Association between remnant cholesterol and heart failure: A prospective cohort study.
Elevated remnant cholesterol (RC) is associated with a higher risk of various cardiac diseases. Heart failure (HF) usually occurs at the end stage of various cardiac diseases. However, there is limited research on the association between RC and the risk of HF. Therefore, we aimed to provide relevant evidence by determining whether a high RC level also influences the risk of HF. In this secondary analysis of the Atherosclerosis Risk in Communities (ARIC) study, we included 12,595 participants without coronary heart disease. We determined the association of the RC level as a continuous or categorical variable with the risk of HF using the multivariable-adjusted Cox proportional hazards models and restricted cubic spline curve. During a median follow-up of 22.5 years, 2,029 (16.1%) cases of HF occurred in all included participants. Compared with participants in the RC < 0.50 mmol/L group, the adjusted hazard ratio (HR) for HF increased progressively in participants with the RC level of 0.50 to 0.99 mmol/L, 1.00 to 1.49 mmol/L, and ≥1.50 mmol/L, from 1.17 (95% confidence interval [CI]: 1.05-1.30) to 1.27(95% CI: 1.08-1.49) and to 1.50 (95% CI: 1.14-1.97) (P for trend < 0.001). Cubic spline curves also revealed that the risk of HF increased with the RC level. In the general population without coronary heart disease, a higher level of RC was significantly associated with a higher risk of HF, indicating that a higher RC level might be a potential risk factor for HF. Therefore, the management of blood cholesterol to reduce the risks of HF should focus not only on the traditional blood lipid parameters but also on the RC level.


Office spirometry correlates with laboratory spirometry in patients with symptomatic asthma and COPD.
Spirometry remains underutilized in the evaluation of obstructive lung disease. While office spirometry (OS) has been compared to formal laboratory-based spirometry (LS) in healthy subjects, the correlation has never been formally assessed in patients with symptomatic obstructive lung disease. The aim of this study was to investigate the correlation in this population. We used a retrospective study design to analyze spirometry data from patients that underwent both OS and LS. Two flow sensing office (portable) spirometers were used and compared with laboratory-based (body plethymosgraph) spirometer. Accuracy and reliability were assessed using Bland Altman analysis. Among 185 patients with symptomatic obstructive lung disease, 129 had undergone both OS and LS. Of these, 107 patients had both tests performed less than 90 days apart and were included in final analyses. Mean age was 54 years with mean FEV1 of 1.97 L (65% predicted). Ninety-two patients had airflow obstruction, as determined by a FEV1/FVC ratio of <70%. We found significant correlation in the values between OS and LS for both FEV1 and FVC (r = 0.937 and 0.90, respectively, P < 0.001). Eighty-seven percent of patients had a concordant spirometry in terms of airflow obstruction. Correlation was independent of the office spirometer (and hence the Flow-sensing mechanism) used. In patients with known asthma and chronic obstructive pulmonary disease (COPD), OS is accurate and reliable when compared to formal laboratory-based spirometry. Routine use of OS should be encouraged to improve spirometry utilization and healthcare outcomes in patients with Asthma and COPD.


[Pre-analytical quality in fluid samples cytopathology: Results of a survey from the French Society of Clinical Cytology].
The pre-analytical step includes sample collection, preparation, transportation and storage in the pathology unit where the diagnosis is performed. The pathologist ensures that pre-analytical conditions are in line with expectations. The lack of standardization for handling cytological samples makes this pre-analytical step difficult to harmonize. Moreover, this step depends on the nature of the sample: fresh liquid or fixed material, air-dried smears, liquid-based cytology. The aim of the study was to review the different practices in French structures of pathology on the pre-analytical phase concerning cytological fluids such as broncho-alveolar lavage (BALF), serous fluids and urine. A survey was conducted on the basis of the pre-analytical chapter of the ISO 15189 and sent to 191 French pathological structures (105 public and 86 private). Fifty-six laboratories replied to the survey. Ninety-five per cent have a computerized management system and 70% a manual on sample handling. The general instructions requested for the patients and sample identification were highly correctly filled with a short time routing and additional tests prescription. By contrast, information are variable concerning the clinical information requested and the type of tubes for collecting fluids and the volumes required as well as the actions taken in case of non-conformity. For the specific items concerning BALF, serous fluids and urine, this survey has shown a great heterogeneity according to sample collection, fixation and of clinical information. This survey demonstrates that the pre-analytical quality for BALF, serous fluids and urine is not optimal and that some corrections of the practices are recommended with a standardization of numerous steps in order to increase the reproducibility of additional tests such as immunocytochemistry, cytogenetic and molecular biology. Some recommendations have been written.


Inhibiting transcription factor/DNA complexes using fluorescent microgonotropens (FMGTs).
Fluorescent microgonotropens (FMGTs) are A/T selective, minor groove-binding bisbenzimidazole ligands. Basic side chains extending from these agents electrostatically contact the major groove side of the phosphodiester backbone of DNA, endowing them with high binding affinity. Here, we evaluate the potential of these agents as inhibitors of transcription factor (TF) binding to DNA and explore whether their ability to contact both grooves enhances their inhibitory activity. A series of FMGTs (L2-L5), with polyamine tails of varying lengths and degrees of branching, were compared to an analog lacking these basic side chains (L1), and the classical bisbenzimidazole Hoechst 33342 for effects on TF complex formation on the c-fos serum response element (SRE). Although L1 could not inhibit TF/SRE interactions, L2-L5 did so at submicromolar concentrations. Moreover, the FMGTs were up to 50 times more potent than Hoechst 33342 in inhibiting TF complex formation in electrophoretic mobility shift assays. The FMGTs also inhibited c-fos promoter-driven cell-free transcription and topoisomerase II activity in nuclei. These studies establish the potential of FMGTs as TF/DNA complex inhibitors in cell-free systems, provide insight into the relationship between their structure and biological activities, and demonstrate the benefits of functionalizing minor groove binding-agents with major groove-contacting groups.


Myopathy with hyperaldosteronism. An electron-microscopic study.
In the case reported, an overproduction of aldosterone was accompanied by paretic attacks, a decrease in the serum potassium level, and in muscle tone and the deep tendon reflexes. The decrease of serum potassium level was consistent, but moderate, being to just below the normal lower limit. Loading with carbohydrate produced an attack, forearm ischaemic exercise resulted in less lactic acid production than normally. In the limb-girdle muscles there was also evidence of slight but permanent weakness. The results of histological and ultrastructural examination of a muscle biopsy are reported. It seems probable that the disturbance in the mineralo-corticoid metabolism led periodically to a decrease in the serum potassium, while in some muscle fibres the glycogen content increased and the SR became dilated and partially destroyed. In the attack-free periods tubular aggregates were produced, supposedly through an attempt at regeneration of the SR. During attacks portions of the muscle fibres were destroyed irreversibly and in consequence moderate permanent weakness resulted. Some spheromembranous degradation products which were observed might be regarded as remnants of degenerated tubular aggregates.


The Measure Matters: An Investigation of Evaluative and Experience-Based Measures of Wellbeing in Time Use Data.
Measures of subjective wellbeing (SWB) are used to understand how people think and feel about their lives and experiences. But the measure used matters to conclusions about how well people's lives are going. This research compares life evaluations and experienced SWB using nationally representative time use diaries, advancing previous research because diaries are less subject to recall biases than other, more popular methods. Analyses of over 20,000 US residents in 2012-2013 show life evaluations are more closely associated with positive and negative affect than experienced meaningfulness. Women have higher SWB than men except for negative affect, older age groups have higher SWB than middle age groups except for experienced meaningfulness, and younger age groups report the lowest experienced meaning. The unemployed have low life evaluations but experiences of SWB are similar across employment groups. A complete picture of SWB requires a complete set of measures.


Feasibility and safety of exercise training and nutritional support prior to haematopoietic stem cell transplantation in patients with haematologic malignancies.
Prehabilitation with regular exercise and nutritional care for patients undergoing surgeries for malignant disease was recently introduced to increase physiologic reserve prior to the procedure, accelerate recovery and improve outcomes. This study aimed to investigate the feasibility and safety of combined exercise training and nutritional support in patients with haematologic malignancies prior to haematopoietic stem cell transplantation (HSCT). In this single-arm pilot study, 34 HSCT candidates were enrolled at least two weeks before admission for the procedure. Patients performed aerobic exercises at least 4 days per week for 20-30 min and strength exercises 3 days per week for 10-20 min. They received daily supplements of whey protein (0.3-0.4 g/kg body weight) and oral nutritional supplements if needed. The primary endpoints were feasibility (acceptability > 75%, attrition < 20%, adherence > 66%) and safety. The secondary endpoints were fat-free mass (FFM), muscle strength, physical performance and health-related quality of life (HRQoL) at HSCT. The rate of acceptability, attrition and adherence to aerobic exercise, strength exercise and protein supplement consumption was 82.4, 17.8, 71, 78 and 80%, respectively. No severe adverse events were reported. Twenty-eight patients participated in the study for a median of 6.0 weeks (range, 2-14). They performed aerobic exercises 4.5 days per week for 132 min per week and strength exercises 3.0 times per week. Patients consumed 20.7 g of extra protein daily. At the end of the programme, we recorded increases of 1.1 kg in FFM (p = 0.011), 50 m in walking distance in the 6-min walking test (6MWT) (p < 0.001), 3.3 repetitions in the 30-s chair-stand test (30sCST) score (p < 0.001) and 2.6 kg in handgrip strength (p = 0.006). The EORTC QLQ-C30 scores improved by 8.6 (p < 0.006) for global health status, 8.3 (p = 0.009) for emotional functioning, and 12.1 (p = 0.014) for social functioning. There was less fatigue, nausea and insomnia (p < 0.05). Our study shows that a multimodal intervention programme with partially supervised exercise training combined with nutritional support prior to HSCT is feasible and safe. Patients showed improvements in FFM, physical performance and HRQoL. Additional research is needed to assess the possible positive effects of such interventions.


