Cervical spinal cord infarction due to impingement of an anomalous right vertebral artery by thoracic osteophyte.
Spinal cord infarction in a young, otherwise healthy individual is a rare occurrence. The anterior spinal artery and posterior spinal arteries are the primary contributors to the vascular supply of the cervical supply, and these arteries arise as descending branches of the vertebral arteries. Historically, many cases have demonstrated individual variations in the vertebral arteries, such as differences in dominancy, patency, origin, and insertion. The clinical significance of these variations remains poorly understood. We present a patient who sustained a spinal cord infarction at C2-C5 resulting in incomplete quadriplegia. The mechanism of injury was unclear, although the patient reported an awkward jumping motion earlier that day that preceded the onset of upper extremity weakness. After resolution of the acute phase, he was diagnosed with "Man-in-the-Barrel" syndrome. Angiographic evaluation revealed an anomalous non-dominant right vertebral artery with several pathological features: origin at the descending aorta, insertion into the right posterior inferior cerebellar artery, and impingement along its course by an anterior thoracic osteophyte. The vertebral arteries play an important role in the vascular supply of the cervical spine. While vertebral artery pathology such as dissection or occlusion have been documented in rare cases to result in spinal cord infarction, this case illustrates an example of clinically significant sequelae that can occur in the setting of anomalous vertebral arteries even in the absence of occlusion or dissection. Furthermore, to our knowledge this is the first reported case of a spinal cord infarction resulting from osteophytic vertebral artery impingement.


Neuropsychological function in ecstasy users: a study controlling for polydrug use.
A number of studies have compared ecstasy users to control groups on various measures of neuropsychological function in order to determine whether ecstasy use results in lasting cognitive deficits. However, few of those studies controlled adequately for non-ecstasy illicit drug use. The aim of this study was to investigate neuropsychological function in chronic ecstasy users while controlling for polydrug use. Neuropsychological function was assessed in four groups-30 current 3,4-methylenedioxymethamphetamine (MDMA) users with a little history of illicit drug use other than ecstasy and cannabis, 30 polydrug controls, 30 drug-naïve controls and 20 ex-MDMA users-using a battery of well-validated, computerized neuropsychological tests. The battery focused on memory, executive function, impulsivity and risk-taking. Few differences were apparent between the groups, and on no measure were the current MDMA users impaired significantly relative to the polydrug controls. However, within the current MDMA users, questionnaire-measured impulsivity correlated with performance on a number of tests-a relationship that was not apparent in the controls. These data highlight the complexity in understanding the current ecstasy literature and suggest that some individuals may be particularly vulnerable to cognitive impairment following chronic use. Although no differences were identified between the current MDMA users and the controls, trait impulsiveness was significantly correlated with impairment on a number of neuropsychological outcome measures in the MDMA users, but not in the controls. These data suggest that impulsive individuals may be those most at risk for the development of cognitive impairment following chronic ecstasy use.


A model for analyzing the aging of local populations: Illinois counties between 1950 and 1970.
The article develops a model which explains the aging of local populations, expressed in terms of percent of the population over sixty-five years, in terms of the net movement of the young and the elderly, as well as socio-economic characteristics of the local population. The model is illustrated for data from Illinois counties for the period 1950-1960 and 1960-1970. The model represents the data for the 1960's more accurately than the data for the 1950's.


Notch signaling: numb makes the difference.
During Drosophila sensory organ precursor cell development, Numb segregates asymmetrically and functions as a cell fate determinant. Recent work now demonstrates in vivo that Numb inactivates Notch by promoting its endocytosis.


