Targeted chemotherapy: chronic myelogenous leukemia as a model.
Many of the therapeutic agents used for cancer chemotherapy today are based on decades-old agents which are highly cytotoxic but are nonselective for cancer cells. The hallmark of chronic myelogenous leukemia (CML) is the Philadelphia chromosome translocation t(9;22), which results in the bcr-abl fusion gene. As an alteration that is nearly universal in CML cells, bcr-abl presents a therapeutic target that is unique to the pathological cells in CML patients. Advances in the understanding of the molecular mechanisms which sustain leukemic cells in CML have enabled the development of selective therapies for this disease. We review here the molecular pathogenesis and current treatment of CML. We also discuss the development of imatinib mesylate, a selective inhibitor of Bcr-Abl which has shown promise in clinical trials with CML. This recent advance in CML therapy represents a novel approach to rational design and development of new anticancer drugs.


The lattice Fokker-Planck equation for models of wealth distribution.
Recent work on agent-based models of wealth distribution has yielded nonlinear, non-local Fokker-Planck equations whose steady-state solutions describe empirical wealth distributions with remarkable accuracy using only a few free parameters. Because these equations are often used to solve the 'inverse problem' of determining the free parameters given empirical wealth data, there is much impetus to find fast and accurate methods of solving the 'forward problem' of finding the steady state corresponding to given parameters. In this work, we derive and calibrate a lattice Boltzmann equation for this purpose. This article is part of the theme issue 'Fluid dynamics, soft matter and complex systems: recent results and new methods'.


Examining the boundaries between ICD-11 PTSD/CPTSD and depression and anxiety symptoms: A network analysis perspective.
Two newly identified sibling disorders - ICD-11 PTSD and CPTSD - have been well validated in the last few years. Although these trauma-related disorders are suggested to be neatly separated from depression and anxiety, no study has used a network analysis to examine those definitions' construct validity when they also interplay with symptoms of depression and anxiety. Additionally, no research has focused upon the specific boundaries between these four disorders' symptoms, the bridges between them, and the ways they influence each other among clinical populations. A sample of 234 men drawn randomly from a national sample of 1,600 Jewish men receiving treatment for domestic violence in Israel completed the ICD-11 International Trauma Questionnaire (ITQ) and Brief Symptom Inventory (BSI). The ICD-11 CPTSD, depression and anxiety clustering network results revealed, within the EGA, a four-cluster solution in which PTSD and CPTSD symptoms are differentiated from two other distinct clusters of anxiety and depression symptoms. Feelings of worthlessness and avoiding internal reminders of the experience were the most central symptoms. Due to the use of a cross-sectional design, causal interpretation of the network correlation between symptoms should be made cautiously. These findings strengthen the approach that ICD-11 PTSD and CPTSD have a distinct construct; however, they also reflect a strong positive connection to anxiety and depression symptoms and no clear boundaries between disorders. Specifically, dysphoria/avoidance-related symptoms act as a bridge between the disorders, which may be important targets for specific assessments and related interventions.


Rare multiple congenital anomalies-hypotonia-seizures syndrome type 1 (MCAHS1) - the clinical and molecular summary.
Multiple congenital anomalies-hypotonia-seizures syndrome type 1 (MCAHS1) is a rare autosomal recessive genetic disease belonging to glycosylphosphatidylinositols biosynthesis defects (GPIBD), a group of recessive disorders characterized by intellectual disability, hypotonia, and seizures. Glycosylphosphatidylinositols (GPIs) are glycolipids that anchor and remodel cell proteins. These processes are highly conserved and fundamental in the metabolism of all eukaryotes, including humans. Here, we have reported a male patient presenting with hypotonia, intellectual disability, and epilepsy, who underwent whole exome sequencing (WES). The analysis revealed the presence of two deleterious variants in PIGN that encodes GPI ethanolamine phosphate transferase-1 - one novel (c.1247_1251delAAGTG; p.Glu416Glyfs*22), and one that has been previously reported in the medical literature (c.1434+5G>A) resulting in MCAHS1. The detailed clinical assessment followed by the medical literature review also pointed out transient macrosomia and unreported in MCAHS1 advanced bone age and postnatal tall stature. These symptoms suggest that MCAHS1 shares a phenotypic overlap with disorders associated with overgrowth. To conclude, our case report and summary of the medical literature may be helpful for clinicians and geneticists who diagnose patients presenting with hypotonia accompanied by tall stature, advanced bone age, and transient macrosomia.


Effect of high dose oral zinc in mice with severe infection with Streptococcus pneumoniae.
Zinc is important for normal function of the immune system and inflammation increases the demand for zinc. We hypothesized that high doses of zinc given during acute pneumococcal illness would alter the severity of infection. 24 six-week-old BALB/c mice were anaesthetized and infected intranasally with Streptococcus pneumoniae. Zinc intake was controlled by administering zinc through an intragastric tube. One group was given normal doses (5 microg/d) and the other group high doses of zinc (225 microg/d). We counted the number of bacteria from venous blood at 24 and 48 h, and from heart puncture and nasal wash at 72 h after intranasal challenge. Mice given excess zinc had 2.65 micromol/l, i.e. 25% higher (p= 0.05) mean plasma zinc concentration compared to those given normal amounts. 75% of mice in both groups developed pneumococcal bacteraemia. There were no differences in the numbers of S. pneumoniae colony forming units (CFUs) in blood or nasal wash between the groups. Thus, high doses of zinc did not alter the severity of systemic pneumococcal infection in mice.


Age-related peculiarities of contractile activity of rat myocardium during blockade of hyperpolarization-activated currents.
Contractile activity of atrial and ventricular myocardial strips isolated from rats of various age was examined under conditions of blockade of non-selective hyperpolarization-activated cation currents. Addition of ZD7288, a blocker of non-selective hyperpolarization-activated cation currents, to the perfusion solution increased the contraction force of atrial and ventricular strips in 1-, 8-, and 20-week rats, but produced an opposite effect on contractile activity of atrial and ventricular strips in 3-week rats.


A novel and ultrasensitive sandwich-type electrochemical immunosensor based on delaminated MXene@AuNPs as signal amplification for prostate specific antigen (PSA) detection and immunosensor validation.
In this study, an ultra-sensitive electrochemical immunosensor for PSA detection was designed. Firstly, gold nanoparticles (AuNPs)/p-aminothiophenol (ATP) functionalized graphene oxide (GO) composite (AuNPs-ATPGO) was constructed and modified to glassy carbon electrode (AuNPs-ATPGO/GCE). AuNPs-ATPGO/GCE was utilized as immunosensor platform to increase the amount of PSA antibody1 (Ab1). After that, self-assembled delaminated MXene-gold nanoparticles (d-Ti3C2TX MXene@AuNPs) was used to label PSA seconder antibody2 (Ab2) as signal amplification. The prepared AuNPs-ATPGO, d-Ti3C2TX MXene@AuNPs and electrochemical immunosensor was charecterized by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), scanning electron microscope (SEM), x-ray diffraction (XRD) method, x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR). The linearity range and detection limit (LOD) were obtained as 0.01-1.0 pg mL-1 and 3.0 fg mL-1, respectively.


Esophageal carcinoma. Ex vivo endoluminal magnetic resonance imaging.
The authors evaluate ex vivo the role of endoluminal magnetic resonance imaging (MRI) in the tumor and regional lymph node staging of esophageal carcinoma. Nine esophagus specimens with carcinoma (seven adenocarcinoma, two squamous cell carcinoma) were studied directly after resection. Tumor (T) and regional lymph nodes (N) were classified, and the results were compared to histopathology. T classification with endoluminal MRI was correct in eight of the nine tumors. One Tis tumor was staged as T1 tumor because of submucosal edema. MRI detected 35 of 91 lymph nodes. Of these 35 nodes, 14 were true-positives, 5 were false-positives, 1 was a false-negative, and 15 were true-negatives. The majority of the 56 missed lymph nodes were outside the field of view, including two specimens with a tight stricture. These lymph nodes included seven nodes with metastatic involvement. TN classification was correct in six specimens (67%). This ex vivo pilot study demonstrates that T classification of esophageal carcinoma using endoluminal MRI is feasible. The results of lymph node classification are less favorable, predominantly because of the limited field of view.


A life cycle assessment study of dairy farms in northern Germany: The influence of performance parameters on environmental efficiency.
Recently, consumers concerns towards an environmental friendly food production are growing. The dairy sector contributes to the production of important greenhouse gases such as methane. The life cycle assessment (LCA) method enables to quantify the emissions and the use of resources throughout the entire life cycle of a product. The aim of the current study was to investigate the influence of performance parameters on the level of important environmental impacts (global warming potential (GWP), freshwater eutrophication (FE), terrestrial acidification (TA) and agricultural land occupation (ALO)) associated with milk production. Therein, the environmental impacts were analyzed using LCA considering two separate datasets (total, continuous) from Northern German farms throughout the years 2004-2013. Therefore, the performance parameters determining the level of environmental impacts were identified using the partial least square method. Thereby, a differentiated analysis among regions with various soil characteristics (Heath, Hill, Marsh) was conducted additionally. Further, linear mixed models were applied to each of the environmental impact categories. Energy-corrected milk yield (ECM), ECM from roughage, feed efficiency and the use of concentrates were identified as the most important determinants of environmental impacts. In general, an increase in productivity, especially an increase in ECM per cow and an increase in the amount of ECM produced per area of agricultural land accompanied with an improvement in environmental efficiency. The type of feed used had the major impact on the level of environmental impacts, whereby both concentrates and roughage had disadvantages. These results were in line with previous studies. Although, this study provides additional information relating the most important determinants of different environmental impacts, including a differentiated consideration of the relationship between performance parameters and environmental efficiency among regions. Further analyses on specific soil characteristics and their impact on environmental efficiency are recommended. In line with the concept of eco-efficiency, useful mitigation strategies in practice need to be applied depending on individual framework conditions.


