Interleukin-1beta promoter (-31T/C and -511C/T) polymorphisms in major recurrent depression.
To elucidate a genetic predisposition to major depressive disorder, we investigated two polymorphisms (-31T/C and -511C/T) in the interleukin-1beta promoter region in patients who suffered from major recurrent depression. The aim of the current work was to compare alleles and genotype layout between patients with major recurrent depression and healthy people. We would like to indicate such combination of genotypes which corresponds with major recurrent depression. Correlations between genotypes for analyzed polymorphisms and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset were investigated as well. The study group consisted of 94 patients diagnosed with major recurrent depression. The control group included 206 healthy individuals. Both groups involved representatives of Caucasian population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. A specific haplotype, composed of the C allele at -31 and the T allele at -511, has a tendency to have a statistically significant difference (p = 0.064) between patients and control group. Correspondence analysis revealed that genotype T/T at -31 and genotype C/C at -511 are associated with major recurrent depression. No association was found between genotypes for studied polymorphic sites and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset.


Molecular mechanism of negative cooperativity of ferredoxin-NADP + reductase by ferredoxin and NADP(H): role of the ion pair of ferredoxin Arg40 of and FNR Glu154.
Ferredoxin-NADP+ reductase (FNR) in plants receives electrons from ferredoxin (Fd) and converts NADP+ to NADPH at the end of the photosynthetic electron transfer chain. We previously showed that the interaction between FNR and Fd was weakened by the allosteric binding of NADP(H) on FNR, which was considered as a part of negative cooperativity. In this study, we investigated the molecular mechanism of this phenomenon using maize (Zea mays L.) FNR and Fd, as the 3D structure of this Fd:FNR complex is available. Site-specific mutants of several amino acid residues on the Fd:FNR interface were analysed for the effect on the negative cooperativity, by kinetic analysis of Fd:FNR electron transfer activity and by Fd-affinity chromatography. Mutations of Fd Arg40Gln and FNR Glu154Gln that disrupt one of the salt bridges in the Fd:FNR complex suppressed the negative cooperativity, indicating the involvement of the ion pair of Fd Arg40 and FNR Glu154 in the mechanism of the negative cooperativity. Unexpectedly, either mutation of Fd Arg40Gln or FNR Glu154Gln tends to increase the affinity between Fd and FNR, suggesting the role of this ion pair in the regulation of the Fd:FNR affinity by NADPH, rather than the stabilization of the Fd:FNR complex.


Range of motion in junior tennis players participating in an injury risk modification program.
This study evaluated changes in range of motion (ROM) in competitive male and female junior tennis players participating in a specific conditioning program over a two-year period. Subjects were also compared to an age and sex-matched control group of players not performing the exercises. Fifty-one tennis players, 29 male (mean age 13.6) and 22 female (mean age 13.2) entered the study. Baseline ROM measurements were performed on all players upon entering the study. The conditioning program employed standardised stretch-hold-relax flexibility exercises for all the areas tested. These exercises were taught to the players and each athlete was given a video of the exercises. Compliance with the program was assessed by exercise logs, the parents, and the athletes. High compliers were compared to low compliers. Mean changes in the combined ROM measurements over time indicate improvement in flexibility in most anatomical areas after one year of participation, with small improvements in the second year. With the exception of forearm supination, there were no differences between high compliers and low compliers. Compared to controls, the experimental group showed significant improvement in sit and reach, dominant and nondominant shoulder internal rotation, dominant and nondominant shoulder external rotation, nondominant gastrocnemius, dominant iliotibial band, dominant and nondominant hip internal rotation, dominant and nondominant hip external rotation, dominant and nondominant forearm pronation, and dominant wrist flexion. The areas of greatest significant change were in the shoulder and back, which correspond to the areas of most clinical risk of Injury. In conclusion, joint ROM can be positively influenced with a specific conditioning program.


Prediction of major pulmonary complications after esophagectomy.
Pulmonary complications are the most frequent morbid event after esophagectomy. Understanding factors that are associated with pulmonary complications may help in patient selection and postoperative management. We performed a retrospective review of patients who underwent esophagectomy between 1980 and 2009. Univariate analysis was used to identify potential covariates for the development of major pulmonary complications. Multivariable logistic regression analysis was used to identify predictors of complications. A scoring system was developed, and its ability to predict complications was assessed. A total of 516 patients (382 men [74%]) with a mean age of 59.0±12.5 years underwent esophagectomy for cancer (398 [77%]) or benign disease. Major pulmonary complications occurred in 197 patients (38%) and were associated with a 10-fold increase in operative mortality (2.5% vs 28%; p<0.001). Independent predictors included patient age, forced expiratory volume in 1 second (% predicted), diffusion capacity of the lung for carbon monoxide (% predicted), performance status, serum creatinine, current cigarette use, and transthoracic resection. The scoring system (based on weighted scores for the first 4 covariates listed above) predicted pulmonary complications with an accuracy of 70.8% (p<0.001). Score groups identified an incremental risk of complications of 0 to 2, 12%; 3 to 4, 18%; 5 to 6, 46%; 7 to 8, 52%; and 9 to 13, 60% (p<0.001). Major pulmonary complications are frequent after esophagectomy and can be predicted using commonly available clinical information. A scoring system identifying the risk of such complications may assist in patient selection and in providing appropriate resources for postoperative management of higher-risk patients.


Benefits of digital breast tomosynthesis: A lesion-level analysis.
To compare outcome metrics of digital breast tomosynthesis (DBT) breast cancer screening with full-field digital mammogram (FFDM); specifically, to compare recall rates by the type of recalled finding, and to assess if screening with DBT versus FFDM changes biopsy recommendations and if the likelihood of malignancy varied by lesion type, if detected on DBT or FFDM screening mammogram. The outcomes of 22,055 FFDM and DBT screening mammograms were retrospectively reviewed. The exams were performed at an academic institution between August 2015 and September 2016. Performance of screening with FFDM versus DBT was compared in terms of recall rate and percentage of recalled lesions resulting in a cancer diagnosis, with subset analyses performed for specific mammographic findings. The recall rate was 10.6% for FFDM and 8.0% for DBT (p < 0.001). Architectural distortion was more likely to be recalled on DBT screening than FFDM (p = 0.002), and was associated with an increased likelihood of malignancy (p = 0.008). Asymmetries were less likely to be recalled on DBT than FFDM (p < 0.001) screening mammogram, but more likely to be recommended for biopsy when detected on DBT. Calcifications more frequently required short-term follow-up or biopsy on both DBT and FFDM. DBT screening confers an advantage in detection of architectural distortion representing malignancy. Recall rate of asymmetries are reduced with screening DBT, probably due to reduction of tissue superimposition. Calcifications pose a particularly difficult diagnostic challenge for breast imagers, regardless of screening mammogram type.


Evaluation and Management of Snoring.
Snoring can be harmless (primary) or a symptom of sleep-disordered breathing (secondary) and should alert the physician to evaluate the patient for risks thereof. Phenotypes of snoring and sleep-disordered breathing (SDB) are anatomic and nonanatomic and identifying these phenotypes and their interrelationships are critical to effective therapy. Mouth breathing alerts the physician to nasal airway obstruction, signals orofacial growth changes in children, and heralds the progression of SDB. Systematic evaluation to establish phenotypes includes assessing sleep habits, comorbidities, upper airway examination, polysomnography, and drug-induced sleep endoscopy. Strategies for treatment should be personalized and precise to the phenotype(s) to achieve the most benefit.


Clinical spectra-color ultrasonography.
Results of preliminary clinical trials of spectra-color ultrasonography are presented. The instrumentation is calibrated so that normal ocular tissues produce a near-white display. Scans of eyes with various diseases differ from the scans of normal eyes, indicating a variation in frequency responses.


Suppression of pelvic pain during hysteroscopy with a transcutaneous electrical nerve stimulation device.
To evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) as a pain control method during office hysteroscopy. A prospective, randomized study. Centre for Minimally Invasive Surgery, Department of Gynecological Science and Perinatology, "La Sapienza" University, Rome, Italy. One hundred forty-two patients undergoing office hysteroscopy. Application of a TENS device on the patient's abdomen before and during office hysteroscopy. The level of pain experienced by the patients was assessed using a 10 cm visual analog scale; the side effects and changes in the hemodynamic parameters were evaluated. The patients treated with TENS during hysteroscopy (group A, n = 71) were compared with a control group (group B, n = 71) on whom the TENS device was not used. The women in the TENS group experienced a significantly lower level of pain during hysteroscopy. No differences in side effects were observed between both group. TENS is a simple, efficient, and safe method of relieve pain during office hysteroscopy.


Quality evaluation of Angelicae acutilobae radix: individual differences and localization of (Z)-ligustilide in Angelica acutiloba root.
It has been difficult to evaluate the quality of Angelicae acutilobae Radix (Toki) because of large differences in the contents of its chemical constituents. In this research, we revealed individual differences and localization of (Z)-ligustilide in Toki cultivated and processed under the same conditions. Thirteen Toki samples (dry weight: 68.2 g-132.3 g) were divided and categorized into 13 parts and the (Z)-ligustilide content of each part was quantified. Total (Z)-ligustilide content ranged from 0.08% to 0.22% and the maximum difference between samples was approximately 2.8-fold. In addition, the localization of (Z)-ligustilide was examined. (Z)-Ligustilide content was the highest in lateral root at 0.19%, followed by main root at 0.13%, and the lowest in root head at 0.09%. Furthermore, the content tended to increase as the root became thinner. In particular, the difference in content between the inner side of upper root head (removed 5 mm from the epidermis 0.06%) and the 1.1-3.0 mm in diameter lateral root (0.24%) was largest at approximately 4.1-fold. We revealed that not only differences among individuals but also localization is a factor affecting the quality of Toki. In contrast, individuals with higher root part (main root + lateral root) weight ratio in whole root dry weight had higher (Z)-ligustilide content. The difference in (Z)-ligustilide content among individuals is due to the balance between root head part and root other than head part. It is possible to predict (Z)-ligustilide content from weight ratio of root part to whole root.


