Modulation of muscimol state-dependent memory by α2-adrenoceptors of the dorsal hippocampal area.
In the present study, the effects of bilateral intra-dorsal hippocampal (intra-CA1) injections of α2-adrenoceptor agonist and antagonist, on muscimol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Administration of muscimol (0.1 μg/mouse, intra-CA1) 15 min before training or testing induced impairment of memory retention. Injection of the same dose of the drug 15 min before testing restored memory retention impaired under pre-training muscimol influence. Pre-test intra-CA1 administration of the α2-adrenoceptor agonist clonidine (0.5 and 1 μg/mouse) impaired memory retention, although the low dose of the drug (0.25 μg/mouse) did not affect memory retention. Pre-test intra-CA1 administration of the α2-adrenoceptor antagonist yohimbine (1 and 2 μg/mouse) improved memory retention, although the low dose of the drug (0.5 μg/mouse) did not affect memory retention. In other series of experiments, pre-test co-administration of certain doses of clonidine (0.125 and 0.25 μg/mouse, intra-CA1), doses which were ineffective when given alone, and muscimol (0.1 μg/mouse, intra-CA1) significantly inhibited muscimol state-dependent memory. Pre-test intra-CA1 administration of certain doses of yohimbine (0.25 and 0.5 μg/mouse), doses which were ineffective when given alone, improved pre-training muscimol (0.1 μg/mouse)-induced retrieval impairment. Moreover, pre-test co-administration of yohimbine (0.25 and 0.5 μg/mouse, intra-CA1) and muscimol (0.025 μg/mouse, intra-CA1), an ineffective dose, significantly restored the retrieval and induced muscimol state-dependent memory. It may be concluded that the α2-adrenoceptors of the dorsal hippocampal area play an important role in muscimol state-dependent memory.


Tailoring clopidogrel dose according to multiple electrode aggregometry decreases the rate of ischemic complications after percutaneous coronary intervention.
Multiple studies have shown a correlation between high on-treatment platelet reactivity (HPR) and ischemic complications after percutaneous coronary interventions (PCI); however, the role of platelet reactivity testing in order to adjust clopidogrel dose is debated. We sought to determine whether a strategy incorporating platelet reactivity testing with the Multiplate analyzer to tailor the dose of clopidogrel is superior to standard clopidogrel treatment after PCI. Between May 2008 and June 2009, 192 consecutive patients undergoing PCI were randomized to a tailored treatment strategy using the Multiplate analyzer or to uniform administration of 75 mg clopidogrel. In the tailored group, platelet function was assessed 24 h after clopidogrel loading, and patients with HPR (>46 U) received an additional 600 mg loading dose and 150 mg clopidogrel thereafter for one month. The primary endpoint was the composite of cardiac death, myocardial infarction, ischemic stroke or definite/probable stent thrombosis during six months. In the tailored group, a repeated loading dose of 600 mg clopidogrel significantly decreased platelet reactivity in patients with HPR (61.0 U [IQR: 52.5-71.5] vs. 21.5 U [15.8-30.5]; P < 0.0001) that remained unchanged during the maintenance phase on 150 mg clopidogrel (25.0 U [IQR: 19.8-27.0]; P = 0.20). The incidence of the primary endpoint was significantly higher in the standard clopidogrel group as compared to the Multiplate-tailored arm (5.3% vs. 0%, P = 0.03). In parallel, MACCE-free survival significantly improved in patients with Multiplate-tailored therapy (Kaplan-Meier log-rank: P = 0.02). Increasing the dose of clopidogrel according to the Multiplate assay may reduce ischemic complications in patients on clopidogrel after PCI.


Cardiovascular risk factor management is poorer in diabetic patients with undiagnosed peripheral arterial disease than in those with known coronary heart disease or cerebrovascular disease. Results of a nationwide study in tertiary diabetes centres.
To assess whether patients with Type 2 diabetes mellitus and unrecognized peripheral arterial disease (PAD), detected by the ankle-brachial index (ABI), have poorer cardiovascular risk factor management (CVRFs) and receive fewer medications than patients previously diagnosed with coronary heart disease (CHD) or cerebrovascular disease (CVD). In 31 diabetes centres throughout Spain, 1303 patients with Type 2 diabetes mellitus were screened for PAD using the ABI. Patient history of CHD and CVD and treatment and control of CVRFs were recorded. Forty-one patients had an ABI > 1.30 and were excluded, leaving 1262 patients (age 65.3 +/- 7.7 years) for the study. Of those screened, 790 patients had a normal ABI (ABI > 0.9) and no known history of CHD or CVD (no CHD/CVD/PAD group), 194 had unrecognized PAD (ABI < or = 0.9) with no known history of CHD or CVD (undiagnosed PAD group) and 278 had a known history of CHD and/or CVD (CHD/CVD group). The undiagnosed PAD group had higher low-density lipoprotein (LDL) cholesterol (2.9 +/- 0.83 vs. 2.4 +/- 0.84 mmol/l; P < 0.001) and systolic blood pressure (150 +/- 20 vs. 145 +/- 21 mmHg; P < 0.001) compared with the CHD/CVD group. They were less likely to take statins (56.9 vs. 71.6%; P < 0.001), anti-hypertensive agents (75.9 vs. 90.1%, P = 0.001), and anti-platelet agents (aspirin, 28.7 vs. 57.2%; P < 0.001; clopidogrel, 5.6 vs. 20.9%; P < 0.001) and more likely to smoke (21.0 vs. 9.2%; P < 0.001). Higher LDL in the undiagnosed PAD group was associated with the underutilization of statins. Measurement of ABI detected a significant number of patients with PAD, who did not have CHD or CVD, but whose CVRFs were under treated and poorly controlled compared with subjects with CHD and/or CVD.


Radioligand binding of antagonists of platelet-activating factor to intact human platelets.
Two new antagonists of platelet-activating factor (PAF), the pyrrolothiazole derivative 52770 RP and the triazolodiazepine WEB 2086, have been studied as radioligands in intact human platelets. [3H]52770 RP and [3H]WEB 2086 bound specifically to high-affinity sites with dissociation constants (Kd) of 14.8 and 6.1 nM, respectively. The maximal number of sites for [3H]52770 RP binding was approx. 15-fold higher than for [3H]PAF and [3H]WEB 2086. In addition, C16-PAF, lyso-PAF, WEB 2086 and 52770 RP had Ki values which were nearly identical for both [3H]PAF and [3H]WEB 2086, whereas only 52770 RP competed for [3H]52770 RP-binding sites. These results demonstrate that in human platelets the sites of [3H]WEB 2086 binding are identical to [3H]PAF-binding sites, whereas those of [3H]52770 RP are not. [3H]WEB 2086 appears, therefore, to be a suitable antagonist radioligand for labelling PAF receptors.


Gcn5 and sirtuins regulate acetylation of the ribosomal protein transcription factor Ifh1.
In eukaryotes, ribosome biosynthesis involves the coordination of ribosomal RNA and ribosomal protein (RP) production. In S. cerevisiae, the regulation of ribosome biosynthesis occurs largely at the level of transcription. The transcription factor Ifh1 binds at RP genes and promotes their transcription when growth conditions are favorable. Although Ifh1 recruitment to RP genes has been characterized, little is known about the regulation of promoter-bound Ifh1. We used a novel whole-cell-extract screening approach to identify Spt7, a member of the SAGA transcription complex, and the RP transactivator Ifh1 as highly acetylated nonhistone species. We report that Ifh1 is modified by acetylation specifically in an N-terminal domain. These acetylations require the Gcn5 histone acetyltransferase and are reversed by the sirtuin deacetylases Hst1 and Sir2. Ifh1 acetylation is regulated by rapamycin treatment and stress and limits the ability of Ifh1 to act as a transactivator at RP genes. Our data suggest a novel mechanism of regulation whereby Gcn5 functions to titrate the activity of Ifh1 following its recruitment to RP promoters to provide more than an all-or-nothing mode of transcriptional regulation. We provide insights into how the action of histone acetylation machineries converges with nutrient-sensing pathways to regulate important aspects of cell growth.


Effects of Voice Therapy on Laryngeal Motor Units During Phonation in Chronic Superior Laryngeal Nerve Paresis Dysphonia.
Injury to the superior laryngeal nerve can result in dysphonia, and in particular, loss of vocal range. It can be an especially difficult problem to address with either voice therapy or surgical intervention. Some clinicians and scientists suggest that combining vocal exercises with adjunctive neuromuscular electrical stimulation may enhance the positive effects of voice therapy for superior laryngeal nerve paresis (SLNP). However, the effects of voice therapy without neuromuscular electrical stimulation are unknown. The purpose of this retrospective study was to demonstrate the clinical effectiveness of voice therapy for rehabilitating chronic SLNP dysphonia in two subjects, using interspike interval (ISI) variability of laryngeal motor units by laryngeal electromyography (LEMG). Both patients underwent LEMG and were diagnosed with having 70% recruitment of the cricothyroid muscle, and 70% recruitment of the cricothyroid and thyroarytenoid muscles, respectively. Both patients received voice therapy for 3 months. Grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, stroboscopic examination, aerodynamic assessment, acoustic analysis, and Voice Handicap Index-10 were performed before and after voice therapy. Mean ISI variability during steady phonation was also assessed. After voice therapy, both patients showed improvement in vocal assessments by acoustic, aerodynamic, GRBAS, and Voice Handicap Index-10 analysis. LEMG indicated shortened ISIs in both cases. This study suggests that voice therapy for chronic SLNP dysphonia can be useful for improving SLNP and voice quality.


Phosphoproteomics in cereals.
Cereals are the most important crop plant supplying staple food throughout the world. The economic importance and continued breeding of crop plants such as rice, maize, wheat, or barley require a detailed scientific understanding of adaptive and developmental processes. Protein phosphorylation is one of the most important regulatory posttranslational modifications and its analysis allows deriving functional and regulatory principles in plants. This minireview summarizes the current knowledge of phosphoproteomic studies in cereals.


Sponges as libraries: Increase in microplastics in Cinachyrella alloclada after 36 years.
Many studies investigated the presence and effects of microplastics in marine species, but data about sponges are still incipient. We quantified these pollutants in a population of the tropical sponge Cinachyrella alloclada, comparing museum specimens sampled in 1981 with specimens sampled in 2017. The mean number of microplastics in specimens collected decades ago was one order of magnitude lower (0.13 ± 0.40/g of sponge tissue) than those sampled more recently (1.37 ± 0.94/g). We observed microplastics in only 10 % of the specimens collected in 1981 but in 80 % of those from 2017. According to Raman spectroscopy, fibers in C. alloclada consisted of polypropylene. Our results reinforce the importance of natural history collections to reduce the gap of knowledge on the interaction between marine sponges and microplastics.