Variable agreement between wearable heart rate monitors during exercise in cystic fibrosis.
In people with cystic fibrosis (CF), greater cardiorespiratory fitness is associated with improved survival and quality of life. Wearable activity monitors are a popular method of monitoring exercise, with measures of heart rate used to indicate exercise intensity. We assessed the agreement of heart rate recordings obtained using the Fitbit Charge HR™, Polar® H7 heart rate sensor and Masimo SET® Rad-5v pulse oximeter with the three-lead ECG during continuous and interval exercise. Adults with CF completed two exercise sessions, of 15-min duration per session, on a cycle ergometer while wearing the previously mentioned monitors. Firstly, participants cycled at 30% of estimated peak workload (W peak). Secondly, participants cycled at 1-min intervals at 60% of W peak interspersed with 2 min of unloaded cycling. Heart rate readings on all devices were recorded at minute intervals and their agreement was analysed using the Bland-Altman method. The Polar® H7 heart rate sensor had the best agreement with three-lead ECG, with a bias of 0±1 bpm during both continuous and interval exercise. The Masimo SET® Rad-5v pulse oximeter had good agreement, with a bias of 1±7 bpm and 1±5 bpm during continuous and interval exercise, respectively. The Fitbit Charge HR™ demonstrated less agreement, with a bias of 9±17 bpm and 5±13 bpm during continuous and interval exercise, respectively. The Fitbit Charge HR™ is not recommended for assessing heart rate during exercise in adults with CF. Findings support the use of the Polar® H7 for accurate heart rate monitoring.


Alkaline phosphatase reaction of canine mammary mixed tumours: a light and electron microscopic study.
Alkaline phosphatase (ALK-P) reactions at the light and electron microscopic levels were performed on eight canine mammary mixed tumours. In the morphologically normal gland next to the tumours, the myoepithelial cells and the stromal tissues near the acinar basement membranes both showed a positive ALK-P reaction by light microscopy. At the electron microscopic level, those parts of the myoepithelial cell membrane that were in contact with other cells--myoepithelial or lumenal epithelial--showed an ALK-P-positive reaction, as did the adjacent stromal tissue. The characteristic tumour cells, at sites of early proliferation, were ALK-P-positive, while in the mucoid and chondroid areas of the mixed tumours they were largely ALK-P-negative by light microscopy. By electron microscopy, those neoplastic cells which were in contact with other cells typically showed a positive ALK-P reaction, while those cells which were in contact with mucoid or chondroid matrix were largely negative. Although the cytoplasmic filaments of the neoplastic cells were 10 nm thick, and those of normal myoepithelial cells were 6 to 8 nm thick, the observations reported provide further evidence for the view that the essential cells of the canine mammary mixed tumour are derived from myoepithelial cells.


The workings of an action learning program for building mental health promotion capacity - A realist evaluation.
Action learning is a promising approach for building mental health promotion (MHP) capacity. The aim of this study is to explore how action learning processes can strengthen MHP capacity within and across organizations in a community setting. We applied an embedded case study design and a realist evaluation framework to explore key combinations of mechanisms and contextual factors that generated the emergent MHP capacity outcomes of an action learning program, i.e. context-mechanism-outcome-configurations (CMO-configurations). Data consisted of 18 semi-structured face-to-face interviews, 10 telephone interviews, two group interviews, observations, and documents. Interviewees (n = 21) were participants and management employees. Our analytical provision of CMO-configurations provides insights into how contextual factors, such as participant motivation, organizational support, and existing task descriptions, in combination with certain program mechanisms, such as legitimization of specific agendas, learning-by-doing, and collaborations across organizational boundaries, explain the identified outcomes. Outcomes ranged across implementation of MHP initiatives, personal development among participants, and relational and collaborative development. Taken together, our results strengthen the notion that mechanisms of action learning hold the potential to build MHP capacity on an individual, organizational, and community level. This study, also, illustrates that realist evaluation offers a relevant methodology for investigating the underlying workings of capacity building programs.


Subjective taste and smell changes in treatment-naive people with solid tumours.
Taste and smell changes (TSCs) are common in head and neck (H&N) cancer and during and after chemotherapy (CT) and radiotherapy (RT). It is an area that has been under-investigated, particularly in the treatment-naive, but can negatively impact nutritional status. This study examined the prevalence, severity and characteristics of TSCs in people with non-H&N solid tumours, before CT and RT, and their relationship with co-occurring symptoms. A prospective, observational study was conducted. Forty consecutive pre-treatment cancer patients, referred to radiation oncology outpatients over 6 weeks, were recruited. Data on TSCs, symptoms and nutritional status were obtained using the 'Taste and Smell Survey' and the 'abridged Patient-Generated Subjective Global Assessment' (abPG-SGA). BMI was measured. SPSS® was used for statistical analysis. Two-sided P values <0.05 were considered statistically significant. Most patients were newly diagnosed (n = 28; 70 %). Nineteen (48 %) reported TSCs; nine noted a stronger sweet and seven a stronger salt taste. Of these, four reported a stronger and four a weaker smell sensation. Those at nutritional risk reported more TSCs (n = 13/20). TSCs were significantly associated with dry mouth (P < 0.01), early satiety (P < 0.05) and fatigue (P < 0.05). TSCs preceded CT or RT in almost half of treatment-naive patients with solid tumours, notably stronger sweet and salt tastes. Half of the study group were at nutritional risk; the majority of these reported TSCs. TSCs were significantly associated with other symptoms. Future research and clinical guidelines, with a common terminology for assessment, diagnosis and management of cancer TSCs, are needed.


Seepage, objectivity, and climate science.
Based on the disproportionate amount of attention paid by climate scientists to the supposed global warming hiatus, it has recently been argued that contrarian discourse has "seeped into" climate science. While I agree that seepage has occurred, its effects remain unclear. This lack of clarity may give the impression that climate science has been compromised in a way that it hasn't-such a conclusion should be defended against. To do this I argue that the effects of seepage should be analyzed in terms of objectivity. I use seven meanings of objectivity to analyze contrarian discourse's impact on climate science. The resulting account supports the important point that climate science has not been compromised in a way that invalidates the conclusions its scientists have drawn, despite the reality of seepage having occurred.


Removal of Cd and Zn from inorganic industrial waste leachate by ion exchange.
This paper presents a study of the removal of Cd and Zn present in the leachate from an inorganic industrial waste landfill using cationic exchange resins (Amberlite 200, 252-C, IR-120, Duolite C-464), a chelating resin, Amberlite IRC 718, and an adsorbent resin, XAD-2. The chelating resin Amberlite IRC 718 presented the higher removal in batch experiments for both metals (93% for Zn and 50% for Cd). Five hundred ten bed volumes of leachate were treated in column experiments using this material, reducing the concentrations of Cd and Zn from 18 mg/dm3 to 0.1 and 1.0mg/dm3, respectively. Regeneration of the saturated bed was achieved with 11 BV of 2M HCl.


The structure and oxidation of two palladium ceramic fusing alloys.
The oxides formed at the surface of an alloy during preheating at about 1000 degrees C prior to the firing of ceramic are vital for the formation of a strong chemical bond between alloy and porcelain. Replacing Au used as the basic constituent in the ceramic fusing alloys with Pd seems to have a rather small effect on the behaviour of the elements Sn and In which were found to oxidize internally. However, no external oxidation of the transition metal component Co was found, in contrast to Ni in Au-based alloys. After ceramic firing a zone enriched with Co and In is found in the interaction area between alloy and ceramic. In another alloy Ga was observed to oxidize internally and much more easily than Cu due to its much lower free energy of formation. A solid solution was produced in both the alloys by ceramic firing as shown by SEM studies.


Modeling the sequential photodechlorination of hexachlorobenzene in surfactant micelles.
A five-stage consecutive irreversible model is derived to predict the photodegradation of hexachlorobenzene (HCB) in a surfactant solution, which was proven to be a useful treatment process following the surfactant-aided soil washing or remediation. The photodegradation of HCB in surfactant micelles is dominated by photodechlorination, which sequentially removes chlorides one at a time. The minor pathways of photoisomerization and photochlorination were neglected in the kinetic model. The results show that the derived consecutive irreversible model can accurately predict the decay of HCB and the formation (and decay) of its less-chlorinated congeners. The initial rate approach was used to identify the proper range of decay rate of each chlorinated benzene; so the overall rate constants can be determined easier by trial. The decreased performance of a completely mixed flow reactor (CMFR) with continuous input is also quantified compared to a batch reactor.


Subclinical decrease in cardiac autonomic and diastolic function in patients with metabolic disorders: HSCAA study.
Heart failure due to decreased diastolic function, HFpEF, is a growing health concern with rising prevalence. We examined subclinical cardiac autonomic and diastolic functions in 605 patients with metabolic diseases classified as pre-heart failure. Presence of glucose intolerance or diabetes, or visceral adiposity was significantly associated with reduced cardiac autonomic and diastolic functions. Higher autonomic functions were significantly associated with a parameter of better cardiac diastolic function (E/A) (SDNN: r = 0.306, p < 0.01; HF: r = 0.341, p < 0.01), with the association independent of diabetes, body mass index, visceral adiposity and insulin resistance index. Thus, reduced autonomic function may be a potential predictor for decreased cardiac diastolic functions in metabolic disorders.


Impact of ozonation and biological activated carbon filtration on ceramic membrane fouling.
Ozone pre-treatment (ozonation, ozonisation) and biological activated carbon (BAC) filtration pre-treatment for the ceramic microfiltration (CMF) treatment of secondary effluent (SE) were studied. Ozone pre-treatment was found to result in higher overall removal of UV absorbance (UVA254) and colour, and higher permeability than BAC pre-treatment or the combined use of ozone and BAC (O3+BAC) pre-treatment. The overall removal of colour and UVA254 by ceramic filtration of the ozone pre-treated water was 97% and 63% respectively, compared to 86% and 48% respectively for BAC pre-treatment and 29% and 6% respectively for the untreated water. Ozone pre-treatment, however, was not effective in removal of dissolved organic carbon (DOC). The permeability of the ozone pre-treated water through the ceramic membrane was found to decrease to 50% of the original value after 200 min of operation, compared to approximately 10% of the original value for the BAC pre-treated, O3+BAC pre-treated water and the untreated water. The higher permeability of the ozone pre-treated water was attributed to the excellent removal of biopolymer particles (100%) and high removal of humic substances (84%). The inclusion of a BAC stage between ozone pre-treatment and ceramic filtration was detrimental. The O3+BAC+CMF process was found to yield higher biopolymer removal (96%), lower humic substance (HS) component removal (66%) and lower normalized permeability (0.1) after 200 min of operation than the O3+CMF process (86%, 84% and 0.5 respectively). This was tentatively attributed to the chemical oxidation effect of ozone on the BAC biofilm and adsorbed components, leading to the generation of foulants that are not generated in the O3+CMF process. This study demonstrated the potential of ozone pre-treatment for reducing organic fouling and thus improving flux for the CMF of SE compared to O3+BAC pre-treatment.


