Fractionated half-body irradiation for pain palliation in widely metastatic cancers: comparison with single dose.
To explore fractionated half-body irradiation (HBI) for pain palliation and determine if it is more efficient and effective than single dose HBI. During the last 13 years, 75 out of 115 HBIs (64%) at the University of Maryland Medical Center were given for palliation of various widely metastatic cancers (28% prostate, 25% breast, 12% lung). The HBI fields were 28% upper, 25% mid, and 47% lower; three patients had both upper and lower HBI. An initial performance status (PS) 3&4 with a life expectancy < 3 months was found in 50% of patients. The HBI techniques used on consecutive patients were: single dose (SD) in 54% with escalating doses of 4-10 Gy; split-course (SC) in 12% with two 4 Gy single doses separated by 2 weeks; and daily fractionated (DF) in 34% with five fractions of 3 Gy each. There were 68 of 75 HBI (91%) given for pain control purposes. The percent total (complete) pain relief was SD-73(32), SC-50(13), and DF-96(49). Time to maximum and (complete) relief was: SD 5 days each and DF HBI 7(11) days. Pain-free survival (PFS) was short but so was overall survival (OS). PFS was SD-5, SC-4.5, and DF-19 weeks. The percent of the remaining patient's life spent pain free without retreatment (NPR) was SD-38, SC-34, and DF-68. Differences in pain relief, PFS, OS, and NPR were significant and carried over primary tumor types; prostate, breast, and surprisingly GI were very responsive (90, 84, and 83%, respectively). On multivariate analysis only the PS and degree of relief were independent variables. Despite lack of premedication in DF-HBI, toxic reactions were identical to SD-HBI with premedication. No Grade 4 toxicities occurred. Grade 3 toxicities were 4%. Retreatment was 3% in SD and 13% in fractionated HBI; these differences were not significant. HBI is still the most effective and efficient way to palliate pain from widely disseminated cancer. Fractionating HBI eliminates need for the premedication and close patient monitoring required for SD-HBI. It also allows for an increase in total dose which can produce better responses in pain relief, duration of relief, PFS, OS, and quality of life.


COVID-19: Brain Effects.
Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for the coronavirus disease (COVID-19), affects the brain. Neurologic and neuropsychiatric symptoms may manifest in the acute and post-acute phases of illness. The vulnerability of the brain with aging further increases the burden of disease in the elderly, who are at the highest risk of complications and death from COVID-19. The mechanisms underlying the effects of COVID-19 on the brain are not fully known. Emerging evidence vis-à-vis pathogenesis and etiologies of COVID-19 brain effects is promising and may pave the way for future research and development of interventions.


Bacterial inoculation positively affects the quality and quantity of flax under deficit irrigation regimes.
The present research was conducted to investigate the effect of plant growth-promoting rhizobacteria (PGPR) and deficit irrigation on quality and quantity of flax under field and pot conditions to determine bacterial efficiency and to decrease water deficit effects. Initially, in vitro experiments were performed to determine the growth-promoting characteristics of bacteria. Then in the field, the effects of bacterial inoculation (control, Azotobacter chroococcum, Azospirillum lipoferum, Bacillus amyloliquefaciens, Bacillus sp. strain1 and Pseudomonas putida) on flax traits were evaluated at different irrigation levels (100, 75 and 50% crop water requirement). Bacterial treatments in the pot experiment were selected based on the field experiment results. The irrigation regimes in the pot and field experiments were the same and bacterial treatments included single, doublet and triplet applications of the bacteria. All the bacterial strains could solubilize phosphate, produce ammonia (except for Bacillus sp. strain1), indole acetic acid and siderophore (except P. putida). Field results indicated that the bacteria significantly mitigated the effects of water deficit. Compared with control plants, bacterial treatments increased the oil, linolenic acid, protein and sulphur content; the number of shoots and capsules; and the harvest index in the flax plants. Pot experimental results revealed that the combined inoculations were more effective than single inoculum treatments. Bacterial inoculation alleviates deficit irrigation effects in flax plants. The effectiveness of applying A. chroococcum, B. amyloliquefaciens and Bacillus sp. strain1 was confirmed, especially as a combination to protect flax against water deficit and to improve its nutritional quality and growth.


Solitary congenital Langerhans cell histiocytoma: A pattern of benign, spontaneous regression in patients with single lesion disease.
Langerhans cell histiocytosis (LCH) is the neoplastic proliferation of dendritic langerin-positive histiocytes manifesting as either single system unifocal, single system multifocal, or multisystem disease. The designation Hashimoto-Pritzker, or self-healing LCH, has fallen out of favor since it is impossible to predict at time of diagnosis whether the disease is truly self-remitting or capable of spreading to other organ systems. We review the English literature on solitary congenital Langerhans cell histiocytoma, draw novel conclusions from the data provided by 81 cases in the literature, and illustrate a typical presentation of the diagnosis with a previously unreported patient. Each of the patients diagnosed with solitary congenital histiocytoma experienced spontaneous resolution and had no signs of systemic disease at latest follow-up. Furthermore, we offer an analysis of the histopathological findings available from the 81 cases and our patient. Based on our study observations, we propose solitary congenital Langerhans cell histiocytoma may portend a good prognosis and represent a distinct entity. However, until further confirmation with prospective studies, we recommend clinicians continue conducting appropriate workup to rule out systemic involvement.


In silico modelling and characterization of eight blast resistance proteins in resistant and susceptible rice cultivars.
Nucleotide-binding site-leucine-rich repeat (NBS-LRR) resistance genes are the largest class of plant resistance genes which play an important role in the plant defense response. These genes are better conserved than others and function as a recognition-based immune system in plants through their encoded proteins. Here, we report the effect of Magnaporthe oryzae, the rice blast pathogen inoculation in resistant BR2655 and susceptible HR12 rice cultivars. Transcriptomic profiling was carried out to analyze differential gene expression in these two cultivars. A total of eight NBS-LRR uncharacterized resistance proteins (RP1, RP2, RP3, RP4, RP5, RP6, RP7, and RP8) were selected in these two cultivars for in silico modeling. Modeller 9.22 and SWISS-MODEL servers were used for the homology modeling of eight RPs. ProFunc server was utilized for the prediction of secondary structure and function. The CDvist Web server and Interpro scan server detected the motif and domains in eight RPs. Ramachandran plot of eight RPs confirmed that the modeled structures occupied favorable positions. From the present study, computational analysis of these eight RPs may afford insights into their role, function, and valuable resource for studying the intricate details of the plant defense mechanism. Furthermore, the identification of resistance proteins is useful for the development of molecular markers linked to resistance genes.


[Effect of nonachlazine on the adenylate cyclase system of the rabbit heart].
The influence of nonachlazine on the adenylate cyclase system of the rabbit heart was investigated. The faint beta-blocking activity (displacement of up to 20% of [3H]-dihydroalprenolol and inhibition of isoproterenol-stimulated activity) as well as the ability to stimulate basal activity in micromolar concentrations has been observed. Such combination of properties may be important in the realization of some positive effects of nonachlazine pharmacological activity.


Anticipation of radiation dose to the conceptus from occupational exposure of pregnant staff during fluoroscopically guided electrophysiological procedures.
Conceptus dose from occupational exposure. A female employee working in the electrophysiology suite has the right to know potential radiation hazards to the unborn child before she is pregnant or before she decides to formally declare her pregnancy. Moreover, the employer of a declared pregnant worker must evaluate the work situation and ensure that the conceptus dose is kept below the maximum permissible level during the remaining gestation period. The aim of this study was to develop a method for conceptus dose anticipation and determination of maximum workload allowed for the pregnant employee who participates in fluoroscopically guided electrophysiological procedures. A C-arm fluoroscopy system, an anthropomorphic phantom, and a radiation meter were used to obtain scattered air kerma dose rates separately for each of the three fluoroscopic projections typically used in the electrophysiology suite. Air kerma to conceptus dose conversion factors for all trimesters of gestation were calculated using Monte Carlo simulation. A formula is presented for the anticipation of the conceptus dose from occupational exposure of pregnant staff during fluoroscopically guided electrophysiological procedures. Normalized data are provided for conceptus dose estimation from occupational exposure of pregnant staff working in any electrophysiology laboratory. A methodology for estimation of maximum workload allowed for each month of the remaining gestation period of a worker who declared her pregnancy is proposed, which ensures that the regulatory dose limits are not exceeded. Data presented may be used for the implementation of a radiation protection program designed for pregnant staff working in an electrophysiological suite.


Trypanosoma brucei: susceptibility to hydrogen peroxide and related products of activated macrophages.
The susceptibility of procyclic, trypsinized, or bloodstream forms of Trypanosoma brucei to lysis by hydrogen peroxide and by activated mouse macrophages was investigated in vitro using the release of biosynthetically labeled proteins as an assay. Uncoated parasites were more resistant than coated bloodstream forms in both cases. Macrophage trypanolysis upon triggering with phorbol myristate acetate occurred extracellularly and seemed to depend on the release of hydrogen peroxide, as it was prevented by catalase. However, when presented trypanosomes in presence of fresh immune serum which was itself lytic, macrophages did not show any additional lytic effect, and phagocytosis was related to already damaged parasites.


The ventilatory response to hypoxia is blunted in some preterm infants during the second year of life.
Preterm birth and subsequent neonatal ventilatory treatment disrupts development of the hypoxic ventilatory response (HVR). An attenuated HVR has been identified in preterm neonates, however it is unknown whether the attenuation persists into the second year of life. We investigated the HVR at 12-15 months corrected postnatal age and assessed predictors of a blunted HVR in those born very preterm (<32 weeks gestation). HVR was measured in infants born very preterm. Hypoxia was induced with a three-step reduction in their fraction of inspired oxygen (FIO2) from 0.21 to 0.14. Respiratory frequency (f), tidal volume (V T), minute ventilation (V E), inspiratory time (t I), expiratory time (t E), V T/t I, tI/t TOT, V T/t TOT, area under the low-volume loop and peak tidal expiratory flow (PTEF) were measured at the first and third minute of each FIO2. The change in respiratory variables over time was assessed using a repeated measures ANOVA with Greenhouse-Geisser correction. A blunted HVR was defined as a <10% rise in V E, from normoxia. The relationship between neonatal factors and the magnitude of HVR was assessed using Spearman correlation. Thirty nine infants born very preterm demonstrated a mean (SD) HVR of 11.4 (10.1)% (increase in V E) in response to decreasing FIO2 from 0.21 to 0.14. However, 17 infants (44%) failed to increase V E by ≥10% (range -14% to 9%) and were considered to have a blunted response to hypoxia. Males had a smaller HVR than females [ΔV E (-9.1%; -15.4, -2.8; p = 0.007)]. Infants surviving very preterm birth have an attenuated ventilatory response to hypoxia that persists into the second year of life, especially in males.