CPT1A Over-Expression Increases Reactive Oxygen Species in the Mitochondria and Promotes Antioxidant Defenses in Prostate Cancer.
Cancers reprogram their metabolism to adapt to environmental changes. In this study, we examined the consequences of altered expression of the mitochondrial enzyme carnitine palmitoyl transferase I (CPT1A) in prostate cancer (PCa) cell models. Using transcriptomic and metabolomic analyses, we compared LNCaP-C4-2 cell lines with depleted (knockdown (KD)) or increased (overexpression (OE)) CPT1A expression. Mitochondrial reactive oxygen species (ROS) were also measured. Transcriptomic analysis identified ER stress, serine biosynthesis and lipid catabolism as significantly upregulated pathways in the OE versus KD cells. On the other hand, androgen response was significantly downregulated in OE cells. These changes associated with increased acyl-carnitines, serine synthesis and glutathione precursors in OE cells. Unexpectedly, OE cells showed increased mitochondrial ROS but when challenged with fatty acids and no androgens, the Superoxide dismutase 2 (SOD2) enzyme increased in the OE cells, suggesting better antioxidant defenses with excess CPT1A expression. Public databases also showed decreased androgen response correlation with increased serine-related metabolism in advanced PCa. Lastly, worse progression free survival was observed with increased lipid catabolism and decreased androgen response. Excess CPT1A is associated with a ROS-mediated stress phenotype that can support PCa disease progression. This study provides a rationale for targeting lipid catabolic pathways for therapy in hormonal cancers.


Association of COL1A1 polymorphism in Turkish patients with otosclerosis.
To evaluate the role of COL1A1 gene polymorphism in the etiology of otosclerosis. Peripheric blood samples are obtained from 28 patients diagnosed with otosclerosis and 50 control subjects. DNA's of all samples are isolated and amplified by using the PCR technique. The products are restricted by appropriate enzymes and the allele distributions were compared. SS (homozygous normal), Ss (heterozygous mutant) and ss (homozygous mutant) alleles of the otosclerotic and control subjects were significantly different from each other. Otosclerosis is a disease with progressive hearing loss. There are viral, hormonal, immunologic and genetic hypothesis of etiology. In this study, we concluded that the polymorphism seen in the COL1A1 gene resulting in production of excessive type 1 collagen, could play a role in the pathogenesis of otosclerosis.


Induction of the six c/sec spike and wave by diphenhydramine hydrochloride in healthy male adults.
Diphenhydramine hydrochloride (DPHm) solution 1.5% was given intravenously to 375 healthy males (mean age; 23.8 years) at a rate of 30 mg/min. The dosages injected were 2 mg/kg (N=157); 1.5 mg/kg (N=94); 10 mg/kg (N=72); 0.5 mg/kg (N=52). As a result, the 6 c/sec spike and wave discharges (WSP) was found in 19.7%, 9.6%, 20.8%, and 15.4% of cases, respectively. Comparisons were made between the WSP incidence versus past histories and Cornell Medical Index results, and between WSP positive and WSP negative subjects. No significant differences were observed in any of these parameters.


PD1 expression and correlation with its ligands in oral cancer specimens and peripheral blood.
This study analyzed the expression of the PD1 receptor in tumor tissue and peripheral blood of oral squamous cell carcinoma (OSCC) patients, and correlated it with the PD1 ligands PD-L1 and PD-L2. The currently low response rates of checkpoint inhibitor treatment in OSCC could be increased by a better understanding of immune checkpoint biology. Despite evidence in the literature for upregulation of PD1 checkpoint ligands in OSCC tissue, there has been no correlation analysis of the PD1 receptor with its ligands in tissue specimens and peripheral blood of OSCC patients. An RT-qPCR analysis of PD1 mRNA expression was performed in oral cancer specimens, healthy mucosa, and corresponding blood samples. A cut-off point (COP) was determined and a chi-square (χ2) test was carried out. PD1 expression was correlated with previously reported PD-L1 and PD-L2 expression values using the Spearman test. Tissue and blood specimens of 48 OSCC patients and 26 healthy individuals were analyzed. PD1 expression in OSCC specimens was significantly increased (p = 0.006) compared with healthy oral mucosa. PD1 overexpression in tissue samples showed a significant association with the presence of malignancy (p = 0.006). PD1 expression in tissue samples showed a significant positive correlation (p < 0.001) with the ligands PD-L1 and PD-L2. In contrast, there was no correlation between PD1 and its ligands in blood samples. However, there was a significant positive correlation (p < 0.001) between the ligands PD-L1 and PD-L2, both in tissue and blood samples. Increased PD1 expression might be a manifestation of T-cell exhaustion in OSCC specimens, leading to immune tolerance. PD-L1/PD-L2-PD1 interaction may be a major mediator of local immunosuppression in OSCC, requiring advanced multimodal treatment protocols.


Absence of ganglioside GM1 in astroglial cells from 21-day old rat brain: immunohistochemical, histochemical, and biochemical studies.
A procedure was developed for the cultivation of cells derived from the cerebral hemispheres of the 21-day old rat. Approximately 98 percent of the cells in a 10 day culture are astrocytes that contain glial fibrillary acidic protein. Analysis of the extracted gangliosides by thin layer chromatography revealed that ganglioside GM1 was absent and that the predominant ganglioside was GM3. Very small amounts of the polysialogangliosides GD1a, GD1b, and GT1b were detected. The concentration of gangliosidic NeuNAc per mg protein in these astrocytes was only 3 percent that observed in the 5 day culture of a mixed cell preparation from newborn rat brain. Immunohistochemical and histochemical studies were performed on the mixed cell population of the minced tissue of 21-day old rat brain prior to cultivation. Astrocytes did not stain for hyaluronectin. These cells also did not provide a positive staining reaction for ganglioside GM1 utilizing the antiganglioside GM1 peroxidase-antiperoxidase procedure and the biotinylated choleragen-avidin-peroxidase procedure. These two histochemical methods for ganglioside GM1 also did not stain astrocytes that had been cultured for 5 days. Oligodendroglial cells, which were also present in the uncultured 21-day-old minced brain tissue, stained positively for ganglioside GM1 and hyaluronectin. Hyaluronectin had previously been shown to be a marker for oligodendroglia. Oligodendroglial cells which were present in the 5 day cultures of 21-day old brain tissue also provided a positive reaction for ganglioside GM1. It is concluded that ganglioside GM1 is absent in astroglia. The presence of small amounts of polysialogangliosides in the "pure" astrocyte preparation is discussed.


The effect of L-theanine and S-ketamine on d-serine cellular uptake.
Decreased extracellular level of d-Serine (D-Ser), a co-agonist of the N-methyl-d-aspartate (NMDA) receptors was connected to receptor hypofunction in the brain and the related deficit of cognitive functions. Extracellular D-Ser concentration is modulated by ASCT neutral amino acid transporters. L-Theanine (L-Tea), a neutral amino acid component of green tea was reported to improve cognitive functions. We thus intended to investigate the possible inhibitory effect of L-Tea on the D-Ser uptake of SH-SY5Y neuroblastoma cells, which was previously found as a good model of D-Ser transport into astrocytes. Cells were incubated with D-Ser and various concentrations of L-Tea or the reference compound S-ketamine (S-Ket). The effect on the uptake was assessed by measuring the intracellular D-Ser concentration using a capillary electrophoresis - laser induced fluorescence detection method. L-Tea competitively inhibited D-Ser uptake into SH-SY5Y cells with an IC50 value of 9.68 mM. Having previously described as an inhibitor of ASCT-2 transporter, S-Ket was intended to be used as a positive control. However, no acute inhibition of D-Ser transport by S-Ket was observed. Its long-term effect on the transport was also examined. No significant difference in D-Ser uptake in control and S-Ket-treated cells was found after 72 h treatment, although the intracellular D-Ser content of the 50 μM S-Ket pre-treated cells was significantly higher. L-Tea was found to be a weak competitive inhibitor of the ASCT transporters, while S-Ket did not directly affect D-Ser uptake or modify the uptake kinetics after a long-term incubation period.


Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: findings from the NIMH CATIE study.
The field of schizophrenia is redefining optimal outcome, moving beyond clinical remission to a more comprehensive model including functional recovery and improved subjective well-being. Although numerous studies have evaluated subjective outcomes within the domain of subjective quality of life in patients with schizophrenia, less is known about global evaluations of subjective well-being. This study examined the effects of antipsychotic medication on overall life satisfaction in patients with chronic schizophrenia. Data were drawn from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study, where participants with a DSM-IV diagnosis of schizophrenia were randomized to receive olanzapine, perphenazine, quetiapine, risperidone or ziprasidone under double-blind conditions (N=753). The primary outcome measure was prospective change in subjectively evaluated overall life satisfaction scores following 12 months of antipsychotic treatment. Psychopathology, medication side effects and functional status were also evaluated, among other variables. Patients experienced modest improvements in overall life satisfaction (d=0.22, p<0.001), with no differences between antipsychotic medications (all tests, p>0.05). Change in severity of positive, negative, and depressive symptoms as well as functional status each demonstrated a small, albeit statistically significant, association with change in life satisfaction (r=0.10-0.21, p׳s<0.01). In a multivariate regression model, change in clinical symptoms and functional status had limited independent predictive value for change in life satisfaction scores (explained variance <3%). These data suggest that despite antipsychotic medications being effective for symptom-based psychopathology, such clinical effectiveness does not necessarily translate to improved general satisfaction with life. Clinicians should be aware that these two domains are not inextricably linked.


Dissipative Quantum Control of a Spin Chain.
A protocol is discussed for preparing a spin chain in a generic many-body state in the asymptotic limit of tailored nonunitary dynamics. The dynamics require the spectral resolution of the target state, optimized coherent pulses, engineered dissipation, and feedback. As an example, we discuss the preparation of an entangled antiferromagnetic state, and argue that the procedure can be applied to chains of trapped ions or Rydberg atoms.


