Neonatal surgical outcomes after prenatal diagnosis of complex congenital heart disease: experiences of a perinatal integrated diagnosis and treatment program.
This study aimed to evaluate neonatal surgical outcomes of patients diagnosed with complex congenital heart disease (CHD) during pregnancy and treated by the newly initiated "perinatal integrated diagnosis and treatment program (PIDTP)". We reviewed clinical data of 207 neonates (surgical age ≤ 28 days) who underwent cardiac surgeries in a single center from January 2017 to December 2018, including 31 patients with referrals from the "PIDTP" (integration group) and 176 patients with routine referral treatment (non-integrated group). In the integration group, median admission age was 0 days and median age at surgery was 4 days. In the non-integrated group, median admission age was 8 days (P = 0.001) and median age at surgery was 13 days (P = 0.001). The emergency surgery rate in patients with duct-dependent defects was 36% in the integration group and 59% (P = 0.042) in the non-integrated group, respectively. The in-hospital mortality was 16% in the integration group and 14% (P = 0.78) in the non-integrated group. The 2-year cumulative survival rate after surgery was 83.9% ± 6.6% in the integration group and 80.3% ± 3.1% (P = 0.744) in the non-integrated group. According to multivariable regression analysis, independent risk factors for early mortality of overall neonatal cardiac surgery were low body weight, high serum lactate level, postoperative extracorporeal membrane oxygenation (ECMO) support and prolonged cardiopulmonary bypass (CPB) time. PIDTP shortens the postnatal transit interval, reduces the emergency operation rate of neonatal critical CHD, and provides better preoperative status for surgery. Patients treated by the PIDTP tend to have more complicated anatomical deformity and a greater requirement for the operation and postoperative management, but early outcome and follow-up prognosis are satisfactory.


Child-rearing Support Provided by Public Health Nurses to People with Mental Illness: Qualitative Descriptive Study.
The growing rates of deinstitutionalization in Japan have resulted in an increase in the number of children being raised by parents with mental illness. Given this situation, public health nurses working for local governments play an important role. The purpose of this qualitative descriptive study was to describe the child-rearing support provided by public health nurses to parents with mental illness. Seven nurses identified 28 cases of parents with mental illness. Descriptions of the goals and details of the appropriate nursing support were extracted from transcripts, coded, and categorized. Parents with mental illness diagnosed with addiction and personality disorders were more difficult to support than those diagnosed with mood disorders or schizophrenia. Public health nurses supported parents with mental illness with the aim of achieving goals such as "building continuous consultative relationships," "ensuring living conditions had a minimum level of safety and comfort," "parents playing their roles," "parents and children living together in the community," and "fostering children's growth." While they provided support by "assessing their relationships with parents," "building consultative relationships with parents," "assessing parents' illnesses/disorders and supporting," "assessing child-rearing abilities and supporting," and "cooperating with related agencies," they tended to focus on the growth of the children rather than the recovery of parents. Consultative relationships were the beginning of support, as well as the most important and difficult skill. Public health nurses need to provide support for the recovery of parents with mental illness and learn about personality disorders and addiction.


Polysaccharide nanofiber made from euglenoid alga.
We have fabricated a polysaccharide nanofiber made from paramylon (β-1,3-glucan), a storage polysaccharide stored as a micrometer-sized particle in the cell of euglenoid alga. Preparation of this nanofiber primarily hinges on the bottom-up approach. First, paramylon, which is originally present in the form of a bundle of nanofibers in a particle, was fibrillated to a randomly coiled polymer by dissolving the particle in a 1.0-mol/L NaOH aqueous solution. Second, the randomly coiled polymer was allowed to self-assemble into a triplex as the NaOH concentration was reduced to 0.25-0.20mol/L. Third, a 20-nm-width nanofiber made from the triplex emerged in the solution when the NaOH concentration was reduced to approximately 0.20mol/L.


Death due to diabetic ketoacidosis: Induction by the consumption of synthetic cannabinoids?
We present a case study on a man who suffered from diabetic ketoacidosis, probably following consumption of synthetic cannabinoids. In blood from a femoral vein AB-CHMINACA, AB-FUBINACA, AM-2201, 5F-AMB, 5F-APINACA, EAM-2201, JWH-018, JWH-122, MAM-2201, STS135 and THJ 2201 could be detected by LC-MS/MS. Diagnosis of ketoacidosis as cause of death was carried out using biochemical measurements of glucose and lactate concentrations in vitreous humour (sum formula: 463 mg/dl) and cerebrospinal fluid (sum formula: 506 mg/dl), of acetone (163 mg/l in femoral venous blood) and of HbA1c (98 mmol/mol). Death due to hyperglycaemia could have been induced by skipping of insulin doses due to his intoxicated state or by the cannabinoids which were described to be able to produce hyperglycaemia themselves.


Morphological changes in the hippocampal CA3 region induced by non-invasive glucocorticoid administration: a paradox.
Repeated stress induces atrophy, or remodeling, of apical dendrites in hippocampal CA3 pyramidal neurons. In rats, the stress effect is blocked by adrenal steroid synthesis inhibitors, and mimicked by daily injection of corticosterone. We report that non-invasive administration of corticosterone in the drinking water (400 micrograms/ml) also produced atrophy of apical dendrites in CA3. Unexpectedly, the combination of daily stress and oral corticosterone negated the effects of either treatment alone, and no changes in the apical dendritic length or branching pattern of CA3 pyramidal neurons were observed compared to control unstressed rats.


Efficacy and safety of flavocoxid, a novel therapeutic, compared with naproxen: a randomized multicenter controlled trial in subjects with osteoarthritis of the knee.
Flavocoxid is a novel flavonoid-based "dual inhibitor" of the 5-lipoxygenase (5-LOX) enzyme and the cyclooxygenase (COX) enzymes. This study was designed to compare the effectiveness and safety of flavocoxid to naproxen in subjects with moderate to severe osteoarthritis (OA) of the knee. In this randomized, multicenter, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. The trial was structured to show noninferiority of flavocoxid to naproxen. Primary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subscales and a timed walk. More than 90% of the subjects in both groups noted significant reduction in the signs and symptoms of knee OA. There were no statistically significant differences in efficacy between the flavocoxid and naproxen groups when the entire intent-to-treat population was analyzed. The flavocoxid group had significantly fewer upper gastrointestinal (UGI) and renal (edema) adverse events (AEs) as well as a strong trend toward fewer respiratory AEs. Flavocoxid, a first-in-class flavonoid-based therapeutic that inhibits COX-1 and COX-2 as well as 5-LOX, was as effective as naproxen in managing the signs and symptoms of OA of the knee. Flavocoxid demonstrated better UGI, renal (edema), and respiratory safety profiles than naproxen.


Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed.
Phosphocholine (PC) is the immunodominant epitope found on the surface of a number of microorganisms, including Streptococcus pneumoniae (SPn), and is thought to play a vital role in the pathogenesis of SPn. B cells expressing M167Hκ24L immunoglobulin receptors specific for PC have been shown to be autoreactive in that they undergo clonal deletion in both X-linked immune-deficient and Rag(-/-) mice. We have now shown that B cells expressing M603Hκ8L PC-specific receptors also delete in Rag(-/-) mice, whereas those expressing T15Hκ22L transgenes do not delete. However, T15Hκ22L B cells are lost in normal heterozygous transgenic mice because they cannot compete with normal B cells. These data indicate that M167Hκ24L and M603Hκ8L PC-specific B cells are recognizing an autoantigen expressed on membranes which causes them to downregulate their receptors and clonally delete, while T15Hκ22L B cells are tolerized by a soluble form of PC-antigen which results in their being trapped in the spleen. Thus, the types of tolerance seen in autoreactive PC-specific B cells are dependent on the idiotype of the receptors expressed.


Evaluation of a computer-based nutrition education tool.
To evaluate the efficacy and feasibility of using a computer-based teaching tool (http://www.coolfoodplanet.org) for nutrition and lifestyle education developed for primary school children. This was a 2-week school-based intervention in third and fourth grades. The study design was multi-factorial with repeated measures of nutrition knowledge, at three points in time, of dependent samples from control and intervention groups. Control schools (n=7) used 'traditional' nutrition education materials and intervention schools (n=8) additionally used the computer-based educational tool. Qualitative information was collected in focus group discussions with student teachers and pupils, and by observing the nutrition lessons. Pupils aged 8-11 years (n=271) from participating schools in Vienna, Austria. Nutrition knowledge increased significantly in both intervention and control schools, irrespective of the teaching tool used (P<0.001). The significant effect was maintained at 3 months' follow-up. There was no detectable difference in nutrition knowledge post intervention or at follow-up between the two study groups. In intervention schools, younger pupils (8-9 years) had better nutrition knowledge than older pupils (10-11 years) (P=0.011). This computer-based tool increases the possibilities of school-based nutrition education. If the tool's weaknesses identified during the formative evaluation are eliminated, it has the potential to make learning about nutrition more enjoyable, exciting and effective. This is of great importance considering that 'healthy' nutrition is not necessarily a topic that easily attracts pupils' attention and in view of the potential long-term health benefits of early and effective nutrition education.


Emergency thoracotomy.
There continues to be a debate on the indications for and value of the emergency department thoracotomy, especially with regard to the subject of thoracotomy performed by the emergency physician. The current literature does not deal specifically with thoracotomies performed in the emergency department by an emergency physician on trauma patients. This article describes a technique for emergency department thoracotomy that can be performed by an emergency physician.


[Evaluation of lactate measurement in blood and plasma with biosensor technology: a comparison of methods].
The introduction of biosensor technology for near bedside measurement of plasma lactate concentrations has been a promising step for critical care profiling. However, methodological drawbacks and relevant inaccuracy have been reported. With the advent of a new biosensor (Chiron Diagnostics) and a revised NOVA Biomedical device, accuracy was expected to be improved. The goal of the present investigation was to evaluate the accuracy of both methods. Two devices (System 860, Chiron Diagnostics; StatProfile 9, NOVA Biomedical) were simultaneously analysed using 9 biosensors in both fresh frozen plasma and citrated whole blood. The results were compared with an established photometric method (Lactat PAP, Analyticon). Measurements were performed as duplicates (n = 1120) before and after the addition of 1 molar sodium lactate solution (2-24 mmol/L). For the estimation of between-day precision commercially available aqueous and serum-based quality controls were analysed daily over a period of 60 days. Reproducibility in blood was 2.6 +/- 2.8% (Chiron), 4.1 +/- 4.0% (NOVA) and 1.5 +/- 2.1% (Analyticon), in plasma respectively 2.1 +/- 2.4%, 2.1 +/- 2.9% and 1.0 +/- 1.1%. Mean inaccuracy in plasma presented to be -0.2 +/- 16.4% (plasma) and +7.2 +/- 13.1% (blood) for Chiron, +9.4 +/- 18.4% and +18.7 +/- 16.7% for NOVA, and -37.8 +/- 18.2% and -27.5 +/- 17.6% for Analyticon. Calculated between-day-precision (variation coefficients mean values) was 11.5 +/- 4.9% (Chiron) and 14.0 +/- 5.9% (NOVA). Although accuracy of lactate concentrations obtained with biosensor technology has improved (mean 0-18%), the variability of the results still poses a problem (mean 13-18%). Therefore, from the methodological point of view, interpretation of a single lactate value requires caution when applying to the critically ill, particularly with view to threshold values, and should be considered vis-à-vis other options.