Degrading FLT3-ITD protein by proteolysis targeting chimera (PROTAC).
Clinical FLT3 mutations caused poor therapeutic benefits toward the present FLT3 inhibitors, and degradation of the FLT3 mutant protein may be a promising alternative approach to protect against acute myeloid leukemia (AML). Herein, we report the discovery of small molecule FLT3 degraders based on the proteolysis targeting chimera (PROTAC). FLT3 degraders were designed, synthesized, and evaluated for FLT3 degradation. Promising PF15 significantly inhibited the proliferation of FLT3-ITD-positive cells, induced FLT3 degradation and downregulated the phosphorylation of FLT3 and STAT5. An in vivo xenograft model and survival period evaluation verified the efficacy of PROTAC. These findings laid a robust foundation for FLT3-PROTAC molecules as an effective strategy for treating AML.


Anti-vaccination movements and their interpretations.
Over the last two or three decades, growing numbers of parents in the industrialized world are choosing not to have their children vaccinated. In trying to explain why this is occurring, public health commentators refer to the activities of an anti-vaccination 'movement'. In the light of three decades of research on (new) social movements, what sense does it make to attribute decline in vaccination rates to the actions of an influential anti-vaccination movement? Two sorts of empirical data, drawn largely from UK and The Netherlands, are reviewed. These relate to the claims, actions and discourse of anti-vaccination groups on the one hand, and to the way parents of young children think about vaccines and vaccination on the other. How much theoretical sense it makes to view anti-vaccination groups as (new) social movement organizations (as distinct from pressure groups or self-help organizations) is as yet unclear. In any event there is no simple and unambiguous demarcation criterion. From a public health perspective, however, to focus attention on organized opponents of vaccination is appealing because it unites health professionals behind a banner of reason. At the same time it diverts attention from a potentially disruptive critique of vaccination practices; the critique in fact articulated by many parents. In the light of current theoretical discussion of 'scientific citizenship' this paper argues that identifying anti-vaccination groups with other social movements may ultimately have the opposite effect to that intended.


Applicability of the Global Lung Function Initiative prediction equations in Hong Kong Chinese children.
This study aimed to assess the applicability of the Global Lung Function Initiative (GLI) prediction equations for spirometry in Hong Kong children and to develop prediction equations based on the Generalized Additive Models for Location, Scale, and Shape (GAMLSS) modeling. Healthy Chinese children and adolescents aged 6-17 years old were recruited from randomly selected schools to undergo spirometry. The measurements were transformed to z-score according to the GLI-2012 equations for South East (SE) Asians and the GLI-2022 global race-neutral equations. Prediction equations for spirometric indices were developed with GAMLSS modeling to identify predictors. A total of 886 children (477 boys) with a mean age of 12.5 years (standard deviation [SD] 3.3 years) were included. By the GLI-2012 SE Asian equations, positive mean z-scores were observed in forced expiratory volume in 1 s (FEV1 ) (boys: 0.138 ± SD 0.828; girls: 0.206 ± 0.823) and forced vital capacity (FVC) (boys: 0.160 ± 0.930; girls: 0.310 ± 0.895) in both sexes. Negative mean z-scores were observed in FEV1 /FVC ratio (boys: -0.018 ± 0.998; girls: -0.223 ± 0.897). In contrast, negative mean z-scores in FEV1 and FVC, and positive mean z-scores in FEV1 /FVC were observed when adopting the GLI-2022 race-neutral equations. The mean z-scores were all within the range of ±0.5. By GAMLSS models, age and height were significant predictors for all four spirometric indices, while weight was an additional predictor for FVC and FEV1 . Our study provided data supporting the applicability of the GLI prediction equations in Hong Kong Chinese children. The GLI-2012 equations may underestimate FEV1 and FVC, while the GLI-2022 equations may overestimate the parameters, but the differences lie within the physiological limits. By GAMLSS modeling, weight was an additional predictor for FVC and FEV1 .


In vivo endogenous proteolysis yielding beta-casein derived bioactive beta-casomorphin peptides in human breast milk for infant nutrition.
Objective Beta-casein is a major protein in breast milk and an important source for several bioactive peptides that are encrypted within the sequence. Beta-casomorphins (BCMs) are short-chain proteolytic peptides that are derived from the beta-casein protein and have opioid effects in newborns. Human milk is known to contain naturally occurring milk-protein-derived bioactive peptides but the identification of naturally occurring beta-casein-derived BCMs in human breast milk has been limited due to difficulties in the detection of BCM peptides, which are small and circulate in low concentrations. Methods The present study aimed to identify the naturally occurring BCM peptides from beta-casein in human breast milk using liquid chromatography-tandem mass spectrometry. The BCM peptides identified in the breast milk were analysed to predict the milk proteases responsible for the cleavage patterns using a computational tool EnzymePredictor. Results In-depth peptidomics analysis of breast milk samples that were collected at different lactation stages during human lactation revealed the presence of BCMs including BCM-8, -9, -10, and -11 as well as precursors and truncated forms of the original peptide, which suggests that milk protease activity in the mammary gland generates biologically relevant BCMs. Conclusions To our knowledge, this is the first report to describe the presence of naturally occurring human BCM-10 and -11 in breast milk. Our study provides evidence of beta-casein-derived BCM peptides in human milk before infant digestion. Proteases that are present in milk are likely specific in their proteolysis of beta-casein. The identified bioactive BCM-8, -9, -10, and -11 as well as the precursor peptides meet the structural requirements to elicit opioid, immunomodulatory, antioxidative, and satiety functions in newborns.


Hormonal regulation of membrane receptors and cell responsiveness: a review.
Hormone receptors are those components of target-cells that specifically bind hormones and convey the hormonal message to the intracellular machinery. Such receptors can be localized inside the cell, such as the nuclear receptors of thyroid hormones and the nuclear and cytoplasmic receptors of steroid hormones, or on the outer surface of the plasma membrane, such as the membrane-bound receptors of polypeptide hormones and neurotransmitters. Extensive studies during recent years have shown that the interaction between hormone and membrane-bound receptor can affect the receptor characteristics in at least two ways. Firstly, receptor occupancy can modify, by way of cooperativity, the affinity of homologue receptors for the given hormone. Secondly, the binding capacity of a target cell appears to vary as a function of the preexposure of the cell to the hormone. The latter phenomenon has been related to the so-called states of subsensitivity, desensitization, or refractoriness, and might be responsible for the physiologic regulation of the target cell sensitivity and for the hormone resistance which accompanies various metabolic disorders. In this review we attempt to describe the major findings related to hormone desensitization or resistance of these hormones that have plasma-membrane-bound receptors. Data from the literature are presented independently for each hormone and when applicable, conflicting results are discussed in each section. The various theories which might explain hormone desensitization are outlined in the last section of this paper.


Manipulating the nature of embryonic mitotic waves.
Early embryogenesis is characterized by rapid and synchronous cleavage divisions, which are often controlled by wave-like patterns of Cdk1 activity. Two mechanisms have been proposed for mitotic waves: sweep and trigger waves.1,2 The two mechanisms give rise to different wave speeds, dependencies on physical and molecular parameters, and spatial profiles of Cdk1 activity: upward sweeping gradients versus traveling wavefronts. Both mechanisms hinge on the transient bistability governing the cell cycle and are differentiated by the speed of the cell-cycle progression: sweep and trigger waves arise for rapid and slow drives, respectively. Here, using quantitative imaging of Cdk1 activity and theory, we illustrate that sweep waves are the dominant mechanism in Drosophila embryos and test two fundamental predictions on the transition from sweep to trigger waves. We demonstrate that sweep waves can be turned into trigger waves if the cell cycle is slowed down genetically or if significant delays in the cell-cycle progression are introduced across the embryo by altering nuclear density. Our genetic experiments demonstrate that Polo kinase is a major rate-limiting regulator of the blastoderm divisions, and genetic perturbations reducing its activity can induce the transition from sweep to trigger waves. Furthermore, we show that changes in temperature cause an essentially uniform slowdown of interphase and mitosis. That results in sweep waves being observed across a wide temperature range despite the cell-cycle durations being significantly different. Collectively, our combination of theory and experiments elucidates the nature of mitotic waves in Drosophila embryogenesis, their control mechanisms, and their mutual transitions.


Potentially deleterious effect of cornstarch glove powder in tubal reconstructive surgery.
Even with the most painstaking techniques, cornstarch granules used as surgical glove powder are deposited in the abdominal cavity during laparotomy. In tubal reconstructive surgery, aimed at the elimination of fibrous adhesions, this deposition may have undesirable consequences. After a successful operation, starch particles introduced in the abdominal cavity may result in the formation of new adhesions. It is therefore desirable to develop an alternative, completely nonreactive, glove powder.


Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study.
Fifty patients affected by histologically confirmed gastrointestinal tract cancer (GTC) were treated with oral tegafur (TG) 1,000 mg m-2 p.o. on days 1-14 repeated after a 14 day interval. Out of 42 evaluable patients seven patients had a partial response (PR. 17%) with a median duration of 20.5 weeks, three had a minimal response (7%) with a median duration of 23.7 weeks, nine showed a stabilisation which lasted a median of 31.3 weeks, and 23 progressed (55%). No response was obtained in patients affected by carcinoma of the pancreas and the hepatobiliary system. All PRs were achieved in patients with metastatic disease to the liver. No response was seen in patients with bone, lung or nodal metastasis. Three PRs were obtained in patients resistant to 5-fluorouracil. The difference in survival between patients who achieved PR and those who had a stabilisation was not statistically significant. On the other hand the survival of patients with PR was significantly longer than that of patients who progressed. Oral TG was well tolerated by most patients. WHO grade 1-2 gastrointestinal and neurological toxicities were seen respectively in 36% and 25% of cases. Five patients had grade 3 nausea/vomiting and one had grade 3 diarrhoea. Our data suggest that oral TG is effective in the treatment of stomach and colorectal cancers.