Influence of preoperative propranolol on cardiac index during the anhepatic phase of liver transplantation.
Liver transplantation is the best therapeutic option for end-stage liver disease. Non-selective beta-blocker medications such as propranolol act directly on the cardiovascular system and are often used in the prevention of gastrointestinal bleeding resulting from HP. The effects of propranolol on cardiovascular system of cirrhotic patients during liver transplantation are not known. Evaluate the influence of propranolol used preoperatively on cardiac index during the anhepatic phase of liver transplantation. 101 adult patients (73 male [72.2%]) who underwent cadaveric donor orthotopic liver transplantation by piggyback technique with preservation of the retrohepatic inferior vena cava performed at Hospital das Clinicas, Federal University of Minas Gerais were evaluated. There was no difference in severity between groups by the MELD system, p=0.70. The preoperative use of propranolol and the cardiac index outcome were compared during the anhepatic phase of liver transplantation in 5 groups (I: increased cardiac index, II: cardiac index reduction lower than 16%, III: cardiac index reduction equal to or greater than 16% and less than 31%, IV: cardiac index reduction equal to or greater than 31% and less than 46%, V: cardiac index reduction equal to or greater than 46%). Patients in group I (46.4%) who received propranolol preoperatively were statistically similar to groups II (60%), III (72.7%), IV (50%) and V (30.8%), p=0.57. The use of propranolol before transplantation as prophylaxis for gastrointestinal bleeding may be considered safe, as it was not associated with worsening of cardiac index in anhepatic phase of liver transplantation.


Filgrastim, a Recombinant Form of Granulocyte Colony-stimulating Factor, Ameliorates 3-nitropropionic Acid and Haloperidol-induced Striatal Neurotoxicity in Rats.
Striatal neurotoxicity is the pathological hallmark for a heterogeneous group of movement disorders like Tardive dyskinesia (TD) and Huntington's disease (HD). Both diseases are characterized by progressive impairment in motor function. TD and HD share common features at both cellular and subcellular levels. Filgrastim, a recombinant methionyl granulocyte colony-stimulating factor (GCSF), shows neuroprotective properties in in-vivo models of movement disorders. This study seeks to evaluate the neuroprotective effect of filgrastim in haloperidol and 3-NP-induced neurotoxicity in rats. The study was divided into two: in study one, rats were administered with haloperidol for 21 days, filgrastim at the dose of (20, 40, 60 µg/kg,s.c.) was administered once a day before haloperidol treatment and the following parameters (orofacial movements, rotarod, actophotometer) were performed to assess TD. Similarly, in the second study, rats were administered with 3-NP for 21 days, filgrastim at a dose of (20 and 40 µg/kg, s.c.) was administered, and the following parameters (rotarod, narrow beam walk, and open field test) were assessed for HD. On the 22nd day, animals were sacrificed and cortex and striatum isolated for oxidative stress (LPO, GSH, SOD, catalase, and nitrate) marker assessment. Results revealed that haloperidol and 3-NP treatment significantly impaired motor coordination, and oxidative defense inducing TD and HD-like symptoms. Treatment with filgrastim significantly averted haloperidol and 3-NP-induced behavioral and biochemical alterations. Conclusively, the neuroprotective effect of filgrastim is credited to its antioxidant properties. Hence, filgrastim might be a novel therapeutic candidate for the management of TD and HD.


Preputial skin as a model for the demonstration of substance P-like immunoreactive human peripheral nerve endings.
Preputial skin from circumcisions has been used to demonstrate the localization of substance P-like immunoreactivity. It is observed mainly in the dermis, as isolated fibers beneath the basal layer of the epidermis and near the blood vessel walls, and in nerve bundles in the deeper layers. Some fibers even penetrate the epidermis very deeply, until the stratum corneum.


[Skeletal characteristics of the hand in cervical cancer].
Under consideration is the status of hand skeleton studied electroradiographically in patients with cervical cancer and in females of the same age without cancer. It is shown that in cervical cancer patients skeleton ageing was less pronounced. The value of electroradiography for determining skeleton age is emphasized. An attention is given to the necessity of a more careful observation over persons with "young" skeleton age.


Impaired activation-induced telomerase activity in PBMC of early but not chronic rheumatoid arthritis patients.
Although telomerase activity is important in normal immune function, it is unclear whether telomerase or telomerase (dys)regulation plays a role in the pathogenic immune response in autoimmune diseases like rheumatoid arthritis (RA). In this study, we evaluated the dynamics of the activation-induced human telomerase reverse transcriptase (hTERT) response in RA patients and non-RA controls. The expression of the catalytic subunit of telomerase, hTERT, was measured in peripheral blood mononuclear cells (PBMC) of RA patients and controls after in vitro stimulation with anti-CD3 monoclonal antibody (mAb) using real-time PCR. Anti-CD3 mAb stimulation induced activation and proliferation of the T cells in all populations studied. In early RA patients with a disease duration of less than 1 year, the activation-induced hTERT mRNA levels were found to be reduced as compared to healthy controls (HC). Chronic RA patients, with a disease duration of more than 1 year, did not show these impaired hTERT mRNA levels after stimulation with anti-CD3 mAb. Decreased hTERT mRNA levels were also found in multiple sclerosis patients and patients suffering from flu-like symptoms, indicating that these deviations are not disease-specific. The impaired activation-induced hTERT response in PBMC may be a general response of the immune cells in cases of acute or chronic immune activation, presumably to control unwanted clonal expansions and to maintain the diversity of the TCR repertoire. Our results also indicate that clonal T cell expansions, described in RA, are probably not mediated by an elevated potency to express hTERT.


The effects of various carbohydrates on sympathetic activity in heart and interscapular brown adipose tissue of the rat.
The present studies were undertaken to determine the effect of various carbohydrates on sympathetic nervous system (SNS) activity. Tritiated-norepinephrine (3H-NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of rats fed either chow or chow plus 50% caloric supplements of fructose, sucrose, dextrose, or corn starch. Additional studies were performed to examine whether absorption of carbohydrate plays a role in the SNS response, and to determine whether sweet taste in the form of artificial sweeteners may influence SNS activity. After five to ten days on the respective diets, 3H-NE turnover was increased to a similar extent by all carbohydrates tested (from 38% to 160% greater than controls in different studies). Addition of acarbose (which impairs sucrose absorption) to a sucrose-supplemented diet abolished the SNS stimulatory response, whereas cholestyramine (a drug that blocks fat absorption) had no effect. Finally, the addition of saccharin or aspartame to a chow diet failed to alter SNS activity. Thus, caloric supplementation with several carbohydrates, in addition to sucrose, stimulates both cardiac and IBAT SNS activity, absorption of carbohydrate is required for this effect, and noncaloric sugar substitutes do not alter SNS function.


The Charm or Chasm of Digital Personalized Learning in Education: Teachers' Reported Use, Perceptions and Expectations.
Although digital personalized learning (DPL) is assumed to be beneficial for the student as well as the teacher, the implementation process of DPL tools can be challenging. Therefore, the aim of our study is to scrutinize teachers' perceptions towards the implementation of DPL in the classroom. A total of 370 teachers from primary and secondary education (students aged 6-18 years old) were questioned through an online survey. An overview of descriptive results is presented regarding (1) teachers' reported technology use, (2) their perceptions towards adaptivity and dashboards in DPL tools and (3) their expectations of support in view of implementing DPL. Based on a cluster analysis, three teacher clusters are distinguished. Results reveal all three clusters had positive perceptions towards DPL. Nevertheless, there is great variety in reported use of DPL tools.


Community psychology in Hong Kong: past, present, and future.
The expansion of mental health services during the 1960s from a single remote mental hospital to centers and clinics in mainstream communities fostered the development of community psychology in Hong Kong. Few psychologists were initially involved in the local community mental health movement, but its momentum resulted in increasing numbers of practitioner psychologists working in community-based service settings. Community psychology in Hong Kong today consists primarily of service delivery, but also includes applied research, community organization/consultation, and community education. Despite having many parallels with the American situation, key concepts underpinning the practice of community psychology in the Territory possess their own character as a reflection of nuances in the local scene. Prospects for the continued development of community psychology in Hong Kong appear favorable. Of special relevance is the field's potential contribution to a better understanding of the psychological phenomena associated with the Territory's sociopolitical transformation in 1997.


Analysis of the major lipid classes in human peripheral nerve biopsies. Age group differences and abnormalities of ganglioside level in perhexiline maleate therapy.
We report here the results of a simple and reproducible technique which can be used in semi-routine analysis of peripheral nerve biopsy specimens, so as to have a quantitative analysis of the major lipid classes, i.e. cholesterol, cerebrosides, ethanolamine phospholipids, phosphatidyl-choline, phosphatidyl-serine + phosphatidylinositol, sphingomyelin and gangliosides. Glycolipid hexoses, cholesterol and total phospholipids have been compared in different age groups. Although all lipid classes increased from the younger to the older age group, the molar ratio of cholesterol to phospholipid differed less than the glycolipid to phospholipid ratio. Both increased significantly, even between age group 10--16 and older patients (36, 54, 61, 68, 72 and 73 years old). Although individual variations in lipid content are noteworthy, it must be emphasized that evolution with age of the lipid composition must be taken into account. Furthermore, this study confirms and extends earlier findings of increased ganglioside levels in some cases of peripheral neuropathies observed during perhexiline maleate therapy where characteristic lipid-like polymorphous inclusions have been demonstrated.


A neurobiological nonalternative: rejoinder to Lewis, Baumeister, and Mailman.
Certain misrepresentations of our theory of self-stimulatory behavior by Lewis, Baumeister, and Mailman (1987) are corrected and several questions raised by the commentators are answered. Their proposed neurobiological alternative is considered briefly and judged to be insufficiently detailed, inadequate in scope, and therefore premature.


On the (Non-)Rationality of Human Enhancement and Transhumanism.
The human enhancement debate has over the last few decades been concerned with ethical issues in methods for improving the physical, cognitive, or emotive states of individual people, and of the human species as a whole. Arguments in favour of enhancement defend it as a paradigm of rationality, presenting it as a clear-eyed, logical defence of what we stand to gain from transcending the typical limits of our species. If these arguments are correct, it appears that adults should in principle be able to make rational and informed decisions about enhancing themselves. In this paper, however, we suggest that a rational and informed choice to enhance oneself may in some cases be impossible. Drawing on L. A. Paul's work on 'transformative experience', we argue that some enhancements-such as certain moral or cognitive modifications-may give rise to unbridgeable epistemic gaps in key domains. Importantly, such gaps could prove to be not merely contingently unbridgeable due to a lack of information at a given moment, but radically unbridgeable, making someone in a non-enhanced state inherently unable to conceive of what it would be like to be enhanced in a particular way. Where this experience is key to understanding what values are being pursued by the enhancement itself, it may prove impossible for a person to be sufficiently informed, and to make a rational decision about whether or not to enhance herself. This poses a challenge for human enhancement proponents in general, and for transhumanists in particular.