The effects of inferotemporal cortex lesions on Konorski delayed pair comparison in monkeys.
Rhesus monkeys were trained on a pair comparison recognition memory task, running concurrently with a signal detection (attention) problem. The animals were given bilateral posterior or anterior inferotemporal cortex lesions once satisfactory performance had been reached. The former group sustained attentional but only transient mnemonic impairments. Anterior lesions impaired visual learning and memory, but not attention. We confirm that inferotemporal cortex is sub-divided into at least two distinct regions, serving visual attention and other cognitive processes. The role of inferotemporal cortex in recognition memory is discussed, and it is concluded that task-related problems do not permit an unambiguous resolution of this question.


Systematic development and optimization of chemically defined medium supporting high cell density growth of Bacillus coagulans.
With determined components and experimental reducibility, the chemically defined medium (CDM) and the minimal chemically defined medium (MCDM) are used in many metabolism and regulation studies. This research aimed to develop the chemically defined medium supporting high cell density growth of Bacillus coagulans, which is a promising producer of lactic acid and other bio-chemicals. In this study, a systematic methodology combining the experimental technique with flux balance analysis (FBA) was proposed to design and simplify a CDM. The single omission technique and single addition technique were employed to determine the essential and stimulatory compounds, before the optimization of their concentrations by the statistical method. In addition, to improve the growth rationally, in silico omission and addition were performed by FBA based on the construction of a medium-size metabolic model of B. coagulans 36D1. Thus, CDMs were developed to obtain considerable biomass production of at least five B. coagulans strains, in which two model strains B. coagulans 36D1 and ATCC 7050 were involved.


Effects of length-dependent positive feedback on length distributions of microtubules undergoing hydrolysis.
Despite a rapid turnover of subunits, how cells control the lengths of cytoskeletal filaments (such as microtubules) is a fundamental question in cell biology. Here, we theoretically investigate how microscopic processes affect the length distributions of multiple microtubules growing stochastically in a shared subunit pool. In particular, we consider length-dependent positive feedback on filament growth and the chemical conversion from GTP-tubulin to GDP-tubulin (hydrolysis) inside a filament. We found different dynamical regimes for a single filament by simulating a model of microtubule kinetics, where both bimodal and unimodal (bell-shaped) length distributions emerge in the steady state. More significantly, the length distributions of multiple filaments were not unimodal, predicting a collective effect for more than one filament. Interestingly, when length distributions were bimodal, we also observed bistable toggling of individual lengths. Therefore, regulation of biophysical parameters (e.g., hydrolysis rate and feedback strength) can lead to length diversity in an ensemble of multiple microtubules.


Comparison of the long-term effects of simple total abdominal hysterectomy with transcervical endometrial resection on urinary incontinence.
To test the hypothesis that the hospital referral rate for urinary incontinence (UI) symptoms, within 10 years of a simple total abdominal hysterectomy (TAH) for dysfunctional uterine bleeding (DUB), would differ to that after a transcervical resection of the endometrium (TCRE). Retrospective case note review. Teaching hospital in north east Scotland. All women who had a TAH (316) or a TCRE (229) for DUB, during the period from 1 January 1990 to 31 December 1994, who had never been referred for symptoms of UI prior to their operation. Independent t tests, Mann-Whitney U tests and Chi-squared tests were used to compare the two study groups in terms of demographic details and outcome measures. Newcombe's method for the comparison of two unpaired proportions was used to calculate 95% CIs for the differences in outcome measures between the two operations. Logistic regression was conducted to investigate associations with hospital referral for UI. Hospital referral for UI at 10 years follow up. There were significantly more hospital referrals for UI in the TAH group compared with the TCRE group (46 [15%] versus 16 [7%]; OR 2.27, 95% CI 1.25-4.12). More women were referred for urological investigations after a TAH than after a TCRE (39 [12%] versus 13 [6%], 95% CI for the difference in proportions 2-11%). A higher, but statistically nonsignificant, proportion of women had objectively demonstrated UI after a TAH than after a TCRE (25 [8%] versus 10 [4%], 95% CI for the difference in proportions -1 to 8%). There were a greater number of hospital referrals for treatment of UI in the TAH group (36, 11%) than in the TCRE group (12, 5%), 95% CI for the difference in proportions (1-11%). After adjusting for age, weight, smoking status and mode of delivery, the increased rate of hospital referral for UI after TAH remained, with an odds ratio of 2.31, 95% CI 1.24-4.30. TAH is associated with a significantly increased incidence of hospital referral for UI, urological investigations and treatment for UI at 10 years of follow up compared with TCRE.


Development of an indirect fluorescent antibody test, using microfluorometry as a diagnostic test for bovine anaplasmosis.
The indirect fluorescent antibody test for the diagnosis of Anaplasma marginale infection in cattle was modified for use with microfluorometry. The test was standardized by use of a fluorometer that measures intensity of fluorescence. Standardization included A marginale-infected blood smears on microscope slides as antigen, serum from an inoculated calf as a positive control containing specific antibody, and an affinity-purified fluorescein-conjugated anti-bovine immunoglobulin as 2nd antibody. The modified test and microfluorometry allowed for titration of sera from A marginale (Florida isolate)-inoculated cattle with a degree of accuracy exceeding visual determinations. In addition, the fluorometric test was more sensitive than the complement fixation or card agglutination tests in identifying cattle that had previous Anaplasma infections.


"This is the child we were given": A qualitative study of Danish parents' experiences of a prenatal Down syndrome diagnosis and their decision to continue the pregnancy.
Termination rates when Down syndrome (DS) is diagnosed prenatally are high in most countries. Thus, the present study aimed to explore how parents of prenatally diagnosed children with DS experienced the diagnostic process and their decision to continue the pregnancy. Data from a semi-structured, qualitative interview study with eight mothers and five fathers of prenatally diagnosed children with DS born between 2008 and 2017 were analyzed using thematic analysis. Several couples emphasized how they had not hoped for a child with DS, but following the diagnosis they strongly felt that this was the child that they "were given." The couples stressed that DS was not the worst that could happen. All couples sought experiential knowledge outside the hospital setting to explore the potential for living a fulfilling life with DS. Five couples had positive recollections of the delivery of the DS result. Three couples had negative recollections, mainly because the intention to terminate had been taken for granted. After the decision to continue pregnancy was made, their interaction with health-care professionals was generally experienced as positive and supporting. However, some couples still felt vulnerable because they were aware that their decision was uncommon. Health-care professionals must be careful to speak in unprejudiced ways throughout the diagnostic process and present both termination and continuation of pregnancy as equally legitimate options. Nevertheless, the couples may still experience doubt and feel vulnerable following their decision to continue the pregnancy.


The olfactory glomerulus: a cortical module with specific functions.
The axons of many olfactory receptor cells converge on an individual glomerulus in the olfactory bulb, where they make contacts with the distal dendrites of mitral and tufted cells. Each glomerulus is targeted by olfactory receptor neurons expressing a single type of olfactory receptor protein. The glomerulus provides a unique model in which the function of a cortical module can be unambiguously established. Here we review the increasing evidence that a key functional operation of the glomerulus is to act as a signal-to-noise enhancing device in the processing of sensory input and that this function is critical across vertebrate and invertebrate species for the ability to detect specific odor stimuli within "noisy" odor environments and to carry out discriminations between odor molecules that are structurally closely related.


The effects of bilayer thickness and tension on gramicidin single-channel lifetime.
Measurements have been made of gramicidin single-channel lifetimes in monoacylglycerol bilayers chosen so that their thickness ranged from above to below the length of the gramicidin channel. Contact angles, electrical capacities and bulk-phase interfacial tensions have also been determined for these systems. The mean channel lifetime decreased with the hydrocarbon thickness of the membrane until the latter reached 2.2 nm, after which the lifetime was relatively constant. A theoretical model has been proposed which relates the mean channel lifetime (or dissociation constant) to both the thickness and the tension of the bilayers. The analysis of the present results and of those of previous studies has led to the idea that aggregates of water molecules may play an important rôle in the dissociation of the gramicidin channel.


Monoclonal antibody OKT17 recognizes most cases of T-cell malignancy.
Membrane phenotype analysis with monoclonal antibodies (McAb) has demonstrated great heterogeneity within the T-cell malignancies. We describe here the reactivity with an anti-T cell McAb, OKT17, in 80 leukaemia samples. Cells from all types of T-cell leukaemia (48 cases), except from the small group of pre-T-ALL, strongly expressed the antigen identified by OKT17 whereas none of the 32 non-T leukaemias were OKT17 positive. When the reactivity of OKT17 was compared with that of other pan-T markers, OKT17 was positive in a larger number of T-cell leukaemias: 87% of cases compared with 74% with E-rosettes and 73% with the McAb 3A1. In the mature or post-thymic proliferations OKT17 was positive in 96% of cases, compared with 77% with E-rosettes and 61% with 3A1. The latter reagent, on the other hand, was better than OKT17 for detecting leukaemias with a thymic phenotype, 100% and 68% of positive cases respectively. The combined use of OKT17, 3A1 and terminal transferase permits a more precise classification of all the T-cell leukaemias according to the main stages of T-cell differentiation.