Robot-assisted thoracoscopic brachytherapy for lung cancer: comparison of the ZEUS robot, VATS, and manual seed implantation.
Interstitial brachytherapy is becoming an accepted treatment option for lung cancer patients for whom surgery poses a high risk. Robotic surgery has the potential to deliver brachytherapy seeds into tumors while keeping surgeons at a safe distance from the radioactive source. Our aim was to compare the accuracy, number of attempts, and time needed to place seeds next to a target when using a manual technique, video-assisted thoracoscopic surgery (VATS), and the ZEUS robot for minimally invasive surgery (MIS). A brachytherapy seed injector was developed and attached to one of the ZEUS robotic arms. Four subjects each inserted inactive dummy brachytherapy seeds into clear agar-gelatin cubes containing a 1.6-mm stainless steel ball target. Two orthogonal radiographs were taken of each agar cube, and the corresponding distances were measured in triplicate using ImageJ processing software. The mean distance between the center of each seed and the corresponding target was calculated using the Pythagorean theorem. Comparisons were made using analysis of variance, t-tests, and Kruskal-Wallis tests, as appropriate. A total of 384 tests (128 for each technique) were performed. The median accuracies for the manual technique, VATS, and ZEUS were 1.8 mm (range: 0.9-6.7 mm), 2.4 mm (range: 1.0-11.3 mm), and 3.6 mm (range: 1.3-16.7 mm), respectively (p < 0.01). The median numbers of attempts for the manual technique, VATS, and ZEUS were 1 (range: 1-5), 4 (range: 1-14), and 3 (range: 1-20), respectively (p < 0.01). The median times for the manual technique, VATS, and ZEUS were 3.0 s (range: 1-43 s), 86.5 s (range: 6-372 s), and 64.5 s (range: 5-356 s), respectively (p < 0.01). The manual technique is the most accurate, least traumatic, and fastest method of inserting seeds into tumors. The ZEUS robotic platform was able to place seeds beside a target within a clinically acceptable distance, with an acceptable amount of trauma and time required. It achieved results equal to or better than those obtained with VATS.


Pulse velocities in initially stressed arteries.
In this short paper, treating the artery as a thick walled cylindrical shell and employing the large deformation theory, an analytical expression for the pulse wave speed is obtained and the effect of lumen pressure and the axial stretch on the wave speed is discussed. Numerical results indicate that although the wave speed increases with inner pressure, it decreases with increasing axial stretch.


Varying water column stability controls the denitrification process in a subtropical reservoir, Southwest China.
Reservoirs are regarded as hotspots of nitrogen transformation and potential sources of nitrous oxide (N2O). However, it remains unclear how the hydrological conditions due to dam construction control the processes of nitrogen transformation in reservoir waters. To address this issue, we examined the spatial-temporal characteristics of nitrate concentrations, δ15N-NO3-, δ18O-NO3-, δ18O-H2O, relative water column stability (RWCS), and related environmental factors in a subtropical eutrophic reservoir (Hongfeng Reservoir, HFR), Southwest China. We found that denitrification was the most important nitrogen transformation process in the HFR and that higher denitrification intensity was associated with increased RWCS in summer, which suggested hydrological control of the denitrification process. In contrast, low RWCS conditions favored the nitrification process in the HFR in winter. Additionally, dissolved oxygen (DO; p < 0.05) and nitrate concentrations (p < 0.01) had significant impacts on the denitrification rate. We also found that the spatiotemporal RWCS variations were a prerequisite for regulating DO/nitrate stratification and the coupling/decoupling of nitrification-denitrification at the local and global scales. This study would advances our knowledge of the impacts of RWCS and thermal stratification on nitrogen transformation processes in reservoirs.


Comparison of the pattern of metastatic spread of squamous cell cancer and adenocarcinoma of the uterine cervix.
Retrospective review of medical records and autopsy findings in patients dying of squamous cell cancer or adenocarcinoma of the uterine cervix was undertaken to evaluate for possible differences in biologic behavior between these tumor types. Twenty-one patients with each tumor type were evaluated. Patients with adenocarcinoma were found to have a higher incidence of tumor involvement of the paraaortic lymph nodes (13/21 vs 6/20, P less than 0.05), uterine corpus (17/17 vs 12/20, P less than 0.05), and adrenal gland (7/21 vs 0/21, P less than 0.005). Presence of ascites (9/21 vs 2/21, P less than 0.05) and hydrothorax (9/21 vs 3/21, P less than 0.05) was also significantly more frequent in patients with adenocarcinoma. These findings suggest that this tumor may behave differently in regard to pattern of metastatic spread or response to therapy. The therapeutic implications of these findings deserve further study.


Fabrication and pH-Sensitivity Analysis of MOS-HEMT Dimensional Variants for Bio-Sensing Applications.
This work reports the fabrication, characterization and testing for pH sensitivity of dielectric modulated MOS-HEMT(Metal oxide semiconductor- high electron mobility transistor) devices for bio-sensing applications. The primary aim here is to develop high sensing devices for bio-detections. The oxide based gate area is used in ensuring the device performance through pH detection done prior to packaging and metal probing. Device parameters; gate length LG, gate width WG, gate spacing from source-drain ends, LSG and LGD have been varied to investigate the effect on pH sensitivity. The HEMT stack with AlN spacer has been grown through MOCVD (Metal-Organic Chemical Vapor Deposition) technique with no intentional doping on Si (silicon) substrate. Commercial buffer samples for pH values of 4, 7, 9.2 have been used to test the devices using drop casting technique. Drain current (ID) based sensitivity analysis shows that the device having ( [Formula: see text], [Formula: see text] and [Formula: see text]) exhibits a maximum sensitivity of 3.361 mA/pH. The devices exhibit exemplary performance when device dimensions meet the following constraints i.e. LSG: minimum, LG: moderate and LGD > 2*LSG. Average sensitivities attained is in the range 1.69 mA/pH for a device with [Formula: see text], [Formula: see text] and [Formula: see text].


Muscarinic acetylcholine receptor-mediated increase of angiotensin type 2 receptor mRNA in PC12 cells.
The present study examined changes in the angiotensin type 2 (AT2) receptor mRNA level after carbachol exposure in PC12 cells. The AT2 receptor mRNA level increased 2- to 3-fold after 12-18 h of carbachol exposure (100 microM). The up-regulation of AT2 receptor mRNA was antagonized by atropine, which is a muscarinic receptor antagonist, thus suggesting that the increase in AT2 receptor mRNA is mediated via muscarinic acetylcholine receptors. This increase is blocked by NG-nitro-L-arginine-methylester, nitric oxide (NO) synthase inhibitor, and hemoglobin NO trap. Protein kinase C (PKC) inhibitors, H-7 and calphostin C, inhibited the carbachol-induced upregulation. In addition, a G kinase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), inhibited this increase. These findings suggest that the carbachol-induced increases in AT2 receptor mRNA is regulated by the activation of NO-cGMP and/or the PKC pathway.


Biceps tendon subluxation associated with isolated greater tuberosity fracture and bony Bankart lesion without a Hill-Sachs lesion: A case report and review of the literature.
Combined injuries of the glenohumeral joint that involve biceps tendon subluxation associated with isolated greater tuberosity fracture and bony Bankart lesion are extremely rare. As per our knowledge, this is the first case report that includes such combined injuries that were treated arthroscopically. We present the case of a 48-year-old male patient who sustained shoulder trauma after being thrown against the rocks by a wave, was found to have biceps tendon subluxation associated with isolated greater tuberosity fracture and bony Bankart lesion. The operative management resulted in complete restoration of the range of motion of the shoulder, and uneventful healing of the fracture. The patient recovered normal activity including his surfing.


Purification and characterization of two exopolyphosphatases from the marine sponge Tethya lyncurium.
Two exopolyphosphatases (exopolyphosphatase I and II; EC 126.96.36.199) which release orthophosphate from inorganic polyphosphates have been detected and purified for the first time from a marine sponge. Tethya lyncurium. Exopolyphosphatase I has a molecular mass of 45 kDa, a pH optimum of 5.0 and does not require divalent cations for activity, while exopolyphosphatase II has a molecular mass of 70 kDa, a pH optimum of 7.5 and displays optimal activity in the presence of Mg2+ ions. Final purification of the enzymes could be achieved by affinity chromatography on polyphosphate-modified zirconia. The mode of action of both enzymes was found to be processive. Orthophosphate is the sole product formed by exopolyphosphatase I, while degradation of linear polyphosphates by exopolyphosphatase II occurs to pyrophosphate as end product, which is hydrolyzed, if at all, only very slowly. Significant amounts of polyphosphate (approximately 30 micrograms/g wet weight) were found to be present in the sponge organism. Polyphosphate is shown to inhibit the formation of ATP by adenylate kinase activity present in T. lyncurium extracts in a competitive manner. The inhibitory effect of long-chain polyphosphates was higher than that of short-chain polyphosphate, suggesting a potential role of polyphosphate metabolism in regulating intracellular concentrations of adenylate nucleotides.


Effects of smoking on fetoplacental-maternal system during pregnancy.
Fetoplacental function and maternal nutritional condition were assessed in order to clarify the mechanism of retarded fetal growth in pregnant women who smoked. Dehydroepiandrosterone sulfate (DHA-S) loading tests and measurements of cotinine, which is a major metabolite of nicotine, were also made. In heavy smokers, urinary estriol and serum levels of human placental lactogen (hPL) were lower than those in nonsmokers. There was no difference in maternal nutrition between smokers and nonsmokers. Heavy smokers demonstrated a lower conversion of DHA-S to estradiol than did nonsmokers. Levels of cotinine in maternal blood and umbilical cord blood of heavy smokers were remarkably higher than those in nonsmokers. Microscopic examination showed atrophic and hypovascular changes in placental villi from mothers who smoked. These results suggest that retarded fetal growth in heavy smokers is due to impairment of uteroplacental circulation as a result of the vasoconstricting effect of nicotine.


Enhancement of hyperthermia-induced apoptosis by non-thermal effects of ultrasound.
To determine the effect of ultrasound on hyperthermia-induced apoptosis, we exposed U937 cells (in air-saturated suspension) to continuous 1 MHz ultrasound at intensities 0.5 or 1.0 W/cm(2), considered non-thermal and sub-threshold for inertial cavitation, while at 44.0 degrees C for 10 min. We found that 0.5 W/cm(2), in combination with hyperthermia, synergistically induced apoptosis. On the other hand, 1.0 W/cm(2) in combination with hyperthermia showed an augmented instant cell lysis but no significant change in the ratio of apoptosis. This result might be useful when apoptosis induction is desired over instant cell killing in cancer therapy.