The care of SCI patients in the developing nations--can we stem the rot?
The aims, objectives and results of the Madras Paraplegia Project at the Government General Hospital, Madras is presented. Eight hundred and forty four Spinal Cord Injury (SCI) patients have been treated in 8 years and 4 months. The Madras Model offers an alternative strategy for the total care of SCI patients. The merits and drawbacks are highlighted. The results to date commend replication of the model in areas of the world where the services for SCI Care are meagre or non-existent.


Antihypertensive therapy in diabetic patients. The use of indapamide.
Abnormalities in glucose tolerance in nondiabetic patients and rapid alteration in non-insulin-dependent diabetics have been reported with antihypertensive drugs such as beta-blockers or thiazide diuretics. Such deleterious effects on a cardiovascular risk factor could limit the long-term benefit of an antihypertensive treatment. Indapamide is a nonthiazide antihypertensive agent that appears to respect the glucose tolerance in hypertensive patients. The present study was conducted to assess the effects of indapamide 2.5 mg in 10 hypertensive non-insulin-dependent diabetic patients treated for a one-year period. Glucose tolerance was evaluated using a 50-g oral glucose test, with measurements of plasma glucose and insulin before and after treatment. At the end of the one-year treatment, both systolic and diastolic blood pressure were significantly reduced, whereas there was no significant alteration in either plasma glucose or plasma insulin levels. Thus, indapamide appears as an effective antihypertensive agent in the diabetic patient, with no adverse effects on the glucose tolerance.


Isolation of Chinese hamster ovary cells with reduced poly(ADP-ribose) polymerase activity.
The biological function of poly(ADP-ribose) polymerase in DNA repair, cell-cycle regulation and cellular differentiation has yet to be defined. Isolation of cells which are deficient in poly(ADP-ribose) synthesis would greatly facilitate the determination of the biological role of this enzyme. A method is described for isolating Chinese hamster ovary (CHO) cells deficient in the poly(ADP-ribose) polymerase activity by direct screening of colonies for enzyme activity. Colonies with decreased production of poly(ADP-ribose) are recovered from nylon replicas for further analysis. Using this method we have isolated a series of CHO cells which have 50% or less poly(ADP-ribose) polymerase activity. These mutants have normal generation times and are 20% more sensitive to the effects of DNA (m)ethylating agents than the parental cell. However, these mutants display normal sensitivity to gamma-rays.


Analysis of Putative Epitope Candidates of Mycobacterium tuberculosis Against Pakistani Human Leukocyte Antigen Background: An Immunoinformatic Study for the Development of Future Vaccine.
Tuberculosis (TB), a chronic disease caused by Mycobacterium tuberculosis (Mtb), is a global health issue across the world. Pakistan ranks fifth among the countries, which are facing, a significantly great number of mortalities and morbidities due to TB. Unfortunately, all previously reported treatments are not successful for the eradication of TB. Here in this study, we report an emerging treatment option for this disease. We have applied immunoinformatics to predict highly conserved B and T-cell epitopes from Mtb, showing significant binding affinities to the frequent HLA alleles in the Pakistani population. A total of ten highly referenced and experimentally validated epitopes were selected from the Immune Epitope Database (IEDB), followed by their conservancy analysis using weblogos. The consensus sequences and variants derived from these sequences were examined, for their binding affinities, with prevalent HLA alleles of Pakistan. Moreover, the antigenic and allergenic natures of these peptides were also evaluated via Vaxijen and AllerTOP, respectively. Consequently, all potentially allergenic and non-antigenic, peptide fragments, were excluded from the analysis. Among all putative epitopes, three CD8 + T-cell epitopes were selected, as ideal vaccine candidates and, population coverage analysis revealed that the combination of these three peptides was covering, 67.28% Pakistani Asian and 57.15% mixed Pakistani populations. Likewise, eleven linear and six conformational or discontinuous B-cell epitopes were also marked as potential vaccine candidates based on their prediction score, non-allergenic nature, and antigenic properties. These epitopes, however, need the final validation via wet-lab studies. After their approval, these epitopes would be effective candidates for the future designing of epitope-based vaccines against Mtb infections in Pakistan.


On the analysis of chromatographic biopharmaceutical data by curve resolution techniques in the framework of the area of feasible solutions.
Monitoring preparative protein chromatographic steps by in-line spectroscopic tools or fraction analytics results in medium or large sized data matrices. Multivariate Curve Resolution (MCR) serve to compute or to estimate the concentration values of the pure components only from these data matrices. However, MCR methods often suffer from an inherent solution ambiguity which underlies the factorization problem. The typical unimodality of the chromatographic profiles of pure components can support the chemometric analysis. Here we present the pure components estimation process within the framework of the area of feasible solutions, which is a systematic approach to represent the range of all possible solutions. The unimodality constraint in combination with Pareto optimization is shown to be an effective method for the pure component calculation. Applications are presented for chromatograms on a model protein mixture containing ribonuclease A, cytochrome c and lysozyme and on a two-dimensional chromatographic separation of a monoclonal antibody from its aggregate species. The root mean squared errors of the first case study are 0.0373, 0.0529 and 0.0380 g/L compared to traditional off-line analytics. The second case study illustrates the potential of recovering hidden components with MCR from off-line reference analytics.


Gonadotropin-Releasing Hormone Agonist Therapy and Longitudinal Bone Mineral Density in Congenital Adrenal Hyperplasia.
Children with congenital adrenal hyperplasia (CAH) are at risk for early puberty. Gonadotropin-releasing hormone analog (GnRHa) is frequently used, and can decrease bone mineral density (BMD). Our aim was to investigate the effect of GnRHa therapy on BMD in a longitudinal study of patients with CAH spanning both childhood and adulthood. Sixty-one patients with classic CAH due to 21-hydroxylase deficiency (20 treated with GnRHa) were followed with DXA scans at puberty onset, attainment of adult height, and during early adulthood. Whole body, lumbar spine, femoral neck, total hip, distal radius BMD z-score at adult height. Longitudinal BMD and adult height were also assessed. Twenty patients received GnRHa for an average of 4.5 ± 2 years. There were no differences in BMD between GnRHa treated and untreated groups at adult height for all sites. Overall, the follow up DXA during early adulthood, showed decreases in BMD z-scores for whole body (p = 0.01), lumbar spine (p < 0.0001), femoral neck (p = 0.06), total hip (p = 0.009), and distal radius (p = 0.05). GnRHa treatment correlated with improved height outcomes compared to predicted height at puberty onset after adjusting for midparental height (p = 0.02). Patients in both groups achieved similar adult height. In children with CAH, GnRHa does not compromise BMD. However, BMD decreases with time and during the second and third decades of life, a possible effect of chronic supraphysiologic glucocorticoids. Children with CAH who experience early puberty benefit from GnRHa treatment as evidenced by the positive effect on height.


Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus.
Serotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. However, the assessment of the serotonergic system in the human hypothalamus in vivo is difficult as delineation of the hypothalamus is cumbersome with conventional region-of-interest analysis. In the present study, we aimed to develop a method to visualize serotonin transporters (SERT) in the hypothalamus. Additionally, we tested the hypothesis that hypothalamic SERT binding ratios are different between patients with hypothalamic impairment (HI), pituitary insufficiency (PI), and control subjects (C). SERT availability was determined in 17 subjects (6 HI, 5 PI, and 6 healthy controls), 2 h after injection of 123I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ([123I]FP-CIT), using single-photon emission computed tomography (performed on a brain-dedicated system) fused with individual magnetic resonance imaging (MRI) scans of the brain. The hypothalamus (representing specific SERT binding) and cerebellum (representing nonspecific binding) were manually delineated on each MRI to assess [123I]FP-CIT binding and specific-to-nonspecific binding ratios. In each healthy subject, [123I]FP-CIT binding was higher in the hypothalamus than in the cerebellum, and the mean hypothalamic binding ratio of SERT was 0.29 ± 0.23. We found no difference in hypothalamic binding ratios between HI, PI, and control subjects (HI 0.16 ± 0.24, PI 0.45 ± 0.39, C 0.29 ± 0.23, p value 0.281). We were able to demonstrate SERT binding in the human hypothalamus in vivo. However, we did not find altered hypothalamic SERT binding in patients with hypothalamic impairment. Netherlands Trial Register: NTR2520.


Monitoring Fatigue Status with HRV Measures in Elite Athletes: An Avenue Beyond RMSSD?
Among the tools proposed to assess the athlete's "fatigue," the analysis of heart rate variability (HRV) provides an indirect evaluation of the settings of autonomic control of heart activity. HRV analysis is performed through assessment of time-domain indices, the square root of the mean of the sum of the squares of differences between adjacent normal R-R intervals (RMSSD) measured during short (5 min) recordings in supine position upon awakening in the morning and particularly the logarithm of RMSSD (LnRMSSD) has been proposed as the most useful resting HRV indicator. However, if RMSSD can help the practitioner to identify a global "fatigue" level, it does not allow discriminating different types of fatigue. Recent results using spectral HRV analysis highlighted firstly that HRV profiles assessed in supine and standing positions are independent and complementary; and secondly that using these postural profiles allows the clustering of distinct sub-categories of "fatigue." Since, cardiovascular control settings are different in standing and lying posture, using the HRV figures of both postures to cluster fatigue state embeds information on the dynamics of control responses. Such, HRV spectral analysis appears more sensitive and enlightening than time-domain HRV indices. The wealthier information provided by this spectral analysis should improve the monitoring of the adaptive training-recovery process in athletes.


Morphogenesis of vascular and neuronal networks and the relationships between their remodeling processes.
Vascular and neuronal networks represent important examples of body structures created by processes of branching morphogenesis. Migration to an appropriate target in both axons and blood vessels are mediated by chemo-repulsive and attractive signals and the proximity of nerves and blood vessels suggest that there may be a molecular crosstalk and common cues between nerves and blood vessels. Vascular endothelial growth factor (VEGF), a key angiogenetic factor, has direct effects on the nervous system in terms of axon outgrowth and survival. Conversely, nerve growth factor (NGF), a well-known neurotropic molecule, exhibits angiogenic properties. Available data on the morphogenesis of vascular and neuronal networks and on the relationships between their remodeling processes will be the focus of the present study.