Genotoxicity of intermittent co-exposure to benzene and toluene in male CD-1 mice.
Benzene is an important industrial chemical. At certain levels, benzene has been found to produce aplastic anemia, pancytopenia, myeloblastic anemia and genotoxic effects in humans. Metabolism by cytochrome P450 monooxygenases and myeloperoxidase to hydroquinone, phenol, and other metabolites contributes to benzene toxicity. Other xenobiotic substrates for cytochrome P450 can alter benzene metabolism. At high concentrations, toluene has been shown to inhibit benzene metabolism and benzene-induced toxicities. The present study investigated the genotoxicity of exposure to benzene and toluene at lower and intermittent co-exposures. Mice were exposed via whole-body inhalation for 6h/day for 8 days (over a 15-day time period) to air, 50 ppm benzene, 100 ppm toluene, 50 ppm benzene and 50 ppm toluene, or 50 ppm benzene and 100 ppm toluene. Mice exposed to 50 ppm benzene exhibited an increased frequency (2.4-fold) of micronucleated polychromatic erythrocytes (PCE) and increased levels of urinary metabolites (t,t-muconic acid, hydroquinone, and s-phenylmercapturic acid) vs. air-exposed controls. Benzene co-exposure with 100 ppm toluene resulted in similar urinary metabolite levels but a 3.7-fold increase in frequency of micronucleated PCE. Benzene co-exposure with 50 ppm toluene resulted in a similar elevation of micronuclei frequency as with 100 ppm toluene which did not differ significantly from 50 ppm benzene exposure alone. Both co-exposures - 50 ppm benzene with 50 or 100 ppm toluene - resulted in significantly elevated CYP2E1 activities that did not occur following benzene or toluene exposure alone. Whole blood glutathione (GSH) levels were similarly decreased following exposure to 50 ppm benzene and/or 100 ppm toluene, while co-exposure to 50 ppm benzene and 100 ppm toluene significantly decreased GSSG levels and increased the GSH/GSSG ratio. The higher frequency of micronucleated PCE following benzene and toluene co-exposure when compared with mice exposed to benzene or toluene alone suggests that, at the doses used in this study, toluene can enhance benzene-induced clastogenic or aneugenic bone marrow injury. These findings exemplify the importance of studying the effects of binary chemical interactions in animals exposed to lower exposure concentrations of benzene and toluene on benzene metabolism and clastogenicity. The relevance of these data on interactions for humans exposed at low benzene concentrations can be best assessed only when the mechanism of interaction is understood at a quantitative level and incorporated within a biologically based modeling framework.


Alterations in brain morphology by MRI in adults with neurofibromatosis 1.
Neurofibromatosis 1 (NF1) is a rare autosomal dominant disease that causes the dysregulated growth of Schwann cells. Most reported studies of brain morphology in NF1 patients have included only children, and clinical implications of the observed changes later in life remain unclear. In this study, we used MRI to characterize brain morphology in adults with NF1. Planar (2D) MRI measurements of 29 intracranial structures were compared in 389 adults with NF1 and 112 age- and sex-matched unaffected control subjects. The 2D measurements were correlated with volumetric (3D) brain measurements in 99 of the adults with NF1 to help interpret the 2D findings. A subset (n = 70) of these NF1 patients also received psychometric testing for attention deficits and IQ and was assessed for clinical severity of NF1 features and neurological problems. Correlation analysis was performed between the MRI measurements and clinical and psychometric features of these patients. Four of nine corpus callosum measurements were significantly greater in adults with NF1 than in sex- and age-matched controls. All seven brainstem measurements were significantly greater in adults with NF1 than in controls. Increased corpus callosum and brainstem 2D morphology were correlated with increased total white matter volume among the NF1 patients. No robust correlations were observed between the 2D size of these structures and clinical or neuropsychometric assessments. Our findings are consistent with the hypothesis that dysregulation of brain myelin production is an important manifestation of NF1 in adults.


Guideline No. 410: Prevention, Screening, Diagnosis, and Pregnancy Management for Fetal Neural Tube Defects.
This revised guideline is intended to provide an update on the genetic aspects, prevention, screening, diagnosis, and management of fetal neural tube defects. Women who are pregnant or may become pregnant. Neural tube defect screening should be offered to all pregnant women. For prevention: a folate-rich diet, and folic acid and vitamin B12 supplementation, with dosage depending on risk level. For screening: second-trimester anatomical sonography; first-trimester sonographic screening; maternal serum alpha fetoprotein; prenatal magnetic resonance imaging. For genetic testing: diagnostic amniocentesis with chromosomal microarray and amniotic fluid alpha fetoprotein and acetylcholinesterase; fetal exome sequencing. For pregnancy management: prenatal surgical repair; postnatal surgical repair; pregnancy termination with autopsy. For subsequent pregnancies: prevention and screening options and counselling. The research on and implementation of fetal surgery for prenatally diagnosed myelomeningocele has added a significant treatment option to the previous options (postnatal repair or pregnancy termination), but this new option carries an increased risk of maternal morbidity. Significant improvements in health and quality of life, both for the mother and the infant, have been shown to result from the prevention, screening, diagnosis, and treatment of fetal neural tube defects. The benefits for patient autonomy and decision-making are provided in the guideline. Harms include an unexpected fetal diagnosis and the subsequent management decisions. Harm can also result if the patient declines routine sonographic scans or if counselling and access to care for neural tube defects are delayed. Cost analysis (personal, family, health care) is not within the scope of this clinical practice guideline. A directed and focused literature review was conducted using the search terms spina bifida, neural tube defect, myelomeningocele, prenatal diagnosis, fetal surgery, neural tube defect prevention, neural tube defect screening, neural tube defect diagnosis, and neural tube defect management in order to update and revise this guideline. A peer review process was used for content validation and clarity, with appropriate ethical considerations. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). Maternity care professionals who provide any part of pre-conception, antenatal, delivery, and neonatal care. This guideline is also appropriate for patient education. RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).


Pediatric urinary diversion and undiversion.
Many things have changed in our management of the urinary tract of children and young adults. Important contributions from many sources have resulted in the refinement of therapy and the progression from diversion to undiversion and reconstruction. Primary urinary diversion is now uncommon. Patients with exstrophy, for example, are treated with primary bladder closure as newborns, and newborns with valves often are treated with primary valve ablation. Children with neurogenic bladder dysfunction resulting from myelodysplasia are rarely diverted, but are started at an early age with ICC. It is hoped that in future the contents of this article on diversion techniques and undiversion will be of historical interest, however. Note: The editors also have found the use of the Mitrofanoff procedure, utilizing a nonrefluxing tunnel and a catheterizable stoma made out of the ureter or appendix, to be a very valuable addition to the reconstructive surgeon's armamentarium. We also feel that use of detubularized bowel for either bladder augmentation or replacement provides more efficient storage capability. Occasional reports of extremely significant diarrhea after removal of the ileocecal segment from the intestinal tract have been reported in children with myelodysplasia.


Large ulceration of the oropharynx induced by methotrexate-associated lymphoproliferative disorders.
We present a case of a 67-year-old Japanese man with a serious oropharyngeal ulceration that at first seemed to be destructive malignant lymphoma or oropharyngeal carcinoma. We suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About 3 weeks after simple discontinuation of MTX, complete regression of the disease was observed, confirming our diagnosis.


Respiratory management of children with spinal muscular atrophy (SMA).
Spinal muscular atrophy (SMA) causes a predominantly bilateral proximal muscle weakness and atrophy. The respiratory muscles are also involved with a weakness of the intercostal muscles and a relatively spared diaphragm. This respiratory muscle weakness translates into a cough impairment, resulting in poor clearance of airway secretions and recurrent pulmonary infections, restrictive lung disease due to a poor or insufficient chest wall and lung growth, nocturnal hypoventilation and, finally, respiratory failure. Systematic and regular monitoring of respiratory muscle performance is necessary in children with SMA in order to anticipate respiratory complications, such as acute and chronic respiratory failure, and guide clinical care. This monitoring is based in clinical practice on volitional and noninvasive tests, such as vital capacity, sniff nasal inspiratory pressure, maximal static pressures, peak expiratory flow and peak cough flow because of their simplicity, availability and ease. In young children, those with poor cooperation or severe respiratory muscle weakness, other, mostly invasive, tests may be required to evaluate respiratory muscle performance. A sleep study, or at least overnight monitoring of nocturnal gas exchange is mandatory for detecting nocturnal alveolar hypoventilation. Training for patients and caregivers in cough-assisted techniques is recommended when respiratory muscle strength falls below 50% of predicted or in case of recurrent or severe respiratory infections. Noninvasive ventilation (NIV) should be initiated in case of isolated nocturnal hypoventilation and followed by a pediatric respiratory team with expertise in NIV. Multidisciplinary (neurology and respiratory) pediatric management is crucial for optimal care of children with SMA. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.


Barriers to diabetic foot care in a disadvantaged population: A qualitative assessment.
We explored barriers to proper foot care in this population using a qualitative approach with focus group discussions (FGD). Participants were recruited from clinics at a safety-net hospital in Atlanta, Georgia and stratified into two groups: diabetic foot ulcer (DFU) and minor amputation (below ankle). The FGDs addressed patient experience in receiving care with a goal of understanding: foot care knowledge, barriers to care, and preferred educational methods. Surveys were performed to supplement FGDs. Forty participants (90% Black) were enrolled. Dominant themes emerging from FGDs were: 1-Patients reported adequate understanding of recommended foot care practices; 2-Personal barriers to self-care included lack of motivation, high cost, poor insurance coverage of supplies, and difficulty limiting activity for proper offloading; 3-Hospital system barriers included difficulty making timely appointments and reaching a provider to arrange care; 4-Access to footcare-related information and services improved with greater disease severity. Participants stressed that improved access often came too late to alter their course. They expressed interest in developing peer support groups to facilitate learning and sharing information relating to DFU. We found that patients with DFU or minor amputations have adequate footcare-related knowledge, but personal and systemic barriers limited appropriate foot care.


New cannabinoid receptor antagonists as pharmacological tool.
Synthesis and pharmacological evaluation of a new series of cannabinoid receptor antagonists of indazole ether derivatives have been performed. Pharmacological evaluation includes radioligand binding assays with [3H]-CP55940 for CB1 and CB2 receptors and functional activity for cannabinoid receptors on isolated tissue. In addition, functional activity of the two synthetic cannabinoids antagonists 18 (PGN36) and 17 (PGN38) were carried out in the osteoblastic cell line MC3T3-E1 that is able to express CB2R upon osteogenic conditions. Both antagonists abolished the increase in collagen type I gene expression by the well-known inducer of bone activity, the HU308 agonist. The results of pharmacological tests have revealed that four of these derivatives behave as CB2R cannabinoid antagonists. In particular, the compounds 17 (PGN38) and 18 (PGN36) highlight as promising candidates as pharmacological tools.