Enhanced anaerobic hydrogen production from cotton straws assisted by copper molybdate.
Hydrogen production from dark fermentation has potential application due to its environmental friendliness, low production cost, and sustainability. However, there is still an obstacle to improving the efficiency of bioH2 production to meet the requirements in practical applications. In this research, copper molybdates are synthesized under different pH conditions as additives to study their different influence processes during anaerobic hydrogen production from cotton straws with the pure cultural system. A series of results indicate that CuMoO4 with appropriate experimental conditions has the highest H2 yield at 191.3 mL/g straws at 37 °C, which is 236% higher than the control group. It can be shown that O. ethanolica 8KG-4 has an obvious accompanying with high stability and low cytotoxicity for this clean energy production system as well as the improvement of metabolic pathway. These results extend new thinking of obtaining higher H2 yield as a biofuel in future production.


Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation.
Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients suffering from respiratory or cardiac failure. The ECMO-associated morbidity and mortality depends to a large extent on the underlying disease and is often related to systemic inflammation, consecutive immune paralysis and sepsis. Here we tested the hypothesis that human α1-antitrypsin (SERPINA1) due to its anti-protease and anti-inflammatory functions may attenuate ECMO-induced inflammation. We specifically aimed to test whether intravenous treatment with α1-antitrypsin reduces the release of cytokines in response to 2 h of experimental ECMO. Adult rats were intravenously infused with α1-antitrypsin immediately before starting veno-arterial ECMO. We measured selected pro- and anti-inflammatory cytokines and found, that systemic levels of tumor necrosis factor-α, interleukin-6 and interleukin-10 increase during experimental ECMO. As tachycardia and hypertension developed in response to α1-antitrypsin, a single additional bolus of fentanyl and midazolam was given. Treatment with α1-antitrypsin and higher sedative doses reduced all cytokine levels investigated. We suggest that α1-antitrypsin might have the potential to protect against both ECMO-induced systemic inflammation and immune paralysis. More studies are needed to corroborate our findings, to clarify the mechanisms by which α1-antitrypsin inhibits cytokine release in vivo and to explore the potential application of α1-antitrypsin in clinical ECMO.


[The treatment of fractures of the distal phalanx with avulsion of the nail].
The delicate function of the fleshy portion of the fingers, in all its components--skin, bone and nail--, requires precise anatomical restoration. The nail constitutes a precious support for healing of the fracture and regrowth of the injured nail itself.


A photobioreactor using Nannochloropsis oculata marine microalgae for removal of polycyclic aromatic hydrocarbons and sorption of metals in produced water.
The objective of the present work is to evaluate the potential of the removal of PAHs and metal sorption for the treatment of petroleum produced water using a photobioreactor system with Nannochloropsis oculata microalgae. A set of photobioreactors with different gradients of produced water concentration diluted in saline water was designed, establishing five gradients (v/v): 0, 25, 50, 75 and 100%. These concentrations were established to test the removal of PAHs. The microalgal growth was monitored daily, noting the adaptation of microalgae to the addition of produced water as a culture medium, with cell growth of 5.24 × 107 cells mL-1 from 25% (v/v), 4.09 × 107 cells mL-1 from 50% (v/v), 2.77 × 107 cells mL-1 from 75% (v/v), and 1.17 × 107 cells mL-1 from 100%. The total removal efficiency of PAHs in the produced water was 94%. Organic compounds such as naphthalene, benzo(a)pyrene, benzo(b)fluoranthene, and acenaphthylene showed higher removal percentages, between 89 and 99% efficiency in produced water. Iron and zinc were the metals detected in the water produced, and iron reduced from 1.57 ± 0.08 mg L-1 to <0.1 mg L-1 after 28 days of cultivation, whereas zinc increased by 0.23 ± 0.05 to 3.90 ± 0.46 mg L-1. The PAHs removal may have occurred in two ways, by intracellular bioaccumulation or biodegradation by oxidoreductase enzymes. 0.2 g of dry biomass with maximum extraction of oil obtained 3.07% and generation of 3.70% of protein was considered as value-added products for biodiesel and bioplastics.


2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses apoptosis and leads to hyperphosphorylation of p53 in rat hepatocytes.
Inhibition of apoptosis of preneoplastic cells is thought to represent a major mechanism of action of tumor promoters. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent promoter of liver carcinogenesis in rodents, suppressed apoptosis in rat hepatocytes pretreated in vitro with an apoptogenic dose of UV light. This effect, which was also observable in DNA fragmentation analysis, coincided with a pronounced inhibition of the p53 increase usually seen after UV irradiation of rat hepatocytes. Interestingly, TCDD also led to a very minor but consistent enhancement of DNA fragmentation and to a slight increase in p53. Furthermore, TCDD resulted in a dose-dependent increase in p53 phosphorylation in intact cells. The concentration-response curves of the effects of TCDD on p53 phosphorylation and aromatic hydrocarbon receptor (AhR)-dependent induction of cytochrome P450 1A1 activity were almost superimposable, suggesting that TCDD induces p53 phosphorylation via an AhR-linked kinase activity. In an extract prepared from rat liver homogenate, 1 nM TCDD also stimulated p53 phosphorylation. Since the tyrosine kinase c-src was previously shown by others to be activated upon binding of TCDD to the AhR, extracts were pretreated with anti-src-antibodies. This treatment almost completely abrogated the effect of TCDD on p53 phosphorylation suggesting a key role for AhR-associated c-src. This mode of action may result in the observed suppression of the p53 response to apoptogenic UV irradiation, and may contribute to the inhibition of apoptosis.


Investigation of the salivary 18-hydroxycorticosterone:aldosterone ratio in man using a direct assay.
A method for the direct determination of 18-hydroxycorticosterone (18OHB) in human saliva has been developed and validated. Saliva was collected at 30 min and 1 h intervals between 0600 and 2200 h from healthy men and women for the determination of 18OHB (SHB), aldosterone (SA) and glucocorticoids (SGC = cortisol + cortisone). SHB was highly correlated with SA (r = 0.75; P less than 0.001) but even more highly with SGC (r = 0.89; P greater than 0.001). Multiple regression analysis confirmed that SGC was a more important determinant of SHB than was SA. Though the concentrations of 18OHB and aldosterone were highly correlated there was considerable variation in the 18OHB:aldosterone ratio during the period of saliva collection. This ratio tended to be highest in the morning and lowest in the evening and was weakly correlated with SGC level (r = 0.62; P less than 0.01). The 18OHB:aldosterone ratio in saliva approximates to, and is highly correlated with, that in plasma. We suggest that the fluctuations in SHB:SA ratio correspond to the relative rates of secretion of 18OHB and aldosterone and that this ratio is modulated either by ACTH or by cortisol. Whether this indicates that 18OHB is a by-product of glucocorticoid as well as aldosterone metabolism, or whether this implies a separate physiological role for the steroid remains to be clarified.


In vitro activity of new tetracycline analogues omadacycline and eravacycline against clinical isolates of Helicobacter pylori collected in China.
Omadacycline and eravacycline are newly approved tetracycline analogues with excellent activity against a broad spectrum of Gram-positive and Gram-negative microorganisms; however, no data are available regarding Helicobacter pylori. The susceptibility of 201 clinical isolates of H. pylori collected in China to omadacycline, eravacycline, and the comparator tetracycline was determined by an agar dilution method. They showed greater activity than tetracycline. The MIC50/90 values of omadacycline, eravacycline, and tetracycline were 0.125/0.25 μg/mL, 0.063/0.125 μg/mL, and 0.25/1 μg/mL, respectively. Omadacycline and eravacycline were potent in vitro against all the isolates tested, including tetracycline-resistant strains, and warrant further investigation as potential antibiotics for H. pylori treatment.


Engineering sleep disorders: from classical CPAP devices toward new intelligent adaptive ventilatory therapy.
Among the most common sleep disorders are those related to disruptions in airflow (apnea) or reductions in the breath amplitude (hypopnea) with or without obstruction of the upper airway (UA). One of the most important sleep disorders is obstructive sleep apnea (OSA). This sleep-?disordered breathing, quantified by the apnea??hypopnea index (AHI), can produce a significant reduction of oxygen saturation and an abnormal elevation of carbon dioxide levels in the blood. Apnea and hypopnea episodes are associated with arousals and sleep fragmentation during the night and compensatory response of the autonomic nervous system.


Respiratory Syncytial Virus in Greece, 2016-2018.
Human respiratory syncytial virus (RSV) is the leading cause of acute bronchiolitis in infants and young children. Children under the age of 2 years, hospitalized for bronchiolitis in the pediatric clinic of a tertiary hospital in northern Greece, were tested for RSV infection during two RSV seasons (2016-2017 and 2017-2018). RSV was detected in 37 of 71 (52.1%) patients, most of them younger than 6 months. Both RSV subtypes were detected - RSV-A (54.1%) and RSV-B (45.9%) - with predominance of RSV-A during the 2016-2017 and RSV-B during the 2017-2018 season. RSV-A and RSV-B sequences clustered within the ON1 and BA genotypes, respectively. Compared to the prototype strains, several amino acid substitutions were observed in the duplication region of the G gene. The study provides a first insight into the molecular epidemiology of RSV in Greece.


Adjuncts in diagnosis, prognosis, and clinical monitoring of breast, gynecologic, and hematolymphopoietic malignancies: Third Joint International Workshop, Lacco Ameno d'Ischia, Italy, October 2001.
The aim of the third edition of this workshop was to address the most relevant topics and the latest achievements in the diagnosis, prognosis, and clinical monitoring of breast, gynecologic, and hematolymphopoietic malignancies. As with the two previous editions, scientific leaders in the fields of pathology, clinical oncology, and basic research have been gathered together to promote a continuous flow of theoretical and practical information among basic research, diagnosis, and therapeutic innovation in order to achieve timely and effective progresses in defeating human cancer.


Simple and efficient method for producing high radionuclidic purity 111In using enriched 112Cd target.
In this work, a simple and efficient method for producing high radionuclidic purity 111In from an enriched 112Cd target was developed. The enriched 112Cd metal target formed by cyanide-free electroplating was bombarded with protons of 21 MeV in a CS-30 cyclotron. Then, we explored a purification scheme using CL-P204 cation exchange resin wherein 98% of the 111In in the bombarded target could be extracted in less than 1 h. The purified 111In in the form of [111In]In-chloride had a high radionuclidic purity (99.9%) and a low impurity concentration (<1.2 ppm). The yield of 111In via the reaction of 112Cd (p, 2n) 111In was measured to be 222 ± 5 MBq/μA∙h. In addition, a chemical procedure for collecting the unreacted 112Cd at a recovery rate of 96.6% was explored.