A survey on advanced machine learning and deep learning techniques assisting in renewable energy generation.
The sustainability of the earth depends on renewable energy. Forecasting the output of renewable energy has a big impact on how we operate and manage our power networks. Accurate forecasting of renewable energy generation is crucial to ensuring grid dependability and permanence and reducing the risk and cost of the energy market and infrastructure. Although there are several approaches to forecasting solar radiation on a global scale, the two most common ones are machine learning algorithms and cloud pictures combined with physical models. The objective is to present a summary of machine learning-based techniques for solar irradiation forecasting in this context. Renewable energy is being used more and more in the world's energy grid. Numerous strategies, including hybrids, physical models, statistical approaches, and artificial intelligence techniques, have been developed to anticipate the use of renewable energy. This paper examines methods for forecasting renewable energy based on deep learning and machine learning. Review and analysis of deep learning and machine learning forecasts for renewable energy come first. The second paragraph describes metaheuristic optimization techniques for renewable energy. The third topic was the open issue of projecting renewable energy. I will wrap up with a few potential future job objectives.


Solitary and combined negative influences of diabetes, obesity and hypertension on health-related quality of life of elderly individuals: A population-based cross-sectional study.
The health-related quality of life (HRQoL) is a matter of concern in elderly people with chronic diseases. The objective of this study was to investigate the impact of obesity, hypertension and diabetes on HRQoL among elderly. A population based cross sectional study was conducted with 750 representative sample of elderly people aged 60-90 years in Babol, the northern Iran. The demographic data and the measurement of blood pressure and other anthropometric measures were collected. The validated short form (SF-36) questionnaire was used to assess the HRQoL. A multiple linear regression model was applied to assess the impact of obesity, abdominal obesity, hypertension and diabetes on QoL. The mean age (SD) of participants was 68.0±7.6 and 67.7±7.9 years for men and women respectively. Diabetes exerted the most negative effect on QoL score (adjusted coefficient=-9.2, 95% CI: -11.7, -6.5 points) followed by abdominal obesity and hypertension. Whereas a combination of three conditions was associated with a greater significant reduction in QoL scores in both sexes(adjusted coefficient=-14.5, 95% CI: -19.0, -9.9 points). However, the negative influence of obesity and hypertension on QoL was significant only in women. Most components of the QoL is affected by diabetes, obesity and hypertension particularly in women. Diabetes alone or in combination with other conditions has a negative influence in both sexes with greater effect in women. These findings justify further professional support to compensate the negative influences chronic conditions on health-related QoL especially for older obese diabetic women.


Cryoablation inhibits the recurrence and progression of bladder cancer by enhancing tumour-specific immunity.
Recurrence and metastasis of bladder cancer are major factors affecting patient prognosis. Endoscopic cryoablation achieved a better clinical outcome among clinical patients and could be synergistic with ICIs. Thus, this study aimed to evaluate the immunological mechanism of cryoablation for bladder cancer to reveal the therapeutic mechanism. We systematically reviewed the clinical prognosis of patients underwent cryoablation at Huashan Hospital in these first-in-human studies (ChiCTR-INR-17013060). Murine models were constructed to explore cryoablation-induced tumour-specific immunity, which was further confirmed by primary bladder tumour organoids and autologous lymphocytes cocultured system. Cryoablation improved progression-free survival and recurrence-free survival respectively. Assessment of murine models after cryoablation confirmed microenvironment remodelling and tumour-specific T cells expansion. Enhanced antitumour effects were found after coculture of organoids with autologous lymphocytes collected from post-cryoablation. We also demonstrated cryoablation-induced tumour elimination required IFNGR expression on tumour cells. In addition, a long-lasting antitumour memory response is achieved by cryoablation and could be enhanced after combination with ICIs. This study revealed endoscopic cryoablation is an efficient and safe therapy for bladder tumour treatment. The tumour-specific immune responses induced by cryoablation could reduce tumour recurrence and metastasis.


Fabrication of novel nanoporous array anodic alumina solid-phase microextraction fiber coating and its potential application for headspace sampling of biological volatile organic compounds.
In the study, nanoporous array anodic alumina (NAAA) prepared by a simple, rapid and stable two-step anodic oxidization method was introduced as a novel solid-phase microextraction (SPME) fiber coating. The regular nanoporous array structure and chemical composition of NAAA SPME fiber coating was characterized and validated by scanning electron microscopy and energy dispersive spectroscopy, respectively. Compared with the commercial polydimethylsiloxane (PDMS) SPME fiber coating, NAAA SPME fiber coating achieved the higher enrichment capability (1.7-4.7 folds) for the mixed standards of volatile organic compounds (VOCs). The selectivity for volatile alcohols by NAAA SPME fiber coating demonstrated an increasing trend with the increasing polarity of alcohols caused by the gradually shortening carbon chains from 1-undecanol to 1-heptanol or the isomerization of carbon chains of some typical volatile alcohols including 2-ethyl hexanol, 1-octanol, 2-phenylethanol, 1-phenylethanol, 5-undecanol, 2-undecanol and 1-undecanol. Finally, NAAA SPME fiber coating was originally applied for the analysis of biological VOCs of Bailan flower, stinkbug and orange peel samples coupled with gas chromatography-mass spectrometry (GC-MS) detection. Thirty, twenty-seven and forty-four VOCs of Bailan flower, stinkbug and orange peel samples were sampled and identified, respectively. Moreover, the contents of trace 1-octanol and nonanal of real orange peel samples were quantified for the further method validation with satisfactory recoveries of 106.5 and 120.5%, respectively. This work proposed a sensitive, rapid, reliable and convenient analytical method for the potential study of trace and small molecular biological VOCs by the novel NAAA SPME fiber coating.


Therapeutic management of orally treated type 2 diabetic patients, by French general practitioners in 2010: the DIAttitude Study.
To describe the behaviour of French general practitioners (GP) regarding intensification of hypoglycaemic agents in orally treated type 2 diabetic (T2D) patients, according to their HbA(1c) level. General practitioners were recruited from a panel of office-based general practitioners. T2D patients who had been orally treated for at least 6 months were included in the study; their characteristics were recorded, and their HbA(1c) values and hypoglycaemic treatments over the previous 24 months extracted from electronic records The major reasons for intensification (or no intensification) of hypoglycaemic agents were recorded at the inclusion visit. A total of 236 general practitioners recruited 2109 T2D patients: 1732 had at least one HbA(1c) value recorded in the previous 6 months, and 52%, 33% and 14% had been treated, with oral hypoglycaemic agents in monotherapy, bitherapy or tri-or quadritherapy, respectively. Of these patients, 702 (41%) remained uncontrolled (47%, 39% and 20% respectively) and according to the current French guidelines needed treatment intensification. Only 46 (7%) had their treatment intensified at inclusion. Of those without intensified treatment, 60% were treated with monotherapy; the main reason given by the general practitioners for not intensifying treatment was a satisfactory HbA(1c) level (53%), although 32% had an HbA(1c)>7%. Other reasons were: lifestyle advice had greater priority (20%); decision was postponed until the next visit (11%); HbA(1c) had decreased since last visit (7%; not confirmed by available data in 58% of cases); a medical priority other than diabetes (6%) and other reasons related to the patient (3%). For T2D patients managed by French general practitioners, guidelines are not consistently followed: HbA(1c) should be monitored more frequently and treatment adjusted according to HbA(1c) levels.


Herpes simplex virus type 7 and Epstein-Barr virus as strange causes of a gastric ulcer.
Esophageal, gastric and duodenal ulcers are found in immunocompromised patients due to virus, mainly cytomegalovirus (CMV), and less frequently Epstein-Barr virus (EBV), varicella zoster virus (VZV) and herpes simplex virus (HSV) type 1 or 2.


Anaesthesia for patients with arthrogryposis multiplex congenita: what is the risk of malignant hyperthermia?
Arthrogryposis multiplex congenita has been linked with malignant hyperthermia. A review of the anaesthetic experience at the Royal Alexandra Hospital for Children over a 32-year period revealed no episode of malignant hyperthermia occurring in patients with arthrogryposis multiplex congenita despite many and varied exposures to known triggering agents.


Combining Molecular Scaffolds from FDA Approved Drugs: Application to Drug Discovery.
We have enumerated all linear combinations of ring systems from FDA approved drugs, up to three rings in length and up to four bonds linkers to give an in silico database of approximately 14 million molecules. This virtual library was compared with molecular databases of published and commercially available compounds to assess the prevalence of drug ring combinations in modern medicinal chemistry and to identify areas of under-represented, but clinically validated, chemical space. From the 10 trillion molecular comparisons, we found that less than 1% of the possible combinations of drug ring systems appear in commercially available libraries. This key observation highlights significant opportunities to design new fragment-like and lead-like libraries aimed at improving success rates and reducing risk in small molecule drug discovery, as, based on our previous analysis ( Taylor J. Med. Chem. 2014 , 57 , 5845 - 5849 ), approximately 70% of all new drugs are made up of only ring systems that have been used in existing drugs.


Sub-synaptic localization of Cav3.1 T-type calcium channels in the thalamus of normal and parkinsonian monkeys.
T-type calcium channels (Cav3) are key mediators of thalamic bursting activity, but also regulate single cells excitability, dendritic integration, synaptic strength and transmitter release. These functions are strongly influenced by the subcellular and subsynaptic localization of Cav3 channels along the somatodendritic domain of thalamic cells. In Parkinson's disease, T-type calcium channels dysfunction in the basal ganglia-receiving thalamic nuclei likely contributes to pathological thalamic bursting activity. In this study, we analyzed the cellular, subcellular, and subsynaptic localization of the Cav3.1 channel in the ventral anterior (VA) and centromedian/parafascicular (CM/Pf) thalamic nuclei, the main thalamic targets of basal ganglia output, in normal and parkinsonian monkeys. All thalamic nuclei displayed strong Cav3.1 neuropil immunoreactivity, although the intensity of immunolabeling in CM/Pf was significantly lower than in VA. Ultrastructurally, 70-80 % of the Cav3.1-immunoreactive structures were dendritic shafts. Using immunogold labeling, Cav3.1 was commonly found perisynaptic to asymmetric and symmetric axo-dendritic synapses, suggesting a role of Cav3.1 in regulating excitatory and inhibitory neurotransmission. Significant labeling was also found at non-synaptic sites along the plasma membrane of thalamic neurons. There was no difference in the overall pattern and intensity of immunostaining between normal and parkinsonian monkeys, suggesting that the increased rebound bursting in the parkinsonian state is not driven by changes in Cav3.1 expression. Thus, T-type calcium channels are located to subserve neuronal bursting, but also regulate glutamatergic and non-glutamatergic transmission along the whole somatodendritic domain of basal ganglia-receiving neurons of the primate thalamus.


