungal Infection in Adult Amputees in Shanghai, China.
The stump site of amputees is clinically vulnerable and prone to various skin diseases. Data regarding the impact on quality of life (QoL) of amputees with amputation stump skin disease (ASSD) and risk factors of ASSD and stump fungal infection in the Shanghai area are yet unknown. This study aims to evaluate the QoL of amputees with ASSD and explore the risk factors of ASSD and stump fungal infection in the Shanghai area. A total of 104 amputees from Shanghai Hebin Rehabilitation Hospital, Otto Bock (China) Industries Co., Ltd., Shanghai Tongji Hospital, and Shanghai Rehabilitation and Vocational Training Center for the Disabled were enrolled in this study. We collected demographic, clinical, and skin fungal examination data from these amputees from April 2015 to May 2021. Dermatology life quality index (DLQI) questionnaire was used to evaluate the QoL. The risk factors for ASSD and fungal skin infection were analyzed by the univariate analyses. The median age of the 104 amputees was 57.9 ± 11.9 years with an average amputation time of 17.7 ± 15.1 years, and 73% of cases were men. The mean DLQI score of amputees with ASSD was13.6, suggesting the severe impairment of QoL. Among amputees, 41 (39.4%) had confirmed ASSD, of whom 24 (58.5%) suffered from fungal skin infection and the remaining were subjected to intertriginous dermatitis and eczema (22%), cutaneous keratosis (12.2%), and others (7.3%). Aspergillus (50.0%) was the most common species. The other fungal organisms included Trichophyton rubrum (33.3%), Candida krusei (8.3%), T. mentagrophytes (4.2%), and C. albicans (4.2%). ASSD rather than non-ASSD was more common in men (80.4%) and summer (46.3%). Summer (OR = 3.31, 95% CI = 1.19-9.17) was an established risk factor for ASSD compared to spring. The daily artificial limb wearing time > 8 h was associated with stump fungal infection. The QoL of amputees with ASSD was severely affected and the ASSD was characterized by fungal infection (tinea), intertriginous dermatitis, eczema, and skin keratosis. Summer and daily prosthesis wearing > 8 h was a risk factor for ASSD. Aspergillus was the most common fungal species, especially when the stump was exposed in summer.


Effects of high-intensity focused ultrasound combined with levonorgestrel-releasing intrauterine system on patients with adenomyosis.
It is very important to treat adenomyosis which may cause infertility, menorrhagia, and dysmenorrhea for women at the reproductive age. High-intensity focused ultrasound (HIFU) is effective in destroying target tumor tissues without damaging the path of the ultrasound beam and surrounding normal tissues. The levonorgestrel-releasing intrauterine system (LN-IUS) is a medical system which is inserted into the uterine to provide medicinal treatment for temporary control of the symptoms caused by adenomyosis. This study was to investigate the effect of HIFU combined with the LN-IUS on adenomyosis. In the HIFU treatment, the parameters of the ultrasound were transmission frequency 0.8 MHz and input power 50-400 W (350 ± 30), and the temperature in the target tissue under these conditions would reach 60-100 °C (85 °C ± 6.3 °C). Size reduction and blood flow signal decrease were used to assess the effect of combined treatment. In this study, 131 patients with adenomyosis treated with HIFU combined with LN-IUS were retrospectively enrolled. The clinical and follow-up data were analyzed. After treatment, the volume of the uterine lesion was significantly decreased with an effective rate of 72.1%, and the adenomyosis blood flow signals were significantly reduced, with an effective rate of 71.3%. At six months, the menstrual cycle was significantly (P < 0.05) decreased from 31.4 ± 3.5 days before treatment to 28.6 ± 1.9 days, the menstrual period was significantly shortened from 7.9 ± 1.2 days before HIFU to 6.5 ± 1.3 days, and the menstrual volume was significantly (P < 0.05) decreased from 100 to 49% ± 13%. The serum hemoglobin significantly (P < 0.05) increased from 90.8 ± 6.2 g/L before treatment to 121.6 ± 10.8 g/L at six months for patients with anemia. Among seventy-two (92.3%) patients who finished the six-month follow-up, sixty-five (90.3%) patients had the dysmenorrhea completely relieved, and the other seven (9.7%) patients had only slight dysmenorrhea which did not affect their daily life. Adverse events occurred in 24 (18.3%) patients without causing severe consequences, including skin burns in two (1.5%) patients, skin swelling in four (3.1%), mild lower abdominal pain and low fever in 15 (11.5%), and subcutaneous induration in three (2.3%). Six months after treatment, no other serious side effects occurred in any patients with follow-up. In conclusions, the use of high-intensity focused ultrasound combined with the levonorgestrel-releasing intrauterine system for the treatment of adenomyosis is safe and effective even though the long-term effect remains to be confirmed.