Pre-treatment ratio of periprostatic to subcutaneous fat thickness on MRI is an independent survival predictor in hormone-naïve men with advanced prostate cancer.
Epidemiological studies have shown an association between obesity and prostate cancer (PCa) aggressiveness. However, little is known about periprostatic fat (PPF) and its relationship with overall fat deposition in PCa. PPF is thought to contribute to PCa growth and migration via secreted factors and induction of chronic inflammation. We investigated if pre-treatment PPF thickness correlates with overall survival (OS). We reviewed 85 hormone-naïve men with advanced PCa who had received androgen deprivation therapy (ADT). PPF thickness was measured by magnetic resonance imaging (MRI) and compared with subcutaneous fat (SCF) thickness as an internal control. Visceral fat (VF) area measured by computed tomography served as an additional control. We evaluated the relationship between laboratory data, pathology results, and obesity parameters and OS. Median follow-up was 50.6 months. Thirty-six patients died during follow-up. Univariate analysis revealed that nadir PSA titer, Gleason score, N stage, M stage, extent of disease by bone scan grade, hemoglobin, lactate dehydrogenase, alkaline phosphatase, and PPF/SCF ratio were associated with OS. Multivariate analysis revealed that nadir PSA titer, N stage, and PPF/SCF ratio were independent prognostic factors for survival. The 5-year OS in the patients with higher PPF/SCF ratio (≥ 1) and lower PPF/SCF ratio (< 1) was 49.5% and 66.5%, respectively (P = 0.039). Pre-treatment ratio of PPF-to-SCF thickness on MRI is an independent predictor of survival in hormone-naïve men with advanced PCa. This could be useful for predicting which patients are more likely to develop castration-resistant PCa.


Effects of tetrodotoxin on changes in extracellular free calcium induced by repetitive electrical stimulation and iontophoretic application of excitatory amino acids in the sensorimotor cortex of cats.
Extracellular free calcium ([Ca2+]o) was measured with double barreled ion-sensitive reference electrodes in the sensorimotor cortex of cats before and after application of tetrodotoxin (TTX). Electrical stimulation of the cortical surface or of the thalamic ventrobasal complex resulted in reductions of [Ca2+]o (delta Ca) by up to 0.45 mM (baseline 1.2--1.3 mM). Iontophoretic applications of the excitatory amino acids glutamate, aspartate and DL-homocysteate evoked delta Ca by up to 1.2 mM. delta Ca were largest at a depth of 100-300 micron below cortical surface. After application of 10(-5) M TTX to the cortical surface, the delta Ca evoked by electrical stimulation disappeared and the accompanying slow negative potentials were reduced in amplitude. In contrast, delta Ca evoked by excitatory amino acids were only slightly affected. It is suggested that excitatory amino acids activate voltage-dependent postsynaptic Ca2+ conductances in neocortical neurones.


Conditions for omitting invasive long-term monitoring before surgical resection in patients with temporal lobe epilepsy.
The omission of invasive long-term monitoring before surgical resection in patients with epilepsy should be permitted only for those in whom the epileptogenic focus is presumed to localize unilaterally in the mesial aspect of the temporal lobe. The localization may well be confirmed through noninvasive measures. Retrospective analyses of data obtained from noninvasive investigations (scalp-recorded and sphenoidal EEGs, neuroimages, and electroclinical seizure manifestations) were carried out in 58 patients. The localization of their epileptogenic focus was subsequently confirmed by the implantation of both intracerebral and subdural electrodes; the focus had an amygdalohippocampal origin in 41 patients and a lateral temporal origin in 17 patients. From the comparison of noninvasive findings between these two groups, we propose the following indispensable conditions for omitting an invasive evaluation: 1. Appearance of focal epileptic discharges unilaterally in the sphenoidal lead observed during the simple phase of partial seizures, or unilateral discharges with predominancy in the sphenoidal lead during the early phase of complex partial seizures. 2. Interictal spikes on scalp-recorded EEGs localizing unilaterally in the anterior region of the temporal lobe, and if bilaterally independent, presenting with unilateral predominancy in a ratio of greater than 4:1. 3. Presence of autonomic signs in the initial phase of signal symptoms. 4. Neuroimaging findings in the mesial temporal region: elongated T2 on MRI and hippocampal atrophy, or a tumorous lesion. The lateralization conforms to interictal and ictal paroxysmal EEG findings. There were 8 patients with seizure of amygdalohippocampal origin who satisfied all the indispensable condition, but not a single patient with seizures of lateral temporal origin.(ABSTRACT TRUNCATED AT 250 WORDS)


Host genetic variability and pneumococcal disease: a systematic review and meta-analysis.
Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD). We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis. We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04-2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18-2·66) and none of the outcome polymorphisms. Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.


Evaluation of the Harvest Dates for Three Major Cultivars of Blue Honeysuckle (Lonicera caerulea L.) in China.
Blue honeysuckle (Lonicera caerulea L.) is an emerging fruit crop; however, determining its proper harvest time in commercial cultivation remains challenging due to its rapid fruit development characteristics. In this study, we investigated 17 agronomic traits of three blue honeysuckle cultivars harvested on 5 successive dates within their respective harvest windows. 'Lanjingling', 'Wulan', and 'Berel' showed solid-acid ratios (SS:TA) ranging from 10.00 to 16.01, 8.13 to 10.23, and 5.77 to 7.11, respectively; anthocyanin contents ranged from 233.85 to 276.83 mg/100 g, 236.38 to 312.23 mg/100 g, and 235.71 to 334.98 mg/100 g, respectively; vitamin C contents ranged from 88.43 to 99.68 mg/100 g, 108.13 to 191.23 mg/100 g, and 89.71 to 120.40 mg/100 g, respectively; phenolic contents ranged from 25.22 to 37.59 mg/g, 25.40 to 36.52 mg/g, and 37.66 to 50.00 mg/g, respectively. The results revealed the SS:TA value consistently increased with delayed harvesting and were significantly negatively correlated with fruit firmness, total acidity, shelf life, and respiration intensity, suggesting it is an ideal maturity indicator for blue honeysuckle berries. The factor analysis suggests that the suitable harvest date for 'Lanjingling' could be either 47 days after flowering (DAF) with an SS:TA value of approximately 10.0, characterized by high firmness, extended shelf life, and elevated levels of anthocyanins and phenolics; or 67 DAF (SS:TA ≈ 16.0), characterized by high vitamin C content and sweetness, and larger size and weight. For 'Wulan', it suggests the suitable harvest date is either 54 DAF (SS:TA ≈ 9.0), yielding fruit with high levels of anthocyanins and vitamin C; or 62 DAF (SS:TA > 10.0), yielding fruit with high sweetness and large size and weight. For 'Berel', it is suggested to be either 52 DAF (SS:TA ≈ 6.5), resulting in fruit with high levels of anthocyanins and vitamin C; or 62 DAF (SS:TA > 7.0), resulting in balanced levels of the fruit quality traits.


NaV1.7 channels are expressed in the lower airways of the human respiratory tract.
NaV channels expression have been reported in upper airways and tracheal smooth muscle cells controlling the generation and propagation of action potentials in the respiratory tract sensory neurons, but information about the presence of these proteins in the bronchioalveolar structures in human lungs was missing. The main objective covered in this work was to determine whether the NaV1.7 channels are expressed in lower airways, and to identify the cellular identities expressing these proteins. We detected high levels of the mRNA coding for NaV1.7 channels in isolated lung fibroblasts obtained from both normal lungs, and fibrotic lungs of patients with respiratory diseases. The protein was detected with two different antibodies in the bronchioalveolar tissue, alveolar endothelium, and capillary endothelium, in normal and pathologic lungs. These evidences are useful in the dissection of molecular mechanisms of pulmonary pathologies, and lead to consider the NaV1.7 channels as potential therapeutic targets for the treatment of pulmonary diseases.


Association of Daily Aspirin Therapy With Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis C Virus Infection.
Aspirin therapy has been associated with reduced risk of colon cancer, but there is only limited evidence for its effects on risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We aimed to investigate the association of daily aspirin therapy with HCV-related HCC risk. In this cohort study, based on Taiwan's National Health Insurance Research Database, we screened 237,963 patients with chronic HCV infection for the period of 1997 through 2011. We excluded patients with confounding conditions and 2478 patients who continuously received daily aspirin therapy for 90 days or more (treated group) were randomly matched 1:2 with 4956 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores. Cumulative incidence of, and hazard ratio (HR) for, HCC development were analyzed after we adjusted for patient mortality as a competing risk event. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group over 5 years (4.67%; 95% CI, 3.74%-5.59% vs 7.32%; 95% CI, 6.33%-8.30%; P<.001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.78, 95% CI, 0.64-0.95; P = .011), after adjustment for age per year, male sex, cirrhosis, liver decompensation, hyperlipidemia, statin use, and interferon therapy. Sensitivity subgroup analyses also verified this association (all HRs<1.0). In addition, older age (HR, 1.03 per year; 95% CI, 1.02-1.04), male sex (HR, 1.46; 95% CI, 1.21-1.77), and cirrhosis (HR, 3.13; 95% CI, 2.55-3.84) were independently associated with an increased HCC risk. In a nationwide cohort study in Taiwan, we found aspirin therapy to be significantly associated with a reduced risk of HCV-related HCC.


Plasmid R46 fails to protect Escherichia coli against double-strand DNA-binding agents but increases their mutagenic activities.
Plasmid R46 was tested for its ability to increase survival and mutagenesis of Escherichia coli strain AB1157 following exposure to agents that produce a variety of structural defects in DNA. The plasmid enhanced the mutagenic activities of adriamycin (ADM), N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), bleomycin (BLM), methyl methanesulphonate (MMS), mitomycin C (MTC), nitrofurazone (NFZ), 4-nitroquinoline-N-oxide (NQO), cis-platinum (II) diaminodichloride (PDD) and proflavine (PF). Furthermore, R46, which is known to protect against BLM and MMS, increased the survival of strain AB1157 following exposure to NFZ, NQO or PDD but not ADM, BCNU, MTC or PF. In fact the plasmid appeared to slightly sensitise its host to the latter drugs. The results are discussed in terms of the nature of the DNA damage produced by these inhibitors and the possible role of plasmid-encoded products in the repair of DNA.