Word frequency and memory: effects on absolute versus relative order memory and on item memory versus order memory.
Word frequency can produce opposite effects on recognition and order memory: Low-frequency words produce greater recognition accuracy, whereas high-frequency words produce superior order memory. The present experiments further delineate the relationship between word frequency and order memory. Experiment 1 indicates that low-frequency words produce worse performance on a measure of absolute order memory but not on a test of relative order, which is consistent with the idea that different forms of information underlie different types of order judgments (Greene, Thapar, & Westerman, 1998). Experiment 2 contrasted high-, low-, and very low-frequency words on recognition memory and absolute order memory. In comparison with high-frequency words, low-frequency words enhanced recognition, whereas very low-frequency words did not. Both low- and very low-frequency words, however, produced worse memory for absolute order. Thus, the relationship between frequency and item memory is an inverted U-shaped function, whereas the relationship between frequency and absolute order memory is direct. This implies that the item-enhancing effects of lower word frequency may be dissociated from its order-disrupting effects.


Prevalence of overweight/obesity and related factors in Keerqin District, Tongliao City: A cross-sectional study.
This study aimed to analyze the prevalence of overweight/obesity and the factors influencing these conditions among 9- to 18-year-old adolescents in Keerqin District of Tongliao City. We explored whether overweight/obesity is accompanied by differences in eating habits, lifestyle, and mental health. A cross-sectional survey was administered to 1,736 adolescents in November 2020. A physical examination was performed for each participant, and an online questionnaire was adopted to collect information. The association of several risk factors with overweight/obesity was explored using a logistic regression model. The prevalence of overweight/obesity in the study population was 43.32%. The risk of overweight/obesity was higher among nonresident students (odds ratio [OR] = 1.564, 95% CI = 1.182-2.069) who had an average of 3-4 (OR = 2.164, 95% CI = 1.087-4.308) or 5 or more (OR = 2.114, 95% CI = 1.376-3.248) PE classes per week. The risk of overweight/obesity was lower among girls (OR = 0.485, 95% CI = 0.396-0.593), students aged 15-16 years (OR = 0.288, 95% CI = 0.135-0.617) and those aged 17-18 years (OR = 0.282, 95% CI = 0.124-0.639), students who ate sweets more than once a week (OR = 0.570, 95% CI = 0.366-0.887), students who spent less than 1 hour per day on the computer each week (OR = 0.776, 95% CI = 0.620-0.971), students with depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D] score ≥ 16) (Model 2: OR = 0.618, 95% CI = 0.385-0.990; Model 3: OR = 0.623, 95% CI = 0.388-1.000), and students with depressed affect (Model 2: OR = 0.921, 95% CI = 0.877-0.967; Model 3: OR = 0.929, 95% CI = 0.885-0.976). Overweight/obesity was influenced by eating habits and lifestyle factors. In addition, overweight/obesity adolescents had a lower risk of depressed than those with normal weight.


Impact of Frequent and Persistent Use of Continuous Glucose Monitoring (CGM) on Hypoglycemia Fear, Frequency of Emergency Medical Treatment, and SMBG Frequency After One Year.
We assessed the impact of "almost daily" use of continuous glucose monitoring (CGM) in adults with type 1 diabetes who had at least 1 year of CGM experience. In this single-center survey, we utilized a 16-item questionnaire to assess changes hypoglycemia fear, incidence of emergency medical treatment and utilization of self-monitoring of blood glucose (SMBG) before and after 1 year of CGM use. Participation was restricted to individuals who used the same brand of CGM system to avoid confounding responses due to differences between commercial devices. Participants were recruited on an "as-seen" basis from a major, urban internal medicine clinic and associated diabetes education center. The questionnaire was completed during the clinic visit. Responses to the survey were analyzed by standard descriptive statistics. Seventy-four patients completed the survey: 42.9 years (range: 23-71 years), 38 (51%) female, 59 current insulin pump users. Most (84%) reported wearing their devices "almost daily" (n = 58) or 3 weeks per month (n = 4). "Almost daily" users reported an 86% reduction in incidence of emergency medical treatment events (P = .0013) and >50% reduction in daily SMBG frequency (P < .0001). Reductions in hypoglycemia fear were apparent but not statistically significant (P = .7359). "Almost daily" use of CGM with the Dexcom G4 system reduced incidence of emergency treatment events and daily SMBG utilization among survey respondents and a trend toward reduced hypoglycemia fear. This may indicate cost savings in reduction of emergency medical intervention and likely improved quality of life without increasing safety concerns related to hypoglycemia.


The evolution of the labor curve and its implications for clinical practice: the relationship between cervical dilation, station, and time during labor.
The assessment of labor progress is germane to every woman in labor. Two labor disorders-arrest of dilation and arrest of descent-are the primary indications for surgery in close to 50% of all intrapartum cesarean deliveries and are often contributing indications for cesarean deliveries for fetal heart rate abnormalities. Beginning in 1954, the assessment of labor progress was transformed by Friedman. He published a series of seminal works describing the relationship between cervical dilation, station of the presenting part, and time. He proposed nomenclature for the classification of labor disorders. Generations of obstetricians used this terminology and normal labor curves to determine expected rates of dilation and fetal descent and to decide when intervention was required. The analysis of labor progress presents many mathematical challenges. Clinical measurements of dilation and station are imprecise and prone to variation, especially for inexperienced observers. Many interrelated factors influence how the cervix dilates and how the fetus descends. There is substantial variability in when data collection begins and in the frequency of examinations. Statistical methods to account for these issues have advanced considerably in recent decades. In parallel, there is growing recognition among clinicians of the limitations of using time alone to assess progress in cervical dilation in labor. There is wide variation in the patterns of dilation over time and most labors do not follow an average dilation curve. Reliable assessment of labor progression is important because uncertainty leads to both over-use and under-use of cesarean delivery and neither of these extremes are desirable. This review traces the evolution of labor curves, describes how limitations are being addressed to reduce uncertainty and to improve the assessment of labor progression using modern statistical techniques and multi-dimensional data, and discusses the implications for obstetrical practice.


How to be responsible in all the steps of a data science pipeline: The case of the Italian public sector.
The paper highlights how each step of a data science pipeline can be performed in a "responsible" way, taking into account privacy, ethics, and quality issues. Several examples from the Italian public sector contribute to clarifying how data collections and data analyses can be carried out under a responsible view.


MTHFR polymorphism as a predictive biomarker for gastrointestinal and hematological toxicity in North Indian adenocarcinoma patients.
In the present study, we investigated the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and overall survival, toxicity and treatment response for North Indian adenocarcinoma patients. The polymorphisms of MTHFR gene in north Indian adenocarcinoma patients were assessed by PCR-RFLP. Our data observed that patients with mutant genotype (C/C) for 1298 A>C) polymorphism showed higher trend of median survival time compared to patients bearing the wild type genotype (A/A) (MST= 13.93 vs. 7.97, p=0.12). Further, we observed patients with the heterozygous genotype for A1298C polymorphism had 12-fold risk of diarrhea (AOR =12.54, 95% CI = 1.54-101.86, p=0.018). The patients with heterozygous genotype (CT) of the C677T polymorphism had 5.34-fold increased risk of developing neutropenia (AOR=5.34, 95% CI=1.49-19.06, p=0.009). Our results suggest that MTHFR polymorphisms are associated with hematological toxicity. MTHFR polymorphism might impact the development of pemetrexed and platinum-related toxicities but not as a clinical predictor of efficiency.


Oxidative coupling and the irreversible adsorption of phenol by graphite.
Uptake of phenol by graphite, and regeneration by methanol extraction, was measured to evaluate irreversible adsorption of phenols to carbon surfaces. The emphasis of this work was to identify the role of oxidative coupling, which has been invoked to explain irreversible phenol sorption by activated carbons. Graphite was chosen as a model carbon surface to eliminate potentially confounding effects of microporosity present in other types of carbonaceous sorbents. The isotherm data were well described by the Langmuir-Freundlich isotherm from pH 3 to 9. At pH 12, measured uptakes were higher than expected based on model predictions, suggesting the occurrence of an adsorption mechanism besides physisorption. One oxidative coupling product, 2,2'-dihydroxybiphenyl, was obtained exclusively after adsorption at pH values above 7, and appeared both in aqueous solution and in the methanol regenerant solution. The fraction of total uptake that was not recoverable by methanol extraction decreased with increasing phenol concentration in solution, suggesting preferential sorption by high-energy sites. However, absolute irreversible adsorption increased with phenol concentration in solution. Both fractional irreversible adsorption and 2,2'-dihydroxybiphenyl oxidative coupling product recovery as a function of pH and contact time demonstrated that irreversible sorption of phenol by graphite could not be explained by an oxidative coupling mechanism alone.


Color match of ultra-translucency multilayer zirconia restorations with different designs and backgrounds.
The purpose of this in vitro study was to assess the color match of ultra-translucency multilayer zirconia restorations with different designs and backgrounds. Thirty ultra-translucency multilayer zirconia crown specimens were made in VITA classical shade B2 for a prepared maxillary central incisor. The specimens were divided into three groups based on the restoration design: veneered zirconia with a trestle design (VZT), veneered zirconia with a dentin core design (VZD), and full-contour zirconia (FCZ). In the groups VZT and VZD, the zirconia specimens were layered with a feldspathic veneering ceramic. The specimens were seated on five different backgrounds: shade B2 composite resin, shade B2 zirconia, copper-colored metal alloy, silver-colored metal alloy, and the prepared central incisor. CIELab values of the labial middle sections of the crown specimens were measured with a spectrophotometer. Color differences between the specimens and a shade B2 VITA classical tab (as a control) were calculated from the ΔE* ab formula and compared with an acceptability threshold (ΔE* ab = 3.7) to be clinically explicated. Mean ΔE* ab values ranged between 1.17 and 8.48. The restoration design, the background type, and their interaction affected the ΔE* ab (p < 0.001). The mean ΔE* ab values for VZT with all backgrounds and for VZD with the silver-colored metal background were greater than the threshold (p < 0.001), whereas the mean ΔE* ab values for VZD with the other backgrounds and FCZ with all backgrounds were less than the threshold (p = 1). Restoration design and background type affected the color match of ultra-translucency multilayer zirconia restorations. VZT restorations on all backgrounds and VZD restorations on a silver-colored metal background showed color mismatches. However, VZD restorations on the other backgrounds and FCZ restorations on all backgrounds demonstrated color matches.