The increase of neuropathic symptoms in diabetic patients is related with osteopenia.
To investigate the relationship between the intensity of neuropathic pain and the severity of osteopenia in type 2 diabetic patients with painful diabetic peripheral neuropathy (painful DPN). In 220 patients with type 2 diabetes included in the screening, the presence of neuropathic pain was evaluated using the Douleur Neuropathique 4 Questions (DN4) scoring system. One hundred forty-five patients with painful DPN were identified and included in the study. Socio-demographic and laboratory evaluations were made and bone mineral density (BMD) of these patients was evaluated by the dual-energy x-ray absorptiometry (DEXA) method. There was a significant correlation between the neuropathic pain score and the total T scores of the lumbar spine and femur in patients with painful DPN. According to the regression analysis (standard coefficients), the DN4 score (0.498); the level of vitamin D (- 0.246) and the female sex (0.236) for the lumbar spine region; age (0.387); DN4 score (0.261); and vitamin D level (- 0.155) for the femur region were independently influencing factors on the development of osteoporosis. When osteoporosis (T score ≤ - 2.5) of the lumbar spine was analyzed by binary logistic regression, the risk of osteoporosis in women was 4.4 times higher, and the risk increased with increasing DN4 score. The increase of neuropathic symptoms in patients with DPN is an effective and important factor in the development of diabetic osteopenia.


Role of neoadjuvant chemotherapy in the treatment of multiple colorectal metastases to the liver.
The role of neoadjuvant chemotherapy for patients with multiple (five or more) bilobar hepatic metastases irrespective of initial resectability is still under scrutiny. The purpose of this study was to compare the outcome of hepatectomy alone with that of hepatectomy after neoadjuvant chemotherapy for multiple bilobar hepatic metastases from colorectal cancer. Retrospective data were collected from 71 patients after hepatectomy for five or more bilobar liver tumours. The outcome of 48 patients treated by neoadjuvant chemotherapy followed by hepatectomy was compared with that of 23 patients treated by hepatectomy alone. Patients who received neoadjuvant chemotherapy had better 3- and 5-year survival rates from the time of diagnosis than those who did not (67.0 and 38.9 versus 51.8 and 20.7 per cent respectively; P = 0.039), and required fewer extended hepatectomies (four segments or more) (39 of 48 versus 23 of 23; P = 0.027). Multivariate analysis showed neoadjuvant chemotherapy to be an independent predictor of survival. In patients with bilateral multiple colorectal liver metastases, neoadjuvant chemotherapy before hepatectomy was associated with improved survival and enabled complete resection with fewer extended hepatectomies.


Mechanism of salidroside in the treatment of endometrial cancer based on network pharmacology and molecular docking.
Salidroside is a natural product of phenols, which has a wide scape of pharmacological effects, but its pharmacological effects and molecular mechanism on endometrial cancer are not clear. To systematically explore the pharmacological effects and molecular mechanisms of salidroside on endometrial cancer through the method of network pharmacology. The possible target genes of salidroside were obtained through different pharmacological databases and analysis platforms, and then the relevant target genes of endometrial cancer were obtained through the GeneCards website, and the target genes were uniformly converted into standardized gene names with Uniprot. The collected data were then processed to obtain common target genes and further analyzed through the String website to construct a protein-protein interaction (PPI) network, followed by gene ontology (GO) functional annotation and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analysis. We further interpreted the molecular mechanism of salidroside for the treatment of endometrial cancer by constructing a "drug component-target gene-disease" network. Finally, we performed molecular docking to validate the binding conformation between salidroside and the candidate target genes. There were 175 target genes of salidroside after normalization, among which 113 target genes interacted with endometrial cancer. GO analysis indicated that the anti-endometrial cancer effect of salidroside may be strongly related to biological processes such as apoptosis and response to drug. KEGG analysis indicated that its mechanism may be related to pathway in cancer and PI3K-AKT signaling pathway. Molecular docking showed that salidroside had high affinity with five key genes. Based on the novel network pharmacology and molecular docking validation research methods, we have revealed for the first time the potential mechanism of salidroside in the therapy of endometrial cancer.


Dentritic range of the neurons of the intermediate gray at the levels of the first and second lumbar segments of the spinal cord in the cat. 3. The range of dendrites of the lateral region neurons.
The first and second lumbar segments of the spinal cord in kittens and mature cats were examined with Golgi method. It was found that the dendrites of large and medium neurons situated in the lateral region of the intermediate gray penetrated lamina V dorsally, and lamina VIII and motor nuclei ventrally. Laterally these dendrites reached the lateral horns and even the lateral funicles. Paracentrally they ran along the whole intermediate gray of the cord, entered the thoracic nucleus, and even the white commisure.