Closed fluid description of relativistic, magnetized plasma interacting with radiation field.
A closed set of averaged fluid equations for a relativistic plasma immersed, simultaneously, in a slowly varying magnetizing field and a sharply varying electromagnetic field (radiation field, for example) of arbitrary intensity is derived. The modifications due to the radiation field on the plasma stress tensor and the Lorentz force are explicitly displayed. The resulting equations include the effects of radiation reaction as well as radiation pressure.


Complete androgen insensitivity syndrome in a 13-year-old Lebanese child, reared as female, with bilateral inguinal hernia: a case report.
Androgen insensitivity syndrome is a rare X-linked disorder of sex development, caused by mutations in the androgen receptor. In this case, a 13-year-old child, reared as female, presenting for primary amenorrhea, was diagnosed with complete androgen insensitivity syndrome. A 13-year-old Caucasian child, reared as female, presents with primary amenorrhea. Physical examination revealed female appearance and a short vagina with blind-ended pouch. Laboratory examination showed high levels of testosterone and anti-Müllerian hormone; uterus and ovaries were absent. Karyotype confirmed a 46,XY pattern. Deoxyribonucleic acid analysis of the androgen receptor gene revealed a homozygous mutation p.R856C in exon 7. Gender was assigned as female, and she was started on hormonal therapy and underwent gonadectomy. Androgen insensitivity syndrome comprises a large spectrum of presentations. High index of suspicion is needed. Investigation of girls with bilateral inguinal hernia is critical.


Comparing cardiovascular magnetic resonance strain software packages by their abilities to discriminate outcomes in patients with heart failure with preserved ejection fraction.
Cardiovascular magnetic resonance (CMR) myocardial strain analysis using feature tracking (FT) is an increasingly popular method to assess cardiac function. However, different software packages produce different strain values from the same images and there is little guidance regarding which software package would be the best to use. We explored a framework under which different software packages could be compared and used based on their abilities to differentiate disease from health and differentiate disease severity based on outcome. To illustrate this concept, we compared 4-chamber left ventricular (LV) peak longitudinal strain (GLS) analyzed from retrospective electrocardiogram gated cine imaging performed on 1.5 T CMR scanners using three CMR post-processing software packages in their abilities to discriminate a group of 45 patients with heart failure with preserved ejection fraction (HFpEF) from 26 controls without cardiovascular disease and to discriminate disease severity based on outcomes. The three different post-processing software used were SuiteHeart, cvi42, and DRA-Trufistrain. All three software packages were able to distinguish HFpEF patients from controls. 4-chamber peak GLS by SuiteHeart was shown to be a better discriminator of adverse outcomes in HFpEF patients than 4-chamber GLS derived from cvi42 or DRA-Trufistrain. We illustrated a framework to compare feature tracking GLS derived from different post-processing software packages. Publicly available imaging data sets with outcomes would be important to validate the growing number of CMR-FT software packages.


Serum immunoreactive somatomedin-C levels in growth failure and delayed puberty associated with chronic hepatosplenic schistosomiasis.
Eleven patients, five males, six females, aged 14-20 years with hepatosplenic schistosomiasis (HSS), growth failure and delayed puberty were submitted to endocrine evaluation. All patients had well preserved parenchymal liver function although several changes were present in the portal system, showing a poorly vascularized liver. Bone age was retarded, thyroid function was normal, the human growth hormone response to hypoglycaemia was within the normal limits and the prolactin response to TRH was normal. LH and FSH basal levels were normal and a normal rise was observed after a provocative test with LHRH. Gonadal function, expressed as serum testosterone or oestradiol levels, was abnormally low for the chronological age. Serum somatomedin-C levels were also low (range 0.11-2.10 U/ml) for the respective Tanner stage or bone age of each individual patient. One year after a splenorenal shunting in the three patients that returned for follow-up, it was observed that sexual maturation reached Tanner stage III, linear growth increment ranged from 9.0 to 11.5 cm and serum somatomedin-C levels increased to 4.3-5.6 U/ml. We concluded that a combination of undernutrition and marked vascular changes in the liver, present in HSS, are associated with decreased serum sex steroids and somatomedin-C concentrations, resulting in growth failure and delayed puberty in these patients.


Visual Impact of Early Hydroxychloroquine-Related Retinal Structural Changes in Patients with Systemic Lupus Erythematosus.
The aim of the study was to assess the early retinal structural changes due to hydroxychloroquine (HCQ) use and its impact on visual acuity (VA) of patients with systemic lupus erythematosus (SLE). The study was conducted as a case-control study that included 60 eyes of 30 SLE patients treated with HCQ compared with 50 eyes of 25 healthy individuals. Patients were kept on 200 or 400 mg as daily maintenance dose. SLE patients were subgrouped into patients with normal VA and patients with decreased VA. All participants were assessed by the optical coherence tomography (OCT), and early structural abnormalities were recorded. The main outcomes and measures were best-corrected VA, drug exposure time, central macular thickness (CMT), inner segment-outer segment (IS-OS) junction disruption, ganglion cell complex † (GCC†, ganglion cell layer + inner plexiform layer), ganglion cell complex †† (GCC††, nerve fiber layer + GCC†), and peripapillary retinal nerve fiber layer. The characteristics of HCQ retinal toxicity were correlated to VA. All OCT parameters were found to be significantly lower (p < 0.001) in HCQ patients with decreased VA than in controls. Patients receiving a daily dose of 400 mg had lower (p < 0.05) parameters than those receiving 200 mg. Patients with IS-OS disruption had lower CMT, GCC †, and GCC †† than those without (p < 0.05). VA was significantly correlated (p < 0.05) with CMT and drug exposure time. The HCQ use caused OCT changes that precede clinically visible retinopathy and might be associated with slight VA reduction. Screening with OCT of patients receiving HCQ is essential to detect early vision loss.


Definition and comparability of nosocomial infection rates.
Nosocomial infection rates are frequently calculated by dividing the number of infections acquired during a month by the number of patients discharged during that month. This method does not allow for prediction of future events or comparability between locations for statistical analysis. A more appropriate rate is the number of infections divided by patient-days spent in the hospital. This rate avoids the problems associated with the commonly used method. On the basis of the rate of infections per patient-day, it is possible to test for interhospital and intrahospital differences as well as for differences over time.


Patella fractures treated with suture tension band fixation.
Patella fractures requiring surgery are traditionally treated using metallic implants, which are associated with high re-operation rates, mainly due to implant prominence. To overcome the problem of prominent metallic implants, we present a technique based purely on braided sutures. This technique is described in a step-wise, standardised way based on our findings on six patients treated at our institution. This technique can be adapted to all types of patella fractures. The described suture configuration allows maintenance of inter-fragmentary reduction until bony union without symptoms from the suture material. We believe that this technique is a safe and promising alternative to traditional metallic fixation methods.


Differentiating littering, urban runoff and marine transport as sources of marine debris in coastal and estuarine environments.
Marine debris is a burgeoning global issue with economic, ecological and aesthetic impacts. While there are many studies now addressing this topic, the influence of urbanisation factors such as local population density, stormwater drains and roads on the distribution of coastal litter remains poorly understood. To address this knowledge gap, we carried out standardized surveys at 224 transect surveys at 67 sites in two estuaries and along the open coast in Tasmania, Australia. We explored the relative support for three hypotheses regarding the sources of the debris; direct deposition by beachgoers, transport from surrounding areas via storm water drains and coastal runoff, and onshore transport from the marine system. We found strong support for all three mechanisms, however, onshore transport from the marine reservoir was the most important mechanism. Overall, the three models together explained 45.8 percent of the variation in our observations. Our results also suggest that most debris released into the marine environment is deposited locally, which may be the answer to where all the missing plastic is in the ocean. Furthermore, local interventions are likely to be most effective in reducing land-based inputs into the ocean.


The effects of chronic glucocorticoid excess, adrenalectomy and stress on neuropeptide Y in individual rat hypothalamic nuclei.
Several lines of evidence indicate a role for neuropeptide Y (NPY) in the modulation of the corticotroph axis. In two separate studies reported here, the concentrations of NPY and noradrenaline (NA), as well as corticotropin-releasing factor (CRF) and arginine vasopressin (AVP), were measured in extracts of individual rat hypothalamic nuclei after various manipulations producing either a state of chronic glucocorticoid excess or depletion, and also following repeated restraint stress. Alterations induced in the activity of hypothalamic neurones were inferred from the respective changes in these concentrations. 12 days after bilateral adrenalectomy (ADX), NPY levels were decreased by 24% in the arcuate nucleus (ARC) and 23% in the paraventricular nucleus (PVN, p < 0.05 vs controls). Forced immobilization of the animals for 4 h each day for 9 consecutive days (repeated stress) also decreased NPY content of the ARC by 25% (p < 0.01 vs controls), an effect blocked by the administration of glucocorticoids. NA levels in both hypothalamic nuclei were unaffected by repeated stress or ADX. Administration of glucocorticoids in the first of these studies induced decreases in NA levels by 15% and 25% in the ARC and PVN respectively (p < 0.05 vs controls). However, in subsequent experiments no significant effect of glucocorticoids on NA was observed. Our results demonstrate that the activity of the hypothalamic NPY-ergic neurones is modulated by glucocorticoids and by chronic stress. They also suggest that brainstem catecholaminergic and hypothalamic NPY-ergic neurones are differentially affected by altered glucocorticoid concentrations or by chronic stress, possibly in a stimulus-specific way.