Comparison of measured and calculated doses in a Rando phantom with a realistic lung radiotherapy treatment plan including heterogeneities.
In this work, dose measurements were performed to evaluate an external radiotherapy treatment plan and, particularly, to validate dose calculations for a lung lesion case. Doses were calculated by the Varian Eclipse treatment planning system using the AAA anisotropic analytical algorithm. The measurements were performed using a Rando anthropomorphic phantom and TLD700 thermoluminescent dosimeters. The comparison between doses calculated and doses measured by means of thermoluminescence (TL) shows compatibility except for a few points, due to the limitations in the heterogeneity correction used for the case studied here. The deviation between the calculated and measured doses is about 6.5% for low (< 0.5 Gy) doses and about 1% for higher doses (> 0.5 Gy).The deviation between AAA-calculated and TL-measured doses was also found to be higher in proximity to heterogeneous tissue interfaces.


Blue-gray pigmentation in a patient receiving doxorubicin.
A 64-year-old Japanese female who was treated for hepatocellular carcinoma with doxorubicin developed diffuse blue-gray pigmentation of the face, fading out on the upper trunk. Skin biopsy revealed many melanin granules in the upper dermis. It is believed that the pigmentation was induced by doxorubicin.


Origins of homophobia in males. Psychosexual vulnerabilities and defense development.
To better understand the origins of homophobia among males. Literature review and clinical illustration. Data suggest that there is a range of homophobic attitudes. We illustrate how homophobic attitudes can be associated with a hierarchy of defensive styles. We propose that these defensive styles are used to manage a range of psychosexual developmental anxieties in boys and men.


Comparison of extracorporeal shock-wave lithotripsy and surgical lithotomy regarding patient satisfaction.
A series of 19 patients who underwent extracorporeal shock-wave lithotripsy (ESWL) for urolithiasis was compared with 26 patients who were treated with surgical lithotomy (SL). A historical clinical trial was conducted using hospital chart records and telephone interviews to determine differences in outcome between the two groups. The ESWL group had significantly (p less than 0.05) shorter duration of post-procedural pain, fewer requirements for pain medications, and decreased anxiety toward repetition of the procedure than did the SL group. In addition, the ESWL group had significantly (p less than 0.05) shorter hospital stays, faster return to work on discharge from the hospital, and less physical limitation after the procedure. There was no appreciable difference in the occurrence of post-procedure urinary tract infections or in the patient's perception of the effectiveness of the procedure. These findings support the conclusion that treatment of urolithiasis by ESWL, is preferable to open flank SL.


Biosensor-assisted evolution for high-level production of 4-hydroxyphenylacetic acid in Escherichia coli.
4-Hydroxyphenylacetic acid (4HPAA) is an important building block for synthesizing drugs, agrochemicals, and biochemicals, and requires sustainable production to meet increasing demand. Here, we use a 4HPAA biosensor to overcome the difficulty of conventional library screening in identification of preferred mutants. Strains with higher 4HPAA production and tolerance are successfully obtained by atmospheric and room temperature plasma (ARTP) mutagenesis coupled with adaptive laboratory evolution using this biosensor. Genome shuffling integrates preferred properties in the strain GS-2-4, which produces 25.42 g/L 4HPAA. Chromosomal mutations of the strain GS-2-4 are identified by whole genome sequencing. Through comprehensive analysis and experimental validation, important genes, pathways and regulations are revealed. The best gene combination in inverse engineering, acrD-aroG, increases 4HPAA production of strain GS-2-4 by 37% further. These results emphasize precursor supply and stress resistance are keys to efficient 4HPAA biosynthesis. Our work shows the power of biosensor-assisted screening of mutants from libraries. The methods developed here can be easily adapted to construct cell factories for the production of other aromatic chemicals. Our work also provides many valuable target genes to build cell factories for efficient 4HPAA production in the future.


[Congenital galactosemia in newborn infant with vascular malformation of the internal organs].
The paper describes a case of hereditary thesaurismosis - galactosemia in neonate infant with mutation of GALT-gene (Q188R/N) and vascular malformation of the internal organs.


Binding of glucocorticoids to liver nuclei and chromatin of fetal, immature and adult rats.
The interaction of dexamethasone with nuclei and chromatin was investigated following incubation of liver slices from fetal, immature (6-day-old) and adult rats with the labeled steroid at 37 degrees. The number of specific binding sites for dexamethasone in purified liver nuclei increases with the age of the animal in a manner similar to that previously reported for the cytoplasmic receptor. The high affinity nuclear binding approaches saturation at 40 and 500 nM dexamethasone in fetal and adult liver, respectively. In comparison with dexamethasone, the relative efficiency of corticosterone to accumulate in the nucleus is 9 percent in fetal liver and only 1 percent in adult liver. Specifically bound dexamethasone in adult nuclei exists in at least three forms; a Tris-soluble, a KC1-soluble, and a residual (non-extractable with KC1 or DNase) form. Part of the Tris-soluble steroid is associated with macromolecules sedimenting at about 4 S both in the presence and absence of 0.4 M KC1. This form of the receptor was not detected in fetal liver nuclei. In liver chromatin, bound dexamethasone exists in a KC1-soluble and a residual form, the latter comprising the major fraction of steroid associated with chromatin from both fetal and adult tissue (60 and 75 percent, respectively). Treatment with Triton X-100 releases about 20 percent of the radioactivity in adult liver nuclei, but has no effect on fetal liver nuclei. In contrast with the above observations in the intact tissue, the major fraction of steroid bound to chromatin in cell-free systems is KC1- and DNase-soluble, only 30 percent remaining in the residual pellet.


Access to medical care in a medically indigent population.
To study nature and extent of barriers to access to medical care in a single county and to define the nature of the illnesses in a population affected by those barriers. Descriptive study of consecutive patients not able to obtain medical care because of financial or other barriers. Financial barriers and medical diagnoses were categorized and the severity of illness and impact of unavailability of medical services were judged by a panel of internists using consensus analysis. The likelihood of obtaining care after refusal of assistance was also evaluated. A social services eligibility office on the grounds of an urban, university teaching hospital that serves a largely medically indigent population. 200 patients who presented to eligibility workers seeking financial assistance. None. Sixty percent could not obtain care because they were illegal aliens, 40% could not obtain care because they did not meet the strict criteria of the assistance programs. Sixty percent of patients had a moderate to high likelihood of long-term disability from their illnesses; 38% of a subgroup were not able to find care four weeks after entering the study, and these patients appeared to have more severe disease than those who were able to find care. Many medically indigent persons with significant illnesses face serious financial barriers to access to medical care.


Copper stress in grapevine: Consequences, responses, and a novel mitigation strategy using 5-aminolevulinic acid.
Improper application of copper-based fungicides has made copper stress critical in viticulture, necessitating the need to identify substances that can mitigate it. In this study, leaves of 'Shine Muscat' ('SM') grapevine seedlings were treated with CuSO4 solution (10 mM/L), CuSO4 + 5-aminolevulinic acid (ALA) (50 mg/L), and distilled water to explore the mitigation effect of ALA. Physiological assays demonstrated that ALA effectively reduced malondialdehyde accumulation and increased peroxidase and superoxide dismutase activities in grapevine leaves under copper stress. Copper ion absorption, transport pathways, chlorophyll metabolism pathways, photosynthetic system, and antioxidant pathways play key roles in ALA alleviated-copper stress. Moreover, expression changes in genes, such as CHLH, ALAD, RCA, and DHAR, play vital roles in these processes. Furthermore, abscisic acid reduction caused by NCED down-regulation and decreased naringenin, leucopelargonidin, and betaine contents confirmed the alleviating effect of ALA. Taken together, these results reveal how grapevine responds to copper stress and the alleviating effects of ALA, thus providing a novel means of alleviating copper stress in viticulture.


Analysis of the Primary and Post-Treatment Antibiotic Resistance of Helicobacter pylori in the Nanjing Area.
Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. The study was aimed to understand the current situation of antibiotic resistance in Nanjing and to provide a reasonable basis for clinical selection of antibiotics to cure H. pylori. To investigate the current status of H. pylori antibiotics resistance in the Nanjing area, and analyze the primary and post-treatment antibiotic resistance of H. pylori in this area. During the period from July 2017 to December 2019, 1533 gastric mucosal specimens from patients with positive H. pylori confirmed by a breath test or rapid urease test were collected for isolation and identification of H. pylori. The agar dilution method was used for the antibiotic resistance test. The result showed that the resistance rates of H. pylori to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 2.74%, 47.03%, 33.59%, 0.91%, 0.52% and 80.76%, respectively in the period of July 2017 to December 2019. The resistance rates of H. pylori (primary vs. post-treatment) to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 1.83% vs. 6.08%, 38.62% vs. 77.81%, 27.41% vs. 56.23%, 0.58% vs. 2.13%, 0.33% vs. 1.22%, 78.57% vs. 88.75%, respectively. Antibiotic resistance of H. pylori remained a problem for the effective eradication of this pathogen and its associated diseases in the Nanjing area. For post-treatment eradication patients, clinicians should take into account regional antibiotic resistance rate, personal antibiotic exposure history, economic benefit ratio, adverse antibiotic reactions, antibiotic availability and other aspects.


A new diagnostic index for predicting cervical infection with either Chlamydia trachomatis or Neisseria gonorrhoeae.
To develop and test a diagnostic index for estimating the probability of cervical infection with either Chlamydia trachomatis or Neisseria gonorrhoeae. Prospective, cross-sectional study in two phases: 1) to develop a diagnostic index based on independent predictors of cervical infection; 2) to test the index. A hospital-based clinic and a student health service. Development phase: 190 nonpregnant women seen in the gynecology clinic; testing phase: 588 women seen in the gynecology clinic (n = 372) or the student health service (n = 216). Experienced clinicians recorded historical, physical, and microscopic findings on standard forms and tested women for chlamydial and gonococcal infections. Three independent predictors of cervical infection were identified and weighted: age (two points if less than 20 years and one point if 20-29 years); a new sex partner or one suspected of having a genital infection (one point); purulent vaginal discharge (one point). In the testing groups, cervical infection was present in none of 62 women with no points, seven of 269 (3%) with one point, 14 of 188 (7%) with two points, and 19 of 69 (28%) with three or four points (p less than 0.001). The index estimated the probability of infection more accurately (p less than 0.01) than did clinicians, performed well in each site, and remained accurate when C. trachomatis and N. gonorrhoeae were considered separately. The diagnostic index accurately estimates the probability of cervical infection with either C. trachomatis or N. gonorrhoeae and may be useful in selecting women for definitive diagnostic testing.