Simultaneous purification of nitrile hydratase and amidase of Alcaligenes sp. MTCC 10674.
Alcaligenes sp. MTCC 10674 has a bienzymatic system for the hydrolysis of nitriles. The nitrile hydratase and amidase have been purified simultaneously to homogeneity using a combination of (NH)4SO4 precipitation, ion exchange chromatography and gel permeation chromatography. Nitrile hydratase and amidase have molecular weight of 47 and 114 kDa, respectively and exist as heterodimer. Optimum temperatures for maximum activity of nitrile hydratase and amidase were 15 °C (2.4 U/mg protein) and 45 °C (2.3 U/mg protein), respectively. Nitrile hydratase showed maximum 7.8 U/mg protein at 50 mM acrylonitrile and amidase has 9.2 U/mg protein at 25 mM propionamide. Nitrile hydratase has Vmax 10 μmol/min/mg and Km 40 mM, while amidase has Vmax 12.5 μmol/min/mg and Km 45.5 mM, respectively. Heavy metal ions Hg2+, Ag+, Pb2+ and Cu2+ were strong inhibitors of nitrile hydratase and amidase activity.


Exponential electrophysiological aging: P3 latency.
Forty-nine normal volunteer subjects ranging in age from 15 to 80 years were studied in an 'auditory oddball' event-related potential paradigm. In certain respects our results replicate other studies, finding significant correlations between age and both N2 and P3 latency. Slopes of the linear age/ERP latency regression function increased with component number (i.e., N1 less than P2 less than N2 less than P3). Further analysis disclosed that the age/ERP component latency relationship is non-linear. Separate age/ERP component latency linear regression functions were computed for subjects 15-45 and 46-80. None of these functions were significant for subjects under 45. Age/latency slopes were significant in the older group for P2, N2 and P3. The age/P3 latency slope for the subjects under 45 was 0.53 msec/year, versus 3.14 msec/year for the subjects over 45. The data for P3 latency and age are best fitted with a curvilinear first and second degree orthogonal polynomial, which describes a positively accelerating latency increase with age. Clinical implications of the form of the age/P3 latency regression function (curvilinear vs. linear) are discussed.


Elements of care: nursing environmental theory in historical context.
The natural elements ether, fire, air, water, and earth foundational to many healing traditions are also present in nursing history. Regulation of these elements can be traced to 19th-century nurses' "sickroom management." Nightingale's Notes on Nursing and Coskery's Advices Concerning the Sick provide examples of holistic application of the elements of care.