Decreased expression of microRNA-124 is an independent unfavorable prognostic factor for patients with breast cancer.
MicroRNA-124 (miR-124) has been reported to be downregulated in breast cancer. However, its clinical significance and prognostic value in breast cancer have not been extensively studied. The tissue expression levels of miR-124 were measured using quantitative real-time PCR in 133 breast cancer patients. The correlation between the miR-124 levels and the clinicopathological factors of the patients was also analyzed. Survival and Cox proportional-hazards regression analyses were performed to determine the correlation between miR-124 expression levels and prognosis in the patients. Quantitative real-time PCR analysis showed that miR-124 had lower expression in breast cancer specimens than that in matched adjacent normal breast tissues (0.39 ± 0.16 vs. 1.00 ± 0.39; P < 0.05). Low miR-124 expression level was significantly associated with advanced TNM stage (P = 0.011), lymph node metastasis (P = 0.012), and poorer pathological differentiation (P = 0.023). A significant difference was found that breast cancer patients with low miR-124 expression level had distinctly shorter overall survival than patients with high miR-124 expression level (63.8% vs. 35.2%, P = 0.03). Furthermore, multivariate analysis of the prognosis factors with a Cox proportional hazards model confirmed that low miR-124 expression was a significant independent predictor of poor survival in breast cancer (HR = 3.16, 95% CI: 1.79-9.13, P = 0.017). These findings proved that the decreased expression of miR-124 might be associated with tumor progression and poor prognosis in patients with breast cancer. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3752603721493544.


Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export.
Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations. We identified in multiple families with PFBC mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, implicating XPR1 and phosphate homeostasis in PFBC.


Total anomalous pulmonary venous return with left heart hypoplasia.
A term baby had a total anomalous pulmonary venous return to the inferior vena cava. The infant underwent complete repair, but died 30 hours after operation. The postmortem examination revealed severe endocardial fibroelastosis. This uncommon association is discussed.


Acute effect of clonidine on gastric emptying in patients with diabetic gastropathy and controls.
The treatments available for diabetic gastropathy are frequently ineffective. Clinical observations suggest that clonidine, an a-2 adrenergic agonist, may improve diabetic gastropathy symptoms. To establish whether a single oral dose of clonidine alters the gastric emptying of a solid meal in 10 patients with diabetic gastropathy and their matched controls. A secondary goal was to compare two methods of analysis of the data from gastric emptying studies. Clonidine, 0.3 mg, or a matched placebo were administered orally in a double-blind fashion. Only three of the 10 patients showed an increased gastric residual volume. Gastric emptying rates were comparable in patients and controls. Clonidine had no significant effect on gastric emptying in the controls but increased t1/2 values in the patient group. This effect just reached statistical significance only when calculated by the power exponential method (P=0.05 but not by the linear component model. Delayed gastric emptying is not an invariable characteristic of symptomatic diabetic gastropathy. Clonidine, given as a single dose of 0.3 mg orally, has no gastric prokinetic effects. It may act on gastric afferent innervation or, more likely, at a central site to reduce nausea and vomiting. The analysis of gastric emptying data by the power exponential and the two linear component methods yields equivalent results.


NOTCH3 signaling is essential for NF-κB activation in TLR-activated macrophages.
Macrophage activation by Toll receptors is an essential event in the development of the response against pathogens. NOTCH signaling pathway is involved in the control of macrophage activation and the inflammatory processes. In this work, we have characterized NOTCH signaling in macrophages activated by Toll-like receptor (TLR) triggering and determined that DLL1 and DLL4 are the main ligands responsible for NOTCH signaling. We have identified ADAM10 as the main protease implicated in NOTCH processing and activation. We have also observed that furin, which processes NOTCH receptors, is induced by TLR signaling in a NOTCH-dependent manner. NOTCH3 is the only NOTCH receptor expressed in resting macrophages. Its expression increased rapidly in the first hours after TLR4 activation, followed by a gradual decrease, which was coincident with an elevation of the expression of the other NOTCH receptors. All NOTCH1, 2 and 3 contribute to the increased NOTCH signaling detected in activated macrophages. We also observed a crosstalk between NOTCH3 and NOTCH1 during macrophage activation. Finally, our results highlight the relevance of NOTCH3 in the activation of NF-κB, increasing p65 phosphorylation by p38 MAP kinase. Our data identify, for the first time, NOTCH3 as a relevant player in the control of inflammation.


Contemporaneous carrier-state of two or three "proatherosclerotic" variants of APOE, ICAM1, PPARA and PAI-1 genes differentiate CAD patients from healthy individuals.
Atherosclerosis is the most important cause of coronary artery disease (CAD). Genetic predisposition to CAD is related to polymorphisms of genes encoding products functionally involved in pathogenesis of atherosclerosis. Polymorphisms of genes participating in monocyte adhesion and diapedesis, lipid metabolism and fibrinolysis regulation may be partially responsible for this process. The aim of our study was to assess the polymorphic variants frequencies of ICAM1, APOE, PPARA and PAI-1 genes in CAD patients and healthy blood donors and to find specific arrangement of polymorphic variants which would differentiate both groups. We studied 146 CAD patients and 121 healthy blood donors. Polymorphisms in analyzed genes were examined using PCR-RFLP analysis. We found significantly higher frequency of 5G allele of PAI-1 gene in patients than in control subjects (p = 0.038, OR = 1.44). We observed also a considerably higher frequency of contemporaneous carriers of two or three "proatherosclerotic" variants: 1) PPARA and PAI-1, 2) APOE and ICAM1 and 3) PPARA, ICAM1 and PAI-1 in CAD group comparing to control subjects. The number of "proatherosclerotic" variants carriers differentiate studied groups also independently of specific genotype arrangement. In conclusion, contemporaneous carrier-state of two or three polymorphic variants within analyzed genes is associated with CAD.


A comparison of NSQIP and CESQIP in data quality and ability to predict thyroidectomy outcomes.
The Collaborative Endocrine Surgery Quality Improvement Program tracks thyroidectomy outcomes with self-reported data, whereas the National Surgical Quality Improvement Program uses professional abstractors. We compare completeness and predictive ability of these databases at a single-center and national level. Data consistency in the Collaborative Endocrine Surgery Quality Improvement Program and the National Surgical Quality Improvement Program at a single institution (2013-2020) was evaluated using McNemar's test. At the national level, data from the Collaborative Endocrine Surgery Quality Improvement Program and the National Surgical Quality Improvement Program (2016-2019) were used to compare predictive capability for 4 outcomes within each data source: thyroidectomy-specific complication, systemic complication, readmission, and reoperation, as measured by area under curve. In the single-center analysis, 66 cases were recorded in both the Collaborative Endocrine Surgery Quality Improvement Program and the National Surgical Quality Improvement Program. The reoperation variable had the most discrepancies (2 vs 0 in the National Surgical Quality Improvement Program versus the Collaborative Endocrine Surgery Quality Improvement Program, respectively; χ2 = 2.00, P = .16). At the national level, there were 24,942 cases in the National Surgical Quality Improvement Program and 17,666 cases in the Collaborative Endocrine Surgery Quality Improvement Program. In the National Surgical Quality Improvement Program, 30-day thyroidectomy-specific complication, systemic complication, readmission, and reoperation were 13.25%, 2.13%, 1.74%, and 1.39%, respectively, and in the Collaborative Endocrine Surgery Quality Improvement Program 7.27%, 1.95%, 1.64%, and 0.81%. The area under curve of the National Surgical Quality Improvement Program was higher for predicting readmission (0.721 [95% confidence interval 0.703-0.737] vs 0.613 [0.581-0.649]); the area under curve of the Collaborative Endocrine Surgery Quality Improvement Program was higher for thyroidectomy-specific complication (0.724 [0.708-0.737] vs 0.677 [0.667-0.687]) and reoperation (0.735 [0.692-0.775] vs 0.643 [0.611-0.673]). Overall, 3.44% vs 27.22% of values were missing for the National Surgical Quality Improvement Program and the Collaborative Endocrine Surgery Quality Improvement Program, respectively. The Collaborative Endocrine Surgery Quality Improvement Program was more accurate in predicting thyroidectomy-specific complication and reoperation, underscoring its role in collecting granular, disease-specific variables. However, a higher proportion of data are missing. The National Surgical Quality Improvement Program infrastructure leads to more rigorous data capture, but the Collaborative Endocrine Surgery Quality Improvement Program is better at predicting thyroid-specific outcomes.


A novel constructed wetland based on iron carbon substrates: performance optimization and mechanisms of simultaneous removal of nitrogen and phosphorus.
In recent years, the combination of iron carbon micro-electrolysis (ICME) with constructed wetlands (CWs) for removal of nitrogen and phosphorus has attracted more and more attention. However, the removal mechanisms by CWs with iron carbon (Fe-C) substrates are still unclear. In this study, the Fe-C based CW (CW-A) was established to improve the removal efficiencies of nitrogen and phosphorus by optimizing the operating conditions. And the removal mechanisms of nitrogen and phosphorus were explored. The results shown that the removal rates of COD, NH4+-N, NO3--N, TN, and TP in CW-A could reach up to 84.4%, 94.0%, 81.1%, 86.6%, and 84.3%, respectively. Wetland plants and intermittent aeration have dominant effects on the removal of NH4+-N, while the removal efficiencies of NO3--N, TN, and TP were mainly affected by Fe-C substrates, wetland plants, and HRT. XPS analysis revealed that Fe(0)/Fe2+ and their valence transformation played important roles on the pollutants removal. High-throughput sequencing results showed that Fe-C substrates and wetland plants had considerable impacts on the microbial community structures, such as richness and diversity of microorganism. The relative abundance of autotrophic denitrification bacteria (e.g., Denitatsoma, Thauera, and Sulfuritalea) increased in CW-A than CW-C. The electrons and H2/[H] produced from Fe-C substrates were utilized by autotrophic denitrification bacteria for NO3--N reduction. Microbial degradation was the main removal mechanism of nitrogen in CW-A. Removal efficiency of phosphorus was enhanced resulted from the reaction of phosphate with iron ion. The application of CWs with Fe-C substrates and plants presented great potential for simultaneous removal of nitrogen and phosphorus.


Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA.
Endometrial cancer stem cells (ECSCs) are stem-like cells endowed with self-renewal and differentiation abilities, and these cells are essential for cancer progression in endometrial cancer (EC). As hallmarks of the tumour microenvironment (TME), hypoxia and hypoxia-inducing factors (HIFs) give rise to the dysregulation of tumour stemness genes, such as SOX2. Against this backdrop, we investigated the regulatory mechanisms regulated by HIFs and SOX2 in ECSCs during EC development. Here, ECSCs isolated from EC cell lines and tissues were found to express stemness genes (CD133 and aldehyde dehydrogenase, ALDH1) following the induction of their ECSC expansion. Notably, m6A methylation of RNA and HIF-1α/2α-dependent AlkB homologue 5 (ALKBH5) participate in the regulation of HIFs and SOX2 in EC, as confirmed by the observations that mRNA levels of m6A demethylases and ALKBH5 significantly increase under hypoxic conditions in ECSCs. Moreover, hypoxia and high ALKBH5 levels restore the stem-like state of differentiated ECSCs and increase the ECSC-like phenotype, whereas the knockdown of HIFs or ALKBH5 significantly reduces their tumour initiation capacity. In addition, our findings validate the role of ALKBH5 in promoting SOX2 transcription via mRNA demethylation, thereby maintaining the stem-like state and tumorigenicity potential of ECSCs. In conclusion, these observations demonstrate a critical role for m6A methylation-mediated regulation of the HIF-ALKBH5-SOX2 axis during ECSC expansion in hypoxic TMEs.


Identification, isolation and characterization of impurities of clindamycin palmitate hydrochloride.
Clindamycin palmitate hydrochloride is a water soluble hydrochloride salt of the ester of clindamycin and palmitic acid. It is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin. Total 12 impurities at levels ranging from 0.05% to 0.5% were detected by isocratic reverse-phase high performance liquid chromatography (HPLC) using RI detector. The molecular weights of impurities were determined by LC-MS analysis. Two impurities were starting materials and the remaining impurities were isolated from crude samples/enriched mother liquors using reverse-phase preparative HPLC. Based on the spectral data the structures of these impurities were characterized as, clindamycin palmitate sulphoxides alpha-/beta-isomers (impurity I); clindamycin laurate (impurity II); lincomycin palmitate (impurity III); clindamycin myristate (impurity IV); epiclindamycin palmitate (impurity V); clindamycin palmitate 3-isomer (impurity VI); clindamycin pentadecanoate (impurity VII); clindamycin B-palmitate (impurity VIII); clindamycin heptadecanoate (impurity IX) and clindamycin stearate (impurity X). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and formation of these impurities have been discussed in detail.


Identification and characterization of the Erwinia amylovora rpoS gene: RpoS is not involved in induction of fireblight disease symptoms.
The Erwinia amylovora rpoS gene, encoding the alternative sigma factor RpoS, has been cloned and characterized. Though highly sensitive to a number of environmental stresses, an E. amylovora rpoS mutant was not compromised in its ability to grow or cause disease symptoms within apple seedlings or in an overwintering model.


The medicalization of compulsive buying.
Compulsive buying has recently been the subject of numerous articles from both consumer research and psychiatric perspectives. Identified by some researchers as a compulsion and by others as an addiction, common solutions to the problem have included drug treatments, participation in self-help groups and cognitive behaviour therapy. The purpose of this article is to examine critically the labelling of compulsive buying in terms of medicalization from the perspective of both medical and non-medical social control of "deviant" consumers. We suggest that the attempt to categorize compulsive buying as an illness represents the ongoing trend to medicalize behavioural problems which may be better understood within the wider context of related phenomena such as the fiscal crisis of the 1980s and 1990s and the consumption-driven economy of North America.


In vivo evidence of altered chloride but not potassium secretion in cystic fibrosis rectal mucosa.
In cystic fibrosis, cyclic adenosine monophosphate-mediated chloride secretion is abnormal in respiratory, small intestinal, and rectal mucosa. Calcium-mediated chloride secretion is also aberrant in CF small intestinal mucosa in cystic fibrosis, in contrast to the respiratory epithelia, where it appears to be normal. To determine whether this disparity between calcium- and cyclic adenosine monophosphate-mediated chloride secretion exists in cystic fibrosis rectal mucosa in vivo, transrectal potential difference was measured in age-matched adult cystic fibrosis subjects (n = 8) and control subjects (n = 9) in response to 10-minute luminal perfusions of bethanechol (1 mmol/L) or theophylline (5 mmol/L). In response to bethanechol, an initial (1-minute) negative change in potential difference (-1.4 +/- 1.1 mV; mean +/- SEM) was seen in control subjects, in contrast to a positive change in mean potential difference (+2.5 +/- 1.0 mV) in cystic fibrosis subjects (control vs. cystic fibrosis, P less than 0.05). After 1 minute, mean potential differences changes in both control and cystic fibrosis subjects were positive. Theophylline perfusion resulted in a significant (P less than 0.01) difference in potential difference response between groups; at 10 minutes, the potential difference became more negative (-3.6 +/- 1.4 mV) in control subjects and more positive in cystic fibrosis subjects (+3.9 +/- 1.4 mV). To determine whether second messenger-mediated potassium secretion contributed to the observed potential difference changes in response to bethanechol and theophylline, studies were repeated in the presence of barium chloride, a known blocker of potassium conductance. In the control group, barium chloride significantly enhanced the theophylline-induced negative potential difference change (P less than 0.05) and reduced the positive potential difference change seen with bethanechol alone. In subjects with cystic fibrosis, barium chloride completely abolished the previously seen positive potential difference change in response to either bethanechol or theophylline alone. These in vivo studies suggest that there is active potassium secretion in both control and cystic fibrosis rectal mucosa in response to cyclic adenosine monophosphate- and calcium-dependent secretagogues and that the magnitude of the potential difference changes attributable to barium-inhibitable potassium secretion is the same in cystic fibrosis and control subjects. In contrast, it appears that in cystic fibrosis rectal mucosa in vivo, calcium- as well as cyclic adenosine monophosphate-dependent chloride secretion is aberrant.


Quality of life in the surgical treatment of gynecomastia.
Gynecomastia has an incidence of up to 60% of adolescents, causing pain and self-image disorders for the patient, leading to emotional and physical problems that can be reversed with treatment. This prospective case control study assessed the surgical treatment of gynecomastia and its impact on quality of life. Thirty-three patients aged 18-50 years and with 2-21 years of gynecomastia progression were included in the study. Adenectomy was performed. Preoperatively and 6 months postoperatively, patients completed the Brazilian version of the Short-Form 36 (SF-36) quality of life questionnaire. There was improvement in the SF-36 domains of General Health, Functional Capacity, Social Aspects, Vitality, and Mental Health. The Short-Form 36 questionnaire demonstrated that surgical treatment of gynecomastia afforded positive changes in quality of life.


Variability of vascularity in nasal mucosa as demonstrated by CD34 immunohistochemistry.
Regional anatomical variations in the nasal vasculature have not been studied histologically. Immunohistochemistry performed using marker for CD34 antigen on vascular endothelium biopsied from 5 sites on the lateral nasal wall and compared with one septal biopsy. No significant regional variations in microvascular architecture over the lateral wall of the nose were found. * Lateral wall measurements were significantly different to the septal measurements (P = 0.0003, 0.01). Suggests biopsies can be taken from any site on the lateral wall and give a representative sampling of the vascularity for research purposes.


Quantitative assay of types I and III collagen synthesized by keloid biopsyes and fibroblasts.
Molecular sieve column chromatography was used to determine the amount of type I and III collagen synthesized by normal dermis and keloid biopsies and fibroblasts derived from these tissues. After incubation with radioactive proline, the collagen was extracted and separated into types I and III and then quantitated. There was no significant difference in the percent type III collagen synthesized by fresh keloid biopsies compared to normal dermis. Likewise, there was no significant difference in the percent type III collagen synthesized by keloid fibroblasts compared to normal dermal fibroblasts. However, fibroblasts from both keloid and normal dermis synthesized a lower percentage of type III collagen in cell culture compared to the original biopsies. These findings demonstrate that keloid collagen has the same type distribution as normal dermis and suggest that increased collagen synthesis in these lesions is not related to altered collagen types.


Label-free quantitative proteomics to exploit the impact of sourdough fermentation on reducing wheat allergenic fractions.
The microbial consortia of lactic acid bacteria and yeast of sourdough can partially degrade gluten subunits associated with wheat-related diseases. This study evaluated how sourdough fermentation interferes with wheat protein profiles and if it can be related to the reduction expression of allergenic proteins. Samples from five bread doughs (Saccharomyces cerevisiae -C1; chemical acidification -C2, and three sourdoughs formulations -S1, S2, and S3) were sequentially extracted, digested, and submitted to shotgun label-free proteomic analysis. Eight-five proteins were identified as allergenic, mainly belonging to gliadin fraction, including seven containing the 33-mer peptide sequence. The highest immunogenic potential was found in dough C1 and S3, while the least reactive group consisted of S1 and C2. The two folds down expression of an α-gliadin containing the 33-mer sequence corroborates this. This finding may indicate the role of organic acids produced by the microbiota sourdough type II during fermentation in changing the protein profile.


Identification of ETA and ETB binding domains using ET-derived photoprobes.
Using the structure of ET-1 as a template, a series of photosensitive analogs were developed to investigate the binding domain of ETA and ETB receptors. Accordingly, a p-benzoyl-l-phenylalanine (Bpa) residue was introduced into the peptide chain following a pattern aiming at scanning N- to C-terminal portions of the molecule. Among the analogs, those containing a Bpa amino acid in position 7 ([L-Bpa7, Tyr(125I)13]hET-1) or 12 ([Nle7, L-Bpa12, Tyr(125I)13]hET-1) exhibited the capacity to activate both receptors, thus showing that residues Met-7 and Val-12 of ET-1 do not play a key role in the activation process. The binding capacity of the probes was also evaluated on transfected CHO cells overexpressing either ETA or ETB receptors. Subsequently, these photoprobes were used to label ETA and ETB receptors overexpressed in transfected CHO cells. Enzymatic digestions and chemical cleavages were then performed on ligand-receptor complexes and fragments produced by the lysis were analyzed to point out putative interaction areas on the receptors. Results showed that Phe147-Lys166, covering the second segment of EC I and the top part of TM III, contains a contact point for [Nle7, L-Bpa12, Tyr(125I)13]hET-1 on ETA receptors whereas Ile292-Trp319, spanning from the second half of the intracellular loop III up to the middle turns of TM VI, includes a residue that can interact with [L-Bpa7, Tyr(125I)13]hET-1. Moreover, upon binding of [Nle7, L-Bpa12, Tyr(125I)13]hET-1, it was observed that Thr263-Met266 (EC II) of the ETB receptor would come close with the ligand.