Elucidating cytochrome C release from mitochondria: insights from an in silico three-dimensional model.
Mitochondrial regulation of apoptosis depends on the programmed release of proapoptotic proteins such as cytochrome c (Cyt c) through the outer mitochondrial membrane (OMM). Although a few key processes involved in this release have been identified, including the liberation of inner membrane-bound Cyt c and formation of diffusible pores on the OMM, other details like the transport of Cyt c within complex mitochondrial compartments, e.g., the cristae and crista junctions, are not yet fully understood (to our knowledge). In particular, a remodeling of the inner mitochondrial membrane accompanying apoptosis seen in a few studies, in which crista junctions widen, has been hypothesized to be a necessary step in the Cyt c release. Using a three-dimensional spatial modeling of mitochondrial crista and the crista junction, model simulations and analysis illustrated how the interplay among solubilization of Cyt c, fast diffusion of Cyt c, and OMM permeabilization gives rise to the observed experimental release profile. Importantly, the widening of the crista junction was found to have a negligible effect on the transport of free Cyt c from cristae. Finally, model simulations showed that increasing the fraction of free/loosely-bound Cyt c can sensitize the cell to apoptotic stimuli in a threshold manner, which may explain increased sensitivity to cell death associated with aging.


[Treatment of the primary tumour in oligometastatic prostate cancer].
In the treatment of metastatic prostate cancer, significant improvements have recently been made. In addition to androgen deprivation, various options are available, such as anti-androgen receptor therapies with abiraterone and enzalutamide and taxane-based chemotherapy. It is still being discussed whether oligometastatic patients should only be treated systemically, or whether they benefit from additional local therapy for the primary tumour. Until mid-2018, there was no evidence-based recommendation to perform local prostate irradiation in newly diagnosed prostate cancer with distant metastases. At best, this could be indicated as an individual decision based on data from retrospective series. Accordingly, there were no recommendations in the guidelines. The data from the STAMPEDE study and the HORRAD study were published in 2018 /19 and clearly demonstrate the indication for local irradiation of the primary tumour in oligometastatic prostate cancer with less than 4 bone metastases. The following overview summarises the data from these two studies, evaluates them and finally gives a recommendation for the use of local prostate radiation therapy in the oligometastatic situation.


Long-term safety and tolerability of eptinezumab in patients with chronic migraine: a 2-year, open-label, phase 3 trial.
Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody recently approved in the United States for preventive treatment of migraine in adults, was found to be well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine. The objective of the PREVAIL study was to evaluate the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with chronic migraine. PREVAIL was an open-label, phase 3 trial comprising a 48-week treatment phase followed by a second 48-week treatment phase. Adults with chronic migraine received eptinezumab 300 mg by 30-min intravenous administration every 12 weeks for up to 8 doses. Patients were followed for 20 weeks after the final infusion (end-of-study visit at week 104). Overall, 128 adults (mean age, 41.5 years) with chronic migraine were included. During the 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). The rate of study-drug discontinuation due to adverse events was 6.3%, which included 3 patients with infusion-related hypersensitivity. The incidence of anti-eptinezumab antibodies peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Improvements in patient-reported outcomes were observed at first assessment (week 4) and generally sustained through week 104. In adults with chronic migraine, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years. ClinicalTrials.gov (Identifier: NCT02985398 ).


Partner weight status and subject weight loss: implications for cost-effective programs and public health.
This study examined the difference in body changes of subjects with overweight partners and those with normal weight partners. The 9 subjects with normal weight partners lost significantly more weight than the 14 subjects with overweight partners by the end of the one-year treatment program (27.9 lbs versus 20.2 lbs, respectively) and at 3-month follow-up (29.6 lbs vs. 17.3 lbs, respectively). It was also found that both overweight and normal weight partners lost weight incidental to treatment but as expected, body changes of overweight partners significantly decreased over time whereas body changes of normal weight partners did not. Overweight partners and subjects lost statistical equivalent amounts of weight but there was a significant correlation at posttreatment between body changes of subjects in the overweight partner group and their partners. It was concluded that if body changes of both subjects and their overweight partners are considered, couples programs might be a cost-effective and important public health approach because two individuals lose weight as inexpensively as one and more people are treated. Researchers are encouraged to report weight status and body changes of both subjects and partners in order to understand more fully the relationship between partner weight status and subject weight loss.


Management of paediatric burns in low- and middle-income countries: assessing capacity using the World Health Organization Surgical Assessment Tool.
Burns are a leading cause of global disease burden, with children in low- and middle-income countries (LMICs) disproportionately affected. Effective management improves outcomes; however, the availability of necessary resources in LMICs remains unclear. We evaluated surgical centres in LMICs using the WHO Surgical Assessment Tool (SAT) to identify opportunities to optimize paediatric burn care. We reviewed WHO SAT database entries for 2010-2015. A total of 1121 facilities from 57 countries met the inclusion criteria: facilities with surgical capacity in LMICs operating on children. Human resources, equipment and infrastructure relevant to paediatric burn care were analysed by WHO Regional and World Bank Income Classifications and facility type. Facilities had an average of 147 beds and performed 485 paediatric operations annually. Discrepancies existed between procedures performed and resource availability; 86% of facilities performed acute burn care, but only 37% could consistently provide intravenous fluids. Many, particularly tertiary, centres performed contracture release and skin grafting (41%) and amputation (50%). LMICs have limited resources to provide paediatric burn care but widely perform many interventions necessary to address the burden of burns. The SAT may not capture innovative and traditional approaches to burn care. There remains an opportunity to improve paediatric burn care globally.


Arresting microbiome development limits immune system maturation and resistance to infection in mice.
Disruptions to the intestinal microbiome during weaning lead to negative effects on host immune function. However, the critical host-microbe interactions during weaning that are required for immune system development remain poorly understood. We find that restricting microbiome maturation during weaning stunts immune system development and increases susceptibility to enteric infection. We developed a gnotobiotic mouse model of the early-life microbiome Pediatric Community (PedsCom). These mice develop fewer peripheral regulatory T cells and less IgA, hallmarks of microbiota-driven immune system development. Furthermore, adult PedsCom mice retain high susceptibility to Salmonella infection, which is characteristic of young mice and children. Altogether, our work illustrates how the post-weaning transition in microbiome composition contributes to normal immune maturation and protection from infection. Accurate modeling of the pre-weaning microbiome provides a window into the microbial requirements for healthy development and suggests an opportunity to design microbial interventions at weaning to improve immune development in human infants.


Complete Genome Sequence of Rhizobium sp. Strain RCAM05350 from Shulgan-Tash Karst Cave.
The Shulgan-Tash cave is an extremely interesting object for scientific research, located in the Republic of Bashkortostan (Russia). In this article, we report the complete genome sequence of Rhizobium sp. strain RCAM05350 isolated from the "cave silver" biofilms. The sequence was obtained using Oxford Nanopore Technologies MinION.


Two-dimensional half-metallicity and fully spin-polarized topological fermions in monolayer EuOBr.
Two-dimensional (2D) half-metal and topological states have been the current research focus in condensed matter physics. Herein, we report a novel 2D material named EuOBr monolayer, which can simultaneously show 2D half-metal and topological fermions. This material shows a metallic state in the spin-up channel but a large insulating gap of 4.38 eV in the spin-down channel. In the conducting spin channel, the EuOBr monolayer shows the coexistence of Weyl points and nodal-lines near the Fermi level. These nodal-lines are classified by type-I, hybrid, closed, and open nodal-lines. The symmetry analysis suggests these nodal-lines are protected by the mirror symmetry, which cannot be broken even spin-orbit coupling is included because the ground magnetization direction in the material is out-of-plane [001]. The topological fermions in the EuOBr monolayer are fully spin-polarized, which can be meaningful for future applications in topological spintronic nano-devices.


The global approach to rehabilitation following an osteoporotic fragility fracture: A review of the rehabilitation working group of the International Osteoporosis Foundation (IOF) committee of scientific advisors.
To conduct a review of the current state of the evidence for rehabilitation strategies post-fragility fracture. Narrative review conducted by the Rehabilitation Working Group of the International Osteoporosis Foundation Committee of Scientific Advisors characterizing the range of rehabilitation modalities instrumental for the management of fragility fractures. Multi-modal exercise post-fragility fracture to the spine and hip is strongly recommended to reduce pain, improve physical function, and improve quality of life. Outpatient physiotherapy post-hip fracture has a stronger evidence base than outpatient physiotherapy post-vertebral fracture. Appropriate nutritional care after fragility fracture provides a large range of improvement in morbidity and mortality. Education increases understanding of osteoporosis which in turn increases utilization of other rehabilitation services. Education may improve other health outcomes such as pain and increase a patient's ability for self-advocacy. Rehabilitation interventions are inter-reliant, and research investigating the interaction of exercise, nutrition, and other multi-modal therapies may increase the relevance of rehabilitation research to clinical care.


Simultaneous gastric cancer and breast cancer metastases to the stomach with lymph node collision tumor: a case report.
While double primary cancers are common in breast cancer patients, co-existence of primary gastric cancer and gastric metastases of breast cancer is exceedingly rare. A 51-year-old woman receiving chemotherapy for breast cancer presented with melena and presyncope. A circumferential thickening of the pylorus and small submucosal tumor-like lesions in the gastric fundus and corpus were confirmed on endoscopy. Immunohistochemistry of biopsies revealed that the former was composed of poorly differentiated gastric cancer cells, while the latter were breast cancer metastases. Distal gastrectomy was performed. Pathological evaluation of the resected specimen revealed gastric adenocarcinoma in the pyloric lesion and breast countless cancer metastases throughout the remainder of the stomach, with positive margins. One lymph node had evidence of both stomach cancer and breast cancer metastases, forming a collision tumor. Despite a successful surgery, the patient died 6 months later due to progression of breast cancer. We report a case of synchronous primary gastric adenocarcinoma and gastric metastases of breast cancer. Inter-disciplinary collaboration is crucial in determining the optimal treatment in double cancers.


Quantifying bedside-derived imaging of microcirculatory abnormalities in septic patients: a prospective validation study.
The introduction of orthogonal polarization spectral (OPS) imaging in clinical research has elucidated new perspectives on the role of microcirculatory flow abnormalities in the pathogenesis of sepsis. Essential to the process of understanding and reproducing these abnormalities is the method of quantification of flow scores. In a consensus meeting with collaboraters from six research centres in different fields of experience with microcirculatory OPS imaging, premeditated qualifications for a simple, translucent and reproducible way of flow scoring were defined. Consecutively, a single-centre prospective observational validation study was performed in a group of 12 patients with an abdominal sepsis and a new stoma. Flow images of the microcirculation in vascular beds of the sublingual and stoma region were obtained, processed and analysed in a standardised way. We validated intra-observer and inter-observer reproducibility with kappa cross-tables for both types of microvascular beds. Agreement and kappa coefficients were >85% and >0.75, respectively, for interrater and intrarater variability in quantification of flow abnormalities during sepsis, in different subsets of microvascular architecture. Semi-quantitative analysis of microcirculatory flow, as described, provides a reproducible and transparent tool in clinical research to monitor and evaluate the microcirculation during sepsis.