MR fingerprinting ASL: Sequence characterization and comparison with dynamic susceptibility contrast (DSC) MRI.
MR Fingerprinting (MRF)-based Arterial-Spin-Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T1 in a single scan. However, the previous reports have only demonstrated a proof-of-principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic-susceptibility-contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF-ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improvements. Among the TR patterns tested, a sinusoidal pattern with a period of 125 TRs provided an overall best estimation in terms of spatial consistency. These experimental observations were consistent with those of numerical simulations. In the second study (N = 8), we compared MRF-ASL results with those of DSC MRI. It was found that MRF-ASL and DSC MRI provided highly comparable maps of cerebral blood flow (CBF) and bolus-arrival-time (BAT), with spatial correlation coefficients of 0.79 and 0.91, respectively. However, in terms of quantitative values, BAT obtained with MRF-ASL was considerably lower than that from DSC (p < 0.001), presumably because of the differences in tracer characteristics in terms of diffusible versus intravascular tracers. Test-retest assessment of MRF-ASL MRI revealed that the spatial correlations of parametric maps were 0.997, 0.962, 0.746 and 0.863 for B1+ , T1 , CBF, and BAT, respectively. MRF-ASL is a promising technique for assessing multiple perfusion parameters simultaneously without contrast agent.


Quality of life in patients with prostate cancer: development and application of a hybrid assessment method.
Investigator-derived quality of life (QoL) instruments such as the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire do not allow participants to weight the relative importance of QoL domains. We investigated the effect of allowing patients the ability to weight the relative importance of the five areas included in the FACT-P (Physical, Social, Emotional and Functional well-being, and Additional concerns). Patients (n=150) completed the FACT-P and gauged the relative importance of each QoL domain using a direct-weighting approach. This was then used to provide an adjusted Hybrid QoL score. Patients also completed a Visual Analogue Scale. Patients considered Social well-being to be the most important domain and Additional concerns to be the least important. When patient weightings were taken into account overall QoL scores increased. The validity of the Hybrid score was supported by its ability to distinguish between patients with metastatic and locoregional disease and its ability to detect expected decreases in global QoL over time. Application of the direct-weighting approach to the FACT-P allows assessments to more accurately reflect individual QoL. Unadjusted QoL scores may lead researchers to incorrectly estimate the true QoL of respondents.


Screening tonometry by technicians.
Comparative measurements of intraocular pressure of 200 eyes were statistical analyzed. Goldmann applanation tonometry was performed by the author and was accepted as a reference system for the measurements made by a technician using the Pneumatonograph, the GlaucoTest screening tonometer, the Halberg tonometer and the Schiotz tonometer. The technician was trained in the use of these instruments for two days; The Pneumatonograph results on seated patients were in good agreement with the Goldmann readings. The GlaucoTest screening tonometer proved to be a good screening instrument for ocular hypertensives and required only a short period of training for the technician. The Halberg tonometer did not give precise readings of intraocular pressure, however, it was more difficult for technicians to use. The Sciotz tonometer appeared to be of limited value in screening tonometry. Some aspects of the influence of body position on i.o; pressure in the different tonometric procedures have been discussed.


Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.
Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties.


Prioritization and functional validation of target genes from single-cell transcriptomics studies.
Translation of academic results into clinical practice is a formidable unmet medical need. Single-cell RNA-sequencing (scRNA-seq) studies generate long descriptive ranks of markers with predicted biological function, but without functional validation, it remains challenging to know which markers truly exert the putative function. Given the lengthy/costly nature of validation studies, gene prioritization is required to select candidates. We address these issues by studying tip endothelial cell (EC) marker genes because of their importance for angiogenesis. Here, by tailoring Guidelines On Target Assessment for Innovative Therapeutics, we in silico prioritize previously unreported/poorly described, high-ranking tip EC markers. Notably, functional validation reveals that four of six candidates behave as tip EC genes. We even discover a tip EC function for a gene lacking in-depth functional annotation. Thus, validating prioritized genes from scRNA-seq studies offers opportunities for identifying targets to be considered for possible translation, but not all top-ranked scRNA-seq markers exert the predicted function.


Parental barriers to active transport to school: a systematic review.
We aimed to systematically review parental barriers towards children and adolescents' active transport to school (ATS) in the scientific literature and to provide a categorization of the barriers identified in the studies. A search was conducted through seven online databases, from the beginning of the database to March 2018. A total of 27 of the identified studies met the inclusion criteria. The main parental barriers reported by parents of children (21 studies) were built environment, traffic safety, distance, crime-related safety and social support. The main parental barriers reported by parents of adolescents (6 studies) were built environment (street connectivity), distance, traffic safety and physical and motivation barriers. The parental barriers associated with ATS were mainly related to the built environment and traffic safety. It is crucial to involve parents through interventions to reduce the perception of safety and to increase awareness of the importance of ATS. In addition, these strategies should be complemented by environmental changes performed by local governments.


Are the recommended allowances for dietary antioxidants adequate?
Recommended dietary allowances are standards for maintaining health. Claims that intakes substantially above the allowances may provide protection from xenobiotics and prevent diseases, including cancer, are examined critically for five nutrients that have antioxidant potential. Major criticism is directed at the failure of epidemiologists to recognize that for many of these nutrients, metabolic differences among individuals preclude a direct relationship between dietary intake and plasma or tissue concentration. Also, the fact that no differences in disease incidence have been described within various species of animals that have markedly different metabolic patterns for some of these nutrients has not been considered. It is concluded that the experimental and epidemiological evidence to data that increased intakes of certain nutrients will have beneficial effects on human health are tenuous.


Immunohistochemical localization of serotonin and choline acetyltransferase in sensory neurones of the locust.
Sensory neuronal cell bodies in the leg of locust, Schistocerca gregaria, were visualized with antibodies to locust choline acetyltransferase and with antibodies to serotonin by the avidin-biotin peroxidase technique. Two groups of sensory cells react with the antibody to choline acetyltransferase: One group is associated with external mechanoreceptors (i.e., hair-plate hairs and campaniform sensilla) and the other with internal proprioceptors (i.e., chordotonal organs and multiterminal receptors). Sensory cells which react with the antibody to serotonin are associated only with internal proprioceptors being found in both chordotonal organs and multiterminal receptors. In the metathoracic femoral chordotonal organ indirect evidence suggests that some sensory cells are reactive to both antibodies. Some multiterminal receptors react with anti-choline-acetyltransferase, while others react with antiserotonin. These results support the conclusion that most insect sensory neurones are cholinergic but some are serotoninergic.


Extraforaminal Discal Cyst as Cause of Radiculopathy.
We report the first extraforaminal location of a lumbar discal cyst. The patient was treated by hemilaminectomy, arthrectomy, cyst resection, and unilateral arthrodesis, achieving complete release of the nerve root. Extraforaminal lumbar discal cyst may represent an unexpected cause of sciatic pain with favorable outcome after surgical resection.


The effects of grade and speed on leg muscle activations during walking.
Compared to level walking, additional muscle actions are required to raise and lower the center of mass during uphill and downhill walking, respectively. However, it remains unclear which muscle recruitment strategies are employed at typical grades when walking over a range of speeds. Based on previous reports, we hypothesized that, across a range of walking speeds, hip, knee, and ankle extensor muscle activations would increase with steeper uphill grade, but only knee extensor muscle activations would increase with steeper downhill grade. We also hypothesized that these changes in muscle activations with grade would become more pronounced at faster walking speeds. To test these hypotheses, 10 young adults (5M/5F) walked on a standard treadmill at seven grades (0°, ± 3°, ± 6°, and ± 9°) and three speeds (0.75, 1.25, and 1.75 ms(-1)). We quantified the stance phase electromyographic activities of the gluteus maximus (GMAX), biceps femoris (BF), rectus femoris (RF), vastus medialis (VM), medial gastrocnemius (MG), and soleus (SOL) muscles. On average, compared to level walking, hip (BF: 635%, GMAX: 345%), knee (RF: 165%, VM: 366%), and ankle (MG: 175%, SOL: 136%) extensor muscle activities increased to walk up 9°, but only knee (RF: 310%, VM: 246%) extensor muscle activities increased to walk down 9°. Further, these changes in muscle activations with grade became greater with faster walking speed. We conclude that people employ distinct uphill (hip, knee, and ankle extensors) and downhill (knee extensors) muscle recruitment strategies generally across walking speeds and progressively with steeper grade.


Cortical evoked potentials following stimulation of the urinary bladder in man.
Techniques are described for recording evoked potentials in humans in response to stimulation of the urinary bladder. Twenty patients with various disorders of their urinary function were investigated. Evoked cortical potentials following stimulation of the urinary bladder could be recorded from all patients except subjects with complete transverse spinal cord lesions. The response was most evident at the central site (Cz) and had its most prominent peaks at 45, 65, 82 and 102 msec. This technique may become a useful diagnostic tool in the study of neurogenic bladder dysfunctions.


Study on the impact of pair production interaction on D-T controllable neutron density logging.
This paper considers the effect of pair production on the precision of D-T controllable neutron source density logging. Firstly, the principle of the traditional density logging and pulsed neutron density logging are analyzed and then gamma ray cross sections as a function of energy for various minerals are compared. In addition, the advantageous areas of Compton scattering and pair production interactions on high-energy gamma ray pulse height spectrum and the errors of a controllable source density measurement are studied using a Monte Carlo simulation method. The results indicate that density logging mainly utilizes the Compton scattering of gamma rays, while the attenuation of neutron induced gamma rays and the precision of neutron gamma density measurements are affected by pair production interactions, particularly in the gamma rays with energy higher than 2MeV. By selecting 0.2-2MeV energy range and performing proper lithology correction, the effect of pair production can be eliminated effectively and the density measurement error can be rendered close to the precision of chemical source density logging.


Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram.
Phosphodiesterase catalyzes the hydrolysis of the intracellular second messenger 3',5'-cyclic AMP (cAMP) into the corresponding 5'-nucleotide. Phosphodiesterase 4 (PDE4), the major cAMP-specific PDE in inflammatory and immune cells, is an attractive target for the treatment of asthma and COPD. We have determined crystal structures of the catalytic domain of PDE4B complexed with AMP (2.0 A), 8-Br-AMP (2.13 A) and the potent inhibitor rolipram (2.0 A). All the ligands bind in the same hydrophobic pocket and can interact directly with the active site metal ions. The identity of these metal ions was examined using X-ray anomalous difference data. The structure of the AMP complex confirms the location of the catalytic site and allowed us to speculate about the detailed mechanism of catalysis. The high-resolution structures provided the experimental insight into the nucleotide selectivity of phosphodiesterase. 8-Br-AMP binds in the syn conformation to the enzyme and demonstrates an alternative nucleotide-binding mode. Rolipram occupies much of the AMP-binding site and forms two hydrogen bonds with Gln443 similar to the nucleotides.


Inhibitory histamine H3-receptors on cholinergic nerves in human airways.
The histamine H3-agonist, (R)-alpha-methylhistamine (alpha-MeHA) caused a dose-dependent inhibition of cholinergic contractile responses to electrical field stimulation in human bronchi without affecting the basal tone. alpha-MeHA, but, did not alter the response to acetylcholine. Blockade of H1- and H2-receptors, or alpha- and beta-adrenoceptors failed to prevent the inhibitory effect of alpha-MeHA, whereas the specific H3-antagonist, thioperamide, was effective. Our results indicate that H3-receptors modulate cholinergic neurotransmission in human airways.


Impact of Parents' Knowledge about the Development of Self-Esteem in Adolescents and Their Parenting Practice on the Self-Esteem and Suicidal Behavior of Urban High School Students in Nepal.
Suicide is the third leading cause of death in adolescents worldwide, self-esteem is a strong protective factor, and parents may be able to provide interventions. This cross-sectional study aimed to determine how parents can help enhance their adolescent's self-esteem and prevent suicidal behavior among adolescents in Nepal. Self-administered questionnaires were distributed to adolescents aged 13-19 years and their parents at eight high schools in three provinces in Nepal (n = 575 pairs). The data were analyzed using descriptive and inferential statistics (bivariate and multivariate regression analyses). The mean self-esteem score of adolescents according to the Rosenberg Self-Esteem Scale was 16.59, and the prevalence of suicidal behavior was 11.3%. Parent's knowledge about the development of self-esteem in adolescents was significantly positively related to parenting practice (communication, support, positive reinforcement, etc.) (B = 1.0, 95% confidence interval, CI 0.89-1.11) and authoritative parenting style (B = 0.2, 95% CI 0.15-0.25). Parental authoritativeness was positively associated with the self-esteem of their adolescents (B = 0.1, 95% CI 0.01-0.18), while adolescents with authoritarian parents were prone to suicidal risk behavior (adjusted odds ratio, AOR = 1.1, 95% CI 1.0-1.19). Counseling to parents based on our findings would be helpful to enhance the self-esteem and prevent suicidal risk behavior in their adolescent children.


Retinal arteritis, iridocyclitis, and giardiasis.
The intestinal parasite Giardia lamblia was found in the stools of three patients with retinal arteritis. Iridocyclitis was also present in two of these patients, who had not responded to treatment with systemic corticosteroids. Antiparasitic drug treatment was followed by improvement of ocular and systemic findings.


Salmonella colitis presenting as a segmental colitis resembling Crohn's disease.
Salmonella species have recently been shown to involve the colon in a diffuse fashion resembling ulcerative colitis by radiographic and endoscopic appearance. We describe a case of Salmonella colitis in which the radiographic and colonoscopic features were focal ulcerations, mucosal edema, friability, and a loss of normal vascularity, an appearance resembling Crohn's disease. This is the first well-documented example of this clinical presentation.


Effect of single dose intravenous tranexamic acid on blood loss in tangential excision of burn wounds - A double blind randomised controlled trial.
This study was carried out to evaluate role of intravenous tranexamic acid (TXA) in reducing blood loss during tangential excision of burns. This was a single center, prospective double-blinded parallel arm superiority randomized placebo-controlled trial. Patients (15-55 years) with deep dermal thermal burns <30% undergoing tangential excision were randomly assigned (1:1) to TXA and placebo groups. Patients in TXA and placebo groups received injection TXA 15 mg/kg and 10 ml saline respectively, 10 min preoperatively. Primary outcome was volume of blood loss per square centimeter area of burn excised. Secondary outcomes were total volume of blood loss, postoperative hemoglobin, intraoperative fluid requirement, blood transfusion, graft take and length of hospitalization (LOH). Thirty patients were included. Both groups were comparable in terms of Body Mass Index (BMI) preoperative hemoglobin, area of burn excised, duration of surgery and the intraoperative temperature. The average blood loss per square centimeter burn area excised was found to be significantly lower in TXA when compared to placebo group (mean difference: 0.28 ± 0.025 ml/cm2; p = 0.000). The total volume of blood loss was lower in TXA group (258.7 ± 124.10 ml vs 388.1 ± 173.9 ml; p = 0.07). None of the patients required transfusion. The requirement of intra-operative fluids was similar between the two groups (crystalloids: p = 0.236; colloids: p = 0.238). Postoperative hemoglobin, length of hospitalization and graft-take were comparable between the two groups. TXA reduced blood loss per unit burn area of tangential excision in <30%TBSA burn, however, we found no significant effect on postoperative Hb and transfusion.


Regulating gene expression through control of transcription factor multivalent interactions.
Chong et al. (2022) show how the propensity of transcription factors (TFs) to associate into hubs must be finely regulated for optimal transcription.


The in vivo antimelanoma effect of 4-S-cysteaminylphenol and its n-acetyl derivative.
Phenolic melanin precursors can be utilized for the development of anti-melanoma agents. The sulphur homologue of tyrosine, 4-S-cysteinylphenol (CP) and its decarboxylation product, 4-S-cysteaminylphenol (CAP) were shown to be substrates of melanoma tyrosinase, forming melanin-like pigment. Both, but in particular the 4-S-CAP, exhibited a significant in vivo depigmenting effect. Here, we report on the in vivo anti-melanoma effect of 4-S-CP, and 4-S-CAP and its N-acetyl derivative. In a previous in vitro study, it was shown that 4-S-CP and 4-S-CAP required a catalytic amount of dopa for optimal mammalian tyrosinase activity. To enhance the potential anti-melanoma effect of these two compounds. L-dopa and a decarboxylase inhibitor (carbidopa) were given concomitantly. We found that 4-S-CAP showed a significant growth inhibition of B16 melanoma inoculated s.c. into C57BL/6J mice. The anti-melanoma effect was increased significantly by combination of L-dopa and carbidopa. In addition, we tested the in vivo anti-melanoma effect of an N-acetyl derivative of 4-S-CAP (N-Ac-4-S-CAP). We found that N-Ac-4-S-CAP was the tyrosinase substrate and potent inhibitor of melanoma growth. N-acetyl 4-S-CAP showed a marked increase in water solubility. We suggest that N-Ac-4-S-CAP may prove to be a valuable model for the development of anti-melanoma agent using a metabolic pathway of melanin synthesis.


The effect of feeding methods of bottle and injector on the transition to full breastfeeding and sucking success in preterm newborns: A randomized controlled trial.
This study was conducted to investigate the effects of feeding methods of bottle and injector on the transition to full breastfeeding and sucking success in preterm newborns. This study was a randomized controlled type experimental study. The study sample included 62 preterm newborns, resulting from the strength analysis, who were treated in the neonatal intensive care unit of a university hospital (31 bottle-feeding group, 31 injector feeding group). Data were collected using the Descriptive Information Form, Preterm Infant Follow-up Form and LATCH Breastfeeding Diagnostic Scale. The infants in the syringe and the bottle-feeding group were fed, and the sucking successes and transition times to breastfeeding were evaluated during the first breastfeeding, after 48 h and before discharge. When sucking successes and transition times to breastfeeding were evaluated, LATCH scores of the mothers in the syringe feeding group were significantly higher than the mothers in the bottle-feeding group, and infants switched to full breastfeeding in a shorter time (p < 0.05). When the physical parameter results were evaluated, the mean heart rate of the babies in the bottlefed group was significantly higher than the injector-fed group (p < 0.05). It has been seen that injecting feeding method has a positive effect on the success of the newborn, the time of transition to full breastfeeding and life signs according to the bottle-feeding method. The findings obtained in this study suggest that to increase the success of sucking, shortening the transition time to full breastfeeding and using the injector feding method to maintain stabile physical parameters. The findings obtained in this study suggest that to increase the success of sucking, shortening the transition time to full breastfeeding and using the injector feding method to maintain stabile physical parameters.


Do factors that are important during obstetrics and gynecology residency program selection differ by applicant gender?
The purpose of this study was to examine the relationship between applicant gender and factors that influence obstetrics and gynecology residency program selection. A national survey was conducted of graduates of US allopathic medical schools who were registered with the Electronic Residency Application Service for the year 2003 and who indicated that obstetrics and gynecology was their primary specialty choice. The selection prevalence of 20 possible influential factors was analyzed by gender. Our study cohort consisted of 450 eligible respondents, 80.4% of whom were female. There were no significant differences by gender in regards to applicant age, race, marital status, number of dependents, or geographic region of medical school. Overall, the 4 factors with the highest selection prevalence in both gender groups were all related to workplace environment. Compared with male respondents, female respondents were more likely to consider how well the current residents seemed to work together (99.2% vs 94.3%; P = .002) and the amount of conference/didactic teaching (80.4% vs 68.2%; P = .01). Male respondents were more likely to consider the quality of the hospital facility (92% vs 82%; P = .02), salary (28.4% vs 17.1%; P = .02), and supplemental income (moonlighting) opportunities (18.2% vs 8.6%; P = .008), as compared with female respondents. Significant differences in gender-associated preferences that are related to obstetrics and gynecology residency program selection exist and include both curricular and financial factors.