Phenotypic and molecular characterization of Staphylococcus aureus strains of veterinary, dairy and human origin.
Austrian veterinary (n=91), dairy (n=86), and human strains (n=48) of Staphylococcus aureus were tested for various phenotypic properties including clumping factor, egg-yolk reaction, production of thermonuclease and susceptibility to 14 antibiotics. In addition the expression of enterotoxins (A-E), and the presence of enterotoxin genes sea to sej and tst was determined. Significant differences in antimicrobial susceptibility were found with 84.6% of veterinary, 57.0% of dairy, and 20.8% of human strains susceptible to all antibiotics tested (P<0.0005). More human strains produced enterotoxins (41.7%) than veterinary (9.9%) and dairy strains (12.6%) while 40.7% and 38.5% of veterinary, 47.7% and 52.3% of dairy, and 77.1% and 87.5% of human strains were se- and tst-positive, respectively. AFLP analysis revealed nine clusters with over- or under-representation of strains with specific characteristics. Strains clustered according to origin (veterinary, dairy, and human) and/or presence of toxin genes and antimicrobial resistance.


The physical basis of osmosis.
Osmosis is an important force in all living organisms, yet the molecular basis of osmosis is widely misunderstood as arising from diffusion of water across a membrane separating solutions of differing osmolarities, and hence different water concentrations. In 1923, Peter Debye proposed a physical model for a semipermeable membrane emphasizing the repulsive forces between solute molecules and membrane that prevent the solute from entering the membrane. His work was hardly noticed at the time and slipped out of view. We show that Debye's analysis of van 't Hoff's law for osmotic equilibrium also provides a consistent and plausible mechanism for osmotic flow. A difference in osmolyte concentrations in solutions separated by a semipermeable membrane leads to different pressures at the two water-membrane interfaces because the total repulsive force between solute molecules and the membrane is different at the two interfaces. Water is therefore driven through the membrane for exactly the same reason that pure water flows in response to an imposed hydrostatic pressure difference. In this paper, we present the Debye model in both equilibrium and flow conditions. We point out its applicability regardless of the nature of the membrane with examples ranging from the predominantly convective flow of water through synthetic membranes and capillary walls to the purely diffusive flow of independent water molecules through a lipid bilayer and the flow of a single-file column of water molecules in narrow protein channels.


Stability of human chorionic gonadotropin and its alpha subunit in human blood.
The stability of human chorionic gonadotropin (hCG) and its alpha-subunit in whole blood, plasma, and serum under a variety of sample handling conditions commonly encountered in clinics, hospital wards, physician's offices, and clinical service laboratories was investigated with the use of radioreceptor assay, radioimmunoassays, as well as hormone integrity determinations. The results clearly demonstrate that hCG and its alpha-subunit are stable in unfrozen whole blood, plasma, and serum for at least 6 days and in frozen plasma and serum samples for at least 6 months. Repeated freezing and thawing of the samples during this period had no effect. Separation of plasma or serum from erythrocytes is not needed for at least 12 hours. Hemolysis in samples resulted in a 20% to 30% decrease in hCG and its alpha-subunit levels, which may be attributable to sample dilution.


A novel isoquinoline derivative exhibits anti-inflammatory properties and improves the outcomes of endotoxemia.
Sepsis initiates an inflammatory response that causes widespread injury, and candidates for related myocardial depressant factors include cytokines and nitric oxide (NO). Nuclear factor kappa-B (NF-κB) stimulated by toll-like receptor 4 activation in sepsis mediates the transcription of multiple proinflammatory genes. These inflammatory mediators can cause myocardial dysfunction, which may deteriorate sepsis outcomes. To address this risk, we investigated the potential beneficial effects of a novel isoquinolines derivative, CYY054c, in LPS-induced inflammatory response leading to endotoxemia. The effects of CYY054c on cytokine and inflammatory-related protein production were evaluated in lipopolysaccharide (LPS)-stimulated macrophages. To determine whether CYY054c alleviates inflammatory storm-induced myocardial dysfunction in vivo, LPS was injected in rats, and cardiac function was measured by a pressure-volume loop. CYY054c inhibited LPS-induced NF-κB expression in macrophages and reduced the release of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In the animal studies, CYY054c alleviated LPS-upregulated plasma TNF-α, IL-1β, IL-6, and NO concentrations, as well as cardiac monocyte chemotactic protein-1, iNOS, and COX-2 expression in rats, contributing to the improvement of cardiac function during endotoxemia. The reduction of NF-κB-mediated inflammatory mediators and the maintenance of hemodynamic performance by CYY054c improved the outcomes during endotoxemia. CYY054c may be a potential therapeutic agent for sepsis.