Preliminary experience of oblique occlusion technique in robot-assisted infrahepatic inferior vena cava thrombectomy: step-by-step procedures and short term outcomes.
We aimed to compare the oncological outcomes between the oblique occlusion technique and the traditional technique for robot-assisted radical nephrectomy (RARN) with inferior vena cava (IVC) thrombectomy, and to explore the safety and effectiveness of the oblique occlusion technique. Overall, 21 patients with renal cell carcinoma (RCC) and IVC tumor thrombus (TT) were admitted to our hospital from August 2019 to June 2020. All the patients underwent RARN with IVC thrombectomy, of which the IVC oblique occlusion technique was used in 11 patients and traditional occlusion technique was used in 10 patients. The oblique occlusion technique refers to oblique blocking from the upper corner of the right renal vein to the lower corner of the left renal vein using a vessel tourniquet or a vessel clamp (left RCC with IVCTT as an example). Compared with patients in the traditional group, those in the oblique group had lower serum creatinine at follow-up (3 month) (95 ± 21.1 vs. 131 ± 30.7 μmol/L, P = 0.03). There was no significant difference in operation time [149 (IQR 143-245) min vs. 148 (IQR 108-261) min, p = 0.86], IVC clamping time [18 (IQR 12-20) min vs. 20 (IQR 14-23) min, p = 0.41], and estimated intraoperative blood loss [300 (IQR 100-800) mL vs. 500 (IQR 175-738) mL, p = 0.51] between both groups. During a 16-month (range, 15-23 months) follow-up period, two cases progressed in the oblique group and three cases progressed in the traditional group. The modified IVC oblique occlusion technique procedure is relatively safe and effective in RARN with IVC thrombectomy. The IVC oblique occlusion technique may play a role in the protection of renal function.


Glycosylation-related genes are variably expressed depending on the differentiation state of a bioaminergic neuronal cell line: implication for the cellular prion protein.
A striking feature of the cellular prion protein (PrP(C)) is the heterogeneity of its glycoforms, whose contribution to PrP(C) function has yet to be defined. Using the 1C11 neuronal bioaminergic differentiation model and a glycomics approach, we show here a correlation between differential PrP(C) N-glycosylations in 1C11(5-HT) serotonergic and 1C11(NE) noradrenergic cells compared to their 1C11 precursor cells and a variation of the glycogenome expression status in these cells. In particular, expression of genes involved in N-glycan synthesis or in the modeling of chondroitin and heparan sulfate proteoglycans appeared to be modulated. Our results highlight that, the expression of glycosylation-related genes is regulated during bioaminergic neuronal differentiation, consistent with a participation of glycoconjugates in neuronal development and plasticity. A neuronal regulation of glycosylation processes may have direct implications on some neurospecific functions of PrP(C) and may participate in specific brain targeting of prion strains.


Human cell cultures infected by tumor-inducing and non-tumor-inducing viruses, an electron microscopic study.
This study is dealing with the infection patterns of adenovirus type 2 and type 12 on human fibroblast cell lines, KB, WI and MAF. With the exception of Ad -12 leads to WI, many intranuclear viral particles were present. None of these second passages (Ad-2 WI-WI, Ad-12 WI-WI, Ad-2 MAF-MAF, Ad-12 MAF-MAF) was found to have viral production. This indicates that the injections on both WI and MAF cells caused by both Ad-2 and Ad-12 cannot be serially transmitted. However, when these infected cells were used to expose KB cells, significant viral yields were obtained. This shows that the infected cells might still carry the viral specific antigens although no visible virions were observed.


Towards joint in situ determination of pressure and temperature in the large volume press exclusively from X-ray diffraction.
Since high-pressure devices have been used at synchrotron facilities, accurate determination of pressure and temperature in the sample has been a crucial objective, particularly for experiments that simulate the Earth's interior. However, in some cases using a thermocouple may have a high likelihood of failure or is incompatible with a high-pressure assembly. To address these challenges and similar issues, we aim to expand a previously proposed solution: to jointly estimate pressure and temperature (PT) through in situ X-ray diffraction, to cover a wider range of internal PT calibrants tested over larger PT ranges. A modifiable Python-based software is offered to quickly obtain results. To achieve these aims, in situ large volume press experiments are performed on pellets of intimately mixed powders of a halide (NaCl, KCl, KBr, CsCl) or MgO and a metal (Pt, Re, Mo, W, Ni) in the pressure range 3-11 GPa and temperature range 300-1800 K. Although the pressure range was chosen for practical reasons, it also covers an equally important depth range in the Earth (down to 350 km) for geoscience studies. A thermocouple was used to validate the PT conditions in the cell assemblies. The key results show that choosing the appropriate calibrant materials and using a joint PT estimation can yield surprisingly small uncertainties (i.e. <±0.1 GPa and <±50 K). This development is expected to benefit current and future research at extreme conditions, as other materials with high compressibility or high thermal pressure, stable over large PT ranges, may be discovered and used as PT calibrants.


Long-term oral lithium treatment attenuates motor disturbance in tauopathy model mice: implications of autophagy promotion.
Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective mechanisms including inhibition of glycogen synthase kinase-3 (GSK-3), a major tau kinase. Recently, it has been shown that, in various neurodegenerative proteinopathies, lithium could induce autophagy. To analyze how lithium is therapeutically beneficial in tauopathies, transgenic mice overexpressing human mutant tau (P301L) were treated with oral lithium chloride (LiCl) for 4 months starting at the age of 5 months. At first, we examined the effects of treatment on behavior (using a battery of behavioral tests), tau phosphorylation (by biochemical assays), and number of neurofibrillary tangles (NFTs) (by immunohistopathology). In comparison with control mice, LiCl-treated mice showed a significantly better score in the sensory motor tasks, as well as decreases in tau phosphorylation, soluble tau level, and number of NFTs. Next, we examined lithium effects on autophagy using an antibody against microtubule-associated protein 1 light chain 3 (LC3) as an autophagosome marker. The number of LC3-positive autophagosome-like puncta was increased in neurons of LiCl-treated mice. Neurons containing NFTs were completely LC3-negative, whereas LC3-positive autophagosome-like puncta contained phosphorylated-tau (p-tau). The protein level of p62 was decreased in LiCl-treated mice. These data suggested that oral long-term lithium treatment could attenuate p-tau-induced motor disturbance not only by inhibiting GSK-3 but also by enhancing autophagy in tauopathy model mice.


Protection of neonatal broiler chicks against Salmonella Typhimurium septicemia by DNA containing CpG motifs.
Oligodeoxynucleotides (ODN) containing cytosine-phosphodiester-guanine (CpG-ODN) motifs have been shown to stimulate the innate immune system against a variety of bacterial and protozoan infections in a variety of vertebrate species. The objective of this study was to investigate the immunostimulatory effect of CpG-ODN in neonatal broilers against Salmonella Typhimurium septicemia. Day-old broiler chicks, or embryonated eggs that had been incubated for 18 days, received 50 microg of CpG-ODN, 50 microg of non-CpG-ODN, or saline. Four days after exposure to CpG-ODN or day 2 posthatch, 1 x 10(6) or 1 x 10(7) colony-forming units (cfu) of a virulent isolate of Salmonella Typhimurium was inoculated by the subcutaneous route in the neck. Clinical signs, pathology, bacterial isolations from the air sacs, and mortality were observed for 10 days following challenge with Salmonella Typhimurium. The survival rate of birds in groups receiving either non-CpG-ODN or saline following Salmonella Typhimurium infection was 40%-45%. In contrast, birds receiving CpG-ODN had significantly higher survival rate of 80%-85% (P < 0.0001). Bacterial loads and pathology were low in groups treated with CpG-ODN compared to the groups receiving saline or non-CpG-ODN. Colony-forming units of Salmonella Typhimurium in the peripheral blood were significantly lower in birds treated with CpG-ODN compared to the group that received saline. This is the first time that CpG-ODN has been demonstrated to have an immunoprotective effect against an intracellular bacterial infection in neonatal broiler chickens following in ovo delivery.


Evidence for image-scanning eye movements during transitive inference.
Contrary to earlier work, recent studies have demonstrated a reduction in eye movements during the solution of tasks that seem to require visual imagery, relative to verbal tasks. The present study provides evidence that the nature of the visual imagery required by a task determines whether saccades are evoked and in which spatial pattern. In two experiments, subjects solved transitive inference problems with the relational terms left/right and above/below, while the horizontal and vertical EOG were recorded. Subjects made more horizontal and fewer vertical saccades while solving problems with the left/right terms than while solving identical problems with above/below. The results of silent counting tasks showed that the rate of subvocalization can also influence saccadic rate, especially in the horizontal plane, but cannot explain the eye-movement patterns observed during transitive inference. The results are discussed in terms of a motor theory of voluntary thinking.


Determination of ochratoxin A in liquorice products using HPLC-based analytical methods. Part II: harmonised method and method validation study.
On the basis of the outcome of an European proficiency test series conducted on behalf of the CAOBISCO (Association of the Chocolate, Biscuit and Confectionery Industries of the EU) expert group on ochratoxin A, a new harmonised method was developed for the analysis of ochratoxin A in liquorice extracts. This method works without the use of halogenated solvents because, as the proficiency test showed, an aqueous extraction solution can be used instead of, for example, chloroform, whose use is restricted in the EU. The main objective of this method validation study was to check the performance of this harmonised method. To carry out the method validation study, a set of three different test samples (one liquorice powder and two liquorice pastes) and a liquorice powder sample with an indicated range of ochratoxin A (a so-called sunshine sample) was distributed to 21 laboratories in ten countries throughout Europe and to one laboratory in the USA. The study was evaluated according to internationally recognised guidelines. In terms of its repeatability and reproducibility for determining ochratoxin A in liquorice extracts with a relative standard deviation for repeatability (RSDr) of between 6.68 and 19.95 and a relative standard deviation for reproducibility (RSDR) of between 17.39 and 29.08 the performance of the harmonised method was found to be in the accepted range of the EU directive for the analysis of mycotoxins in several foodstuffs.