Regulation of the cyclin-dependent kinase inhibitor 1A gene (CDKN1A) by the repressor BOZF1 through inhibition of p53 acetylation and transcription factor Sp1 binding.
The human POZ domain and Krüppel-like zinc finger (POK) family proteins play important roles in the regulation of apoptosis, cell proliferation, differentiation, development, oncogenesis, and tumor suppression. A novel POK family transcription factor, BTB/POZ and zinc finger domains factor on chromosome 1 (BOZF-1; also called ZBTB8A), contains a POZ domain and two C2H2-type Krüppel-like zinc fingers and is localized at nuclear speckles. Compared with paired normal tissues, BOZF1 expression is increased in cancer tissues of the prostate, breast, and cervix. BOZF1 repressed the transcription of p21WAF/CDKN1A by acting on the proximal promoter concentrated with Sp1-binding GC boxes. BOZF1 competed with Sp1 in binding to GC boxes 1-5/6 of the CDKN1A proximal promoter. In addition, BOZF1 interacted with p53 and decreased the acetylation of p53 by p300, which reduced the DNA binding activity of p53 at the far distal p53-binding element. BOZF1 blocked the two major molecular events that are important in both constitutive and inducible transcription activation of CDKN1A. BOZF1 is unique in that it bound to all the proximal GC boxes to repress transcription, and it inhibited p53 acetylation without affecting p53 stability. BOZF1 might be a novel proto-oncoprotein that stimulates cell proliferation.


An objective comparison of pre-processing methods for enhancement of liquid chromatography-mass spectrometry data.
Four data pre-processing methods have been applied with different settings to data sets obtained from the analysis of a pharmaceutical drug and its degradation products by liquid chromatography-mass spectrometry (LC-MS). The methods compared were the frequently used component detection algorithm (CODA) and three kinds of digital filters--matched filtration (MF), Gaussian second derivative (GSD) and Savitzky-Golay. The aim was to evaluate the performance and robustness of these methods for extracted ion chromatogram (XIC), total ion chromatogram (TIC) and base peak chromatogram (BPC) in the presence of different types of noise. In accordance with theory, the best improvements in signal-to-noise ratio (S/N) of the XICs were obtained with MF under the ideal case with random white noise. However, when highly coloured noise was present, it was found that no improvements in XIC S/N could be obtained with any of the pre-processing methods studied. GSD and CODA did, however, improve the S/N for both TIC and BPC. GSD and CODA also significantly reduced the background in the spectral domain, thereby facilitating the interpretation of the mass spectra. Another advantage associated with CODA and to some extent also with GSD is their data reduction ability.


Changes in the liver lactate dehydrogenase isozyme profile after induced glycogenolysis.
Treatment with cystamine, phlorrhizin or nicotinic acid, which induced liver glycogenolysis, resulted in the increase of liver lactate dehydrogenase activity. This increase was counteracted by the administration of cycloheximide or actinomycin D and coincided with the increase os isozymes 4 and 3 and the decrease of isozyme 5. The enhancement of liver lactate dehydrogenase activity and the changes observed in the isozyme profile were similar to those observed after starvation. These results suggest that the changes in the lactate dehydrogenase isozyme profile found after cystamine, phlorrhizin or nicotinic acid administration may be related to the glycogenolytic effect of these compounds. These result in an adaptation of the liver lactate dehydrogenase to gluconeogenesis.


Utility of the endobronchial Watanabe spigot for intractable cancer-related pneumothorax: a retrospective observational study.
The use of endobronchial Watanabe spigots for intractable secondary pneumothorax in patients with cancer has not been adequate. This study aimed to investigate the use of endobronchial Watanabe spigots for intractable pneumothorax in patients with malignant tumors. Consecutive patients with malignant tumors who underwent occlusion with an endobronchial Watanabe spigot for intractable pneumothorax associated with perioperative treatment or drug therapy at our institution between January 2014 and February 2022 were reviewed. Of the 32 cases in which an endobronchial Watanabe spigot was used, six were excluded; we thus evaluated 26 cases in which the chest tube was removed. Chest tubes were removed in 19 cases (73.1%) and could not be removed and required surgical treatment under general anesthesia in seven patients (26.9%), of which four (14.8%) underwent open-window thoracostomy. Half of the patients were treated with both an endobronchial Watanabe spigot and pleurodesis. Although thin-slice chest computed tomography revealed a fistula in 15 patients, the chest tube was removed in 11 (57.9%) patients. A significant difference was only observed in patients with a history of heavy smoking. The chest tube removal rate was comparable to those reported in previous studies. An endobronchial Watanabe spigot may be a useful treatment option for intractable cancer-related pneumothorax.


Structural characterization of poly-Si Films crystallized by Ni Metal Induced Lateral Crystallization.
The growth of the poly-Si films was studied by Transmission Electron Microscopy (TEM) after Ni Metal Induced Lateral Crystallization (Ni-MILC) of amorphous Si films at 413 °C. Significant differences in the morphology and the mode of growth of the films were observed, in comparison to films grown at temperatures above 500 °C. It was shown that at 413 °C the Solid Phase Crystallization (SPC), which acts in parallel with the Ni-MILC process at temperatures above 500 °C is suppressed. The suppression of SPC results in substantial change in the mode of growth. The poly-Si film grown at 413 °C consists of whiskers, which can be classified into two categories. Those growing fast along the <111> direction, which were already observed in conventional Ni-MILC above 500 °C and whiskers grown along random crystallographic orientations having significantly slower growth rates. Because of the large difference in growth rates of the whiskers, significant orientation filtering due to growth-velocity competition is observed. The uniform poly-Si films consist of a mixture of fast <111> type whiskers and slow ones, grown in other orientations, resulting in a tweed-like structure.


A retrospective and prospective study to establish a preoperative difficulty predicting model for video-assisted thoracoscopic lobectomy and mediastinal lymph node dissection.
In previous studies, the difficulty of surgery has rarely been used as a research object. Our study aimed to develop a predictive model to enable preoperative prediction of the technical difficulty of video-assisted thoracoscopic lobectomy and mediastinal lymph node dissection using retrospective data and to validate our findings prospectively. Collected data according to the designed data table and took the operation time as the outcome variable. A nomogram to predict the difficulty of surgery was established through Lasso logistic regression. The prospective datasets were analyzed and the outcome was the operation time. This retrospective study enrolled 351 patients and 85 patients were included in the prospective datasets. The variables in the retrospective research were selected by Lasso logistic regression (only used for modeling and not screening), and four significantly related influencing factors were obtained: FEV1/FVC (forced expiratory volume in the first second/forced vital capacity) (p < 0.001, OR, odds ratio = 0.89, 95% CI, confidence interval = 0.84-0.94), FEV1/pred FEV1 (forced expiratory volume in the first second/forced expiratory volume in the first second in predicted) (p = 0.076, OR = 0.98, 95% CI = 0.95-1.00), history of lung disease (p = 0.027, OR = 4.00, 95% CI = 1.27-15.64), and mediastinal lymph node enlargement or calcification (p < 0.001, OR = 9.78, 95% CI = 5.10-19.69). We used ROC (receiver operating characteristic) curves to evaluate the model. The training set AUC (area under curve) value was 0.877, the test set's AUC was 0.789, and the model had a good calibration curve. In a prospective study, the data obtained in the research cohort were brought into the model again for verification, and the AUC value was 0.772. Our retrospective study identified four preoperative variables that are correlated with a longer surgical time and can be presumed to reflect more difficult surgical procedures. Our prospective study verified that the variables in the prediction model (including prior lung disease, FEV1/pred FEV1, FEV1/FVC, mediastinal lymph node enlargement or calcification) were related to the difficulty.


Determination of iron(III) by displacement substoichiometric extraction with labeled silver-dipyridyl.
A substoichiometric radiochemical displacement method has been designed for the estimation of trace quantities of iron. The method involves the displacement of spiked ((110m)Ag) silver from its dipyridyl complex in n-butanol by iron(III) owing to the greater stability of iron-dipyridyl complex compared to that of silver-dipyridyl complex. The interference effects of various closely related foreign ions on the displacement reaction were found to be negligible, thus establishing the selectivity of the proposed technique over other standard analytical techniques available for the estimation of iron(III). The validity of this method has been established by successful estimation of iron from various complex matrices. Investigations have been made.