N,N,N‑trimethyl chitosan modified flaxseed oil based mucoadhesive neuronanoemulsions for direct nose to brain drug delivery.
Here we fabricated flaxseed oil-based neuronanoemulsions (NNEs) which were further surface-modified with a mucoadhesive polymer, N,N,N‑trimethyl chitosan (TMC) to form mucoadhesive neuronanoemulsions (mNNEs). The NNEs were loaded with high partitioning ropinirole-dextran sulfate (ROPI-DS) nanoplex and fabricated using hot high-pressure homogenization (HPH) technique. NNEs were optimized using Central Composite experimental design. TMC modified mNNE have not been prepared yet for direct nose to brain drug delivery. Here, an objective to provide controlled drug release with prolonged residence on the nasal mucosa for the treatment of Parkinson's disease (PD) is at prime consideration. Enhanced brain targeting through BBB bypass drug delivery, improved therapeutic efficacy through enhanced retention of mNNE formulation over nasal mucosal membrane, reduced dose and frequency of administration, and safety were further expected outcomes of this experiment. The mNNE formulation was subjected to 6 month stability assessment. The mNNE formulation was administered to the Swiss albino mice model via intranasal route and both, the plasma and brain pharmacokinetics were estimated. The in vivo studies performed on mice exhibited high brain targeting efficiency of mNNE formulation through nose to brain delivery via olfactory pathway. The prepared intranasal mNNEs could be on the clinics, if investigated more for behavioral and neurotoxicity studies.


[Study of combined chronic effects of gamma radiation and lead on the occurrence and repair of DNA injury in mice].
It has been shown that neither exposure of mice to lead in the drinking water (20 mg/l) for 50 days nor chronic gamma-irradiation of animals (1.5 Gy, 1.3 mGy/h, 50 days) induces single-stranded DNA breaks in thymocytes. Acute gamma-irradiation (1 and 4 Gy) of lead-pretreated mice resulted in an inhibiting of repair of radiation-degraded DNA in thymocytes and in an increasing of the level of DNA lesions detected in erythroblasts of bone marrow by the micronuclear test method. Inhibition of ssDNA break repair in thymocytes caused by lead was not seen upon exposure of mice to combined chronic action of gamma-irradiation and lead. Chronic irradiation did not affect the micronuclei rate increase revealing after acute irradiation of lead-treated mice.


Gastric ulcer development in horses in a simulated show or training environment.
To determine whether conditions representing activities that are typical in the recreational use of horses, including transport to and from show grounds, stall confinement in unfamiliar surroundings, and light exercise, are associated with increased incidence of gastric ulcers in horses. Randomized controlled study. 20 client-owned horses. Horses had no gastric ulcers as determined by endoscopic examination on study day -1. Ten control horses were maintained on-site with no changes in management variables. Ten horses were transported via trailer for 4 hours on day 0 to another site, placed in individual stalls, fed twice daily, and exercised twice daily for 3 days. On day 4, they were transported back to the original site via trailer for 4 hours. On day 5, endoscopic examinations were performed on all horses to assess gastric mucosa status. Horses that were transported and housed off-site had a significantly higher incidence of hyperkeratosis and reddening of the gastric mucosa than control horses. Two control horses and 7 transported horses developed gastric ulcers by day 5. Ulcer scores of transported horses increased significantly from day -1, whereas ulcer scores in control horses did not change significantly from day -1. Activities that are typical in recreational use of horses were ulcerogenic, and ulcers in the gastric squamous mucosa can develop under these conditions within 6 days.


The effects of d-amphetamine on food competition in male rats.
Male Wistar rats were tested in 3 competitive situations to determine the effects of d-amphetamine (AMP) on competitive behavior. Subjects were initially tested in a fixed-pair food competition paradigm. Based on the percentage of pellets obtained, a winner and loser were defined for each pair. AMP (2.0 and 4.0 mg/kg) was then administered to one or both members of pair, and the effects of the drug on the defined winners and losers were determined. AMP did not significantly alter the percentage of pellets obtained by losers except when only the winners were administered AMP (4.0 mg/kg). Subjects were then tested in a round-robin competition paradigm in which each subject was paired with every other subject. The animals were ranked according to the percentage of pellets obtained out of a possible 450 pellets. AMP (2.0 mg/kg) decreased pellet acquisition in higher ranking subjects, whereas pellet acquisition was increased in lower ranking subjects. The effects of AMP were also evaluated in a "worker-parasite" paradigm. Subjects were individually conditioned to press a lever using an FI schedule for presentation of a food pellet. When the lever was located on the wall opposite the food hopper, a worker and parasite were defined for each pair. The worker was the subject that made the most responses on the lever while obtaining fewer reinforcements. Subjects that were defined as winners in the fixed pair food competition emerged as the workers in this situation. AMP (0.8 mg/kg) given concurrently to both subjects resulted in a reversal of roles; the parasites now emitted the majority of responses and obtained less pellets. The data indicate that AMP has a differential effect on participants in competitive situations when all subjects in the situation are treated.


Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy.
To identify conditions on a reproductive carrier screening panel with the potential for carrier manifestations during pregnancy and review the implications for obstetric care. This was a retrospective cross-sectional study of consecutive samples from female patients aged 18-55 years submitted to a commercial laboratory for a 274-gene carrier screening panel (January 2020 to September 2022). A literature review was performed to identify genes on the panel with potential for pregnancy complications in carriers. Carrier expression and published recommendations for clinical management were reviewed. We identified 12 genes with potential for carrier manifestations during pregnancy based on reports in the literature: nine with manifestations irrespective of the fetal genetic status ( ABCB11 , COL4A3 , COL4A4 , COL4A5 , DMD , F9 , F11 , GLA , and OTC ) and three ( CPT1A , CYP19A1 , and HADHA ) with manifestations only if the fetus is affected by the condition. Manifestations included cardiomyopathy, hemorrhage, gestational hypertensive disorders, cholestasis of pregnancy, acute fatty liver, hyperammonemic crisis, and maternal virilization. Published recommendations for carrier management were identified for 11 of the 12 genes. Of 91,637 tests performed during the study period, a pathogenic or likely pathogenic variant was identified in 2,139 (2.3%), giving a carrier frequency for any of the 12 genes of 1 in 43 (95% CI 1/41-45) 1,826 (2.0%) of the study population were identified as carriers for one of the nine genes with the potential for carrier manifestations irrespective of an affected or unaffected fetus. Approximately 1 in 40 female patients were identified as carriers for a condition with potential for maternal manifestations in pregnancy, including some serious or even life-threatening complications. Obstetric care professionals should be aware of the possibility of pregnancy complications among carriers and the available recommendations for management. This study was funded by Natera, Inc.


Association between plasma homocysteine and vascular atherosclerotic disease in older persons.
Plasma homocysteine is a risk factor for coronary artery disease, stroke, extracranial carotid arterial disease, peripheral arterial disease, and aortic atherosclerosis in older persons. Randomized trials are in progress investigating whether multivitamin therapy to decrease plasma homocysteine levels will reduce the risk for cardiovascular disease. (c) 2000 by CHF, Inc.


Macrophage migration inhibitory factor levels are associated with disease activity and possible complications in membranous nephropathy.
Membranous nephropathy (MN) is an autoimmune disease characterized by the deposition of immunoglobulin G (IgG) and complementary components in the epithelium of the glomerular capillary wall. Macrophage migration inhibitory factor (MIF) is an inflammatory mediator released by macrophages. MIF plays a key regulatory function in the pathogenesis of immune-mediated glomerulonephritis. This study aimed to investigate whether MIF level could be associated with the activity of MN. Plasma and urine samples from 57 MN patients and 20 healthy controls were collected. The MIF levels in plasma and urine were determined by an enzyme-linked immunosorbent assay (ELISA) kit. The expression of MIF in the renal specimens from 5 MN patients was detected by immunohistochemistry (IHC). The associations of the plasma and urinary levels of MIF and glomerular MIF expression with clinical and pathological characteristics were analyzed. It was revealed that with the increase of MIF levels in plasma and urine, the severity of renal pathological injury in MN patients gradually increased. Correlation analysis showed that the MIF levels in plasma were positively correlated with the platelet (PLT) count (r = 0.302, P = 0.022), and inversely correlated with the prothrombin time (PT) (r = - 0.292, P = 0.028) in MN patients. The MIF levels in plasma were positively correlated with the C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) (r = 0.651, P < 0.0001; r = 0.669, P < 0.0001) in MN patients. The urinary levels of MIF were positively correlated with ESR (r = 0.562, P < 0.0001). IHC suggested that MIF was expressed in glomerular basement membrane and tubulointerstitial areas. MIF levels in plasma and urine could reflect the severity of MN, and MIF levels in plasma and urine could be associated with venous thrombosis and infectious complications in MN patients. The glomerular MIF expression could be used to indicate the activity of MN.


Effectiveness of a proficiency-based progression e-learning approach to training in communication in the context of clinically deteriorating patients: a multi-arm randomised controlled trial.
To determine the effectiveness of proficiency-based progression (PBP) e-learning in training in communication concerning clinically deteriorating patients. Single-centre multi-arm randomised double-blind controlled trial with three parallel arms. A computer-generated program randomised and allocated 120 final year medical students in an Irish University into three trial groups. Each group completed the standard Identification, Situation, Background, Assessment, Recommendation communication e-learning; group 1 Heath Service Executive course group (HSE) performed this alone; group 2 (PBP) performed additional e-learning using PBP scenarios with expert-determined proficiency benchmarks composed of weighted marking schemes of steps, errors and critical errors cut-offs; group 3 (S) (self-directed, no PBP) performed additional e-learning with identical scenarios to (PBP) without PBP. Primary analysis was based on 114 students, comparing ability to reach expert-determined predefined proficiency benchmark in standardised low-fidelity simulation assessment, before and after completion of each group's e-learning requirements. Performance was recorded and scored by two independent blinded assessors. Post-intervention, proficiency in each group in the low-fidelity simulation environment improved with statistically significant difference in proficiency between groups (p<0.001). Proficiency was highest in (PBP) (81.1%, 30/37). Post hoc pairwise comparisons revealed statistically significant differences between (PBP) and self-directed (S) (p<0.001) and (HSE) (p<0.001). No statistically significant difference existed between (S) and (HSE) (p=0.479). Changes in proficiency from pre-intervention to post-intervention were significantly different between the three groups (p=0.001). Post-intervention, an extra 67.6% (25/37) in (PBP) achieved proficiency in the low-fidelity simulation. Post hoc pairwise comparisons revealed statistically significant differences between (PBP) and both (S) (p=0.020) and (HSE) (p<0.001). No statistically significant difference was found between (S) and (HSE) (p=0.156). PBP e-learning is a more effective way to train in communication concerning clinically deteriorating patients than standard e-learning or e-learning without PBP. NCT02937597.