Immunogenicity and safety of an intradermal fractional third dose of ChAdOx1 nCoV-19/AZD1222 vaccine compared with those of a standard intramuscular third dose in volunteers who previously received two doses of CoronaVac: A randomized controlled trial.
The CoronaVac vaccine is widely used in Thailand to combat the coronavirus disease 2019 (COVID-19) pandemic. The limited immunogenicity of this vaccine is a concern, especially because of expanding delta variant outbreaks. A third boost may enhance antiviral immune responses. This non-inferiority randomized controlled trial evaluated the immunogenicity and safety of an intradermal (ID) fractional third dose of AZD1222 vaccine compared with those of a standard intramuscular (IM) third dose. Participants were enrolled from August 9, 2021 to August 13, 2021 at Chulabhorn Hospital, Bangkok, Thailand. The eligibility criteria were age 18 years or older and prior two-dose Coronavac vaccination completed at least 2 months previously. Participants were randomly assigned to one of three groups by block randomization: (i) standard dose by IM administration (IM), (ii) 20% of the standard dose ID (ID1), or (iii) 40% of the standard dose ID (ID2). The primary endpoint was the geometric mean ratio of anti-receptor binding domain antibody in the ID1/ID2 vs. the IM groups 14 days post-vaccination. A total of 125 participants were randomized (IM, n = 41; ID1, n = 41; and ID2, n = 43). One participant was lost to follow-up by day 14 post-vaccination in the ID1 group. The geometric mean ratio (95% confidence interval) of anti-receptor binding domain antibody was 0.94 (0.80-1.09) in the ID1 group and 1.28 (0.95-1.74) in the ID2 group. Immunogenicity in both ID groups met the non-inferiority criteria. Local adverse events were more common in the ID groups than in the IM group but were mostly mild to moderate in severity. An ID fractional third dose of AZD1222 was non-inferior to a standard IM third dose among individuals previously vaccinated with CoronaVac. Adverse events associated with the ID fractional third dose included mild to moderate local site reactions. This vaccination strategy may help conserve vaccine supply.


CircRNA SCMH1 regulates the miR-200a-3p/ZEB1 signaling axis to promote diabetes-induced retinal epithelial-mesenchymal transition.
Diabetic retinopathy (DR) is one of the common systemic complications of diabetes. Epithelial-mesenchymal transition (EMT) is required for DR progression. Previous studies have explored that circular RNAs (circRNAs) are crucial for DR development. Herein, we focused on the biological functions of circSCMH1 in DR. RT-qPCR determined the expression of circSCMH1, miR-200a-3p and ZEB1. EMT-related proteins were measured by Western blot. Gene combinations were validated by RIP and dual luciferase reporter assays. CCK-8, EdU, TUNEL staining and Transwell analysis were used to assess the cellular function. FISH analysis assessed the localization of circSCMH1 and miR-200a-3p. HE staining was used to detect retinal structures in a mouse DR model. High-glucose (HG) significantly increased circSCMH1 expression in ARPE-19 cells. Additionally, circSCMH1 silencing repressed proliferation, migration, and EMT in HG cells. Mechanistically, circSCMH1 positively regulated ZEB1 expression via targeting miR-200a-3p. Furthermore, circSCMH1 was observed to induce HG cell growth and EMT by regulating the miR-200a-3p/ZEB1 axis. Finally, we verified that downregulation of circSCMH1 or ZEB1 alleviated EMT in the retina of diabetic mice. These findings have implications for new therapeutic targets for DR.


Isolation and characterization of a tamoxifen-resistant cell line derived from MCF-7 human breast cancer cells.
A tamoxifen-resistant variant (R27) was selected by cloning wild type MCF-7 cells. R27 has the same growth rate as MCF-7 under optimal conditions. But tamoxifen has no effect on the growth rate (growth constant of R27 under control condition, 0.071 +/- 0.007 day-1; tamoxifen-treated cells, 0.073 +/- 0.011 day-1) and minimal effects on thymidine incorporation in R27, whereas tamoxifen has a strongly suppressive effect on the growth rate and thymidine incorporation in MCF-7. The estradiol-mediated stimulation of growth in R27 is somewhat less than in MCF-7 (growth constants of R27 and MCF-7 are 0.112 +/- 0.015 and 0.125 +/- 0.009 day-1, respectively. R27 contains unoccupied receptors in both cytoplasmic and crude nuclear extract fractions with slightly higher numbers of cytosol receptors than wild type MCF-7. The same dissociation constant and the same molecular weight estimated by Sephadex chromatography and the same sucrose density behavior were observed in R27 and MCF-7. Extent of competition with estradiol and tamoxifen for cytoplasmic estrogen receptor is the same for R27 and MCF-7. Induction of progesterone receptor following treatment with estradiol is the same for R27 and MCF-7. Estrogen receptor is activated by salt and nucleotide in both MCF-7 and R27; however, the extent of activation is much higher in MCF-7 than R27.


Two primary carcinomas of the lung: adenocarcinoma and a metachronous squamous cell carcinoma. A case report and review of the literature.
The case of a patient who underwent a left lower lobe lobectomy for adenocarcinoma of the lung and developed a metachronous squamous cell carcinoma of the right lung eight years later, is presented. The unusual nature of the case is emphasized utilizing a review of the literature. The criteria for diagnosing metachronous carcinomas are presented and a unified terminology for such cases is proposed. The requirement for life-long follow-up of any patient with cancer is emphasized.


Taurolithocholate can inhibit the biliary discharge of lysosomes in the rat.
The natural bile salt taurolithocholate (TLC) impairs the biliary excretion of lipids and proteins, which are known to reach the canaliculus via vesicles. In this study we examined whether these observations could be extended to the exocytic discharge of lysosomal contents into bile. The single intravenous injection of a cholestatic dose of TLC, 3 micromol/100 g body wt., markedly inhibited the biliary excretion of the lysosomal enzymes acid phosphatase and beta-glucuronidase, despite the excretion of bile salts being normalized after a transient diminution. Under such a condition, TLC did not affect the normal transport to and the processing in lysosomes of the exogenously administered [14C]sucrose-labeled horseradish peroxidase. However, the biliary excretion of the radioactive lysosomal metabolites of the protein was significantly reduced. The results indicate that TLC can inhibit the biliary discharge of lysosomes in the rat without altering the functional integrity of these organelles. Possible explanations for these findings are discussed.


Coordinate expression of the insulin-like growth factor system after microembolisation in porcine heart.
Coronary microembolisation in the pig heart induces angiogenesis in a model of sterile inflammation due to focal necrosis. We have recently shown in this model that insulin-like growth factor I (IGF-I) is involved in inflammation-linked angiogenic processes due to its enhanced transcription after 72 h of ischaemia by infiltrating monocytes in areas of microsphere-induced focal necrosis where capillary sprouting could be detected. To obtain further insights into this process we studied by means of Northern blot analysis and in situ hybridisation the gene expression of other members of the IGF family, i.e. the six IGF binding proteins (IGFBPs), the insulin receptor, and the type I IGF receptor. Myocardial injury was induced by injection of 25 microns non-radioactive microspheres into the left circumflex artery (LCx) in pigs that were killed after 3-24, 72, or 168 h of microembolisation. Tissue was collected from a non-ischaemic control area and the LCx region of the same heart for further analysis. We found decreased IGFBP-5 (2.7-fold; P < 0.02) mRNA concentrations after 72 h of microembolisation in ischaemic tissue versus control tissue from the same heart, preceded by a 1.9-fold elevated level of IGFBP-3 mRNA at 3-24 h (P < 0.05). IGFBP-6 was increased in ischaemic tissue at all time points studied. In situ hybridisation identified myocytes as the main producers of IGFBP-3 and IGFBP-6 mRNA. The mRNA levels of IGFBP-2, IGFBP-4, the insulin receptor, and the type I IGF receptor were constitutively expressed but did not change after microembolisation. Neither in heart nor in other organs studied transcripts of IGFBP-1 could be detected. Furthermore, we demonstrated that mRNA of the other components of the IGF system was expressed in almost all porcine organs except liver. These results indicate a coordinate gene expression of the IGF system in microembolised porcine myocardium, compatible with a role of IGF-I, IGFBP-3, IGFBP-5, and IGFBP-6 in inflammation-linked angiogenesis and/or repair processes.


The importance of housing conditions on behavioral sensitization and tolerance to ethanol.
The differential outcomes of social isolation and crowding environment on the effects of single or repeated administration of ethanol on open-field behavior were examined in female mice. Whereas housing conditions did not alter the increase in locomotor activity induced by ethanol single administration, behavioral sensitization (a progressive increase of a drug effect following repeated drug administration) to the locomotor activating effect of ethanol was significantly greater in crowded mice as compared to isolated and control groups. Single administration of ethanol significantly decreased rearing frequency and increased immobility duration, there being tolerance to these ethanol behavior effects after repeated treatment. Social isolation attenuated the increase in immobility behavior induced by single administration of ethanol and potentiated the tolerance of ethanol-induced rearing decrease, verified after repeated treatment. These results point out that both sensitization and tolerance to the behavioral effects of ethanol can be critically influenced by housing conditions.