Bias reduction improves accuracy and informativity of high-throughput sequencing chimerism assays.
Chimerism monitoring by means of high-throughput sequencing of biallelic polymorphisms has shown promising advantages for patient follow-up after hematopoietic stem cell transplantation. Yet, the presence of method bias precludes achievement of an assay's theoretically attainable informativity rate, as method bias necessitates the exclusion of some markers. This method bias arises because of preferential observation of one allele over the other, and for some allelic constellations because of stochasticity. This paper suggests how preferential allelic observation may lead to method bias, and when and why such bias necessitates the exclusion of markers. It is shown that also markers that remain informative suffer a reduction in trueness and precision due to method bias. A bias reduction approach in the data analysis phase is introduced and shown to improve trueness and precision under all circumstances, meriting its universal adoption. This bias reduction furthermore allows to achieve an assay's theoretically achievable informativity rate, though at the cost of reduced sensitivity. Several strategies to consider in the assay design phase that may lower biases are proposed. Improved design and data analysis of chimerism assays increase the accuracy, applicability, and cost-effectiveness of high-throughput sequencing chimerism assays.


Immunology in the clinic review series: focus on type 1 diabetes and viruses: the role of viruses in type 1 diabetes: a difficult dilemma.
Convincing evidence now indicates that viruses are associated with type 1 diabetes (T1D) development and progression. Human enteroviruses (HEV) have emerged as prime suspects, based on detection frequencies around clinical onset in patients and their ability to rapidly hyperglycaemia trigger in the non-obese diabetic (NOD) mouse. Whether or not HEV can truly cause islet autoimmunity or, rather, act by accelerating ongoing insulitis remains a matter of debate. In view of the disease's globally rising incidence it is hypothesized that improved hygiene standards may reduce the immune system's ability to appropriately respond to viral infections. Arguments in favour of and against viral infections as major aetiological factors in T1D will be discussed in conjunction with potential pathological scenarios. More profound insights into the intricate relationship between viruses and their autoimmunity-prone host may lead ultimately to opportunities for early intervention through immune modulation or vaccination.


Alteration in the nocturnal pulsatile release of GH during the induction of puberty using low dose pulsatile LHRH: a case report.
A 16.4 year old girl with idiopathic hypogonadotrophic hypogonadism had successful induction of puberty by administration of low dose LHRH by pulsatile subcutaneous infusion at night. Peak serum GH was increased with therapy but more importantly, pulsatile secretion of GH which was minimal before treatment, was restored after one week of LHRH treatment.


Retracted: Clinical Application of Evoked Potentials in the Operation of Cervical Spondylotic Myelopathy with Different Imaging.
[This retracts the article DOI: 10.1155/2022/4154278.].


Constitutive association of JAK1 and STAT5 in pro-B cells is dissolved by interleukin-4-induced tyrosine phosphorylation of both proteins.
The bipartite human interleukin-4 (IL-4) receptor was functionally expressed in murine pro-B cells and activated by human IL-4 to evoke intracellular signaling. Mutual association of signal transducing proteins within the receptor complex was then studied in dependence of ligand stimulation. Besides ligand-induced receptor heterodimerization and contacts of the two IL-4 receptor subunits alpha and gamma with Janus kinases JAK1 and JAK3 a prominent constitutive binding between JAK1 and signal transducer and activator of transcription STAT5 was detected. Since both these proteins become phosphorylated in response to IL-4 receptor stimulation, the influence of tyrosine phosphorylation on their mutual contact was analyzed. Association of JAK1 and STAT5 was found to occur exclusively between unphosphorylated proteins.


CRISPR-based DNA methylation editing of NNT rescues the cisplatin resistance of lung cancer cells by reducing autophagy.
Cisplatin is recommended as a first-line chemotherapeutic agent against advanced non-small cell lung cancer (NSCLC), but acquired resistance substantially limits its clinical efficacy. Recently, DNA methylation has been identified as an essential contributor to chemoresistance. However, the precise DNA methylation regulatory mechanism of cisplatin resistance remains unclear. Here, we found that nicotinamide nucleotide transhydrogenase (NNT) was silenced by DNA hypermethylation in cisplatin resistance A549 (A549/DDP) cells. Also, the DNA hypermethylation of NNT was positively correlated to poor prognosis in NSCLC patients. Overexpression of NNT in A549/DDP cells could reduce their cisplatin resistance, and also suppressed their tumor malignancy such as cell proliferation and clone formation. However, NNT enhanced sensitivity of A549/DDP cells to cisplatin had little to do with its function in mediating NADPH and ROS level, but was mainly because NNT could inhibit protective autophagy in A549/DDP cells. Further investigation revealed that NNT could decrease NAD+ level, thereby inactivate SIRT1 and block the autophagy pathway, while re-activation of SIRT1 through NAD+ precursor supplementation could antagonize this effect. In addition, targeted demethylation of NNT CpG island via CRISPR/dCas9-Tet1 system significantly reduced its DNA methylation level and inhibited the autophagy and cisplatin resistance in A549/DDP cells. Thus, our study found a novel chemoresistance target gene NNT, which played important roles in cisplatin resistance of lung cancer cells. Our findings also suggested that CRISPR-based DNA methylation editing of NNT could be a potential therapeutics method in cisplatin resistance of lung cancer.


Monitoring implementation in program evaluation with direct audio coding.
This project explored the reliability and utility of transcription in coding qualitative data across two studies in a program evaluation context. The first study tested the method of direct audio coding, or coding audio files without transcripts, using qualitative data software. The presence and frequency of codes applied in direct audio coding and traditional transcription coding were compared and the two methods produced similar results. Direct audio coding was then employed in an evaluation study to monitor implementation and the method was found to be reliable. Implications are discussed with considerations for both researchers and practitioners.


Bacteremia during esophageal variceal sclerotherapy: its cause and prevention.
Eleven consecutive patients underwent a total of 34 esophageal variceal sclerotherapy (EVS) sessions for bleeding esophageal varices. Blood cultures were drawn pre-, intra-, and post-EVS. All pre- and post-EVS blood cultures were negative. Five of the initial nine patients studied were found to have positive blood cultures, drawn after a mean of six injections. Pseudomonas aeruginosa was cultured from the blood in four patients and Flavobacterium from one. The source of contamination was found to be contaminated water used during the sclerotherapy sessions. By instituting simple techniques to eliminate this contamination, patients undergoing the remaining 25 EVS sessions were culture negative.


Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients.
Follicular lymphoma is clinically heterogenous, and therefore necessitates the identification of prognostic markers to stratify risk groups and optimize clinical management. It is relatively rare in patients younger than 40 years, and the clinicopathologic characteristics and biological behavior in this age group are poorly understood. In the current study, samples from a cohort of 200 patients between 19 and 40 years were evaluated retrospectively with respect to clinical, histologic, and genetic features. These were then correlated with clinical outcome. The median age at presentation was 35 years with a slight female prepoderance (56%). Most of the cases are presented with nodal disease (90%). Concomitant follicular lymphoma and diffuse large B-cell lymphoma were observed in 7 (4%) patients. Immunohistologic studies showed the expression of CD10 (91%), BCL6 (97%), BCL2 (95%), MUM1/IRF4 (12%), MDM2 (17%), and CD23 (25%). BCL2 rearrangement was present in 74%, and BCL6 in 20%. The estimated overall survival of patients was 13 years (mean). The presence of anemia, elevated lactose dehydrogenase, bone marrow involvement, and high-risk follicular lymphoma international prognostic index correlated with adverse overall survival. Our findings revealed that follicular lymphoma in young adults demonstrate similarities with that of older adults, including the frequency of presentation at various anatomic sites, grade, and adverse prognostic factors.


Untangling the Biology of Genetic Cardiomyopathies with Pluripotent Stem Cell Disease Models.
Recently, the discovery of strategies to reprogram somatic cells into induced pluripotent stem (iPS) cells has led to a major paradigm change in developmental and stem cell biology. The application of iPS cells and their cardiac progeny has opened novel directions to study cardiomyopathies at a cellular and molecular level. This review discusses approaches currently undertaken to unravel known inherited cardiomyopathies in a dish. With improved efficiency for mutation correction by genome editing, human iPS cells have now provided a platform to untangle the biology of cardiomyopathies. Multiple studies have derived pluripotent stem cells lines from patients with genetic heart diseases. The generation of cardiomyocytes from these cells lines has, for the first time, enable the study of cardiomyopathies using cardiomyocytes harboring patient-specific mutations and their corrected isogenic counterpart. The molecular analyses, functional assays, and drug tests of these lines have led to new molecular insights in the early pathophysiology of left ventricular non-compaction cardiomyopathy (LVNC), hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and others. The advent of iPS cells offers an exceptional opportunity for creating disease-specific cellular models to investigate their underlying mechanisms and to optimize future therapy through drug and toxicity screening. Thus far, the iPS cell model has improved our understanding of the genetic and molecular pathophysiology of patients with various genetic cardiomyopathies. It is hoped that the new discoveries arising from using these novel platforms for cardiomyopathy research will lead to new diagnostic and therapeutic approaches to prevent and treat these diseases.