Cryotherapy of trichiasis with use of the retinal cryoprobe.
A new method for the treatment of trichiasis is presented. A retinal cryoprobe is used in a freeze-thaw-freeze (double freeze) of the lid. The method is highly successful with no major complications occurring thus far when used on nonpalsied lids.


Effects of nucleotide binding to LmrA: A combined MAS-NMR and solution NMR study.
ABC transporters are fascinating examples of fine-tuned molecular machines that use the energy from ATP hydrolysis to translocate a multitude of substrates across biological membranes. While structural details have emerged on many members of this large protein superfamily, a number of functional details are still under debate. High resolution structures yield valuable insights into protein function, but it is the combination of structural, functional and dynamic insights that facilitates a complete understanding of the workings of their complex molecular mechanisms. NMR is a technique well-suited to investigate proteins in atomic resolution while taking their dynamic properties into account. It thus nicely complements other structural techniques, such as X-ray crystallography, that have contributed high-resolution data to the architectural understanding of ABC transporters. Here, we describe the heterologous expression of LmrA, an ABC exporter from Lactococcus lactis, in Escherichia coli. This allows for more flexible isotope labeling for nuclear magnetic resonance (NMR) studies and the easy study of LmrA's multidrug resistance phenotype. We use a combination of solid-state magic angle spinning (MAS) on the reconstituted transporter and solution NMR on its isolated nucleotide binding domain to investigate consequences of nucleotide binding to LmrA. We find that nucleotide binding affects the protein globally, but that NMR is also able to pinpoint local dynamic effects to specific residues, such as the Walker A motif's conserved lysine residue.


The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.
The hereditary disease Cockayne syndrome (CS) is characterized by a complex clinical phenotype. CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. The cloned CSB gene encodes a member of a protein family that includes the yeast Snf2 protein, a component of the transcriptional regulator Swi/Snf. We report the cloning of the CSA cDNA, which can encode a WD repeat protein. Mutations in the cDNA have been identified in CS-A cell lines. CSA protein interacts with CSB protein and with p44 protein, a subunit of the human RNA polymerase II transcription factor IIH. These observations suggest that the products of the CSA and CSB genes are involved in transcription.


On-line microwave-based preconcentration device for inductively coupled plasma atomic emission spectrometry: application to the elemental analysis of spirit samples.
A microwave-based thermal nebulizer (MWTN) has been employed for the first time as on-line preconcentration device in inductively coupled plasma atomic emission spectrometry (ICP-AES). By the appropriate selection of the experimental conditions, the MWTN could be either operated as a conventional thermal nebulizer or as on-line analyte preconcentration and nebulization device. Thus, when operating at microwave power values above 100 W and highly concentrated alcohol solutions, the amount of energy per solvent mass liquid unit (EMR) is high enough to completely evaporate the solvent inside the system and, as a consequence, the analyte is deposited (and then preconcentrated) on the inner walls of the MWTN capillary. When reducing the EMR to the appropriate value (e.g., by reducing the microwave power at a constant sample uptake rate) the retained analyte is swept along by the liquid-gas stream and an analyte-enriched aerosol is generated and next introduced into the plasma cell. Emission signals obtained with the MWTN operating in preconcentration-nebulization mode improved when increasing preconcentration time and sample uptake rate as well as when decreasing the nozzle inner diameter. When running with pure ethanol solution at its optimum experimental conditions, the MWTN in preconcentration-nebulization mode afforded limits of detection up to one order of magnitude lowers than those obtained operating the MWTN exclusively as a nebulizer. To validate the method, the multi-element analysis (i.e. Al, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Pb and Zn) of different commercial spirit samples in ICP-AES has been performed. Analyte recoveries for all the elements studied ranged between 93% and 107% and the dynamic linear range covered up to 4 orders of magnitude (i.e. from 0.1 to 1000μgL(-1)). In these analysis, both MWTN operating modes afforded similar results. Nevertheless, the preconcentration-nebulization mode permits to determine a higher number of analytes due to its higher detection capabilities.


Dietary fibre in gastrointestinal health and disease.
Epidemiological studies have consistently demonstrated the benefits of dietary fibre on gastrointestinal health through consumption of unrefined whole foods, such as wholegrains, legumes, vegetables and fruits. Mechanistic studies and clinical trials on isolated and extracted fibres have demonstrated promising regulatory effects on the gut (for example, digestion and absorption, transit time, stool formation) and microbial effects (changes in gut microbiota composition and fermentation metabolites) that have important implications for gastrointestinal disorders. In this Review, we detail the major physicochemical properties and functional characteristics of dietary fibres, the importance of dietary fibres and current evidence for their use in the management of gastrointestinal disorders. It is now well-established that the physicochemical properties of different dietary fibres (such as solubility, viscosity and fermentability) vary greatly depending on their origin and processing and are important determinants of their functional characteristics and clinical utility. Although progress in understanding these relationships has uncovered potential therapeutic opportunities for dietary fibres, many clinical questions remain unanswered such as clarity on the optimal dose, type and source of fibre required in both the management of clinical symptoms and the prevention of gastrointestinal disorders. The use of novel fibres and/or the co-administration of fibres is an additional therapeutic approach yet to be extensively investigated.


The development and structural confirmation of the Rhode Island Stress and Coping Inventory.
A new measure, the Rhode Island Stress and Coping Inventory (RISCI), was developed to examine perceived stress and coping independent of specific stress situations. An adult sample (N = 466) was randomly divided into equal halves for developmental and confirmatory instrument development. Initial instrument development used principal components analysis, item analysis, and a measure of internal consistency (Coefficient alpha). Confirmatory factor analysis (CFA) was employed on the confirmatory sample to examine the structure of the refined item set. Several CFA fit indices indicated excellent fit for a model that represents perceived stress and coping as two moderately correlated dimensions. Validity analyses found strong relationships in the expected directions for both RISCI subscales with the 5-item Mental Health Inventory. Further validity analyses supported the utility of the RISCI in applied research with smokers and confirmed past research findings that successful quitters experience less perceived stress and cope better than relapsers.


Severe uterine hemorrhage from blastomycosis of the endometrium. A case report.
A 32-year-old black woman presented in the emergency room with vaginal bleeding. Physical examination revealed a granulomatous lesion on the thigh and a breast abscess. Histopathologic examination and culture of an endometrial biopsy revealed Blastomyces dermatitidis. The breast abscess and thigh lesion were found to contain B. dermatitidis as well.


Role of Lysocardiolipin Acyltransferase in Cigarette Smoke-Induced Lung Epithelial Cell Mitochondrial ROS, Mitochondrial Dynamics, and Apoptosis.
Cigarette smoke is the primary cause of Chronic Obstructive Pulmonary Disorder (COPD). Cigarette smoke extract (CSE)-induced oxidative damage of the lungs results in mitochondrial dysfunction and apoptosis of epithelium. Mitochondrial cardiolipin (CL) present in the inner mitochondrial membrane plays an important role in mitochondrial function, wherein its fatty acid composition is regulated by lysocardiolipin acyltransferase (LYCAT). In this study, we investigated the role of LYCAT expression and activity in mitochondrial oxidative stress, mitochondrial dynamics, and lung epithelial cell apoptosis. LYCAT expression was increased in human lung specimens from smokers, and cigarette smoke-exposed-mouse lung tissues. Cigarette smoke extract (CSE) increased LYCAT mRNA levels and protein expression, modulated cardiolipin fatty acid composition, and enhanced mitochondrial fission in the bronchial epithelial cell line, BEAS-2B in vitro. Inhibition of LYCAT activity with a peptide mimetic, attenuated CSE-mediated mitochondrial (mt) reactive oxygen species (ROS), mitochondrial fragmentation, and apoptosis, while MitoTEMPO attenuated CSE-induced MitoROS, mitochondrial fission and apoptosis of BEAS-2B cells. Collectively, these findings suggest that increased LYCAT expression promotes MitoROS, mitochondrial dynamics and apoptosis of lung epithelial cells. Given the key role of LYCAT in mitochondrial cardiolipin remodeling and function, strategies aimed at inhibiting LYCAT activity and ROS may offer an innovative approach to minimize lung inflammation caused by cigarette smoke.


Potential urinary monitoring of the enhanced permeability and retention effect using MMP-2-responsive poly(ethylene glycol) derivatives.
The enhanced permeability and retention (EPR) effect is fundamental to tumor-targeted drug delivery using nanoparticles. However, recent studies reported heterogeneity of the EPR effect, and companion diagnostics are considered to be key to predicting and optimizing the benefits of the EPR effect. Here, as a new material to simply endow the function of companion diagnostics to nanoparticles, we designed a poly(ethylene glycol) (PEG) derivative conjugated with low molecular fluorescent dye through synthetic substrate linker that can be cleaved in response to MMP-2, which is overexpressed in tumor extracellular matrix. Upon tumor accumulation, the low molecular fluorescent dye is released from the PEG and quickly excreted to urine, thereby reporting its tumor accumulation level as a fluorescent signal in the urine. In this study, this urinary reporter was conjugated with albumin, and the functionalized albumin exhibited efficient accumulation in various tumors. Importantly, the functionalized albumin exhibited significantly higher excretion of the fluorescent dye in the urine in mice with tumors compared with those without tumors. The PEG derivatives proposed in this study may be a promising tool to predict the EPR effect in individual cancer patients.


Impact of Weather Parameters and Population Density on the COVID-19 Transmission: Evidence from 81 Provinces of Turkey.
Weather factors are effective to transmission of various diseases. Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and kinds of influenza can be given as example these diseases. The novel corona virus which is called COVID-19 is the most dangerous problem all around the world in these days. Early studies have revealed that COVID-19 cases are affected by environmental factors. Therefore, the purpose of this paper is to examine the relationship between the number of novel coronavirus cases and several weather parameters in 81 provinces of Turkey. Mean incubation period of COVID-19 is in question. Thus, this paper also aims to provide better understanding of the exact incubation period in Turkey by employing four different timeframe which are on the day (lag 0), 3 days ago (lag 3), 7 days ago (lag 7) and 14 days ago (lag 14). We have considered population density as a control variable. The dataset cover COVID-19 cases, population density, average temperature, humidity, pressure, dew point, wind speed, and sunshine duration for 81 provinces of Turkey. We find that population density has a positive correlation with COVID-19 cases. We also find that in lag 3, all parameters except for sunshine duration are negatively correlated with COVID-19 cases and significant. However, only 3 parameters, temperature, air pressure and dew point are negatively correlated with COVID-19 cases and significant for lag 0, lag 7 and lag 14. In addition, temperature, air pressure and dew point parameters are negative and significant in all timeframes.