Reproducibility of in vivo metabolite quantification with proton magnetic resonance spectroscopic imaging.
To investigate intra- and interscanner in vivo reproducibility of brain metabolite quantification using 1H magnetic resonance spectroscopic imaging (1H-MRSI) (PRESS localization, TE = 30 msec, voxel volume = 2.3 mL) and the linear combination model (LCModel). One subject had a total of nine scans on three occasions at a single site, and three subjects had single scans at two sites. Coefficients of variation (CVs) were estimated using different statistical models applied to intra- and interscanner data; therefore, only qualitative comparisons may be made between results. CV (intra-/interscanner) for metabolite quantifications were choline, 12.3%/10.1%; creatine, 9.9%/10.6%; glutamate + glutamine, 15.8%/13.6%; myo-inositol, 18.5%/14.7%; and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate, 6.1%/7.0%. Overall, total intra- and intersubject variability was greater than intra- and interscanner variability. When quantifying metabolic concentrations using the methods employed in this study, biological factors contribute a greater proportion to measurement variability than measurement errors. Using this technique, intra- and intersite measurement errors are of the same order.


Quality of life as a potential predictor for morbidity and mortality in patients with metastatic hormone-refractory prostate cancer.
The association between HRQL measures with outcomes in patients with metastatic hormone-refractory prostate cancer (HRPC) is unclear. Baseline and 12-week HRQL was collected using the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy - Prostate (FACT-P). Outcomes included: (1) survival; (2) time to disease progression and (3) time to bone pain. Cox proportional hazards regression models were used. The relative predictive performance of each HRQL instrument and domain was compared. Baseline HRQL scores and 12-week change scores > the median were significant predictors of all clinical outcomes but varied by domain. For example, the hazard of death for a change in FACT-P Grand Total Score > median was 49% of the hazard for a change < or = the median. Including baseline or 12-week change in HRQL resulted in improvement in prediction performance. Patients with better baseline HRQL have better predicted survival, time to disease progression and pain prognosis than those with worse HRQL. In addition, the 12-week change in HRQL appears to improve predictive accuracy for most clinical outcomes. It appears that greater deterioration in HRQL is prognostic for rapid disease progression.


Preliminary validation of angle-independent myocardial elastography using MR tagging in a clinical setting.
Myocardial elastography (ME), a radio-frequency (RF) based speckle tracking technique, was employed in order to image the entire two-dimensional (2D) transmural deformation field in full echocardiographic views and was validated against tagged magnetic resonance imaging (tMRI) in normal as well as reperfused (i.e., treated myocardial infarction [MI]) human left ventricles. RF ultrasound and tMRI frames were acquired at the papillary muscle level in 2D short-axis (SA) views at the frame rates of 136 (fps; real-time) and 33 fps (electrocardiogram [ECG]-gated), respectively. In ME, in-plane, 2D (lateral and axial) incremental displacements were iteratively estimated using one-dimensional (1D) cross-correlation and recorrelation techniques in a 2D search with a 1D matching kernel. In tMRI, cardiac motion was estimated by a template-matching algorithm on a 2D grid-shaped mesh. In both ME and tMRI, cumulative 2D displacements were obtained and then used to estimate 2D Lagrangian finite systolic strains, from which polar (i.e., radial and circumferential) strains, namely angle-independent measures, were further obtained through coordinate transformation. Principal strains, which are angle-independent and less centroid-dependent than polar strains, were also computed and imaged based on the 2D finite strains using methodology previously established. Both qualitatively and quantitatively, angle-independent ME is shown to be capable of (1) estimating myocardial deformation in good agreement with tMRI estimates in a clinical setting and of (2) differentiating abnormal from normal myocardium in a full left-ventricular view. The principal strains were concluded to be a potential diagnostic measure for detection of cardiac disease with reduced centroid dependence.


Cardiac conduction system abnormalities as a possible cause of sudden death in young athletes.
Histologic examination of serial sections of the conduction system of the hearts of three young persons who died suddenly while engaged in active sports was performed. In no case were electrocardiogram tracings available. One patient, an 11-year-old girl, had micro-Ebstein's anomaly of the tricuspid valve associated with a septoseptal Kent fascicle through a wide gap of the central fibrous annulus and upper Mahaim fibers. Another patient, a 24-year-old football player, had a focal, 75 per cent obstructing atherosclerotic plaque in the proximal descending coronary artery, with scattered band necrosis and patchy myocardial fibrosis; upper and lower Mahaim fibers joined the atrioventricular node and the left bundle branch with the crest of the interventricular septum. The third patient, a 26-year-old cycling champion, had a conspicuous atrial fascicle of ordinary and transitional myocardium bypassing the atrioventricular node to anastomose with the His bundle (James accessory atrioventricular pathway). These findings indicate that atrioventricular conduction system abnormalities may play a fatal arrhythmogenic role in sudden death and raise questions regarding the prevention of electrical instability in young people engaged in active sports.


Biphasic Metal Films: Intrinsically Stretchable Biphasic (Solid-Liquid) Thin Metal Films (Adv. Mater. 22/2016).
On page 4507, S. P. Lacour and co-workers present highly conductive and stretchable solid-liquid films that are formed by physical vapor deposition of gallium onto an alloying gold layer. The image shows patterns defined by lift-off on an elastomer membrane. The magnified view is a false-color scanning electron microscopy (SEM) image (×5000) of the surface of the films under 50% applied strain, showing the liquid Ga (blue-gray) flowing between the AuGa2 /Ga clusters (gold).


Circadian responses to light: the calmodulin connection.
KN-62, an inhibitor of CaM kinase II, attenuated phase shifts induced by low intensity light pulses and reduced light-induced phosphorylation of the transcription factor, CREB, in the suprachiasmatic nucleus. The calmodulin inhibitor, W-7, had similar effects: neither drug produced a complete block of photic responses. The results support the hypothesis that circadian responses to light are mediated in part by CaM kinase activity and CREB, and suggest that other signal transduction pathways also take part.


[An experimental study on arthroscopic chondrocytes transplantation for repair of osteochondral defects in TMJ].
To certify the feasibility of arthroscopic chondrocytes transplantation in temporomandibular joint (TMJ) and the nature of repaired tissue with autologous chondrocytes transplantation in osteochondral defects. The animal models of osteochondral defects in TMJ were established in 12 rhesus monkeys. Autologous auricular chondrocytes were transplanted to the defects by arthroscope. Healing of the defects was assessed by gross examination, light microscope, immunohistochemical staining. The repaired tissues with chondrocytes transplantation were fibrocartilages. The technique of arthroscopic chondrocytes transplantation is feasible and the nature of repaired tissue is closest to the normal cartilage, compared with those of subchondral drilling and cartilage transplantation.


A historical review of the effects of dental radiography on pregnant patients.
The safety of dental radiography performed on pregnant patients has been a controversial topic since the 1960s. This review synthesizes and consolidates findings, from 1957 through 2021, of the effects dental ionizing radiation could have on a pregnant patient and in utero birth defects. Using PubMed, the following key words were searched: pregnancy, radiology, radiograph, radiation dose, fetus, x-ray, and dental. Criteria evaluation was done on the basis of availability, completeness, quality, relevance, technicality (that is, dental radiography), topicality (that is, pregnant patients), and usability. These results were then filtered on the basis of quantitative and qualitative data as well as the period (decades within the historical framework). The final selection of relevant literature consisted of various studies including cohort studies, systematic reviews, meta-analyses, case reports, and other narrative reviews. If properly performed, the amount of ionizing radiation produced during dental radiographic procedures is so low that it is unlikely to reach the teratogenic threshold. Thus, dental ionizing radiation is unlikely to cause in utero birth defects because it has been detected to have a deterministic (not stochastic) effect. With this information and historical context, this article shows that necessary dental radiography is safe at any stage during pregnancy, as long as proper safety equipment is appropriately used. As technology advances, more research can further clarify ionizing radiation safety for pregnant patients and its potential effects on in utero birth defects, improving overall oral health care. The dental community must remain educated about current ionizing radiation safety guidelines to make better-informed decisions and successfully provide proper oral health care to pregnant patients.


The etiology of schizophrenia: a replication test of the social selection vs. the social causation hypotheses.
A quasi-experimental design was used to test the social causation-social selection hypotheses for the etiology of schizophrenic disorders. It was based on first admissions to psychiatric in-patient facilities for Jerusalem Jewish residents aged 15 years and over. Data were extracted from hospital charts; diagnoses were made based on the NHSI, DSM III and RDC classificatory systems. The results showed that among the lower class the ethnically advantaged had higher rates of schizophrenic disorders than the ethnically disadvantaged. The results were statistically significant when the ethnic contrast was maximized. Though the results support the social selection hypothesis, social stress factors are not entirely ruled out.


Role of prophylactic antiepileptic drugs in chronic subdural hematoma-a systematic review and meta-analysis.
Chronic subdural hematoma is a common neurosurgical pathology, which is more commonly seen in the elderly age group. Few patients with chronic subdural hematoma (cSDH) can have seizures-either before or after surgical intervention. Reported incidence of seizures varies from 0.7-18.5% in patients with cSDH. Many factors which have been proposed to increase the risk of seizures in these patients include the presence of encapsulated membranes, occult cortical injury, mass effect, or an acute hemorrhage. The role of prophylactic antiepileptic drugs is not very clear in cSDH. We reviewed the currently available evidence for the use of prophylactic antiepileptic drugs (AEDs) in patients with cSDH. We included 13 studies in the systematic review and 6 studies compared the incidence of seizures in patients who received antiepileptic drugs with those who did not. Our review did not find any significant reduction in the incidence of seizures in patients with cSDH following administration of antiepileptic drugs.


Understanding circadian regulation of mammalian cell function, protein homeostasis, and metabolism.
Circadian rhythms are ∼24 h cycles of organismal and cellular activity ubiquitous to mammalian physiology. A prevailing paradigm suggests that timing information flows linearly from rhythmic transcription via protein abundance changes to drive circadian regulation of cellular function. Challenging this view, recent evidence indicates daily variation in many cellular functions arises through rhythmic post-translational regulation of protein activity. We suggest cellular circadian timing primarily functions to maintain proteome homeostasis rather than perturb it. Indeed, although relevant to timekeeping mechanism, daily rhythms of clock protein abundance may be the exception, not the rule. Informed by insights from yeast and mammalian models, we propose that optimal bioenergetic efficiency results from coupled rhythms in mammalian target of rapamycin complex activity, protein synthesis/turnover, ion transport and protein sequestration, which drive facilitatory rhythms in metabolic flux and substrate utilisation. Such daily consolidation of proteome renewal would account for many aspects of circadian cell biology whilst maintaining osmotic homeostasis.


Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal cord compression.
We randomly assigned dexamethasone in an initial bolus of 10 mg IV or 100 mg IV followed by 16 mg daily orally to 37 patients with metastatic spinal cord compression. The average pain score before the start of treatment was 5.2 (SD = 2.8) and decreased significantly (p less than 0.001) to 3.8 at 3 hrs, 2.8 at 24 hrs, and 1.4 after 1 week. There were no differences between the conventional and high-dose group on pain, ambulation, or bladder function.