Differential sensitivity to ethidium bromide of replicative DNA synthesis and bleomycin-induced unscheduled DNA synthesis in permeable mouse sarcoma cells.
Replicative DNA synthesis in permeable mouse sarcoma cells was more sensitive to ethidium bromide (EtBr) than bleomycin-induced unscheduled DNA synthesis (UDS). A similar difference in sensitivity to EtBr was observed between DNA polymerases alpha and beta. The difference in sensitivity to EtBr of replicative DNA synthesis and UDS in the present system seems to reflect mainly the sensitivity difference between DNA polymerases alpha and beta.


Effect of Fenton's reagent on O/W emulsions stabilized by black liquor.
The effect of Fenton's reagent (FR) on surface and dispersion properties of black liquor (BL) was investigated. These properties were compared to those of indulin C (IC), a commercial lignin, and egg lecithin (Le). FR was applied at two different bulk concentrations of H2O2 (160 and 320 mM). At pH 8, a minimum in surface tension for the Fenton treated BL was observed. The dispersant ability of BL, IC and Le in oil-in-water (O/W) emulsions was studied by measuring emulsion stability and drop size. It was found that the surface activity and emulsifying capability of BL were higher than those of IC. The emulsifying capability of Le was improved by the FR treatment at low H2O2 concentration.


Short-term hypothyroidism in thyroid cancer patients and cognitive-motor performance relevant for driving.
In patients with differentiated thyroid carcinoma (DTC) who, after thyroidectomy, are to receive radioiodine therapy or diagnostics, a strong TSH stimulus is necessary. Traditionally, this is induced by thyroid hormone withdrawal (THW) over a period of 4-5weeks; alternatively thyroid hormone replacement therapy is continued and recombinant human thyrotropin (rhTSH) is administered. During the hypothyroid state due to THW, patients often report mood disturbances and physical complaints but also an impairment of performance during attention demanding tasks. Based on physiological, self-report and performance test data collected from various studies, we proposed the hypothesis that thyroidectomized DTC patients perform significantly worse in cognitive-motor functions that are relevant for driving when in the THW-induced hypothyroid state compared to when thyroid hormone replacement therapy is continued and rhTSH is administered. We compared 41 DTC patients (age 42.3 (9.4) years; 80.5% female) after 4weeks THW with 41 DTC patients after the application of rhTSH, pairwise matched according to age, gender and educational level, with respect to performance in 4 core tests of the Act-React-Testsystem ART-90, a validated test battery for examining fitness to drive. Contrary to our expectations, no statistically relevant impairment of performance could be confirmed in the THW group in comparison to the rhTSH group for any variable (at adjusted α). At most there is a tendency in the THW group for slowed reaction times in simple-choice reaction tasks; the (standardized) difference to the rhTSH group is however small (d'=0.31). Furthermore, large effects due to THW, as they are suggested by several studies, could be excluded.


Blastocystis: how do specific diets and human gut microbiota affect its development and pathogenicity?
Blastocystis is an enteric parasite that inhabits the gastrointestinal tract of humans and many animals. This emerging parasite has a worldwide distribution. It is often identified as the most common eukaryotic organism reported in human fecal samples. This parasite is recognized and diagnosed more often than ever before. Furthermore, some strains develop resistance against currently recommended drugs, such as metronidazole; therefore, the use of natural remedies or special diets has many positive aspects that may address this problem. The goal of this review is to compare natural treatments and various diets against the efficacy of drugs, and describe their influence on the composition of the gut microbiota, which affects Blastocystis growth and the occurrence of symptoms. This article reviews important work in the literature, including the classification, life cycle, epidemiology, pathogenesis, pathogenicity, genetics, biology, and treatment of Blastocystis. It also includes a review of the current knowledge about human gut microbiota and various diets proposed for Blastocystis eradication. The literature has revealed that garlic, ginger, some medical plants, and many spices contain the most effective organic compounds for parasite eradication. They work by inhibiting parasitic enzymes and nucleic acids, as well as by inhibiting protein synthesis. The efficacy of any specific organic compound depends on the Blastocystis subtype, and, consequently, on its immunity to treatment. In conclusion, the article discusses the findings that human gut microbiota composition triggers important mechanisms at the molecular level, and, thus, has a crucial influence on the parasitic pathogenicity.


Effect of AMP on serum minerals in carbon-tetrachloride hepatotoxicity.
Carbon tetrachloride twenty-four hours after its administration resulted in a significant increase in serum iron, copper, zinc, calcium, potassium and sodium, while for magnesium no significant change was observed. A portion of this rise was due to the known hepatotoxic effect of CCl4 on the liver. Pretreatment with adenosine-5-monophosphate led to a normalization of the level of serum iron, copper and zinc, while in case of calcium, magnesium, potassium and sodium there was no significant change from that found in CCl4. The normalization of serum copper and iron under the influence of AMP may be due to some protective action of AMP on the liver. However, the disturbance in minerals metabolism may be considered as one of the earliest lesions in CCl4 poisoning.


Psychological trauma and depression in recovered COVID-19 patients: a telecommunication based observational study.
Coronavirus disease 2019 (COVID-19) is adversely affecting the mental health of patients infected with the virus and the psychological impact on recovered COVID-19 patients is unclear. The study aimed to assess posttraumatic stress disorder (PTSD) and depression among COVID-19 patients after recovery from the disease. This cross-sectional study was conducted from November 9, 2020, to December 23, 2020. The study used a telemedicine model to enroll recovered COVID-19 patients from a database of patients provided by the health authorities. The National Stressful Events Survey PTSD Short Scale (NSESSS) for adults was used to assess PTSD symptoms and the Patient Health Questionnaire (PHQ-9) was used to assess depression. The study enrolled 503 recovered COVID-19 patients with a mean age of 41.90 years. The majority were asymptomatic (64.6%), while 21.5% had had moderate to severe forms of the disease. Prevalence rates of PTSD symptoms and depression were 56.9 and 29% respectively. COVID-19 patients with severe forms of the disease were significantly more affected by PTSD symptoms (vs. mild, odds ratio [OR] = 18.7, 95%confidence interval [CI] 9.9-35.5) and depression (vs. mild, OR = 19.8, 95% CI 9.9-39.5). Similarly, patients who required oxygen or ventilator support reported significantly higher rates of PTSD symptoms (vs. managed at home, OR = 17.4, 95% CI 8.3-36.4) and depression (vs. managed at home, OR = 22.0, 95% CI 10.1-47.7). This study reports that recovered COVID-19 patients suffered from a significant amount of depression and experienced significant PTSD symptoms. It will help with addressing a major psychological concern among the recovered subjects.


Early diagnosis and endovascular management of uterine artery pseudoaneurysm after laparoscopic-assisted myomectomy.
To describe the diagnosis and management of uterine artery pseudoaneurysm after laparoscopic-assisted myomectomy. Case reports. Departments of Obstetrics and Gynecology and Radiology at General Hospital. A 32-year-old woman and a 41-year-old woman each developed uterine artery pseudoaneurysm after laparoscopic-assisted myomectomy. Uterine artery pseudoaneurysm after laparoscopic-assisted myomectomy was diagnosed on ultrasonography, computerized tomographic angiography, and digital subtraction angiography, and treated by transcatheter arterial embolization. Uterine conservation. Fertility preservation was achieved in both of these women who developed uterine artery pseudoaneurysm after laparoscopic-assisted myomectomy. Early diagnosis and endovascular management of uterine artery pseudoaneurysm after myomectomy are important to prevent life-threatening hemorrhage caused by pseudoaneurysmal rupture.


Performance on the continuous performance test under parametric increase of working memory load in schizophrenia.
We asked 24 schizophrenia patients and 24 healthy comparison subjects to complete a parametric working memory version of the continuous performance test. Patients exhibited a relatively rapid performance decline with increasing working memory demands. We suggest an interaction between sustained attention and working memory abnormalities in schizophrenia.


Validation of the Kriol and Belizean English Adaptation of the Revised Children's Anxiety and Depression Scale for Use With Adolescents in Belize.
To validate a culturally-adapted Kriol and Belizean English version of the Revised Children's Anxiety and Depression Scale (RCADS) through comparison with clinical diagnoses made using the Kiddie Schedule of Affective Disorders and Schizophrenia. Participants comprised of 256 adolescents aged 10-14 years and 15-19 years, who completed the adapted RCADS (10 depression items, 12 anxiety items) in one-on-one interviews, followed by a diagnostic assessment using Kiddie Schedule of Affective Disorders and Schizophrenia administered by trained clinicians. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic odds ratios, area under the curve (AUC), and Youden's Index were calculated for RCADS cutoffs and scores on the total scale and anxiety and depression subscales. For adolescents aged 10-14 years (n = 161), the AUC was 0.72 for the full scale, 0.67 for anxiety subscale, and 0.76 for depression subscale. For adolescents aged 15-19 years (n = 95), the AUCs were 0.82, 0.77, and 0.83. Most depression items performed well in discriminating those with and without diagnoses. Separation anxiety items performed poorly. "Thoughts of death" were common even among adolescents not meeting diagnostic criteria. The RCADS depression subscale presented the strongest psychometric properties with adolescents aged 15-19 years (at cutoff of 13, sensitivity = 0.83, specificity = 0.77, positive predictive value = 0.47, negative predictive value = 0.95, odds ratio = 15.96). The adapted RCADS-22 had acceptable categorization for adolescents aged 10-14 years and excellent categorization for adolescents aged 15-19 years; therefore, the tool is recommended for use among the latter age group. Based on sensitivity and specificity values at different cutoffs, guidance is provided to select different thresholds to suit clinical, public health, or other uses to detect and quantify adolescent depression and anxiety in Belize.