CRISPR-Cas-mediated gene editing in lactic acid bacteria.
The high efficiency, convenience and diversity of clustered regular interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems are driving a technological revolution in the gene editing of lactic acid bacteria (LAB). Cas-RNA cassettes have been adopted as tools to perform gene deletion, insertion and point mutation in several species of LAB. In this article, we describe the basic mechanisms of the CRISPR-Cas system, and the current gene editing methods available, focusing on the CRISPR-Cas models developed for LAB. We also compare the different types of CRISPR-Cas-based genomic manipulations classified according to the different Cas proteins and the type of recombineering, and discuss the rapidly evolving landscape of CRISPR-Cas application in LAB.


DNA adduction by polychlorinated biphenyls: adducts derived from hepatic microsomal activation and from synthetic metabolites.
Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants and complete carcinogens in rodents. Metabolism of lower chlorinated congeners with rat liver microsomes was investigated in earlier studies and DNA adduction was also reported. The current study was designed to compare DNA adducts formed after bioactivation of PCBs with rat, mouse and human hepatic microsomes, and to investigate the role of quinoid PCB metabolites in DNA adduct formation. Eight congeners ranging from mono- to hexachlorinated biphenyls were tested. Metabolites obtained through microsomal bioactivation as well as synthetic quinoid metabolites of 4-monochlorobiphenyl (4-CB) were incubated with calf-thymus DNA (CT-DNA), and the resulting adducts were analyzed by the 32P-post-labelling method. DNA adducts were formed with mono- di- and tri-chlorinated congeners, but not with higher chlorinated congeners. Similar adduct patterns were observed for 2-monochlorobiphenyl (2-CB) activated with hepatic microsomes from rat, mouse and human, while 4-CB, 3,4-dichlorobiphenyl (3,4-CB) and 3,4,5-trichlorobiphenyl (3,4,5-CB) showed similar patterns for two out of the three microsomal systems tested. 4,4' -trichlorobiphenyl (4,4' -CB) showed different adduct patterns in all microsomal systems. Higher adduct levels were obtained with the rodent microsomes compared with human microsomes and were related to higher cytochrome P450 activity. When adducts derived from microsomal activation of 4-CB were compared by co-chromatography with those derived from the incubation of DNA with synthetic 2-(4' -chlorophenyl)-1,4-benzoquinone (4-BQ), one adduct co-migrated in three different chromatography systems. This study demonstrates that rodents as well as human hepatic enzymes metabolize lower chlorinated biphenyl congeners to reactive intermediates that form DNA adducts in vitro and shows that the para-quinone metabolites of PCBs are, in part, involved in direct DNA adduction.


The Do-It-Yourself Electrocardiogram.
Hands-on labs are a critical component of biomedical engineering undergraduate education. Due to both the pandemic and the growing interest in online education, we developed a Do-it-yourself Electrocardiogram (DIY EKG) project. The Arduino-based DIY EKG kit instructed students how to build a circuit to obtain their own EKG and then analyze their EKG data using Matlab. Despite the obstacles of virtually trouble-shooting, 85.4% of students (n = 103) were able to obtain their own EKG at home. We have provided the labelled circuit drawings, step-by-step instructions, Matlab files, and results in this paper. Survey results indicate that 89% of students felt the DIY EKG project was a "challenging yet fulfilling experience." The online version of this article contains supplementary material available 10.1007/s43683-021-00061-0.


Analyzing the Urban-Rural Vaccination Coverage Disparity through a Fair Decomposition in Zhejiang Province, China.
Objectives: Exploring determinants underlying disparities in full vaccination coverage (FVC) can contribute to improved immunization interventions. FVC and its risk factors in Zhejiang province have been studied, yet the determinants explaining the rural-urban disparity in FVC have not been studied. This study aimed to disentangle the factors explaining rural-urban disparities in FVC of vaccine doses scheduled during the first year of life in Zhejiang province. Methods: We used data from a vaccination coverage survey among children aged 24-35 months conducted in 2016. The outcome measure was full vaccination status, and the grouping variable was the area of residence. Descriptive statistics were used to analyze the FVC and rural-urban residence across the exposure variables. The Fairlie decomposition technique was used to decompose factors contributing to explaining the FVC disparity. Results: There were 847 children included in this study, of which 49.6% lived in a rural area. FVC was 94% in rural areas and 85% in urban areas. A disparity of 9% to the advantage of the rural areas and the exposure variables explained 81.1% of the disparity. Maternal factors explained 49.7% of the explained disparity with education, occupation, and ethnicity being the significant contributors to the explained disparity. Children's birth order and immigration status contributed somewhat to the explained inequality. Conclusion: There was a significant disparity in FVC in Zhejiang province, a disadvantage to the urban areas. Policy recommendations or health interventions to reduce the inequality should be focused on eliminating poverty and women's illiteracy, targeted at migrant children or children from minority ethnicities.


Brain-Tumor Interface-Based MRI Radiomics Models to Determine EGFR Mutation, Response to EGFR-TKI and T790M Resistance Mutation in Non-Small Cell Lung Carcinoma Brain Metastasis.
Preoperative assessment of epidermal growth factor receptor (EGFR) status, response to EGFR-tyrosine kinase inhibitors (TKI) and development of T790M mutation in non-small cell lung carcinoma (NSCLC) patients with brain metastases (BM) is important for clinical decision-making, while previous studies were only based on the whole BM. To investigate values of brain-to-tumor interface (BTI) for determining the EGFR mutation, response to EGFR-TKI and T790M mutation. Retrospective. Two hundred thirty patients from Hospital 1 (primary cohort) and 80 patients from Hospital 2 (external validation cohort) with BM and histological diagnosis of primary NSCLC, and with known EGFR status (biopsy) and T790M mutation status (gene sequencing). Contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) fast spin echo sequences at 3.0T MRI. Treatment response to EGFR-TKI therapy was determined by the Response Evaluation Criteria in Solid Tumors. Radiomics features were extracted from the 4 mm thickness BTI and selected by least shrinkage and selection operator regression. The selected BTI features and volume of peritumoral edema (VPE) were combined to construct models using logistic regression. The performance of each radiomics model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). A total of 7, 3, and 3 features were strongly associated with the EGFR mutation status, response to EGFR-TKI and T790M mutation status, respectively. The developed models combining BTI features and VPE can improve the performance than those based on BTI features alone, generating AUCs of 0.814, 0.730, and 0.774 for determining the EGFR mutation, response to EGFR-TKI and T790M mutation, respectively, in the external validation cohort. BTI features and VPE were associated with the EGFR mutation status, response to EGFR-TKI and T790M mutation status in NSCLC patients with BM. 3 Technical Efficacy: Stage 2.


The effect of laminae lesion on thoraco-lumbar fracture reduction.
The treatment of fractures involving the lumbar spine has been controversial. Laminae lesion may be complete or of the greenstick type (incomplete). Dural tears and nerve root entrapment may accompany these laminae fractures. The aim of this study is twofold, to assess the effect of different types of laminae fractures on the anteriorvertebral height restoration in upper lumbar burst fractures and to determine the incidences of the intraoperatively detected dural tear and neural entrapment in complete and incomplete laminae fractures to choose the optimal treatment. A retrospective review was conducted on 112 patients with 114 lumbar burst fractures treated operatively, age ranged from 17 to 55 years (mean age 32). Male to female ratio was (93%/7%), 8 females. Patients were divided into three groups, group 1 patients without lamina fracture, group 2 patients with complete type lamina fracture and group 3 patients with (percutaneous) incomplete type lamina fractures. All clinical charts and radiologic data of these groups were analyzed for their association with dural tears, neural entrapment and the impact of lamina fracture (complete and incomplete types) on the efficacy of anterior vertebral height restoration. The severity of injury was determined using the ASIA (Modified Frankel scale). Out of 114 upper lumbar burst fractures, lamina fracture occurred in 34 patients (29.8%), complete lamina fracture occurred in 21 patients (61.7%), whereas incomplete lamina fracture occurred in 13 patients (38.3%). Dural tear was detected in 16 patients (47%) and was predominantly higher in complete type lamina fracture 12 patients (57%) when compared to 4 dural tears (30%) in incomplete lamina fractures. Analysis of the data revealed no significant difference in the preoperative anterior vertebral height loss and local kyphotic angle between the three groups. However the anterior vertebral height and local kyhpotic angle restoration were found to be affected by the presence of complete lamina fracture when compared to other groups with incomplete lamina fracture and without lamina fracture (P=0.001). In upper lumbar burst fractures, complete lamina fracture is an indicator of injury severity. When detected preoperatively on CT or MRI scanning, it should be operated by open book laminectomy even if the patient is neurologically intact since it carries a high risk of neural entrapment, and its presence affects the intraoperative postural and instrumental trials for anterior vertebral height restoration.


Cadherin-11 localizes to focal adhesions and promotes cell-substrate adhesion.
Cadherin receptors have a well-established role in cell-cell adhesion, cell polarization and differentiation. However, some cadherins also promote cell and tissue movement during embryonic development and tumour progression. In particular, cadherin-11 is upregulated during tumour and inflammatory cell invasion, but the mechanisms underlying cadherin-11 stimulated cell migration are still incompletely understood. Here, we show that cadherin-11 localizes to focal adhesions and promotes adhesion to fibronectin in Xenopus neural crest, a highly migratory embryonic cell population. Transfected cadherin-11 also localizes to focal adhesions in different mammalian cell lines, while endogenous cadherin-11 shows focal adhesion localization in primary human fibroblasts. In focal adhesions, cadherin-11 co-localizes with β1-integrin and paxillin and physically interacts with the fibronectin-binding proteoglycan syndecan-4. Adhesion to fibronectin mediated by cadherin-11/syndecan-4 complexes requires both the extracellular domain of syndecan-4, and the transmembrane and cytoplasmic domains of cadherin-11. These results reveal an unexpected role of a classical cadherin in cell-matrix adhesion during cell migration.


Sudden unexpected deaths after discharge from the neonatal intensive care unit.
The published evidence on the risk of sudden unexpected death in infants after discharge from the neonatal intensive care unit (NICU) is reviewed, together with the relevance of the various identified potentially modifiable post-natal risk factors, particularly sleeping position. Infants of low birthweight, short gestation, and those with adverse perinatal histories are at substantially increased risk of sudden infant death syndrome (SIDS), but the potential benefits from following the measures designed to reduce the risk of SIDS are proportionally greater than for term infants. The use of home apnoea monitors has not been shown to be of value in preventing SIDS, but the importance of maintaining adequate oxygenation in infants with bronchopulmonary dysplasia is emphasised. Evidence based recommendations for care of infants after discharge from the NICU with a view to reducing the risk of SIDS are presented, and do not differ significantly from those for low-risk infants.