[Hygienic working conditions and the health status of workers in the manufacture of the feed concentrate lysine].
The industrial noxious factors during manufacturing of the fodder concentrate lysin are represented by dust, noise, vibration, microclimatic discomfort. Persons working in condition of lysin production showed functional changes of the nervous, cardiovascular and respiratory systems.


Effects of stimulation rate, mode and level on modulation detection by cochlear implant users.
In cochlear implant (CI) patients, temporal processing is often poorest at low listening levels, making perception difficult for low-amplitude temporal cues that are important for consonant recognition and/or speech perception in noise. It remains unclear how speech processor parameters such as stimulation rate and stimulation mode may affect temporal processing, especially at low listening levels. The present study investigated the effects of these parameters on modulation detection by six CI users. Modulation detection thresholds (MDTs) were measured as functions of stimulation rate, mode, and level. Results show that for all stimulation rate and mode conditions, modulation sensitivity was poorest at quiet listening levels, consistent with results from previous studies. MDTs were better with the lower stimulation rate, especially for quiet-to-medium listening levels. Stimulation mode had no significant effect on MDTs. These results suggest that, although high stimulation rates may better encode temporal information and widen the electrode dynamic range, CI patients may not be able to access these enhanced temporal cues, especially at the lower portions of the dynamic range. Lower stimulation rates may provide better recognition of weak acoustic envelope information.


Material-engineered bioartificial microorganisms enabling efficient scavenging of waterborne viruses.
Material-based tactics have attracted extensive attention in driving the functional evolution of organisms. In aiming to design steerable bioartificial organisms to scavenge pathogenic waterborne viruses, we engineer Paramecium caudatum (Para), single-celled microorganisms, with a semiartificial and specific virus-scavenging organelle (VSO). Fe3O4 magnetic nanoparticles modified with a virus-capture antibody (MNPs@Ab) are integrated into the vacuoles of Para during feeding to produce VSOs, which persist inside Para without impairing their swimming ability. Compared with natural Para, which has no capture specificity and shows inefficient inactivation, the VSO-engineered Para (E-Para) specifically gathers waterborne viruses and confines them inside the VSOs, where the captured viruses are completely deactivated because the peroxidase-like nano-Fe3O4 produces virus-killing hydroxyl radicals (•OH) within acidic environment of VSO. After treatment, magnetized E-Para is readily recycled and reused, avoiding further contamination. Materials-based artificial organelles convert natural Para into a living virus scavenger, facilitating waterborne virus clearance without extra energy consumption.


Effect of low back pain on postural stability in younger women: influence of visual deprivation.
This study investigated the effect of low back pain (LBP) on body balance during normal and visual deprivation during standing in a LBP group (10 women) and a control group (10 women). A 3-D force plate was used to measure the center of pressure (COP) anteroposterior and mediolateral displacements, and resultant velocity. ANOVA was used to compare situations. LPB group presented higher amplitudes of COP for anterioposterior direction (p<0.01) in conditions of open (3.07 ± 0.53 cm) and closed eyes (3.70 ± 0.71 cm) than healthy women (1.39 ± 0.17 cm and 1.75 ± 0.36 cm, for open and closed eyes, respectively). Similar results were found for COP involving mediolateralsway. The resultant COP velocity was larger for LBP group (p<0.05) when visual information was removed (3.03 ± 0.68 m/s and 3.63 ± 1.33 m/s for LBP and healthy women, respectively). LBP influenced the stability of young women during quiet standing, and the visual deprivation appears to reinforce LBP effects.


The vertical transmission of salmonellas and formic acid treatment of chicken feed. A possible strategy for control.
The treatment of feed given to laying hens with 0.5% formic acid reduced significantly the isolation rate of salmonellas and was associated with a reduction in the incidence of infection in newly hatched chicks. These improvements were not sustained until slaughter, however, as growing birds acquired salmonellas, probably from feed which was not acid treated. The data indicate that formic acid treatment of chicken food could have important benefits for the public health.


Noninvasive Respiratory Support as an Alternative to Tracheostomy in Severe Laryngomalacia.
To analyze the role of noninvasive respiratory support (NRS) as an alternative to tracheostomy in the management of severe laryngomalacia. We conducted a monocentric retrospective study in a tertiary pediatric care center. All children under the age of 3 years with severe laryngomalacia, treated between January 2014 and December 2019, were included. Patient demographics, medical history, nutrition, surgery, NRS, and outcome were reviewed. Predictors for NRS were analyzed. One hundred and eighty-eight patients were included. Mean age was 4 ± 5 months and mean weight was 4,925 ± 1,933 g. An endoscopic bilateral supraglottoplasty was performed in 183 (97%) patients and successful in 159 (87%). NRS was initiated in 29 (15%) patients at a mean age of 3 ± 2 months (1-11 months): 15 (52%) patients were treated with NRS after surgical failure, 9 (31%) were treated with NRS initiated prior to surgery because of abnormal overnight gas exchange, and 5 (17%) were treated exclusively with NRS due to comorbidities contraindicating an endoscopic procedure. NRS was successfully performed in all patients with a mean duration of 6 ± 11 months. No patient required a tracheostomy. Univariate analysis identified the following predictors of NRS: neonatal respiratory distress (P = .003), neurological comorbidity (P < .001), associated laryngeal abnormality (P < .001), cardiac surgery (P = .039), surgical endoscopic revision (P = .007), and nutritional support (P < .001). NRS is a safe procedure, which may avoid a tracheostomy in severe laryngomalacia, in particular, in case of endoscopic surgery failure, respiratory failure before surgery, and/or severe co-morbidity. 3 Laryngoscope, 132:1861-1868, 2022.


Intracranial Aneurysms in Children: The Role of Stenting and Flow-Diversion.
To report a single-center experience in the endovascular management of cerebral aneurysms in children with stenting and flow-diversion techniques. During a 7-year period, 5 male patients with six intracranial aneurysms (IA) were treated by endovascular therapy with stenting or flow-diversion. The average age was 11 years (range 6-18 years). The etiology of the aneurysms was vasculopathic in 3 cases (50%), traumatic in 2 patients (33.3%), and idiopathic in 1 case (16.7%). Two-thirds of the aneurysms were giant in size. The aneurysms were most frequently located in the anterior circulation (66.7%). Fifty percent of the aneurysms were treated with stenting and coiling, and 50% were treated with flow-diversion stents alone. After treatment, occlusion was graded as: partial in five aneurysms (88.3%) and complete in 1 case (16.7%). Most cases (83.3%) had a good outcome after the procedure. During follow-up, most aneurysms had progressive occlusion (80%), while the rest were unchanged (20%). Most stents and flow-diverter devices remained patent (80%). However, one Pipeline flow-diverter device in the Anterior cerebral artery (ACA) A2 segment had an asymptomatic occlusion. In this series, device-assisted endovascular techniques were a relatively safe and effective method of treatment of pediatric aneurysms. However, continued follow-up is required after treatment, because there are unsolved issues regarding the durability of flow-diverters and stents.


Designing neodymium-doped hexamine complexant as novel IR NLO material with extremely large non-linear optical behavior.
A new complex named HMNd has been basically designed by doping rare-earth neodymium metal inside the hexamine surface HM. Density functional theory (DFT) calculations were carried out using B3LYP functional with split basis set GENECP to examine their geometrical, electronic, and non-linear optical properties of newly designed complex HMNd. After getting stable geometry of HMNd, its optoelectronic properties were compared with pure HM surface to check the influence of doping. HMNd revealed the obvious reduction in band gap energies from 8.4 eV (HM) to 1.79 eV (HMNd) as confirmed through DOS analysis. The highest hyperpolarizability and linear isotropic polarizability values of 6.8 × 105 a.u and 262.81 a.u respectively are perceived in HMNd. Electronic and thermodynamic stability of the designed complex has been confirmed through their vertical ionization and interaction energies. As revealed through the UV-visible analysis, doping with neodymium metal (HMNd) shifts the absorption to IR region with λmax of 2699.63 nm which leads towards the production of new materials. These upshots highlight the adequacy of designed complex providing gateway for designing new IR NLO materials in laser frequency conversion technology having usages in versatile fields.


[The relationship between serum leptin level and metabolic syndrome among a middle-aged Chinese population].
To explore the relationship between serum level of leptin and the components of metabolic syndrome in a group of mid-aged Chinese population. 345 adults (184 men and 161 women) aged 46 - 53 were enrolled from Fetal Origin of Adult Disease (FOAD) cohort to participate the clinic examination including anthropometry, measurements of blood pressure, fasting and 2 hr plasma levels of glucose and insulin, serum levels of lipid and leptin. HOMA-IR index was calculated to estimate individual insulin resistance. Metabolic syndrome (MS) was diagnosed according to the definition criteria issued by the International Diabetes Federation (IDF) in 2005. The prevalences of central obesity, higher serum level of triglyceride (TG), lower serum level of high-density lipoprotein (HDL-C), IFG, higher blood pressure and MS were 53.0%, 47.5%, 34.2%, 26.7%, 33.9%, 31.9% in this mid-aged population, respectively. Serum geometric mean level of leptin was higher in females than in males. Serum level of leptin increased with the prevalence of MS and components of abnormal metabolism. The serum level of leptin compared with central obesity, higher blood pressure, higher serum level of triglyceride (TG), lower serum level of high-density lipoprotein cholesterol (HDL-C), IFG and MS was significantly higher respectively (P < 0.05) without HDL-C in males. The serum level of leptin increased with the number of components of abnormal metabolism subjects had (P < 0.001). The serum level of leptin in this population is significantly associated with MS and components of MS. Hyperleptinemia could be a new component of metabolic syndrome. It might be a target in selection of MS and relative diseases.