Mercury demethylation in waterbird livers: dose-response thresholds and differences among species.
We assessed methylmercury (MeHg) demethylation in the livers of adults and chicks of four waterbird species that commonly breed in San Francisco Bay: American avocets, black-necked stilts, Caspian terns, and Forster's terns. In adults (all species combined), we found strong evidence for a threshold model where MeHg demethylation occurred above a hepatic total mercury concentration threshold of 8.51 +/- 0.93 microg/g dry weight, and there was a strong decline in %MeHg values as total mercury (THg) concentrations increased above 8.51 microg/g dry weight. Conversely, there was no evidence for a demethylation threshold in chicks, and we found that %MeHg values declined linearly with increasing THg concentrations. For adults, we also found taxonomic differences in the demethylation responses, with avocets and stilts showing a higher demethylation rate than that of terns when concentrations exceeded the threshold, whereas terns had a lower demethylation threshold (7.48 +/- 1.48 microg/g dry wt) than that of avocets and stilts (9.91 +/- 1.29 microg/g dry wt). Finally, we assessed the role of selenium (Se) in the demethylation process. Selenium concentrations were positively correlated with inorganic Hg in livers of birds above the demethylation threshold but not below. This suggests that Se may act as a binding site for demethylated Hg and may reduce the potential for secondary toxicity. Our findings indicate that waterbirds demethylate mercury in their livers if exposure exceeds a threshold value and suggest that taxonomic differences in demethylation ability may be an important factor in evaluating species-specific risk to MeHg exposure. Further, we provide strong evidence for a threshold of approximately 8.5 microg/g dry weight of THg in the liver where demethylation is initiated.


The potential of hormones and selective oestrogen receptor modulators in preventing voiding dysfunction in rats.
To investigate whether oestrogen, selective oestrogen receptor modulators (SERMs), and growth hormone (GH) can prevent the development of voiding dysfunction in a postpartum postmenopausal rat model of voiding dysfunction. Immediately after spontaneous delivery, nine primiparous Sprague-Dawley rats served as uninjured controls (sham group) and 54 underwent intravaginal balloon dilation. On day 7, the 54 subject rats underwent bilateral ovariectomy. A week later, six treatment groups of nine rats were randomized to receive: normal saline (injured control group), 17beta-oestradiol (E(2)), raloxifene, levormeloxifene, GH, or GH + E(2). The treatment groups received daily subcutaneous injections for 3 weeks. The effects of hormone treatment were examined by conscious cystometry at the end of the study. Voiding dysfunction was defined to include overactive bladder and sphincter deficiency. The sham rats had a mean (sd) voiding frequency of 3 (0.87) times in 10 min and a bladder capacity of 0.43 (0.13) mL with smooth cystometry curves. The number of rats in each treatment group (each group contained nine rats) that had voiding dysfunction was as follows: E(2), three; raloxifene, six; levormeloxifene, four; and controls, four (P > 0.05 among the groups). Only one rat in the GH-treated group and no rats in the GH + E(2)-treated group had voiding dysfunction, which was significantly less in the GH + E(2)-treated group than in the controls (P = 0.041). This functional data suggest that the development of voiding dysfunction can be prevented by short-term administration of GH and GH + E(2) in our rat model. SERMs and E(2) alone seem to have no therapeutic effect.


Growth promotion of Xanthium italicum by application of rhizobacterial isolates of Bacillus aryabhattai in microcosm soil.
This study was conducted using rhizobacteria, which are able to exert beneficial effects upon plant growth in the infertile soil collected from barren lakeside areas. Four strains of plant growth promoting bacteria were isolated from the rhizosphere of a common wild plant, Erigeron canadensis. Isolated strains LS9, LS11, LS12, and LS15 were identified as Bacillus aryabhattai by 16S rDNA sequence analysis. B. aryabhattai LS9, LS11, LS12, and LS15 could solubilize 577.9, 676.8, 623.6, and 581.3 mg/L of 0.5% insoluble calcium phosphate within 2 days of incubation. Production of indole acetic acid, a typical growth promoting phytohormone auxin, by strain LS15 was 471.3 mg/L in 2 days with the addition of auxin precursor L-tryptophan. All the strains also produced other phytohormones such as indole butyric acid, gibberellins, and abscisic acid, and strain LS15 showed the highest production rate of gibberellin (GA(3)), 119.0 μg/mg protein. Isolated bacteria were used in a microcosm test for growth of wild plant Xanthium italicum, which can be utilized as a pioneer plant in barren lands. Seed germination was facilitated, and the lengths of roots, and shoots and the dry weights of germinated seedlings after 16 days were higher than those of the uninoculated control plants. Root lengths of seedlings of X. italicum increased by 121.1% in LS11-treated samples after 16 days. This plant growth-promoting capability of B. aryabhattai strains may be utilized as an environmentally friendly means of revegetating barren lands, especially sensitive areas such as lakeside lands.


Citric acid-modified Fenton's reaction for the oxidation of chlorinated ethylenes in soil solution systems.
Fenton's reagent, a solution of hydrogen peroxide and ferrous iron catalyst, is used for an in situ chemical oxidation of organic contaminants. Sulfuric acid is commonly used to create an acidic condition needed for catalytic oxidation. Fenton's reaction often involves pressure buildup and precipitation of reaction products, which can cause safety hazards and diminish efficiency. We selected citric acid, a food-grade substance, as an acidifying agent to evaluate its efficiencies for organic contaminant removal in Fenton's reaction, and examined the impacts of using citric acid on the unwanted reaction products. A series of batch and column experiments were performed with varying H2O2 concentrations to decompose selected chlorinated ethylenes. Either dissolved iron from soil or iron sulfate salt was added to provide the iron catalyst in the batch tests. Batch experiments revealed that both citric and sulfuric acid systems achieved over 90% contaminant removal rates, and the presence of iron catalyst was essential for effective decontamination. Batch tests with citric acid showed no signs of pressure accumulation and solid precipitations, however the results suggested that an excessive usage of H2O2 relative to iron catalysts (Fe2+/H2O2<1/330) would result in lowering the efficiency of contaminant removal by iron chelation in the citric acid system. Column tests confirmed that citric acid could provide suitable acidic conditions to achieve higher than 55% contaminant removal rates.


REM sleep loss-induced elevated noradrenaline could predispose an individual to psychosomatic disorders: a review focused on proposal for prediction, prevention, and personalized treatment.
Historically and traditionally, it is known that sleep helps in maintaining healthy living. Its duration varies not only among individuals but also in the same individual depending on circumstances, suggesting it is a dynamic and personalized physiological process. It has been divided into rapid eye movement sleep (REMS) and non-REMS (NREMS). The former is unique that adult humans spend the least time in this stage, when although one is physically asleep, the brain behaves as if awake, the dream state. As NREMS is a pre-requisite for appearance of REMS, the latter can be considered a predictive readout of sleep quality and health. It plays a protective role against oxidative, stressful, and psychopathological insults. Several modern lifestyle activities compromise quality and quantity of sleep (including REMS) affecting fundamental physiological and psychopathosomatic processes in a personalized manner. REMS loss-induced elevated brain noradrenaline (NA) causes many associated symptoms, which are ameliorated by preventing NA action. Therefore, we propose that awareness about personalized sleep hygiene (including REMS) and maintaining optimum brain NA level should be of paramount significance for leading physical and mental well-being as well as healthy living. As sleep is a dynamic, multifactorial, homeostatically regulated process, for healthy living, we recommend addressing and treating sleep dysfunctions in a personalized manner by the health professionals, caregivers, family, and other supporting members in the society. We also recommend that maintaining sleep profile, optimum level of NA, and/or prevention of elevation of NA or its action in the brain must be seriously considered for ameliorating lifestyle and REMS disturbance-associated dysfunctions.