Obesogenic diet and metabolic syndrome among adolescents in India: data-driven cluster analysis.
Metabolic syndrome is on the rise in India and is primarily linked to obesogenic dietary habits. The synergy of both is a prominent risk factor for cardiovascular diseases (CVDs). Hence, the present study aims to unveil clusters at high risk of metabolic syndrome and ascertain cluster characteristics based on dietary patterns among adolescents aged 10-19 years. The study utilizes secondary data, i.e., Comprehensive National Nutrition Survey conducted in 2016-18. The study sample includes children and adolescents aged 10-19 years. An unsupervised learning algorithm was used to ascertain possible clusters in the data based on individuals' dietary patterns. The k-means were used to cluster the data according to their dietary patterns. To determine the number of clusters elbow method was used, and appropriate validation indices were also obtained for the final k. Further, to ascertain the distribution of the obesogenic dietary patterns and metabolic conditions in each cluster was analysed. Bivariate descriptive analysis was used to draw further inferences. The k-means clusters identified five optimum clusters based on 12,318 adolescents (6333 males (mean age:14.2 ± 2.8) and 5985 females (mean age:14.3 ± 2.8)) 17 dietary patterns. Clusters were named based on how prudent these were in terms of consuming a healthy diet. Cluster phenotypic characteristics were defined as follows: a cluster of obesogenic diets (24%) constituted the highest proportion of the total sample and was significantly suffering from obesity (p < 0.001), and greater proportions of lipid anomalies (p = 0.51) and hypertension (p = 0.44) but not statistically significant. In contrast, 21% of the sample comprised a plant-based diet cluster and suffered from all deficiencies but folate (p = 0.625), zinc (p = 0.132), and greater proportion from obesity (p = 0.19; not significant), and diabetes (p < 0.001). A cluster of "convenient" (20%) mainly suffered from lipid anomalies (p = 0.00), diabetes (p = 0.03), and a greater proportion from hypertension (p = 0.56) with deficiencies of all the essential vitamins and minerals but significantly from vitamin A (p < 0.001), folate (p < 0.001), and iron (p = 0.017). Lastly, the cluster of those who follow a "Western diet" (17%) was found to have lipid anomalies (p = 0.003), diabetes (p = 0.016), greater proportion of vitamin B12 (p = 0.136), D (p = 0.002), folate (p < 0.001), and iron deficiencies (p = 0.013). Adolescents in India show a strong association between obesogenic diet and metabolic syndrome. Therefore, the burden of metabolic syndrome at early ages can be prevented by controlling obesogenic dietary practices and addressing micronutrient deficiencies. This may be done by targeted health promotional campaigns in schools and college-going populations in India.


Effect of hemodialysis on protein C levels.
The immunological functions of antithrombin III and protein C were studied in 8 patients before, during and after hemodialysis. After dialysis a significant decrease in protein C and antithrombin III levels was seen. The changes observed in both proteins after hemodialysis should be considered as a component in the genesis of the hypercoagulation state in these patients.


Effect of prostacyclin on myogenic activity and adrenergic neuroeffector interaction in canine isolated veins.
In isolated strips of canine mesenteric vein prostacyclin (PGI2) causes a dose-dependent depression of the amplitude of the spontaneous rhythmic contractions without influencing their frequency. This suggests that prostacyclin affects the events leading from the depolarization of the smooth muscle cells to their contractions, rather than the induction of the myogenic activity itself. Furthermore, prostacyclin reduces the noradrenaline-induced contraction of the canine saphenous vein without affecting the electrically induced responses, suggesting a possible dual effect of the drug: at the smooth muscle it causes depression of the responsiveness to noradrenaline whereas at the adrenergic nerve endings it enhances the evoked release of the adrenergic transmitter.


Coordinated changes in gene expression, H1 variant distribution and genome 3D conformation in response to H1 depletion.
Up to seven members of the histone H1 family may contribute to chromatin compaction and its regulation in human somatic cells. In breast cancer cells, knock-down of multiple H1 variants deregulates many genes, promotes the appearance of genome-wide accessibility sites and triggers an interferon response via activation of heterochromatic repeats. However, how these changes in the expression profile relate to the re-distribution of H1 variants as well as to genome conformational changes have not been yet studied. Here, we combined ChIP-seq of five endogenous H1 variants with Chromosome Conformation Capture analysis in wild-type and H1.2/H1.4 knock-down T47D cells. The results indicate that H1 variants coexist in the genome in two large groups depending on the local GC content and that their distribution is robust with respect to H1 depletion. Despite the small changes in H1 variants distribution, knock-down of H1 translated into more isolated but de-compacted chromatin structures at the scale of topologically associating domains (TADs). Such changes in TAD structure correlated with a coordinated gene expression response of their resident genes. This is the first report describing simultaneous profiling of five endogenous H1 variants and giving functional evidence of genome topology alterations upon H1 depletion in human cancer cells.


Targeting the Residual Leukemia Cells after Chemotherapy.
One of the biggest challenges in treating acute myeloid leukemia (AML) is relapse of aggressive disease after treatment. In this issue of Cancer Cell, Boyd et al. characterize a molecularly distinct population of chemotherapy-induced transient leukemic regenerating cells (LRCs), which can be exploited to prevent AML recurrence.


Mass screening for neuroblastoma at 6 months of age: difficult to justify.
A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data. The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area. From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084). These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.