Rapid inactivation of SARS-CoV-2 with LED irradiation of visible spectrum wavelengths.
Difficulty in controlling SARS-CoV-2 transmission made the ability to inactivate viruses in aerosols and fomites to be an important and attractive risk reduction measure. Evidence that light frequencies have the ability to inhibit microorganisms has already been reported by many studies which, however, focused on ultraviolet (UV) wavelengths, which are known to induce potential injury in humans. In the present study, the effect on suspensions of SARS-CoV-2 of a Light Emitting Diode (LED) device capable of radiating frequencies in the non-hazardous visible light spectrum (VIS) was investigated. In order to evaluate the efficiency of viral inactivation, plaque assay and western blot of viral proteins were performed. The observed results showed a significant reduction in infectious particles that had been exposed to the LED irradiation of visible light. Furthermore, the analysis of the intracellular expression of viral proteins confirmed the inactivating effect of this irradiation technology. This in vitro study revealed for the first time the inactivation of SARS-CoV-2 through LED irradiation with multiple wavelengths of the visible spectrum. However additional and more in-depth studies can aim to demonstrate the data obtained during these experiments in different matrices, in mutable environmental conditions and on other respiratory viruses such as the influenza virus. The type of LED technology can decisively contribute on reducing virus transmission through the continuous sanitation of common environments without risks for humans and animals.


Change in the prevalence of metabolic syndrome in a population of medical students: 6-year follow-up.
Students of a university hospital were assessed in 2007 and later in 2013 to determine the prevalence of metabolic syndrome. Statistical analysis was done with SPSS version 17.0. A total of 213 students were evaluated in both 2007 and 2013 (48.3 % women and 51.7 % men). The diagnosis of overweight and obesity increased from 24.9 to 37.1 % (p < 0.05), central obesity from 17.8 to 28.6 % (p < 0.05), and prevalence of metabolic syndrome from 9.8 to 14.5 % (p ≥ 0.05); up to 20 % in male gender. It is important to implement programs for early diagnosis of metabolic syndrome.


EEG spectral power during halothane anaesthesia. A comparison of spectral bands in the monitoring of anaesthesia level.
The EEG of ten elective abdominal surgery patients was studied during halothane anaesthesia. The EEG was analysed by compressed spectral array. The total power and various power bands were analysed. Anaesthesia was induced by mask with halothane in air. EEG analysis was performed from the data collected before induction and during anaesthesia at steady states of 1 MAC, 1.5 MAC, and 2 MAC. The correlation between deepening anaesthesia and power values was strongest in the 10-14 Hz band power and in the 18-32 Hz band power. This study confirms the usefulness of high frequency power in estimating the effect of halothane in patients.


Superior oblique anterior tenectomy.
To describe a surgical approach to selectively weaken the anterior cyclotorsional fibers of the superior oblique muscle in subjects with incyclotorsion. Retrospective review of five consecutive subjects with diplopia and incyclotorsion who underwent unilateral tenectomy of the anterior fibers of the superior oblique alone or in combination with surgery on another horizontal or vertical rectus muscle. The mean preoperative incyclotorsion was 7.2 degrees . The mean postoperative follow-up was 4 months. Superior oblique anterior tenectomy corrected 5.2 degrees of incyclotorsion. No patient developed pattern strabismus induced vertical deviation or diplopia due to excyclotorsion postoperatively. The mean incyclotorsion present at the last follow-up was 2 degrees . Torsional diplopia persisted in two (40%) subjects. Anterior tenectomy of the superior oblique tendon at the insertion may be helpful in subjects with incyclotorsion who have no vertical deviation in the primary position or in whom there is risk of pattern anisotropia or anterior segment ischemia by operating upon vertical rectus muscles.


Effect of Smaller Left Ventricular Capture Threshold Safety Margins to Improve Device Longevity in Recipients of Cardiac Resynchronization-Defibrillation Therapy.
Device longevity in cardiac resynchronization therapy (CRT) is affected by the pacing capture threshold (PCT) and programmed pacing amplitude of the left ventricular (LV) pacing lead. The aims of this study were to evaluate the stability of LV pacing thresholds in a nationwide sample of CRT defibrillator recipients and to determine potential longevity improvements associated with a decrease in the LV safety margin while maintaining effective delivery of CRT. CRT defibrillator patients in the Medtronic CareLink database were eligible for inclusion. LV PCT stability was evaluated using ≥2 measurements over a 14-day period. Separately, a random sample of 7,250 patients with programmed right atrial and right ventricular amplitudes ≤2.5 V, LV thresholds ≤ 2.5 V, and LV pacing ≥90% were evaluated to estimate theoretical battery longevity improvement using LV safety margins of 0.5 and 1.5 V. Threshold stability analysis in 43,256 patients demonstrated LV PCT stability of <0.5 V in 77% of patients and <1 V in 95%. Device longevity analysis showed that the use of a 0.5-V safety margin increased average battery longevity by 0.62 years (95% confidence interval 0.61 to 0.63) compared with a safety margin of 1.5 V. Patients with LV PCTs >1 V had the greatest increases in battery life (mean increase 0.86 years, 95% confidence interval 0.85 to 0.87). In conclusion, nearly all CRT defibrillator patients had LV PCT stability <1.0 V. Decreasing the LV safety margin from 1.5 to 0.5 V provided consistent delivery of CRT for most patients and significantly improved battery longevity.


Enhanced electron transfer and ion storage in phosphorus/nitrogen co-doped 3D interconnected carbon nanocage toward potassium-ion battery.
Heteroatoms doping strategies are often considered to be an effective approach to provide rich active sites for capacitive-controlled potassium storage, and enlarged interspacing for intercalation process. However, the excess doping level will form a large number of sp3 defects and thus severely damage π-conjugated system, which is unfavorable for electron transfer. Herein, a P/N co-doped three-dimensional (3D) interconnected carbon nanocage (denoted as PN-CNC) is prepared with the help of a template-assisted method. The use of template and P heteroatom can contribute to forming a 3D interconnected carbon nanocage to prevent conductive carbon matrix from being excessively damaged, favoring a high electronic conductivity. The co-existence of P/N doping configurations with suitable content not only generate abundant defects, edge-voids, and micropores for significant capacitive behaviors, but also supply adequate interlayer space for intercalation process, and all these together ensure enhanced ion storage. As a result, the optimized PN-CNC electrode exhibits an exceptional reversible capacity (262 mAh g-1) and a superior rate capability (214.2 mAh g-1). Besides, long-term cycling stability is easily fulfilled by delivering a high capacity of 188.7 mAh g-1 at 2 A g-1 after 3000 cycles.


Blockade of interleukin-8 receptor signalling inhibits cyst development in vitro, via suppression of cell proliferation in autosomal polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent inherited disorder and results in the progressive development of cysts in both kidneys. In recent studies, several cytokines and growth factors secreted by the cyst-lining epithelia were identified to be upregulated and promote cyst growth. According to our previous study, chemokines with a similar amino acid sequence as human interleukin-8 (IL-8) are highly expressed in a rodent model with renal cysts. Therefore, in this study, we focused on whether IL-8 signalling is associated with renal cyst formation, and tested the possibility of IL-8 as a new therapeutic target for ADPKD. Expression of IL-8 and its receptor were screened either by enzyme linked immunosorbent assay (ELISA) or Western blot. Inhibited IL-8 signalling by antagonist for IL-8 receptor or gene silencing was tested in molecular levels, mainly through Western blot. And cell proliferation was measured by XTT assays. Finally, a three-dimensional culture was performed to understand how IL-8 affected cyst formation, in vitro. Interleukin-8 secretion and expression of its receptor highly increased in two different human ADPKD cell lines (WT9-7 and WT9-12), compared to normal human renal cortical epithelial cell line. Cell proliferation, which is mediated by IL-8 signal, was inhibited either by an antagonist or siRNA targeting for IL-8 receptor. Finally, a three-dimensional culture showed an alleviation of cystogenesis in vitro, after blocking the IL-8 receptor signals. These results suggest that IL-8 and its signalling molecules could be new biomarkers and a therapeutic target of ADPKD.


Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence.
COVID-19 affects multiple endocrine organ systems during the disease course. However, follow-up data post-COVID-19 is scarce; hitherto available limited data suggest that most of the biochemical endocrine dysfunctions observed during acute phase of COVID-19 tend to improve after recovery. Hence, we aim to provide a rational approach toward endocrine follow-up of patients during post-acute COVID-19. We performed a literature review across PubMed/MEDLINE database looking into the effects of COVID-19 on endocrine system and subsequent long-term endocrine sequelae. Accordingly, we have presented a practical set of recommendations regarding endocrine follow-up post-acute COVID-19. COVID-19 can lead to new-onset hyperglycemia/diabetes mellitus or worsening of dysglycemia in patients with preexisting diabetes mellitus. Hence, those with preexisting diabetes mellitus should ensure optimum glycemic control in the post-COVID-19 period. New-onset diabetes mellitus has been described post-acute COVID-19; hence, a selected group of patients (aged <70 years and those requiring intensive care unit admission) may be screened for the same at 3 months. Thyroid dysfunction (euthyroid sick syndrome and atypical thyroiditis) and adrenal insufficiency have been described in COVID-19; however, thyroid/adrenal functions usually normalize on follow-up; hence, widespread screening post-acute COVID-19 should not be recommended. Pituitary apoplexy and male hypogonadism have rarely been documented in COVID-19; therefore, appropriate follow-up may be undertaken as per clinical context. Hypocalcemia during COVID-19 is not uncommon; however, routine estimation of serum calcium post-COVID-19 is not warranted. The recommendations herein provide a rational approach that would be expected to guide physicians to better delineate and manage the endocrine sequelae during post-acute COVID-19.