Common and unique multimodal covarying patterns in autism spectrum disorder subtypes.
The heterogeneity inherent in autism spectrum disorder (ASD) presents a substantial challenge to diagnosis and precision treatment. Heterogeneity across biological etiologies, genetics, neural systems, neurocognitive attributes and clinical subtypes or phenotypes has been observed across individuals with ASD. In this study, we aim to investigate the heterogeneity in ASD from a multimodal brain imaging perspective. The Autism Diagnostic Observation Schedule (ADOS) was used as a reference to guide functional and structural MRI fusion. DSM-IV-TR diagnosed Asperger's disorder (n = 79), pervasive developmental disorder-not otherwise specified [PDD-NOS] (n = 58) and Autistic disorder (n = 92) from ABIDE II were used as discovery cohort, and ABIDE I (n = 400) was used for replication. Dorsolateral prefrontal cortex and superior/middle temporal cortex are the primary common functional-structural covarying cortical brain areas shared among Asperger's, PDD-NOS and Autistic subgroups. Key differences among the three subtypes are negative functional features within subcortical brain areas, including negative putamen-parahippocampus fractional amplitude of low-frequency fluctuations (fALFF) unique to the Asperger's subtype; negative fALFF in anterior cingulate cortex unique to PDD-NOS subtype; and negative thalamus-amygdala-caudate fALFF unique to the Autistic subtype. Furthermore, each subtype-specific brain pattern is correlated with different ADOS subdomains, with social interaction as the common subdomain. The identified subtype-specific patterns are only predictive for ASD symptoms manifested in the corresponding subtypes, but not the other subtypes. Although ASD has a common neural basis with core deficits linked to social interaction, each ASD subtype is strongly linked to unique brain systems and subdomain symptoms, which may help to better understand the underlying mechanisms of ASD heterogeneity from a multimodal neuroimaging perspective. This study is male based, which cannot be generalized to the female or the general ASD population.


Does the size of ureteral stent impact urinary symptoms and quality of life? A prospective randomized study.
To evaluate the effect of stent diameter on patients' symptoms and quality of life (QoL) by using dedicated questionnaires. We prospectively enrolled 34 patients with unilateral ureteral obstruction due to urinary stone undergoing to ureteral stenting (17 pts with 4.8 F and 17 pts with 6 F) before treatment of stone disease. Twenty-one patients with lower urinary symptoms from other causes were used as a control group. Two questionnaires, one on QoL and another on stent specific symptoms, were administered to patients one week after stent positioning and 4 week after removal. There was a significant association between stent state and answers on pain and discomfort on QoL questionnaire. A high percentage of patients reported anxiety and depression associated with the stent. Similar significant association was found between stent state and urinary symptoms and pain. No differences in QoL and urinary symptoms and pain were detected using stents with different size. Ureteral stents are invariably associated with urinary symptoms and impaired QoL. We did not find any difference between stent with different size, whereas there was a tendency for stent with smaller diameter to dislodge more often.


Development and utility of the Family-Centered Autism Navigation interview.
When a parent learns of their child's autism diagnosis, they may be overwhelmed, confused, and frustrated. Family navigation services are designed to improve access to care. While these services are a promising intervention to enhance well-being and developmental outcomes, there are limited tools that can systematically facilitate the development of a shared navigation plan that prioritizes the concerns of the family. The Family-Centered Autism Navigation semi-structured interview guide is designed for family navigators to triage and prioritize caregiver's needs to coordinate and navigate systems of care after learning of their child's autism spectrum disorder diagnosis. The goals of the Family-Centered Autism Navigation interview are to (1) identify family and child strengths; (2) identify family/caregiver concerns regarding navigation of services and systems following their child's diagnosis of autism; (3) measure change in caregiver knowledge, ability and skill as it relates to understanding, remembering, and evaluating information they receive; and (4) assist with the development of a shared navigation plan. When using the Family-Centered Autism Navigation guide, family navigators and caregivers co-create a family-centered, prioritized action plan that supports and prepares caregivers as they navigate systems of care. This short report describes the development process of the Family-Centered Autism Navigation semi-structured interview guide. We utilized brief interviews (n = 42), expert feedback (n = 13), and quality improvement strategies (n = 2 family navigators) to develop the questions and determine the usability of the Family-Centered Autism Navigation interview in practice.


Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence - The ANRS CUPILT study.
HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy. From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator's discretion. The primary efficacy end point was a sustained virological response (SVR) 12weeks after the end of treatment. The SVR rate 12weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p<0.0001). A slight but significant reduction in creatinine clearance was reported. No clinically relevant drug-drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs. Treatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence. The recurrence of hepatitis C used to be the first cause of graft failure in infected liver transplanted recipients. Our study demonstrates the great efficacy of one combination of new all-oral direct-acting antiviral, sofosbuvir and daclatasvir, to treat the recurrence of hepatitis C on the graft. Ninety-six per cent of recipients were cured. The safety profile of this combination seemed to be good, especially no relevant drug-drug interaction with immunosuppressive drugs.


[Key definitions and concepts in cytomegalovirus: infection versus disease. Replication, viral load, universal prophylaxis. Preemptive therapy].
Although advances have been made in the prevention, diagnosis and treatment of cytomegalovirus (CMV), this infection continues to be a major complication in transplant recipients, causing considerable morbidity and occasionally mortality. There is wide variability in definitions of CMV infection, which can lead to conceptual errors. The present article attempts to standardize the definitions used, which have recently been revised and recommended by the American Society of Transplantation for the purpose of developing consistent reporting of CMV in clinical trials. The concepts of infection and viral replication, persistence and recurrence of infection, viremia and disease are discussed, together with the diagnostic criteria for febrile syndrome and visceral involvement. Methods for preventing CMV infection, universal prophylaxis and preemptive therapy are also mentioned.


Alcohol increases hypnotic susceptibility.
One approach to hypnosis suggests that for hypnotic experience to occur frontal lobe activity must be attenuated. For example, cold control theory posits that a lack of awareness of intentions is responsible for the experience of involuntariness and/or the subjective reality of hypnotic suggestions. The mid-dorso-lateral prefrontal cortex and the ACC are candidate regions for such awareness. Alcohol impairs frontal lobe executive function. This study examined whether alcohol affects hypnotisability. We administered 0.8 mg/kg of alcohol or a placebo to 32 medium susceptible participants. They were subsequently hypnotised and given hypnotic suggestions. All participants believed they had received some alcohol. Participants in the alcohol condition were more susceptible to hypnotic suggestions than participants in the placebo condition. Impaired frontal lobe activity facilitates hypnotic responding, which supports theories postulating that attenuation of executive function facilitates hypnotic response, and contradicts theories postulating that hypnotic response involves enhanced inhibitory, attentional or other executive function.


Does the Use of Rocuronium-Sugammadex Instead of Succinylcholine in Electroconvulsive Therapy Affect Seizure Duration?
We compared retrospectively the seizure variables of electroconvulsive therapy (ECT) patients after administration of rocuronium-sugammadex or succinylcholine as a muscle relaxant with propofol anesthesia. The sample comprised 134 ECT patients. The mean age was 33.6±10.48 years. Anesthesia induction was provided with propofol one mg kg-intravenously (IV) followed by succinylcholine 0.5 mg kg-1 IV (n=68) (Group S) or rocuronium 0.3 mg kg-1 IV (n=66) (Group R). For patients who were given rocuronium, reversal of the residual neuromuscular block was accomplished with sugammadex (1.5 mg kg-1 IV). First session seizure variables were compared between the two groups. We also presented the clinical outcome with Clinical Global Impression-Improvement (CGI-I) and overall adverse effects. EEG seizure durations in Group R (55.09±36.11 s) and Group S (47.00±26.33 s) were comparable and were not significantly different (p=0.432). The clinical efficacy of ECT measured by CGI-I in both groups was comparable (p=0.075). There were no major complications or death during or after ECT. The results of this study show that the use of rocuronium-sugammadex as a neuromuscular blocker instead of succinylcholine during ECT with propofol anesthesia produces similar results in terms of seizure variables and clinical outcomes.


Effects of inspiratory muscle training on lung volumes, respiratory muscle strength, and quality of life in patients with ataxia telangiectasia.
Ataxia telangiectasia (AT) is a genetic syndrome caused by a mutation of chromosome 11. The clinical features are cerebellar ataxia, telangiectasia, and progressive loss of muscular coordination, including an inefficient cough secondary to progression of neurological disease. To evaluate the effects of inspiratory muscle training (IMT) on ventilation, lung volume, dyspnoea, respiratory muscle strength, and quality of life in patients with AT. A longitudinal study was conducted with 11 AT patients and nine healthy volunteers. Ventilometry, subjective sensation of dyspnoea, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and quality of life were assessed before and after a 24-week IMT program. The IMT load used was set at 60% of the MIP, and the training was performed for 20 min daily. Patients with AT had lower height and weight and also had lower respiratory muscle strength and lung volume compared with healthy volunteers. Furthermore, patients with AT showed a significant improvement when pre- and post-IMT were compared for ventilatory pattern: Vt (476.5 ± 135 ml vs. 583.3 ± 66 ml, P = 0.015) and f (23.3 ± 6 rpm vs. 20.4 ± 4 rpm, P = 0.018), and VC (1,664 ± 463 ml/kg vs. 2,145 ± 750 ml/kg, P = 0.002). IMT also significantly improved the sensation of dyspnoea (median 0.5; minimum 0; maximum 1.0; P = 0.022) and respiratory muscle strength: MIP (-22.2 ± 2 cmH2O vs. -38 ± 9 cmH2O, P < 0.001) and MEP (29 ± 7 cmH2O vs. 40 ± 8 cmH2O, P = 0.001). The health and vitality domains of the SF-36 also showed significant improvement (P = 0.009 and P = 0.014, respectively) post-IMT. IMT was effective in improving ventilatory pattern, lung volume, respiratory muscle strength, and the health and vitality domains for quality of life in patients with AT. IMT may be an effective adjunct therapy to drug treatment for patients with AT.