Longitudinal DRG-based survey of all-cause and pneumococcal pneumonia and meningitis for inpatients in France (2005-2010).
This population-based retrospective study quantified the burden of all-cause and pneumococcal pneumonia and meningitis in the Rhône-Alpes region of France from 2005 to 2010, when the 7-valent pneumococcal conjugate vaccine uptake increased from 50 to>90% in children. Hospital admission data was obtained from the French Diagnosis Related Groups program database (French acronym PMSI). Patients were residents of the Rhône-Alpes region hospitalized for the diseases of interest during 2005-2010. Hospitalization and in-hospital mortality rates were calculated by age, sex, and year on the basis of the Rhône-Alpes region population. Hospitalization and in-hospital mortality rates were compared using Chi(2) tests with statistical significance adjusted for multiple comparisons. The highest hospitalization rates by age group were: all-cause pneumonia, oldest group (>65 years); all-cause and pneumococcal meningitis, youngest group (0-4 years), and pneumococcal pneumonia, youngest and oldest groups. Hospitalization rates significantly decreased for all-cause pneumonia (5-19 years: -12.71%) and all-cause meningitis (20-49 years: -29.22%). Pneumococcal disease rates did not significantly change in any age group. Mortality rates from all-cause pneumonia and meningitis were highest in the oldest age groups. The burden of all-cause and pneumococcal pneumonia and meningitis remains substantial. Significant changes (decreases) between 2005 and 2010 in hospitalization rates were limited and varied among age groups, most likely because this study began 2 years after PCV7 was first introduced in France for children at broadly-defined high risk. Further research is needed on the relationship between serotype epidemiology and clinical patterns of disease.


Improving team meetings to support discharge planning.
Following the establishment of a discharge working group, several concerns were raised about the management of multidisciplinary team (MDT) discharge meetings throughout the trust. A project was established to observe MDT meetings, identify good practice and produce practice guidance to improve standards and achieve consistency throughout the organisation.


Factors affecting health-related quality of life in prostate cancer patients.
Prostate cancer is the most common cancer among men in Lithuania. Quality of life (QoL) assessment plays a key role in the evaluation and treatment of cancer patients. The aim of this study was to evaluate factors affecting the QoL of patients with prostate cancer in Lithuania. A cross-sectional national-level study was performed. QoL was investigated with the EORTC QLQ-C30 questionnaire. Statistical analysis included descriptive statistics, interrelationship analysis between characteristics and multivariate logistic regression to estimate predictors and odds ratios (ORs) for each of the independent variables in the model. The response rate was 74.8% (N = 486). One-quarter of respondents with prostate cancer indicated high QoL scores. Higher QoL scores were given for prostate cancer patients with lower education level [OR = 3.092, 95% confidence interval (CI) 1.007-9.491, p = 0.049], having lower monthly expenses for treatment (OR = 3.653, CI 1.318-10.128, p = 0.013), disease stage II (by patient conveyance) (OR = 10.053, CI 1.015-99.534, p = 0.048), disease stage I (by medical record) (OR = 2.19E + 08, CI 218514200.17-218514200.17, p < 0.001) and in those with undisclosed disease stage (OR = 9.220, CI 1.251-67.965, p = 0.029). Significant predictors for higher QoL scores were education level, own monthly expenses for treatment and disease stage. Patients with undisclosed disease stage more often had higher QoL scores.


First case of subcutaneous zygomycosis caused by Saksenaea vasiformis in India.
The first case of subcutaneous zygomycotic infection caused by Saksenaea vasiformis in a rice mill worker from India is described. The infection, confined to the man's left foot, showed multiple draining sinuses, inflammation, and intermittent low-grade fever following a crushing injury when a log fell on his foot. Histopathologic examination of two biopsy specimens, taken at 3-wk intervals, revealed the presence of broad, sparsely septate, branched, hyaline hyphae characteristic of a zygomycete. When they were grown on a nutritionally deficient medium, two cultures isolated from the biopsied tissues formed numerous, vase-shaped sporangia typical of S. vasiformis. Necrosis of the affected area led to amputation of the fore part of the foot. A split thickness graft was well accepted, and treatment with potassium iodide, following the graft, cured the infection.


Movement-related slow potentials. I. A contrast between finger and foot movements in right-handed subjects.
Movement-related potentials ( MRPs ) preceding a finger flexion and a plantar flexion of the foot on either side were compared over the frontal, central and parietal areas of both hemispheres. MRP amplitudes were larger preceding foot than preceding finger movements. In the first case their onset was earlier and their presence in the frontal area was more marked. Prior to a finger flexion amplitudes over the hemisphere contralateral to the movement side were larger than those recorded over the ipsilateral hemisphere. On the contrary, prior to a plantar flexion of the foot, amplitudes were larger over the hemisphere ipsilateral to the movement. These findings point to differently localized sources of the MRPs in the two cases. In other experiments larger amplitudes preceding foot movements were found near the midline. It is suggested that the ipsilateral preponderance prior to foot movements is caused by a contralateral source in the depth near the longitudinal fissure. The dipoles are presumably directed obliquely to the median plane. The ipsilateral preponderance is present both prior to and following the plantar flexion. This suggests comparable directions of the dipoles in the motor and somatosensory areas.


Odontogenic ameloblast-associated and amelotin are novel basal lamina components.
Odontogenic ameloblast-associated (ODAM) and amelotin (AMTN) are secreted by maturation stage ameloblasts and accumulate at the interface with enamel where an atypical basal lamina (BL) is present. This study aimed at determining and quantifying the ultrastructural distribution of ODAM and AMTN at the cell-tooth interface. Ultrathin sections of enamel organs from the early to mid- and late maturation stage of amelogenesis were processed for immunogold labeling with antibodies against ODAM, AMTN or with the lectins wheat germ agglutinin, Helix pomatia agglutinin (HPA) and Ricinus communis I agglutinin. Immunolabeling showed that both ODAM and AMTN localized to the BL. Quantitative analyses indicated that at the beginning of maturation there is a concentration of ODAM on the cell side of the BL while AMTN appears more concentrated on the enamel side. In the late maturation stage, such differential distribution is no longer apparent. All three lectins are bound to the BL. Competitive incubation with native lectins did not affect the binding efficiency of ODAM; however, AMTN binding was significantly reduced after incubation with HPA. In conclusion, ODAM and AMTN are bona fide components of the BL associated with maturation stage ameloblasts and they organize into different subdomains during the early maturation stage. The data also suggest that the BL is a dynamic structure that rearranges its organization as enamel maturation advances. Finally, the abrogation of AMTN antibody labeling by HPA supports the presence of O-linked sugars in the molecule and/or its close association with other O-glycosylated molecules.


Cardiac angiography and conversion disorder.
Somatoform disorders are disorders in which "psychic energy" is transferred to somatic symptoms secondary to stressors. The concept of somatoform disorders and their associations among patients with cardiac disease is a relatively unfamiliar area. The authors present a case that illustrates how conversion disorder, a specific type of somatoform disorder, may be associated with the psychologic stressor involved with cardiac angiography. The authors will discuss the literature concerning the identification and treatment of this disorder. The relevant literature in the area of conversion disorder and cardiac angiography was reviewed. This report is the first documented case of a woman who developed conversion disorder after coronary catheterization. Using the case, a summary of diagnostic and treatment modalities used in this disorder is provided. The case highlights how conversion disorder can occur as a sequelae of coronary catheterization. The principles involved in the diagnosis and treatment of conversion disorder were successful in managing this patient. It is hoped that the case can aid cardiologists in becoming cognizant of this uncommon psychiatric disorder.


Improving the screening of precancerous anal lesions in high-risk subjects with normal cytology: A longitudinal cohort study using simple tests.
For patients at high risk of anal cancer, annual screening strategies using invasive evaluation methods are stressful. According to a normal examination at baseline using simple and non invasive tests, the aim of the work was to quantify neoplastic events. Data from patients with a normal evaluation at the first visit were retrospectively extracted from a prospective database. The individual follow-up period was at least two years and three evaluations. Patients with abnormal cytology were assessed using high-resolution anoscopy and targeted biopsies. A total of 182 subjects (F/M: 10/90, aged 48.1(10.6) years, HIV: 81%) were followed for 41(11) months. Anal cytology remained normal in 94 patients (52%), but high-grade anal neoplasms occurred in 28 patients (15%). Patients with a negative HPV16 status at baseline had cumulative probabilities of high-grade AIN of 0.4%(0.1%-1.9%), 2.6%(1.2%-5.9%) and 7.5%(4.5%-12.2%) after 1 year, 2 years and 3 years of follow-up, respectively. These probabilities were lower than those of patients with a positive HPV16 at baseline and those with a previous history of AIN. In patients with normal cytology and negative HPV16 at baseline, a three-year interval screening may be a less cumbersome alternative to traditional annual screening.


Expanding and Remixing the Metadata Landscape.
Genomic data sharing accelerates research. Data are most valuable when they are accompanied by detailed metadata. To date, metadata are often human-annotated descriptions of samples and their handling. We discuss how machine learning-derived elements complement such descriptions to enhance the research ecosystem around genomic data.


Improving nitrogen uptake efficiency by chitin nanofiber promotes growth in tomato.
Chitin, an N-acetyl-D-glucosamine polymer, has been known to enhance plant growth. However, this polysaccharide has not been used extensively in experimental work or agriculture practices because its hydrophobic nature makes it difficult to handle. Chitin nanofiber (CNF), which disperses well in water, can feasibly be used to evaluate the effect of chitin on the promotion of plant growth. In this study, we analysed the contents of inorganic elements and global gene expression to obtain an overview of the growth-promoting action of chitins in plants. Significant increases in the biomass of aerial parts and concentration of chlorophyll following treatment with CNF or short-chain chitin oligomers were observed in tomatoes that were hydroponically cultivated under ultralow nutrient concentrations. The results of the quantification of inorganic elements demonstrated that concentrations of nitrogen and carbon significantly increased in whole tomato plant under chitin treatment. Transcriptome analysis of CNF-treated tomatoes by RNA sequencing showed that the expression levels of genes related to nitrogen acquisition and assimilation, nutrient allocation and photosynthesis were altered. These results indicate that the growth-promoting action of chitin treatment is caused by an improvement in nitrogen uptake efficiency and that CNF could be a useful material for nutrient management in tomato production.