Sequence-dependent toxicity and small bowel mucosal injury in neonatal mice treated with low doses of 5-azacytidine and X-irradiation at the late organogenesis stage.
A combined treatment of pregnant mice on day 12 of gestation with both azacytidine and X-irradiation in low doses induces sequence-dependent histological effects. These effects, in turn, induce different symptomatic signs if evaluated either prenatally or neonatally. In the azacytidine treatment/X-irradiation sequence the malformations of the fetal forebrain are predominant. Consequently, these dams show a high incidence in the stillbirth rate. Conversely, the X-irradiation/azacytidine treatment schedule leads only to a mild brain hypoplasia, and does not cause an increased stillbirth rate. In these offspring, however, a severe impairment of small bowel epithelial proliferation capacity was found. This is linked to an outstanding neonatal mortality within 48 h after birth. The pathogenesis of these sequence-dependent effects can be attributed to a selective vulnerability of cells in different stages of the generation cycle. This comprises a high degree of cytolethality affecting the S/G2-stage cells in azacytidine/X-irradiation treatment and the G1/S-stage cells in the reverse combinations (Schmahl 1979). The present observations show the validity of a teratological assay in providing a detailed analysis of the cell kinetic responses after combined noxious influences.


Oxygen transfer and consumption in a thiosulfate oxidizing bioreactor with sulfur production.
To evaluate the contribution of oxygen transfer and consumption in a sulfoxidizing system to increase the elemental sulfur yield from thiosulfate oxidation. A 10 l thiosulfate oxidizing bioreactor with suspended cells operating under microaerophilic conditions and a separated aerator with a variable volume of 0.8--1.7 l were operated with a consortium containing mainly Thiobacillus sp. that oxidizes several sulfide species to elemental sulfur and sulfate. From the gas-liquid oxygen balance, the k(L)a was estimated under different operation conditions. A k(L)a of around 200 h(-1) favoured elemental sulfur production and can serve as scale-up criterion. It was further shown that more than 50% of the oxygen fed to the system was consumed in the aerator. The performance of the sulfoxidizing system can be improved by controlling oxygen transfer. The proposed method for the k(L)a determination was based on the oxygen balance, which incorporates the oxygen concentrations measured in the liquid in steady state, reducing the interference of the response time in the traditional non-steady state methods. This approach can be used to optimize reactors where microaerophilic conditions are desirable.


Early events in the pathogenesis of foot-and-mouth disease in cattle after controlled aerosol exposure.
The goal of this study was to identify the primary sites of replication of foot-and-mouth disease virus (FMDV) in cattle subsequent to aerogenous inoculation. A novel aerosol inoculation method was developed to simulate natural, airborne transmission and thereby allow the identification of early replication sites. Virus distribution after aerosol inoculation was compared at 24h post inoculation with simple nasal instillation. Aerosol inoculation of FMDV consistently resulted in virus detection by real-time reverse transcriptase-polymerase chain reaction and viral isolation in the soft palate, pharynx, and lungs. Viral antigen was also detected in each of these tissues by immunohistochemistry. Aerosol exposure resulted in typical clinical signs of FMD when animals were kept alive long enough to develop disease. This aerosol infection method is highly reproducible regarding inoculum dose and volume, and allowed the detailed study of early events in FMDV-infected cattle. Extensive postmortem sampling and trimodal virus detection system allows a more precise determination of FMDV localization than previously reported.


Severity of COVID-19 patients with coexistence of asthma and vitamin D deficiency.
Coronavirus disease 2019 (COVID-19)-driven global pandemic triggered innumerable health complications, imposing great challenges in managing other respiratory diseases like asthma. Furthermore, increases in the underlying inflammation involved in the fatality of COVID-19 have been linked with lack of vitamin D. In this research work, we intend to investigate the possible genetic linkage of asthma and vitamin D deficiency with the severity and fatality of COVID-19 using a network-based approach. We identified and analysed 41 and 14 differentially expressed genes (DEGs) of COVID-19 being common with asthma and vitamin D deficiency, respectively, through the comparative differential gene expression analysis and their footprints on signalling pathways. Gene set enrichment analysis for GO terms and signalling pathways reveals key biological activities, including inflammatory response-related pathways (e.g., cytokine- and chemokine-mediated signalling pathways, IL-17, and TNF signalling pathways). Besides, the Protein-Protein Interaction network analysis of those DEGs reveals hub proteins, some of which are reported as inflammatory antiviral interferon-stimulated biomarkers that potentially drive the cytokine storm leading to COVID-19 severity and fatality, and contributes in the early stage of viral replication, respectively. Moreover, the regulatory network analysis found these DEGs associated with antiviral and tumour inhibitory transcription factors and micro-RNAs. Finally, drug-target enrichment analysis yields tetradioxin, estradiol, arsenenous acid, and zinc, which have been reported to be effective in suppressing the pro-inflammatory cytokines production, and other respiratory tract infections. Our results yield shared biomarker-driven key hypotheses followed by network-based analytics, demystifying the mechanistic details of COVID-19 comorbidity of asthma and vitamin D deficiency with their potential therapeutic implications.


Nonadiabatic exciton-phonon coupling in Raman spectroscopy of layered materials.
We present an ab initio computational approach for the calculation of resonant Raman intensities, including both excitonic and nonadiabatic effects. Our diagrammatic approach, which we apply to two prototype, semiconducting layered materials, allows a detailed analysis of the impact of phonon-mediated exciton-exciton scattering on the intensities. In the case of bulk hexagonal boron nitride, this scattering leads to strong quantum interference between different excitonic resonances, strongly redistributing oscillator strength with respect to optical absorption spectra. In the case of MoS2, we observe that quantum interference effects are suppressed by the spin-orbit splitting of the excitons.


Nanocellulose-based membrane as a potential material for high performance biodegradable aerosol respirators for SARS-CoV-2 prevention: a review.
The controversy surrounding the transmission of COVID-19 in 2020 has revealed the need to better understand the airborne transmission route of respiratory viruses to establish appropriate strategies to limit their transmission. The effectiveness in protecting against COVID-19 has led to a high demand for face masks. This includes the single-use of non-degradable masks and Filtering Facepiece Respirators by a large proportion of the public, leading to environmental concerns related to waste management. Thus, nanocellulose-based membranes are a promising environmental solution for aerosol filtration due to their biodegradability, renewability, biocompatibility, high specific surface area, non-toxicity, ease of functionalization and worldwide availability. Although the technology for producing high-performance aerosol filter membranes from cellulose-based materials is still in its initial stage, several promising results show the prospects of the use of this kind of materials. This review focuses on the overview of nanocellulose-based filter media, including its processing, desirable characteristics and recent developments regarding filtration, functionalization, biodegradability, and mechanical behavior. The porosity control, surface wettability and surface functional groups resulting from the silylation treatment to improve the filtration capacity of the nanocellulose-based membrane is discussed. Future research trends in this area are planned to develop the air filter media by reinforcing the filter membrane structure of CNF with CNCs. In addition, the integration of sol-gel technology into the production of an air filter can tailor the pore size of the membrane for a viable physical screening solution in future studies.


Preparative purification of a high-mannose type N-glycan from soy bean agglutinin by hydrazinolysis and tyrosinamide derivatization.
The N-linked oligosaccharide from soy bean agglutinin (Man9) was isolated on a preparative scale following derivatization with Boc-tyrosine. The procedure utilized preparative hydrazinolysis to release the oligosaccharide and yielded multi-micromol quantities of Boc-tyrosine-Man9 which was characterized by 1H NMR and ES-MS.


[Preparation and application of polyclonal antibody against amelotin polypeptide].
To prepare and identify the rabbit anti-mouse polyclonal antibody against amelotin polypeptide. The polypeptide was synthesized based on the bioinformatics analysis of amelotin, and coupled with keyhole limpet hemocyanin (KLH) for immunization. The amelotin polypeptide-KLH was injected into New Zealand rabbits to prepare the polyclonal antibody. ELISA technology was used to detect the titer of the antibody. The specificity of the polyclonal antibody was identified by Western blotting. The expression of amelotin in the submandibular tissue of mice was observed by immunohistochemistry. ELISA showed that the titer of amelotin antibody was 1:1,000,000. Western blotting verified that the antibody had a high specificity. Immunohistochemistry indicated that amelotin was highly expressed in odontoprisis full-thick enamel of 3-day-old and 7-day-old mice, and also expressed in duct epithelial cytoplasm of submandibular glands of 7-day-old mice. The polyclonal antibody against amelotin polypeptide has been prepared successfully with high titer and high specificity.


Evaluation of pyrite/sodium hypochlorite for activating purification of arsenic from fractured-bedrock groundwater.
In this work, the effectiveness of pyrite/sodium hypochlorite (FeS2/NaClO) treatment to eliminate arsenic (As) from fractured-bedrock groundwater via oxidative adsorption was evaluated. The As concentration in the tested reactors decreased sharply during the initial 5 min, as the addition of NaClO effectively increased the As removal efficiency, attaining 98.6% removal within 60 min in the presence of 0.05 M NaClO. There was no coexisting anion effect (Cl-, CO3-, HCO3-, NO3-, and F-) on the As removal capacity of FeS2/NaClO, except for the PO43- which resulted in less removal of As. X-ray spectroscopy analysis of As(III)-sorbed FeS2 surfaces revealed that a portion of As(III) was oxidized into As(V) during the adsorption process. Scanning electron microscopy-energy-dispersive spectrometer results of FeS2 exhibited the distribution of adsorbed As on the newly formed iron (oxy) hydroxide surfaces, with an As element ratio of 1.27%. A continuous flow-bed column study further demonstrated the efficiency of FeS2/NaClO treatment to lower the contamination level of As at the removal rates of 0.66-3.02 mg/L·day for 160 h. These results suggest that FeS2/NaClO treatment can be considered an effective strategy for removing As in groundwater of bedrock aquifers.


Adsorption of ochratoxin A, deoxynivalenol and zearalenonein vitro at different pH and adsorbents.
The adsorption of standards of 100 µg/kg Ochratoxin A (OTA), 30 mg/kg Deoxynivalenol (DON) and 30 mg/kg Zearalenone (ZEA) from 2.5 ml phosphate buffer (pH 3.0 and pH 7.0) and pure destilled water were studiedin vitro after addition of 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v) activated charcoal and four adsorbents (A I-A IV). Adsorbent A I was 1.0, 2.5 and 5.0 % modified yeast cell wall+vitamin mixture+plant oil refined. A II was modified yeast cell wall. A III was bentonite+enzymes+modified yeast cell wall+vitamin E+trace elements. A IV was bentonite. The adsorption for OTA and ZEA were 100 % by 0.1 % activated charcoal, but DON adsorption ranged from 47 to 99 % depending on the concentration of charcoal and pH value. However, adsorption of DON by 0.5, 1.0 and 2.5 % charcoal did not differ significantly by different pH buffers. Adsorption of OTA by A I, A II and A III (1.0 and 2.5 %) was higher in pH 7.0 buffer and pure destilled water compared to pH 3.0 buffer. A IV and 5.0 % A II showed an opposite trend. However, adsorption of OTA was by A II>A III>A IV (at pH 7.0 and water). The overall means of adsorption were higher by A II>A III>A IV>A I. Generally, the adsorption ranged from 15 to 60 % depending on kind and concentration of adsorbents and pH values. DON adsorption (30, 16 and 5 mg/kg) was not affected by A I, A II, A III and A IV. Adsorption of ZEA was highest by A I, and the lowest by A III. The means of adsorption at different pH were by A I>A II>A IV (2.5 and 5.0 %)>A III. The overall means show the same trend. Generally, the adsorption ranged from 13 to 57 %.