Diuretics Versus Volume Expansion in the Initial Management of Acute Intermediate High-Risk Pulmonary Embolism.
The very early management of pulmonary embolism (PE), a part from antithrombotic treatment, has been little studied. Our aim was to compare the effects of diuretic therapy (DT) versus volume expansion (VE) in patients hospitalized for PE with RV dysfunction. We conducted a randomized open-label multicentric study including patients with intermediate high-risk PE. Patients were randomized between diuretics or saline infusion. The primary endpoint was time to troponin (Tp) normalization. Secondary endpoints were time to normalization of B-type natriuretic peptide (BNP), changes in echocardiographic RV function parameters and treatment tolerance. Sixty patients presenting intermediate high-risk PE were randomized. Thirty received DT and 30 VE. We noted no changes in Tp kinetics between the two groups. In contrast, faster normalization of BNP was obtained in the DT group: 56 [28-120] vs 108 [48-144] h: p = 0.05, with a shorter time to 50%-decrease from peak value 36 [24-48] vs 54 [41-67] h, p = 0.003 and a higher rate of patients with a lower BNP concentration within the first 12 h (42% vs 12% p < 0.001). RV echocardiographic parameters were unchanged between the groups. One dose 40 mg furosemide was well-tolerated and not associated with any serious adverse events. In the acute management of intermediate high-risk PE, initial therapy including diuretic treatment is well-tolerated and safe. Although changes in Tp kinetics and echocardiographic RV dysfunction parameters did not differ, normalization of BNP is achieved more quickly in the DT group. This finding, which need to be confirmed in trials with clinical end points, may reflects a rapid improvement in RV function using one dose 40 mg furosemide. Clinical Trial Registration NCT02531581.


Stability of corneal topography and wavefront aberrations in young Singaporeans.
The aim was to investigate the differences between and variations across time in corneal topography and ocular wavefront aberrations in young Singaporean myopes and emmetropes. We used a videokeratoscope and wavefront sensor to measure the ocular surface topography and wavefront aberrations of the total-eye optics in the morning, midday and late afternoon on two separate days. Topographic data were used to derive the corneal surface wavefront aberrations. Both the corneal and total wavefronts were analysed up to the fourth radial order of the Zernike polynomial expansion and were centred on the entrance pupil (5.0 mm). The participants included 12 young progressing myopes, 13 young stable myopes and 15 young age-matched emmetropes. For all subjects considered together, there were significant changes in some of the aberrations across the day, such as spherical aberration ( Z(4 0)) and vertical coma ( Z (3 - 1)) (repeated measures analysis of variance, p < 0.05). The magnitude of positive spherical aberration ( Z(4 0)) was significantly lower in the progressing myopic group than in the stable myopic (p = 0.04) and emmetropic (p = 0.02) groups. There were also significant interactions between refractive group and time of day for with and against-the-rule astigmatism ( Z(2 2)). Significantly lower fourth-order root mean square of ocular wavefront aberrations were found in the progressing myopic group compared with the stable myopes and emmetropes (p < 0.01). These differences and variations in the corneal and total aberrations may have significance for our understanding of refractive error development and for clinical applications requiring accurate wavefront measurements.


Recombination in rabbit haemorrhagic disease virus: possible impact on evolution and epidemiology.
Rabbit haemorrhagic disease (RHD) was first recognised in 1984 following the introduction of apparently healthy rabbits into China from Germany. The aetiological agent Rabbit haemorrhagic disease virus (RHDV) has subsequently killed hundreds of millions of domestic and wild rabbits particularly in Europe, China and Australia. Previously, using phylogenetic analysis we have attempted to understand the underlying factors that determine why this virus emerged, and why it has such an unpredictable epidemiology. Here we report the use of tree congruency supported by bootscanning analysis to detect recombination amongst both closely related, and widely divergent strains of RHDV. We show that recombination occurs commonly and in several different regions of the RHDV genome. Moreover, the first identified strain of RHDV, i.e. from China in 1984, showed evidence of recombination in the capsid gene, with a virus or viruses containing lineages in German strains. These observations imply that recombination may play a significant role in the evolution, epidemiology and diversity of RHDV.


Radiation hybrids: irradiation and fusion gene transfer.
Irradiation and fusion gene transfer can be used to construct detailed genetic maps of complex genomes. This technique is complementary to mapping methods based on both physical distance and genetic recombination.


The non-ossified pubis.
A group of syndromes is presented whose common characteristic is the absence of pubic ossification at birth with very slow posterior mineralization. This is a radiological finding of interest as it has not been described in other entities. In all the cases shown, moreover, a variable degree of delay in bone age is observed. The increase of space between the pubic bones described in these syndromes is fictious, as it really signifies the existence of non-ossified cartilage. Therefore, they must be differentiated from those which deal with real widening of the symphysis of pubis.


Cognitive Decline and Risk of Dementia in Individuals With Heart Failure: A Systematic Review and Meta-analysis.
We sought to determine the association between heart failure (HF) and cognitive change and dementia. Systematic search of three electronic databases was performed and 29 eligible studies involving approximately 3 million participants were identified. Twelve studies examined dementia and 20 cognitive change, but only a subset of studies could be included in the meta-analysis. These findings indicated that HF was not significantly associated with dementia (n = 8, hazard ratio 1.18, 95% confidence interval 0.93-1.50), but increased the risk of cognitive impairment (n = 3, hazard ratio 1.80, 95% confidence interval 1.14-2.86) . Additionally, HF was associated with poorer mean cognitive performance in global cognition (Hedges' g -0.73, 95% confidence interval -1.12 to -0.35), memory (Hedges' g -0.57, 95% confidence interval -0.72 to -0.42), executive function (Hedges' g -0.58, 95% confidence interval -0.72 to -0.43), attention/speed (Hedges' g -0.50, 95% confidence interval -0.63 to -0.37) and language (Hedges' g -0.61, 95% confidence interval -1.05 to -0.17). Patients with HF perform worse on all cognitive tests and have an increased risk of cognitive impairment. These findings highlight the need for clinicians to consider cognition as part of routine care for patients with HF.


Time Trends for Incidence and Net Survival of Cervical Cancer in Sweden 1960-2014-A Nationwide Population-Based Study.
The aim was to investigate time trends for incidence and long-term net survival in the morphologic subtypes and stages of cervical cancer in Sweden during the period 1960 to 2014. Women with invasive cervical cancer were identified through the Swedish Cancer Registry. Incidence and net survival were calculated according to morphology, age at diagnosis, and FIGO stage at diagnosis. In total, 29,579 cases of invasive cervical cancer between 1960 and 2014 were included. The age-standardized incidence for squamous cell carcinoma (SCC) decreased until 2000; thereafter, the incidence rate stagnated, and a small increase was found in 2014. The incidence of adenocarcinoma continuously increased. The age-standardized 5-year net survival increased. However, decreasing net survival with increasing age was found. A higher stage at diagnosis showed a worse net survival. SCC and adenocarcinoma did not statistically differ as regards net survival in the last years of the study. Age-standardized 5-year net survival improved between 1960 and 2014. A positive trend for short- and long-term net survival was seen for women ages 18 to 64 years but long-term net survival for women ≥75 years decreased. In this study, age and FIGO stage at diagnosis were found to be important prognostic factors in determining net survival. The morphologies, SCC, and adenocarcinoma did not statistically differ as regards net survival in the last years of the study. This study demonstrates longitudinal data on cervical cancer in Sweden for over 50 years with sub analyses on morphology, age, and stage at diagnosis.


Frontal lobe growth is impaired in fetuses with congenital heart disease.
The primary objective of this study was to assess whether fetuses with congenital heart disease (CHD) have smaller frontal brain areas compared with normal controls. The secondary objective was to evaluate whether there are any differences in frontal brain area between cases with different types of CHD, grouped according to their impact on hemodynamics. This was a retrospective cross-sectional study, including 421 normal fetuses and 101 fetuses with isolated CHD evaluated between 20 and 39 gestational weeks at our fetal medicine and surgery unit in the period January 2016-December 2019. The study group was subdivided, according to the CHD hemodynamics, as follows: (1) hypoplastic left heart syndrome and other forms of functionally univentricular heart defect; (2) transposition of the great arteries; (3) conotruncal defects and other CHDs with large shunts; (4) right ventricular outflow tract obstruction, without a hypoplastic right ventricle; (5) left outflow tract obstruction; (6) others. The transventricular axial view of the fetal head was used as the reference view, on which the frontal lobe anteroposterior diameter (FAPD) and the occipitofrontal diameter (OFD) were measured, assuming the former to be representative of the area of the frontal lobes. The FAPD/OFD ratio was then calculated as FAPD/OFD × 100. These two variables (FAPD and FAPD/OFD ratio) were then evaluated and compared between the study and control groups. Adjustment for gestational age, both via multiple linear regression and by using a-posteriori matching based on the propensity score, was employed. In normal fetuses, FAPD showed a linear positive correlation with gestational age. In fetuses with CHD, the FAPD was shorter than in normal fetuses from the 20th gestational week onwards, with the difference increasing after 30 gestational weeks. FAPD/OFD ratio was significantly smaller in fetuses with CHD than in normal fetuses (P < 0.0001) at all gestational ages, with no apparent differences among the various CHD categories, all of which had smaller FAPD/OFD ratio compared with controls. Fetuses with CHD have a shorter FAPD and a smaller FAPD/OFD ratio compared with normal fetuses. This impaired growth of the frontal area of the brain seems to occur in all types of CHD, regardless of their impact on hemodynamics. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.


Colouration by total internal reflection and interference at microscale concave interfaces.
Many physical phenomena create colour: spectrally selective light absorption by pigments and dyes1,2, material-specific optical dispersion3 and light interference4-11 in micrometre-scale and nanometre-scale periodic structures12-17. In addition, scattering, diffraction and interference mechanisms are inherent to spherical droplets18, which contribute to atmospheric phenomena such as glories, coronas and rainbows19. Here we describe a previously unrecognized mechanism for creating iridescent structural colour with large angular spectral separation. Light travelling along different trajectories of total internal reflection at a concave optical interface can interfere to generate brilliant patterns of colour. The effect is generated at interfaces with dimensions that are orders of magnitude larger than the wavelength of visible light and is readily observed in systems as simple as water drops condensed on a transparent substrate. We also exploit this phenomenon in complex systems, including multiphase droplets, three-dimensional patterned polymer surfaces and solid microparticles, to create patterns of iridescent colour that are consistent with theoretical predictions. Such controllable structural colouration is straightforward to generate at microscale interfaces, so we expect that the design principles and predictive theory outlined here will be of interest both for fundamental exploration in optics and for application in functional colloidal inks and paints, displays and sensors.