Transverse cerebellar diameter in small-for-gestational-age fetuses: pregnancy dating is possible only when growth retardation is secondary to uteroplacental insufficiency.
The objective of this study was to establish whether measurement of the transverse cerebellar diameter to determine gestational age differs in small-for-gestational-age fetuses with normal or abnormal Doppler velocity waveforms. Our secondary objective was to compare the efficacy of measurement of transverse cerebellar diameter with that of femur length in pregnancy dating among small-for-gestational-age fetuses. A total of 107 small-for-gestational-age fetuses with established dates and free from structural and chromosomal abnormalities were considered for this study. According to the Doppler results, fetuses were divided into two groups: group A (n = 64), with normal Doppler values as expressed by a ratio of pulsatility indices between the umbilical artery and middle cerebral artery of <or= 95th centile of our reference limits for gestation; and group B (n = 43), with ratio of > 95th centile. Measurements of transverse cerebellar diameter and femur length were compared to previously established 95th centile prediction intervals. In both groups of small-for-gestational-age fetuses, the values for transverse cerebellar diameter were lower than in normally grown fetuses after normalization for gestational age. The difference was more evident in group A (p <or= 0.001) than in group B (p <or= 0.05). Only 68.7% of transverse cerebellar diameter values of group A fetuses fell within the normal limits for gestation, while this occurred in 90.6% of group B fetuses. When compared to the femur length, the transverse cerebellar diameter measurement appeared to be better for predicting gestational age in both groups of small-for-gestational-age fetuses (p <or= 0.001). However, this measurement may be used to estimate gestational age only in small-for-gestational-age fetuses with abnormal Doppler findings.


Overshooting tipping point thresholds in a changing climate.
Palaeorecords suggest that the climate system has tipping points, where small changes in forcing cause substantial and irreversible alteration to Earth system components called tipping elements. As atmospheric greenhouse gas concentrations continue to rise as a result of fossil fuel burning, human activity could also trigger tipping, and the impacts would be difficult to adapt to. Previous studies report low global warming thresholds above pre-industrial conditions for key tipping elements such as ice-sheet melt. If so, high contemporary rates of warming imply that exceeding these thresholds is almost inevitable, which is widely assumed to mean that we are now committed to suffering these tipping events. Here we show that this assumption may be flawed, especially for slow-onset tipping elements (such as the collapse of the Atlantic Meridional Overturning Circulation) in our rapidly changing climate. Recently developed theory indicates that a threshold may be temporarily exceeded without prompting a change of system state, if the overshoot time is short compared to the effective timescale of the tipping element. To demonstrate this, we consider transparently simple models of tipping elements with prescribed thresholds, driven by global warming trajectories that peak before returning to stabilize at a global warming level of 1.5 degrees Celsius above the pre-industrial level. These results highlight the importance of accounting for timescales when assessing risks associated with overshooting tipping point thresholds.


The noneffectiveness of neomycin ointment when used prophylactically following skin electrodesiccation and curettage.
Neomycin ointment is shown to be no more effective than placebo ointment in preventing site infection after biopsy according to a double-blind, placebo controlled study, analyzed according to an armitage restricted design, two-sided test, sequential analysis.


Psychological defence mechanisms in patients with pain.
There is a long standing position that pain, and especially chronic pain, may arise from psychological mechanisms of defence. We have compared a group of chronic pain patients with a sample of psychiatric patients attending for reasons other than pain. The pain group had less evidence of poor care in childhood (measured by the Parental Bonding Instrument) and tended to use more mature psychological defence mechanisms (assessed with the Defense Mechanisms Inventory), compared with the other group. The pain group also had fewer current psychiatric diagnoses but more evidence of anxiety and depression on the Hospital Anxiety and Depression Scale. We conclude that in general the patients with chronic pain had more normal childhoods and more mature defences than the psychiatric control group. They showed an increase in the diagnosis of depression, attributable to reactive factors. In the sample of patients with pain the majority of the psychological change cannot be attributed to the operation of primitive psychological defences.


Effect of Environmental Regulation on High-quality Economic Development in China-An Empirical Analysis Based on Dynamic Spatial Durbin Model.
In 2017, the 19th National Congress of the Communist Party of China put forward the concept of high-quality economic development, indicating that the Chinese economy has shifted from rapid growth to high-quality development. High-quality economic development is the growth mode of an innovation-driven economy, an innovative, high-efficiency, energy-saving, environmentally friendly, and high-value-added growth mode. Environmental regulation is an important means to solve economic development and environmental pollution and plays an important role in high-quality economic development. In order to explore the impact of China's environmental regulations on the high-quality economic development, this paper based on the panel data of 30 provinces (cities) in China from 2004 to 2015 uses the dynamic spatial Dubin model (DSDM) to analyze the direct and indirect effects of China's environmental regulations on high-quality economic development and regional heterogeneity. It also incorporates R&D (Research and Development) investment, government investment in environmental governance, and fiscal decentralization into the model and analyzes the direct and indirect effects of the above three factors in the process of environmental regulation affecting high-quality economic development. We found that China's high-quality economic development is spatially related between different provinces. And environmental regulations have obvious direct and indirect effects in the impact of high-quality economic development in the central and eastern regions, and this effect phenomenon is not significant in the western region. R&D investment, environmental protection investment, and fiscal decentralization have different adjustment effects on environmental regulation and high-quality economic development, and the same kind of adjustment variable also shows obvious heterogeneity among different regions. Finally, we put forward relevant policy recommendations based on the conclusions, with a view to improving China's high-quality economic development.


Access to prior spatial information.
In six experiments, reading times and probe naming times were measured in order to examine the conditions under which spatial information became accessible and/or reactivated. In Experiments 1-4, reading times were measured for target sentences containing spatial inconsistencies. Spatial inconsistencies did not disrupt processing (Experiment 1) unless there were increases in task demands (Experiment 2), elaboration of the protagonist's location (Experiment 3), or both (Experiment 4). In Experiments 5 and 6, naming times were measured to directly assess the activation of spatial information, specifically objects associated with a protagonist. Spatial information was highly active in memory immediately after being read and less active after four intervening sentences (Experiment 5), but explicit cues (e.g., location or object) as well as references to the current situation model were effective in reactivating previously mentioned spatial information (Experiment 6). The combined results of six experiments are discussed within the context of the RI-Val model.


A Comparative Evaluation of Iliac Crest Cortical-Cancellous Bone Blocks Graft With and Without Concentrated Growth Factors (CGFs) in Secondary Alveolar Bone Grafting: A Retrospective Study.
The purpose of this study was to investigate the clinical effect and bone resorption of iliac crest cortical-cancellous bone block grafts combined with concentrated growth factor (CGF) compared with iliac crest cortical-cancellous bone block grafts only in secondary alveolar bone grafting. Eighty-six patients (43 in the CGF group and 43 in the non-CGF group) with unilateral alveolar clefts were examined. Patients (17 in the CGF group and 17 in the non-CGF group) were randomly chosen for radiologic evaluation. Quantitative evaluation of the bone resorption rate was made with cone-beam computed tomography and Mimics 19.0 software at 1 week and 12 months after surgery. The success rate of bone grafting was 95.3% and 79.1% in the CGF and non-CGF groups, respectively ( P =0.025). The mean bone resorption rate at 12 months postoperatively was 35.66±15.80% and 41.39±19.57% in the CGF and non-CGF groups, respectively ( P =0.355). The bone resorption patterns of the 2 groups were similar on the labial, alveolar process, and palatal sides, and there was no obvious bone resorption on the labial side in either group. Nasal side bone resorption in the CGF group was significantly less than that in the non-CGF group ( P =0.047). Cortical-cancellous bone block grafts reduce labial bone resorption, while CGF reduces nasal bone resorption and improves the success rate. The combination of bone block and CGF in secondary alveolar bone grafting is worthy of further clinical application.


Concentration and surface of absorption: concepts and applications to gastrointestinal patches delivery.
Gastrointestinal patches represent a novel multiparticulate drug delivery system able to increase the intestinal absorption of drugs with poor bioavailability. The number of patches to administer is a critical issue since it is related to the surface and drug concentration at the absorption site. The objective of this article is to evaluate the effect of the number of administered patches on the final absorption of leuprolide, a peptide chosen as model drug, assuming complete adhesion of all the devices to the intestinal membrane. The same dose of leuprolide was encapsulated into 2, 4 and 6 patches; the resulting intestinal absorption profiles were measured with the Ussing chamber ex vivo experimental setup and compared between them. The results showed that varying the number of patches, the final absorption does not present statistically significant changes, indicating that changes in concentration are balanced by change in absorption surface. These experimental findings can also be explained considering the equation that links the drug flow to surface and concentration at the absorption site, showing that the drug flow is related only to the geometry of each individual patch.


LncRNA AB209371 up-regulated Survivin gene by down-regulating miR-203 in ovarian carcinoma.
AB209371 gene has been characterized as an oncogenic lncRNA in liver cancer. However, its involvement in ovarian carcinoma (OC) is unknown. In the present study, we analyzed the roles of AB209371 in OC. We found that AB209371 gene and Survivin gene were up-regulated in OC and positively correlated with OC development. AB209371 over-expression led to up-regulated Survivin in OC cells, while Survivin over-expression failed to affect AB209371. In addition, AB209371 over-expression led to down-regulated miR-203. However, miR-203 over-expression failed to affect AB209371, but down-regulated the expression of Survivin. In addition, over-expressions of AB209371 and Survivin resulted in the increased proliferation rate of OC cells. Over-expression MiR-203 played the opposite role and attenuated the effects of AB209371 over-expression. Therefore, AB209371 may down-regulate miR-203 to up-regulate Survivin, thereby promoting OC cell proliferation. Our study provided novel insights into the pathogenesis of OC.


Surgical, clinical, and functional outcomes of transoral robotic surgery used in sleep surgery for obstructive sleep apnea syndrome: A systematic review and meta-analysis.
We investigated safety and efficacy of transoral robotic surgery (TORS) for base of tongue (BOT) reduction in obstructive sleep apnea syndrome (OSAS) patients. PubMed, Cochrane Library, and Scopus were searched. A meta-analysis was performed. Random effects models were used. Thirty-one cohorts met our criteria (1693 patients). The analysis was based mostly on retrospective studies. The summary estimate of the reduction of Apnea-Hypoxia Index (AHI) was 24.25 abnormal events per hour (95% CI: 21.69-26.81) and reduction of Epworth Sleepiness Scale (ESS) was 7.92 (95% CI: 6.50-9.34). The summary estimate of increase in lowest O2 saturation was 6.04% (95% CI: 3.05-9.03). The success rate of TORS BOT reduction, either alone or combined with other procedures, was 69% (95% CI: 64-79). The majority of studies reported low level of evidence but suggested that TORS BOT reduction may be a safe procedure associated with improvement of AHI, ESS, and lowest O2 saturation.