A high-quality sponge gourd (Luffa cylindrica) genome.
Sponge gourd (Luffa cylindrica) is an important cultivated vegetable and medicinal plant in the family Cucurbitaceae. In this study, a draft genome sequence of the sponge gourd inbred line P93075 was analyzed. Using Illumina, PacBio, and 10× Genomics sequencing techniques as well as new assembly techniques such as FALCON and chromatin interaction mapping (Hi-C), a chromosome-scale genome of approximately 656.19 Mb, with an N50 scaffold length of 48.76 Mb, was generated. From this assembly, 25,508 protein-coding gene loci were identified, and 63.81% of the whole-genome consisted of transposable elements, which are major contributors to the expansion of the sponge gourd genome. According to a phylogenetic analysis of conserved genes, the sponge gourd lineage diverged from the bitter gourd lineage approximately 41.6 million years ago. Additionally, many genes that respond to biotic and abiotic stresses were found to be lineage specific or expanded in the sponge gourd genome, as demonstrated by the presence of 462 NBS-LRR genes, a much greater number than are found in the genomes of other cucurbit species; these results are consistent with the high stress resistance of sponge gourd. Collectively, our study provides insights into genome evolution and serves as a valuable reference for the genetic improvement of sponge gourd.


Detection of novel guanine nucleotide binding proteins in bovine retinal rod outer segments.
In the rod outer segment membranes of the bovine retina at least two members of the small molecular weight guanine nucleotide binding proteins were identified by means of the technique of binding radiolabeled GTP to nitrocellulose Western blots of proteins separated by sodium dodecyl sulphate gel electrophoresis. Such proteins, of 23 and 25 kDa, are able to specifically bind guanine nucleotides after denaturing treatments, and are not labeled by pertussis or cholera toxin-catalyzed ADP-ribosylation. The binding site is specific for GTP.


Twelve-month outcomes of a new refractive lenticular extraction procedure.
To evaluate the 12-month refractive and visual outcomes of Small Incision Guided Human-cornea Treatment (SmartSight®, SCHWIND eye-tech-solutions, Kleinostheim, Germany) in the treatment of myopia corrections with low to moderate astigmatism with the use of a new femtosecond laser system. 221 eyes of 114 patients consecutively treated with SmartSight lenticule extraction were assessed. The mean age of the patients was 28±6 years at the time of treatment with a mean spherical equivalent refraction of -6.26±2.17D and mean astigmatism of 0.92±0.68D. Monocular corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA) were assessed pre- and post-operatively. Refractive changes have been determined in terms of changes in refraction, as well as changes in keratometric readings. The changes in central epithelial thickness have been determined. At twelve months post-operatively, mean UDVA was 20/21±2. Spherical equivalent showed a residual refraction of +0.48±0.31D with refractive astigmatism of 0.13±0.18D postoperatively. There was a slight decrease of -0.1 Snellen lines at 12-months follow-up. The same correction was determined using changes in refraction, as well as changes in keratometric readings. The central epithelial thickness increased by +3±2µm. Spherical equivalent correction within ±0.50D was achieved in 199 eyes (90%), and cylindrical correction in 221 (100%). Preoperative corrected distance visual acuity (CDVA) was 20/20 or better in 213 eyes (96%), and postoperative uncorrected (UDVA) was 20/20 or better in 205 eyes (93%). No eye had lost two or more Snellen lines of CDVA. Myopic astigmatism correction with SmartSight provided good results for efficacy, safety, predictability, and visual outcomes at the twelve months of follow up. The central epithelial thickness barely increased by 3±2µm.


Chronic compression or acute dissociation of dorsal root ganglion induces cAMP-dependent neuronal hyperexcitability through activation of PAR2.
Chronic compression (CCD) or dissociation of dorsal root ganglion (DRG) can induce cyclic adenosine monophosphate (cAMP)-dependent DRG neuronal hyperexcitability and behaviorally expressed hyperalgesia. Here, we report that protease-activated receptor 2 (PAR2) activation after CCD or dissociation mediates the increase of cAMP activity and protein kinase A (PKA) and cAMP-dependent hyperexcitability and hyperalgesia in rats. CCD and dissociation, as well as trypsin (a PAR2 activator) treatment, increased level of cAMP concentration, mRNA, and protein expression for PKA subunits PKA-RII and PKA-c and protein expression of PAR2, in addition to producing neuronal hyperexcitability and, in CCD rats, thermal hyperalgesia. The increased expression of PAR2 was colocalized with PKA-c subunit. A PAR2 antagonistic peptide applied before and/or during the treatment, prevented or largely diminished the increased activity of cAMP and PKA, neuronal hyperexcitability, and thermal hyperalgesia. However, posttreatment with the PAR2 antagonistic peptide failed to alter either hyperexcitability or hyperalgesia. In contrast, an adenylyl cyclase inhibitor, SQ22536, administrated after dissociation or CCD, successfully suppressed hyperexcitability and hyperalgesia, in vitro and/or in vivo. Trypsin-induced increase of the intracellular calcium [Ca(2+)](i) was prevented in CCD or dissociation DRG neurons. These alterations were further confirmed by knockdown of PAR2 with siRNA. In addition, trypsin and PAR2 agonistic peptide-induced increase of cAMP was prevented by inhibition of PKC, but not Gαs. These findings suggest that PAR2 activation is critical to induction of nerve injury-induced neuronal hyperexcitability and cAMP-PKA activation. Inhibiting PAR2 activation may be a potential target for preventing/suppressing development of neuropathic pain.


Oligospermia secondary to müllerian duct cyst. Simple surgical cure.
Fertility evaluation of a twenty-three-year-old male with severe oligospermia revealed a müllerian duct cyst that appeared to compress both ejaculatory ducts. Simple endoscopic unroofing of the cyst was followed by disappearance of the mass felt rectally, improvement of the radiographic appearance of the seminal tracts, and a return of the seminal analyses to well within fertile range. Müllerian duct cysts may be a rare cause of surgically correctable male infertility. Endoscopic unroofing of small müllerian duct cysts appears to be the treatment of choice in young males in whom there is concern for preserving fertility and potency.


The effects of felodipine in angina pectoris.
The clinical response to felodipine, in addition to a beta-blocker, was evaluated and compared with placebo in this double-blind cross-over study. Twenty patients with exertional angina pectoris completed the study. Felodipine reduced the number of angina attacks and the Glyceryl Trinitrate (GTN) consumption. The median exercise capacity was increased 33% after 4 weeks' felodipine treatment compared with placebo. At maximal exercise, systolic blood pressure and rate pressure product were reduced by felodipine while no change was seen in heart rate or ST-depression. Felodipine reduced both supine and erect blood pressure. The mean supine blood pressure at rest was 138/82 mm Hg after four weeks' placebo treatment compared with 114/71 mmHg after felodipine 5-10 mg b.i.d. Felodipine has overall a modest but significant anti-anginal benefit when combined with a beta-blocker.


Diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation: a systematic review and meta-analysis.
Our objective was to elucidate the overall diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation (AIP). Medline, Embase, CINAHL and The Cochrane databases were searched. The ultrasound signs explored were: loss of hypoechoic (clear) zone in the placental-uterine interface, placental lacunae, bladder wall interruption, myometrial thinning, focal exophitic mass, placental lacunar flow, subplacental vascularity, and uterovesical hypervascularity. Twenty studies (3209 pregnancies) were included. Ultrasound had an overall good diagnostic accuracy in identifying the depth of placental invasion with sensitivities of 90.6%, 93.0%, 89.5%, and 81.2% for placenta accreta, increta, accreta/increta, and percreta, respectively; the corresponding specificities were 97.1%, 98.4%, 94.7%, and 98.9%. Placental lacunae had sensitivities of 74.8%, 88.6%, and 76.3% for the detection of placenta accreta, increta, and percreta, respectively. Sensitivity and specificity of loss of the clear zone in identifying placenta accreta were 74.9% and 92.0%, whereas the corresponding figures for placenta increta and percreta were 91.6% and 76.9%, and 88.1% and 71.1%. Lacunar flow had sensitivities of 81.2%, 84.3%, and 45.2% for the detection of placenta accreta, increta, and percreta respectively; the corresponding figures for specificity were 84.0%, 79.7%, and 75.3%. Sensitivity of uterovesical hypervascularity was low for the detection of placenta accreta (12.3%) but high for placenta increta (94.4%) and percreta (86.2%); the corresponding figures for specificity were 90.8%, 88.0% and 88.2%, respectively. Ultrasound has an overall good diagnostic accuracy in recognizing the depth and the topography of placental invasion.


Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance.
The ability to produce vigorous immune responses that spare self tissues and organs depends on the elimination of autoreactive T and B cells. However, purging of immature and mature self-reactive T and B cells is incomplete and may also require the involvement of cells programmed to suppress immune responses. Regulatory T cells (T(reg)) belonging to the CD4(+) T-cell subset may have a role in preventing untoward inflammatory responses, but T-cell subsets programmed to inhibit the development of autoantibody formation and systemic-lupus-erythematosus-like disease have not yet been defined. Here we delineate a CD8(+) regulatory T-cell lineage that is essential for the maintenance of self tolerance and prevention of murine autoimmune disease. Genetic disruption of the inhibitory interaction between these CD8(+) T cells and their target Qa-1(+) follicular T-helper cells results in the development of a lethal systemic-lupus-erythematosus-like autoimmune disease. These findings define a sublineage of CD8 T cells programmed to suppress rather than activate immunity that represents an essential regulatory element of the immune response and a guarantor of self tolerance.


Birth weight influences differently on systolic and diastolic blood pressure in children and adolescents aged 8-15.
Globally, hypertension is one of the main threats to public health and a significant risk factor predisposing individuals to various cardiovascular conditions. Hypertension in the young is particularly complex and challenging. Accumulating evidence has implicated that low birth weight is vital for elevated blood pressure, and birth weight was negatively correlated with blood pressure. However, fewer studies with conflicting results have addressed the associations between birth weight and blood pressure in children and adolescents, and there is no relevant research conducted in the NHANES population. The principal objective of this project was to investigate the relationship between birth weight and blood pressure in children and adolescents in NHANES. A total of 7600 subjects aged 8 to15 were enrolled in the present study from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Outcome variables were systolic blood pressure(SBP) and diastolic blood pressure(DBP). Birth weight was regarded as an independent variable. EmpowerStats software and R (version 3.4.3) were performed to examine the association between birth weight and SBP or DBP. Birth weight was negatively correlated with SBP in the fully-adjusted model(β = -0.02, 95%CI: -0.04 to -0.04, p = 0.0013), especially in non-Hispanic White (β = -0.03, 95%CI: -0.06 to -0.00,p = 0.0446), aged between 13 to 15(β = -0.03, 95%CI: -0.04 to -0.01, p = 0.0027), and male individuals(β = -0.03, 95%CI: -0.05 to -0.01, p = 0.0027). However, there was no unidirectional association between birth weight and DBP in the fully adjusted model(β = -0.01, 95%CI: -0.03 to 0.02, p = 0.5668) and in sub-analysis. An inverted U-shaped and J-shaped relationship was uncovered between birth weight and DBP in those aged 13 or above and Mexican Americans, respectively. The inflection point calculated by a recursive algorithm of birth weight in these groups was all 105 oz. The current study identified that birth weight was negatively related to SBP but not significantly related to DBP in children and adolescents aged 8 to 15, highlighting different potential mechanisms behind high SBP and high DBP in the young. However, an inverted U-shaped and J-shaped relationship between birth weight and DBP was observed, suggesting that targeted intervention measures should be taken for different groups of people rather than generalizations.


Computational molecular modeling for evaluating the toxicity of environmental chemicals: prioritizing bioassay requirements.
The human health risk from exposure to environmental chemicals often must be evaluated when relevant elements of the preferred data are unavailable. Therefore, strategies are needed that can predict this information and prioritize the outstanding data requirements for the risk evaluation. Many modes of molecular toxicity require the chemical or one of its biotransformation products to interact with specific biologic macromolecules (i.e., proteins and DNA). Molecular modeling approaches may be adapted to study the interactions of environmental chemicals with biomolecular targets. In this commentary we provide an overview of the challenges that arise from applying molecular modeling tools developed and commonly used for pharmaceutical discovery to the problem of predicting the potential toxicities of environmental chemicals. The use of molecular modeling tools to predict the unintended health and environmental consequences of environmental chemicals differs strategically from the use of the same tools in the pharmaceutical discovery process in terms of the goals and potential applications. It also requires consideration of the greater diversity of chemical space and binding affinity domains than is covered by pharmaceuticals. Molecular modeling methods offer one of several complementary approaches to evaluate the risk to human health and the environment as a result of exposure to environmental chemicals. These tools can streamline the hazard assessment process by simulating possible modes of action and providing virtual screening tools that can help prioritize bioassay requirements. Tailoring these strategies to the particular challenges presented by environmental chemical interactions make them even more effective.


Biological activity of insect juvenile hormone analogues against the stable fly and toxicity studies in domestic animals.
The insect JHAs are effective inhibitors of adult stable fly development. Laboratory and field evaluation studies demonstrated that area application of the analogues to larval breeding sites was efficacious for stable fly control in cattle feed lots and in marine grasses. Analytical methods by quantification with gas chromatography with flame ionization detection was developed to measure residual properties as well as aging and leaching in fly breeding media. The analogues did not interfere with the oviposition and development of the endoparasites, M. raptor and S. endius. Toxicity studies against swine, hamsters, and sheep showed that when compounds of high purity were used that no toxic effects were observed in any of the species.


Carbon nanotube-coupled cell adhesion peptides are non-immunogenic: a promising step toward new biomedical devices.
Carbon nanotubes functionalized with cell adhesion peptides can be considered as novel, promising candidates for the development of advanced drug delivery systems or for designing new generation of self-assembling nerve 'bridges'. An important step toward the integration of these types of conjugates in living bodies is the assessment of their impact on the immune system. In this direction, an integrin-derived peptide has been covalently conjugated to carbon nanotubes. Following intraperitoneal administration, peptide-carbon nanotubes do not trigger an anti-peptide antibody production. Demonstration of the immune neutrality of peptide-carbon nanotubes reinforces their potential use as substrates for neuronal regeneration in vivo.


Nitroaromatic actuation of mitochondrial bioelectrocatalysis for self-powered explosive sensors.
Oligomycin-inhibited mitochondria-modified electrodes were used to electrochemically sense the presence of nitroaromatics owing to the selective ability of nitroaromatics to decouple the inhibition of pyruvate metabolism by the mitochondria. These oligomycin inhibited mitochondria-modified electrodes were employed as the bioanode in a pyruvate/air biofuel cell. This sensing mechanism could be used as a traditional electrochemical sensor or as a self-powered sensor.


The association between plasma adiponectin level and hypertension.
Lower plasma adiponectin levels are related to dyslipidaemia and components of the metabolic syndrome. It is not clear whether adiponectin levels are independently related to hypertension. Also, previous studies that examined the putative adiponectin-hypertension association studied only men. We examined the relationship between plasma adiponectin and hypertension after controlling for important confounding factors and also performed separate analyses among men and women. Cross-sectional study of 664 participants (mean age: 52.5 years, 50.3% men). Main outcome-of-interest was presence of hypertension (systolic blood pressure (BP) > or = 140 mmHg, diastolic > or = 90 mmHg, or combination of self-reported hypertension diagnosis and antihypertensive medication use). Lower plasma adiponectin levels were found to be positively associated with hypertension. Multivariable odds ratio (OR) (95% confidence intervals [CI]) comparing gender-specific tertile I of plasma adiponectin to tertile 3 (referent) was 3.40 (2.04-5.68), P-trend < 0.0001. This association was consistently present in separate analyses among men (P-trend < 0.0001) and women (P-trend = 0.01). These data provide new evidence clarifying the putative relation between plasma adiponectin and hypertension, suggesting that this association is independent of traditional cardiovascular factors, including dyslipidaemia and renal function and present in both men and women.


Comparison of extraction and quantification methods of perfluorinated compounds in human plasma, serum, and whole blood.
Perfluorinated compounds are ubiquitous in the environment and have been reported to occur in human blood. Accurate risk assessments require accurate measurements of exposures, but identification and quantification of PFCs in biological matrices can be affected by both ion suppression and enhancement in liquid chromatography-tandem mass spectrometry techniques (LC/MS-MS). A study was conducted to quantify potential biases in LC/MS-MS quantification methods. Using isotopically labeled perfluorooctanoic acid ([(13)C(2)]-PFOA), perfluorononanoic acid ([(13)C(2)]-PFNA), and ammonium perfluorooctanesulfonate ([(18)O(2)]-PFOS) spiked tissues, ion-pairing extraction, solid-phase extraction, and protein precipitation sample preparation techniques were compared. Analytical accuracy was assessed using both solvent calibration and matrix-matched calibration for quantification. Data accuracy and precision of 100+/-15% was demonstrated in both human sera and plasma for all three sample preparation techniques when matrix-matched calibration was used in quantification. In contrast, quantification of ion-pairing extraction data using solvent calibration in combination with a surrogate internal standard resulted in significant analytical biases for all target analytes. The accuracy of results, based on solvent calibration was highly variable and dependent on the serum and plasma matrices, the specific target analyte [(13)C(2)]-PFOA, [(13)C(2)]-PFNA, or [(18)O(2)]-PFOS, the target analyte concentration, the LC/MS-MS instrumentation used in data generation, and the specific surrogate internal standard used in quantification. These results suggest that concentrations of PFCs reported for human blood using surrogate internal standards in combination with external solvent calibration can be inaccurate unless biases are accounted for in data quantification.