A new partly external device for extension of skin before excision of skin defects.
Tissue expansion is a well established method for reconstructive surgery. As a complement, a new technique of skin extension has been developed, and tested clinically. The device consists of two holding bars with several straps placed between them, which usually is applied under local anaesthesia. It is an efficient, rapid, and inexpensive way of expanding skin before excision of skin defects. Thirty-two patients have been treated, three patients have had complications, and length of follow up ranged from 2-12 months.


Structural and Thermodynamic Stability of the "1111" Structure Type: A Case Study of the EuFZnPn Series.
Two new compounds with the LaOAgS structure, EuFZnAs (1) and EuFZnSb (2), were obtained via solid state reaction. Both compounds are tetragonal (P4/nmm) with the cell parameters a = 4.1000(1) Å and c = 9.0811(1) Å for 1 and a = 4.2852(1)Å and c = 9.4238(1)Å for 2. The absence of their phosphide analog can be explained based on crystal chemical considerations as well as on quantum-chemical estimates of their thermodynamic stability with respect to EuF2 and EuZn2Pn2. The magnetic response of 1 and 2 is ascribed to the presence of Eu2+ ions. Both compounds are paramagnetic down to low temperatures, where they order antiferromagnetically at ∼5 K and ∼3 K, respectively. They are narrow-gap semiconductors, and EuFZnSb demonstrates a relatively high value of the Seebeck coefficient.


Menstrual cyclic thrombocytopenia.
We studied three patients with cyclic thrombocytopenia which occurred in phase with the menstrual cycle. The platelet count in each patient reached a nadir of 5-20 x 10(9)/l at the onset of menses. Thrombocytopenia was associated with bruising, epistaxis and menorrhagia and was followed 5-14 d later by normal or elevated platelet counts (up to 900 x 10(9)/l). Repeat bone marrow examinations performed at the time of reduced platelet counts showed megakaryocytic hyperplasia. 111In-platelet-disappearance from the circulation was measured in one patient; T50, time to half activity, was shortened to 0.7 d during the period of thrombocytopenia and was prolonged to 3.2 d when the platelet count increased (normal platelet T50 is about 4.8 d). In two of three patients platelet-associated anti-glycoprotein Ib autoantibodies were present and remained elevated despite normalization of the platelet count. In both of two patients the decrease in platelet count at the onset of menses was associated with an increase in the expression of monocyte Fc gamma receptors. Based on the reported capacity of oestrogenic hormones to modulate macrophage Fc gamma receptor expression, we propose that hormonal changes during the menstrual cycle may alter the Fc gamma receptor-mediated clearance of antibody-coated platelets by macrophages, modulate platelet survival, and cause cyclic thrombocytopenia.


Mandibular reconstruction.
Although there is no general agreement, we think immediate reconstruction with free bone graft from the iliac crest or rib is the method of choice for a small mandibular body or arch defect without concomitant significant loss of soft tissue. Soft tissue reconstruction with well-vascularized tissue should always be performed when extensive loss of soft tissue occurs after hemimandibulectomy to avoid tension on the stump and mandibular drift. When postoperative radiation is not anticipated, immediate bone grafting is appropriate. A free bone covered by well-vascularized tissue or a composite graft is our primary choice, but alloplastic trays with cancellous bone can also be considered. If postoperative radiation is anticipated, only soft tissue repair should be performed and osseous reconstruction should be deferred until radiotherapy is completed. Defects of the arch require special attention because of the severe deviation of the mandibular stumps. Immediate reconstruction is recommended in uncomplicated cases, but secondary bone grafting will be needed when the patient is in poor condition, or postoperative radiation places the bone graft in jeopardy. In such cases, immediate stabilization of the bone segments by internal or external fixation is absolutely necessary. Finally, secondary reconstruction should be considered only if there is no evidence of residual tumor. The defect should be recreated, scarred or irradiated tissue resected, and immediate reconstruction obtained with well-vascularized pedicled or free flaps.


Combined radiotherapy and chemotherapy for nasopharyngeal carcinoma.
Among squamous cell carcinomas of the head and neck, nasopharyngeal carcinoma is probably the most radiosensitive and chemosensitive. It also has the highest incidence of distant metastasis. This article reviews the results of randomized trials of combined chemotherapy and radiotherapy for nasopharyngeal carcinoma to date. Induction chemotherapy with bleomycin, epirubicin, and cisplatin was shown to increase disease-free survival but not overall survival in a trial by the International Nasopharyngeal Cancer Study Group. Concurrent radiotherapy and cisplatin followed by adjuvant cisplatin and 5-fluorouracil infusion significantly decreased local, nodal, and distant failures and increased progression-free and overall survival in the Head and Neck Intergroup Trial. The toxicity of combined chemotherapy and radiotherapy, however, primarily acute toxicity, was significantly greater than that of radiotherapy alone. Further clinical trials using novel drugs, altered fractionation radiotherapy and chemotherapy dose schedules, new radiotherapy techniques, and other treatment modifiers are needed to further improve the therapeutic ratio.


Spray drying for making covalent chemistry II: synthesis of covalent-organic framework superstructures and related composites.
Here we report a method that combines the spray-drying technique with a dynamic covalent chemistry process to synthesize zero-dimensional, spherical and microscale superstructures made from the assembly of imine-based COF nanocrystals. This methodology also enables the integration of other functional materials into these superstructures forming COF-based composites.


Incidence and risk factors of postoperative medial shoulder imbalance in Lenke Type 2 adolescent idiopathic scoliosis with lateral shoulder balance.
In clinical practice, there are a significant percentage of Lenke 2 AIS patients suffered from medial shoulder imbalance (MSI) despite achieving good lateral shoulder balance (LSB) following surgery. However, there are few studies evaluating the features of the medial shoulder. The objective of this study was to determine the incidence and independent risk factors of MSI with LSB after Lenke 2 AIS corrective surgery. One hundred and twenty Lenke 2 AIS patients with LSB at the last follow-up were reviewed from 2009 to 2018. Preoperative, and 3-month and the last postoperative follow-up radiographs were measured using a number of specific measurements. At the last follow-up, patients were divided into medial shoulder balance (MSB) group and the MSI group according to whether the T1 tilt was greater than 3°. A stepwise multiple linear regression analysis was used to examine the independent risk factors for MSI. Scoliosis Research Society (SRS)-30 questionnaire was used to assess clinical outcomes. Up to 69.2% of patients suffered from MSI with LSB after Lenke Type 2 AIS corrective surgery. Multiple regression showed that postoperative upper instrumented vertebra tilt (UIVt), proximal thoracic curve (PTC), the ratio of PTC and main thoracic curves (PTC/MTC) and T2 vertebra rotation ratio (T2-VR) were significant predictors for MSI (UIVt: b = 0.398, p < 0.001; PTC/MTC: b = 2.085, p < 0.001; PTC: b = 0.155, p < 0.001; T2-VR: b = 3.536, p = 0.008; adjusted R2 = 0.711). 72 patients completed the SRS-30 questionnaire survey, and the MSB group were scored the higher (p ≤ 0.001) in self-image domain (4.18 ± 0.43 vs. 3.70 ± 0.35), satisfaction domain (4.39 ± 0.54 vs. 3.95 ± 0.46) and total average (4.31 ± 0.23 vs. 4.11 ± 0.19). Although the patients with Lenke 2 AIS achieve LSB after corrective surgery, up to 69.2% of them suffered from MSI. Postoperative UIVt, PTC, PTC/MTC and T2-VR were significant predictors for MSI. Sufficient correction of these variables may facilitate the achievement of MSB.


Radiotherapeutic agents: properties, dosimetry, and radiobiologic considerations.
Radioactive nuclides for treatment have occupied an important but somewhat diminishing role in the total practice of nuclear medicine. Although theoretically they should have important potentialities, particularly in the treatment of various forms of cancer, their development in this field has not kept pace with the progress in other treatment modalities in radiation oncology. Indications for the selection of appropriate isotopes for therapy revolve about the emission of beta particles of sufficient energy, which are administered in a chemical form that reaches the tumor. Methods of calculation of doses delivered to sites of deposition are discussed in the text. Radiobiologic considerations include the possibility of early deleterious effects from overdosage, and consideration of chromosomal changes of circulating lymphocytes and their implications. Late effects that have been of great public concern are confined almost solely to possible carcinogenesis, and this effect has been minimal in patients receiving therapeutic levels of radioactive drugs. Genetic and developmental effects, also, have been negligible. Complications encountered more frequently have been leukemia after extensive therapy of thyroid carcinoma, and local fibrosis after direct injection of radioactive colloids into tumor tissue.


Characterization of mitochondrial genome of Indian Ocean blue-spotted maskray, Neotrygon indica and its phylogenetic relationship within Dasyatidae Family.
The present study characterized complete mitochondrial genome of Blue-spotted maskray, Neotrygon indica and studied the evolutionary relationship of the species within the Dasyatidae family. The total length of the mitogenome was 17,974 bp including 37 genes and a non-coding control region. The average frequency of nucleotides in protein-coding genes was A: 29.1 %, T: 30.2 %, G: 13.0 % and C: 27.7 % with AT content of 59.3 %. The values of AT and GC skewness were -0.018 and -0.338, respectively. Comparative analyses showed a large number of average synonymous substitutions per synonymous site (Ks) in gene NADH4 (5.07) followed by NADH5 (4.72). High values of average number of non-synonymous substitutions per non-synonymous site (Ka) were observed in genes ATPase8 (0.54) and NADH2 (0.44). Genes NADH4L and NADH2 showed high interspecific genetic distance values of 0.224 ± 0.001 and 0.213 ± 0.002, respectively. Heat map analysis showed variation in codon usage among different species of the Dasyatidae family. The phylogenetic tree showed a sister relationship between the Dasyatinae and the Neotrygoninae subfamilies. Neotrygon indica formed as a sister species to the clade consisting of N. varidens and N. orientalis. Based on the present results, Neotrygon indica could have diverged from the common ancestor of the two latter in the Plio-Pleistocene. The present study showed distinct characteristics of N. indica from its congeners through comparative mitogenomics.