Replication-Independent Generation and Morphological Analysis of Flavivirus Replication Organelles.
Positive-strand RNA viruses replicate in distinct membranous structures called replication organelles (ROs). Mechanistic studies of RO formation have been difficult because perturbations affecting viral replication have an impact on viral protein amounts, thus affecting RO biogenesis. Here, we present a detailed guide on how to use a replication-independent expression system, designated pIRO (plasmid-induced replication organelle formation), inducing bona fide flavivirus ROs in transfected cells. This will be useful for mechanistic studies of viral and cellular factors driving flavivirus RO biogenesis. For complete details on the use and execution of this protocol, please refer to Cerikan et al. (2020).


Supplying the sleeping brain.
During sleep, the brain experiences large fluctuations in blood volume and altered coupling between neural and vascular signals.


Immunoreactive thromboxane synthase is measurable in ovine fetal hypothalamus as early as 86 days' gestation.
Thromboxane A2 (TxA2) augments hypothalamus-pituitary-adrenal axis activity in both fetal and adult animals. We have proposed that TxA2 acts as a neuromodulator within the brain to stimulate the release of corticotropin releasing hormone (CRH) or arginine vasopressin (AVP) into the hypophyseal-portal blood. We performed the present experiments to identify immunoreactive thromboxane synthase (TxS) within fetal brain regions and to quantify developmental changes in the TxS immunoreactivity measurable within those regions. We found that immunoreactive TxS was present in fetal hypothalamus, pituitary, brainstem, and lung. In fetal hypothalamus, we found immunoreactive TxS in three identifiable molecular weights, approximately 65, 42, and 35 kD. In fetal pituitary and lung, we found the 65 and 35 kD forms, and in the brainstem we found only the 35 kD form. In fetal pituitary, there was a clear ontogenetic change in TxS immunoreactivity. The 42 kD TxS immunoreactivity was not present in the youngest fetal sheep studied (86-90 days' gestation), but was expressed in the other age groups (125-128, 135-139, 141-term, and postnatal ages). The other molecular weight forms appeared to increase in the older fetuses, but the changes were not significant. In the hypothalamus, all three forms of TxS were measurable at all ages, and there was no significant change in relative abundance. We conclude that immunoreactive TxS is present in the fetal brain throughout the last half of fetal gestation, but that the significance of multiple molecular weight forms is not clear.


Effects of prostaglandin inhibition on the bone activities associated with the spontaneous drift of molar teeth in the rat.
Little is known about local bone regulation that enables spontaneous molar tooth drift. In this study the role of prostaglandins (PGs) were investigated in the rat by inhibiting PG-synthesis with indomethacin (7 mg/kg/d). Untreated animals were killed at the start of the experiment, while treated ones were killed after 3, 7, or 14 days of treatment. Mandibles were processed for histomorphometry without demineralization. Changes in osteoclasts and extent of the different steps of the bone remodeling sequence (resorption, reversal, and formation) were assessed along the remodeling side of the socket of the buccal root of the first molar. The total number of osteoclasts decreased after 7 days of PG inhibition (P < 0.01 vs controls) and then partially recovered. This change was due to a sharp decrease in active cells on day 7 (P < 0.01), while inactive cells remained unchanged throughout the experimental period. The extent of resorption fell on day 7 (P < 0.01) and then recovered almost to the control level on day 14. Reversal at first increased insignificantly and thereafter decreased (P < 0.02) for the remaining 7 days. Formation was modified only on day 14; at that time it had doubled compared with controls. These results show that PGs are involved in the local regulation of bone remodeling accompanying tooth drift. Resorption inhibition was partial, indicating that other factors participate with PGs in this regulation; in addition, the trend to recovery observed at the end of the experimental period suggests that these factors can take over from PGs to achieve the necessary remodeling of the socket.


The effect of PM2.5-related hazards on biomarkers of bronchial epithelial cells (A549) inflammation in Karaj and Fardis cities.
Fine particles (especially PM2.5 particles) in ambient air can cause irreversible effects on human health. In the present study, seasonal variations in toxicity PM2.5 (cell viability and release of pro-inflammatory cytokines) were exposed human lung cells (A549) to concentrations of PM2.5 samples in summer (sPM2.5) and winter (wPM2.5) seasons. Cells were separately exposed to three concentrations of PM2.5 (25, 50, and 100 μg/mL) and three times (12 h, 1 and 2 days). We evaluated cell viability by MTT assay [3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide] and liberation of pro-inflammatory cytokines (interleukin-6 and interleukin-8) by the ELISA method. The toxicological results of this study showed that increasing the concentration of PM2.5 particulates and contact time with it reduces cell viability and increases inflammatory responses. Seasonal cytotoxicity of PM2.5 particles in high-traffic areas at summer season compared to winter season was lower. The lowest percent of viability at 2 days of exposure and 100 μg/mL exposure in the winter sample was observed. Also, PM2.5 particles were influential in the amount of interleukins 8 and 6. The average release level of IL-6 and IL-8 in the cold season (winter) and the enormous exposure time and concentrations (2 days-100 μg/mL) was much higher than in the hot season (summer). These values were twice as high for winter PM2.5 samples as for summer samples. The compounds in PM2.5 at different seasons can cause some biological effects. The samples' chemical characteristics in two seasons displayed that the PMs were diverse in chemical properties. In general, heavy metals and polycyclic aromatic hydrocarbons were more in the winter samples. However, the samples of wPM2.5 had a lower mass quota of metals such as aluminum, iron, copper, zinc, and magnesium. Concentrations of chromium, cadmium, arsenic, mercury, nickel, and lead were more significant in the sample of wPM2.5.


The Matilda Effect: Underrecognition of Women in Hematology and Oncology Awards.
The proportion of women in the field of hematology and oncology (H&O) has increased over recent decades, but the representation of women in leadership positions remains poor. In an effort to close the gender gap in academia, it is important to report on such inequities in hopes to close these gaps and improve career development. We conducted a retrospective, observational study of published award recipients from 1994 to 2019 from the seven major H&O societies in the world. Gender was determined based on publicly available data. The χ2 and Cochran-Armitage tests were used for data analysis. Of the 1,642 awardees over the past 26 years, 915 met inclusion criteria. Award recipients were overwhelmingly men (77.9%) and non-Hispanic White (84.7%). Women awardees received 30.3% of the humanistic and education-related awards, whereas only receiving 16.0% of basic science awards (p < .01). Women represent 35.6% of all hematologists and oncologists but only received 24.0% of awards given to these physicians (p = .004). Black, Hispanic, and Asian awardees represented 3.7%, 3.3%, and 6.8% of the total awardees, respectively. From 1994 to 2019, women were less likely to receive recognition awards from the seven major H&O societies studied compared with men. We also observed a considerably low proportion of minority awardees across all oncology subspecialties. Further studies examining how selection criteria favor either gender would be warranted in order to achieve equal representation in academic awards. In this study, women and minority groups were found to be underrepresented amongst award recipients. Significant disparities were seen in disciplines that have been historically male predominant, such as basic sciences. As awards on an international level enhance academic resumes and assist with career advancement, it is important that awards are being given in an equitable manner. First steps to promote diversity and inclusion in academic medicine is reporting of gender and racial disparities in various areas of academia.


[Anastomoses of the extrahepatic bile ducts with the duodenal stump (duodenocholecystostomy)].
The article generalizes the experience of 11 anastomoses between the bile ducts and the duodenal stump in patients previously operated for ulcer or cancer. These operations were performed in obstruction of the hepatocholedochus resulting from an accidental lesion of bile ducts during resection of the stomach or less frequently by choledocholithiasis, sclerosis of the pancreas head.


Indirect and intragenic suppression of the lexA102 mutation in E. coli B/r.
In Escherichia coli B/r the expression of UV inducible (SOS) functions is under the control of the recA and lexA genes. In this study we have characterized mutants which are altered in their ability to express SOS functions. These mutants were isolated as UV resistant UV nonmutable (Rnm) derivatives of the lexA102 uvrA155 mutant strain WP51. The UV resistance of these Rnm strains is a result of the suppression of lexA102 mediated UV sensitivity. Genetic mapping of rnm mutations shows that the two predominant classes, rnmA and rnmB, map in or very near the lexA and recA genes respectively. rnmA mutations differ from rnmB with regard to recA protein synthesis, rnmA mutations do not restore the ability to express high levels of recA protein after UV treatment whereas rnmB mutations result in constitutive expression of high levels of recA protein. However, both rnmA and rnmB mutant strains inhibit postirradiation DNA degradation. This shows that in rnmA strains, high levels of recA protein are not needed to inhibit postirradiation DNA degradation. The genetic map location and constitutive expression of recA protein synthesis resulting from rnmB mutations suggests that they are operator constitutive mutations of the recA gene. The result that the lexA+ gene is required for the expression of UV mutagenesis in rnmB mutants shows that high levels of recA protein do not circumvent the need for the lexA+ gene product in this process. Thus, while the lexA gene product is required for the induction of recA protein synthesis, lexA must have an additional role in UV induced mutagenesis.


Reflex delays of the trunk muscles in response to postural perturbations: a reliability study.
It has been reported that altered neuromuscular control of the trunk is associated with lower back pain. In this context reflex delays of the trunk muscles have often been assessed but the reliability of the tests has not been well established. The aim of this study was to test the reliability of measuring reflex delays of the trunk muscles after two types of postural perturbations. 24 Healthy subjects participated in the intra-session study and 13 of them repeated the test protocol within 1-3 weeks, to determine inter-session reliability. Postural reflex delays to unexpected loading and unloading of the arms were assessed in a standing unrestrained position. Each subject performed 40 trials of each test in order to evaluate muscle responses of 5 trunk muscles using surface electromyography. Overall reliability increased with higher number of the averaged trials. Good intra-session (ICC3,1>0.75) and moderate (ICC3,1>0.60) inter-session reliability were reached in most of the monitored trunk muscles. Within the performed number of trials we did not observe any significant systematic intra- or inter-session bias effect. Averaging a higher number of consecutive trials would be recommended in future research and clinical practice.