Neutrophil migration in vivo: analysis of a skin window technique.
The applicability of a skin chamber technique for the quantitation of neutrophil migration in vivo was studied in healthy subjects. Skin lesions were generated on lower abdominal skin by separating epidermis from dermis by suction. In 23 subjects the mean chamber cell count at 24 h was 20.9 X 10(6)/cm2 of skin lesion area, and 97.5% of the cells were neutrophils. An analysis of the variance in up to 8 parallel chambers in 10 subjects supported the use of 4 simultaneous replicates. Reproducibility in consecutive experiments was studied by testing 9 persons twice; the results were found to agree closely. Kinetic studies were performed in 15 subjects. The method is useful for the in vivo study of diseases and medications thought to affect leukocyte function.


A novel HPLC procedure for detection and quantification of aminoacetone, a precursor of methylglyoxal, in biological samples.
Increase in methylglyoxal is thought to be involved in different pathological conditions. Deamination of aminoacetone by semicarbazide-sensitive amine oxidase (SSAO) leads to production of methylglyoxal. We have synthesized aminoacetone and developed a novel HPLC procedure for its quantitative determination. The urinary excretion of aminoacetone is approximately 20-30 microg/mouse/day, and the concentration is about 0.5 microg/g in mouse liver and small intestine. SSAO inhibitor increases aminoacetone levels in both tissues and urines. Results confirm that aminoacetone is an endogenous substrate for SSAO. However, data also indicate that deamination is not the only catabolic pathway for aminoacetone.


Psychometric properties of the Albanian version of chewing-function questionnaire CFQ-ALB.
The new Chewing Function Questionnaire (CFQ) was lately developed in Croatia to measure the chewing ability in prosthodontic patients, as a one-dimensional instrument consisting of 10-items. Therefore, the objective of this study was to develop an Albanian version of the CFQ questionnaire and to test its psychometric properties in a new typical environment among the Kosovo population. The original version of CFQ questionnaire was translated and cross-culturally adapted from the English language into Albanian in accordance with international guidelines. Its validity (construct, convergent and discriminative) and internal consistency (reliability) were tested in 205 participants. Test-retest reliability was evaluated in 61 subjects with natural teeth, and responsiveness was evaluated in 51 prosthodontic patients with treatment needs. Internal consistency of CFQ-ALB indicated excellent agreement, with Cronbach's alpha values of 0.974 and average inter-item correlation of 0.792. Intraclass correlation coeficinets for test-retest were found without significant differences by 95 % of confidence intervals (p > 0.05). Construct validity was supported by a single factor that accounted for 81.711 % of the variance observed. Convergent validity was supported by the association between self-reported general satisfactions with chewing and CFQ summary scores. Discriminat validity was supported as statistically significant differences were observed between pre-defined groups. Responsiveness was confirmed by the significant difference between baseline summary scores and the after treatment scores; the mean change was 15.57 (SD =2.49) (p < 0.001). The obtained results suggest excellent psychometric properties of the CFQ-ALB questionnaire for determining chewing function in the Republic of Kosovo.


Somatic mosaicism of the PI3K-AKT-MTOR pathway is associated with hemimegalencephaly in fetal brains.
It is known that somatic activation of PI3K-AKT-MTOR signaling causes malformations of cortical development varying from hemimegalencephaly to focal cortical dysplasia. However, there have been few reports of fetal cases. Here we report two fetal cases of hemimegalencephaly, one associated with mosaic mutations in PIK3CA and another in AKT1. Both brains showed polymicrogyria, multiple subarachnoidal, subcortical, and subventricular heterotopia resulting from abnormal proliferation of neural stem/progenitor cells, cell differentiation, and migration of neuroblasts. Scattered cell nests immunoreactive for phosphorylated-S6 ribosomal protein (P-RPS6) (Ser240/244) were observed in the polymicrogyria-like cortical plate, intermediate zone, and arachnoid space, suggesting that the PI3K-AKT-MTOR pathway was actually activated in these cells. Pathological analyses could shed light on the mechanisms involved in disrupted brain development in the somatic mosaicism of the PI3K-AKT-MTOR pathway.


Genetic analysis of dystrophin gene for affected male and female carriers with Duchenne/Becker muscular dystrophy in Korea.
Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessive disorders caused by mutation in dystrophin gene. We analyzed the results of a genetic test in 29 DMD/BMD patients, their six female relatives, and two myopathic female patients in Korea. As the methods developed, we applied different procedures for dystrophin gene analysis; initially, multiplex polymerase chain reaction was used, followed by multiplex ligation-dependent probe amplification (MLPA). Additionally, we used direct DNA sequencing for some patients who had negative results using the above methods. The overall mutation detection rate was 72.4% (21/29) in DMD/BMD patients, identifying deletions in 58.6% (17/29). Most of the deletions were confined to the central hot spot region between exons 44 and 55 (52.9%, 7/19). The percentage of deletions and duplications revealed by MLPA was 45.5% (5/11) and 27.2% (3/11), respectively. Using the MLPA method, we detected mutations confirming their carrier status in all female relatives and symptomatic female patients. In one patient in whom MLPA revealed a single exon deletion of the dystrophin gene, subsequent DNA sequencing analysis identified a novel nonsense mutation (c.4558G > T; Gln1520X). The MLPA assay is a useful quantitative method for detecting mutation in asymptomatic or symptomatic carriers as well as DMD/BMD patients.


Drug repurposing of dopaminergic drugs to inhibit ataxin-3 aggregation.
The accumulation of mutant ataxin-3 (Atx3) in neuronal nuclear inclusions is a pathological hallmark of Machado-Joseph disease (MJD), also known as Spinocerebellar Ataxia Type 3. Decreasing the protein aggregation burden is a possible disease-modifying strategy to tackle MJD and other neurodegenerative disorders for which only symptomatic treatments are currently available. We performed a drug repurposing screening to identify inhibitors of Atx3 aggregation with known toxicological and pharmacokinetic profiles. Interestingly, dopamine hydrochloride and other catecholamines are among the most potent inhibitors of Atx3 aggregation in vitro. Our results indicate that low micromolar concentrations of dopamine markedly delay the formation of mature amyloid fibrils of mutant Atx3 through the inhibition of the earlier oligomerization steps. Although dopamine itself does not cross the blood-brain barrier, dopamine levels in the brain can be increased by low doses of dopamine precursors and dopamine agonists commonly used to treat Parkinsonian symptoms. In agreement, treatment with levodopa ameliorated motor symptoms in a C. elegans model of MJD. These findings suggest a possible application of dopaminergic drugs to halt or reduce Atx3 accumulation in the brains of MJD patients.


Effects of anoxia and depolarization on the movement of carbon atoms derived from glucose into macromolecular fractions in rat brain slices.
Incorporation of U-14C-glucose into macromolecules (lipid, protein and nucleic acid fractions) of rat brain cortex slices was studied in vitro under conditions of anoxia and reoxygenation. Additionally, the influence of depolarization on control and postanoxic U-14C-glucose metabolism was investigated. Postassium-induced depolarization of the slices lowered their capacity to incorporate 14 from U-14C glucose into proteins and nucleic acids without any changes in the labeling the lipids. Fifteen and 30 minutes of anoxia depressed the rate of 14C incorporation into each of the above macromolecules was partly restored compared to the control. Excess of potassium in the medium during the reoxygenation period inhibited restoration of the synthetic capacity of the slices execpt lipids, into which incorporation of 14C was even stimulated under depolarizing conditions. The influence of anoxia and depolarization were investigated also in different classes of lipids and proteins. 14C incorporation into SDS-extractable and residual proteins and phospholipid fraction containing phosphoinositol was closest to the control during reoxygenation which suggests the relatively highest resistance of these fractions of anoxia.


Lung cancer patients' CD4(+) T cells are activated in vitro by MHC II cell-based vaccines despite the presence of myeloid-derived suppressor cells.
Advanced non-small cell lung cancer (NSCLC) remains an incurable disease. Immunotherapies that activate patients' T cells against resident tumor cells are being developed; however, these approaches may not be effective in NSCLC patients due to tumor-induced immune suppression. A major cause of immune suppression is myeloid-derived suppressor cells (MDSC). Because of the strategic role of CD4(+) T lymphocytes in the activation of cytotoxic CD8(+) T cells and immune memory, we are developing cell-based vaccines that activate tumor-specific CD4(+) T cells in the presence of MDSC. The vaccines are NSCLC cell lines transfected with costimulatory (CD80) plus major histocompatibility complex class II (MHC II) genes that are syngeneic to the recipient. The absence of invariant chain promotes the presentation of endogenously synthesized tumor antigens, and the activation of MHC II-restricted, tumor-antigen-specific CD4(+) T cells. Potential vaccine efficacy was tested in vitro by priming and boosting peripheral blood mononuclear cells from ten NSCLC patients who had varying levels of MDSC. CD4(+) T cell activation was quantified by measuring Type 1 and Type 2 cytokine release. The vaccines activated CD4(+) T cells from all ten patients, despite the presence of CD33(+)CD11b(+) MDSC. Activated CD4(+) T cells were specific for NSCLC and did not cross-react with tumor cells derived from non-lung tissue or normal lung fibroblasts. The NSCLC vaccines activate tumor-specific CD4(+) T cells in the presence of potent immune suppression, and may be useful for the treatment of patients with NSCLC.


Association between rheumatic fever and Takayasu's arteritis - Case report.
Takayasu's arteritis (TA) and rheumatic fever are diseases that can start with cardiac features, making the diagnosis difficult. There are reports of association of RF with Takayasu's arteritis beginning with cardiac involvement in pediatric patients. The aim of this study is to report the possible association of RF and TA in patients with cardiac abnormalities. We describe the case of an adolescent initially diagnosed with RF who progressed with changes that allowed making the diagnosis of TA. TA and RF are two important causes of valve involvement that may have systemic manifestations.