Modeling lipid layers of atopic skin and observation of changes in lipid layer properties with changes in ceramide content.
Studies have shown that there is a high correlation between atopic dermatitis and decrease in ceramide content in the lipid bilayer of skin. Moreover, it has been shown that the reduction in ceramide content in the stratum corneum is unique to atopic dermatitis, indicating that there are particular structural differences between the lipid bilayers of normal and atopic skin. This study aimed to compare the lipid bilayer of the atopic skin with that of the healthy skin and to establish a structural model of the lipid bilayer for atopy. Molecular dynamics simulations were performed using NAMD 2.8. Models of lipid bilayers of normal skin and atopic skin, and a model of lipid bilayer containing only ceramide were built with CHARMM-GUI. The thickness, area occupied per lipid, and alignment of lipids were compared among the three models. Potential mean force (PMF) of the sodium laureth sulfate (SLES) on lipid bilayers was calculated to predict the affinity between SLES and lipid bilayers. Potential mean force calculations showed that the lipid bilayer of atopic skin was able to absorb the surfactant more easily than that of normal skin. When the ceramide ratio is low, the thickness of lipid bilayer is reduced and its structure is weakened. Other structural differences between the lipid layers of normal and atopic skin included increased area per lipid and poor alignment of lipids. Further, the atopy lipid bilayer model was found to absorb more SLES than the normal skin lipid bilayer model.


Can essential fatty acids reduce the burden of disease(s)?
Coronary heart disease, stroke, diabetes mellitus, hypertension, cancer, depression schizophrenia, Alzheimer's disease, and collagen vascular diseases are low-grade systemic inflammatory conditions that are a severe burden on health care resources. Essential fatty acids (EFAs) and their metabolites: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) and their products: prostaglandin E1, prostacyclin, lipoxins, resolvins, and protectins suppress inflammation, augment healing, and are of benefit in the prevention and management of these conditions. Hence, supplementation of EFAs could reduce burden of these disease(s).


Possibilities and limitations of quadrupole mass spectrometric detector in fast gas chromatography.
In this work the application and limitations of a common bench top quadrupole mass spectrometer was evaluated for the qualitative and quantitative measurement of n-alkanes and pesticides of a wide range of volatilities and polarities with fast GC separations using 0.15 mm I.D. narrow-bore capillary columns. It was found that the spectra acquisition rate has a great impact on sensitivity (peak areas, peak shapes and S/N ratios). The quality of the obtained spectra is not significantly influenced in the full scan monitoring mode for the fastest scan rates. For quantitative analysis a selected ion monitoring mode is able to acquire the sufficient number of data-points for the proper peak shape reconstruction and good repeatability of peak areas measurements expressed by RSD (< 5%) for all tested dwell times shorter than 75 ms. However, for shorter dwell times, S/N ratio is lower, while peak areas are not influenced.


Mitochondrial metabolism mediated macrophage polarization in chronic lung diseases.
As the first line of defence in the lung, alveolar macrophage contributes to maintaining lung immune homoeostasis. Characterized by the heterogeneity and plasticity, macrophages polarize into two pro-inflammatory and anti-inflammatory phenotypes regarding the biological and pathological environment. In the past decade, numerous studies have revolutionized the relationship between cellular metabolism and macrophage functions. Mitochondria dysfunctions, which results in altered cellular metabolic profile, were observed in the alveolar macrophages during chronic lung diseases. In addition, alveolar macrophages adapt metabolic reprogramming to produce an immune response against the pathogens. Here, we outline the role of mitochondria in the development of macrophage phenotypes and functions and highlight the mitochondrial dysfunction in the setting of chronic lung diseases. Lastly, we emphasize the therapeutic relevance of targeting metabolic pathways in alveolar macrophages, which may shed light on developing novel strategies against chronic lung diseases.


Distributions of substance P- and VIP-immunoreactive nerve fibres in the colonic circular muscle in children.
In children with severe chronic constipation, abnormal distribution of substance P (SP) and vasoactive intestinal peptide (VIP), which represent excitatory and inhibitory nerves, respectively, has been reported. The normal distribution of these neuropeptides, however, is not well known. The aim of this study was to determine the populations of SP- and VIP-immunoreactive nerve fibres in the circular muscle of the colon in children. Surgically resected specimens were collected from a 6-year-old girl with familial polyposis coli (total colon) and nine patients with anorectal malformations aged 0-4 years (sigmoid colon). Double-labelling immunofluorescence was employed using neuron-specific enolase (NSE) with SP and NSE with VIP to count the percentage of SP- or VIP-labelled nerve fibres. These specimens showed normal submucous and myenteric plexuses stained with NSE. The population of SP- immunoreactive fibres was 15%-21% throughout the colon, and VIP was 39% in the caecum and 63%-65% in the transverse, descending, and sigmoid colon. In the four neonatal specimens (day 1 to 4), the SP population was only 1%-6% and the VIP population was also low (22%-33%). After 3 weeks of age, the populations had stabilised at 18%-26% for SP and 52%-62% for VIP. SP-immunoreactive nerve fibres were scarce in the neonatal period, and showed a rapid increase by 3 weeks and a similar though less dramatic increase in VIP-immunoreactive fibres. VIP-immunoreactive fibres were fewer in the caecum that at other colonic levels, where they accounted for 60% of NSE-labelled fibres; the SP population, however, was comparable at all levels of the colon at about 20% of NSE-labelled fibres.


Diagnosis of normal-pressure hydrocephalus using CT with CSF enhancement.
Cisternography with the water-soluble contrast medium metrizamide provides substantial advantages for CT demonstration: the discrimination and sharpness of definition of the basal cisterns can be considerably improved by the positive demonstration of the subarachnoid spaces. Studies of CSF dynamics make it possible to differentiate between a communicating hydrocephalus aresorptivus and a hydrocephalus within the scope of a brain atrophy. Brain substance defects and subarachnoid cysts can be clarified with respect to communication with the CSF space. Apart from providing static insights, the cisternographic use of metrizamide through repeated CT examinations also makes it possible to make conclusive statements about CSF dynamics.


Identification of Noncanonical Transcripts Produced by Systematic Nucleotide Exchanges in HIV-Associated Centroblastic Lymphoma.
Noncanonical transcriptions include transcriptions that systematically exchange nucleotides, also called bijective transformations or swinger transformations. Swinger transformation A↔T+C↔G recovers identities of 8 among 9 unknown RNAs differentially expressed in centroblastic lymphoma, a human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma. The identified RNAs align with human genes with known anti-HIV1 or oncogenic activities. Function disruption through swinger-transformed transcription potentially enables avoiding antiviral responses and contributes to cancer induction.


Real-world genomic profiling of acute myeloid leukemia and the impact of European LeukemiaNet risk stratification 2022 update.
Acute myeloid leukemia (AML) is a myeloid neoplasm associated with a high morbidity and mortality. The diagnosis, risk stratification and therapy selection in AML have changed substantially in the last decade with the progressive incorporation of clinically relevant molecular markers. In this work, our aim was to describe a real-world genomic profiling experience in AML and to demonstrate the impact of the European Leukemia Net 2022 update on risk stratification in AML. One hundred and forty-one patients were evaluated with an amplicon-based multi-gene next-generation sequencing (NGS) panel. The most commonly mutated genes were FLT3, DNMT3A, RUNX1, IDH2, NPM1, ASXL1, SRSF2, NRAS, TP53 and TET2. Detection of FLT3 ITD with NGS had a sensitivity of 96.3% when compared to capillary electrophoresis. According to ELN 2017, 26.6%, 20.1%, and 53.3% of patients were classified as having a good, moderate, or unfavorable risk. When ELN 2022 was used, 15.6%, 27.8%, and 56.6% of patients were classified as favorable, moderate, or unfavorable risk, respectively. When ELN 2022 was compared to ELN 2017, thirteen patients (14.4%) exhibited a different risk classification, with a significant decrease in the number of favorable risk patients, what has immediate clinical impact. In conclusion, we have described a real-world genomic profiling experience in AML and the impact of the 2022 ELN update on risk stratification.


Electron microscopy by specimen design: application to strain measurements.
A bewildering number of techniques have been developed for transmission electron microscopy (TEM), involving the use of ever more complex combinations of lens configurations, apertures and detector geometries. In parallel, the developments in the field of ion beam instruments have modernized sample preparation and enabled the preparation of various types of materials. However, the desired final specimen geometry is always almost the same: a thin foil of uniform thickness. Here we will show that judicious design of specimen geometry can make all the difference and that experiments can be carried out on the most basic electron microscope and in the usual imaging modes. We propose two sample preparation methods that allow the formation of controlled moiré patterns for general monocrystalline structures in cross-section and at specific sites. We developed moiré image treatment algorithms using an absolute correction of projection lens distortions of a TEM that allows strain measurements and mapping with a nanometer resolution and 10-4 precision. Imaging and diffraction techniques in other fields may in turn benefit from this technique in perspective.


Differences in acute pain perception between patients and physicians in the emergency department.
Pain is a subjective complaint that comprises a vast majority of emergency department (ED) visits. Owing to its subjectivity, pain reporting is prone to variations that could impact patient care. We aimed to determine the extent of differences in pain rating-scores between patients and their physicians in the ED and impact on patient satisfaction. A prospective cross-sectional sample of eligible patients was recruited from two centers in Saudi Arabia. Pain scorings were performed using validated online questionnaires during patients' ED stay. Pain rating scores by physicians was lower than that by patients (6.3 ± 2.0 versus 7.0 ± 3.1, p = 0.004). Additionally, severe pain rating (8-10 rating) was given less frequently by physicians compared with that by patients (26.0% versus 48.1%, p = 0.004). Comparing the ratings by physicians with those by patients, underestimation was observed in 70.1%, overestimation in 16.9%, and matching rating in 13.0% cases. The most frequent analgesic medication administered was paracetamol (79.2%), followed by diclofenac (26.0%), morphine (10.4%), and ketorolac (9.1%). The medications were administered mainly intravenously (87.0%) and, to a lesser extent, intramuscularly (31.2%). Majority of patients (62.5%) reported not to have sufficient pain relief after treatment. Most physicians tend to underestimate the level of pain perceived by their patients, which often leads to under-treatment and lower patient satisfaction. The present study revealed a significant difference in pain ratings between patients and physicians.