Irradiation is not sufficient to eradicate residual immortalized erythroid cells in in vitro-generated red blood cell products.
The generation of immortalized erythroid progenitor cell lines capable of producing enough red blood cells (RBCs) for blood transfusion typically requires the overexpression of oncogenes in stem cells or progenitor cells to permanently proliferate immature cells. It is essential that any live oncogene-expressing cells are eliminated from the final RBC products for clinical use. It is believed that safety issues may be resolved by using a leukoreduction filter or by irradiating the final products, as is conventionally done in blood banks; however, this has never been proven to be effective. Therefore, to investigate whether immortalized erythroblasts can be completely removed using γ-ray irradiation, we irradiated the erythroblast cell line, HiDEP, and the erythroleukemic cell line, K562 that overexpress HPV16 E6/E7. We then analyzed the extent of cell death using flow cytometry and polymerase chain reaction (PCR). The cells were also subjected to leukoreduction filters. Using γ-ray irradiation at 25 Gy, 90.4% of HiDEP cells, 91.6% of K562-HPV16 E6/E7 cells, and 93.5% of non-transduced K562 cells were dead. In addition, 5.58 × 107 HiDEP cells were passed through a leukoreduction filter, and 38 intact cells were harvested, revealing a filter removal efficiency of 99.9999%. However, both intact cells and oncogene DNA were still detected. Irradiation cannot induce total cell death of oncogene-expressing erythroblasts and leukocyte filter efficiency is not 100%. Therefore, our findings imply that for clinical applications, safer methods should be developed to completely remove residual nucleated cells from cell line-derived RBC products.


Identification of the B-cell epitopes on N protein of type 2 porcine reproductive and respiratory syndrome virus, using monoclonal antibodies.
Porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein (N) is the immunodominant region of PRRSV viral proteins. However, B cell epitopes present on N protein have not been well characterized. In this study, The ORF7 gene was amplified by RT-PCR and inserted into the expression vector pET-28a, the constructed pET-28a-N was transformed into Escherichia coli BL21. After expression, purification and identification, the recombined N protein was used as the target to generate monoclonal antibody (mAb). Strains of hybridoma cells secreting anti-N mAbs were obtained by the hybridoma technique. Three of them (named 1G4, 1C6, 3D11) were specifically reacted with PRRSV by IPMA and IFA. To identify the B-cell epitopes within PRRSV N protein, six serial overlapping synthesized peptides (P1-P6) covering the whole region of N were used to define the epitopes recognized by 1G4, 1C6, 3D11. Importantly, after the identification of dot-ELISA and indirect ELISA, we found that 1-15aa was a new epitope which had never been reported before and that it was highly conserved among some HP-PRRSV isolates of type 2 PRRSV. The results of this study might open new perspectives on the detection of PRRSV and have important implications for studing the structure of the N protein.


Repair of Lafosse I subscapularis injury adds no additional value in anterosuperior rotator cuff injury.
The study aimed to explore the additional value of repair of Lafosse I subscapularis injury compared with debridement in anterosuperior rotator cuff injury. The prospective study was conducted on a total of 41 patients with supraspinatus tendon tear combined with Lafosse I subscapularis injury. Eighteen patients were divided into the repair group and 23 patients were divided into the non-repair group. The two groups were compared for intraoperative parameters, pain score, range of motion of the shoulder joint, shoulder joint function and quality of life (QoL) at pre-operation, 3 and 6 months postoperatively and the final follow-up visit. The width of supraspinatus tendon tear did not exceed 3 cm and did not retract beyond the glenoid in among patients. There was no statistical difference of preoperative data between two groups, including age, course of disease, positive Jobe test, positive Bear-hug test, positive Lift-off test, Patte stage, longitudinal tear and pain severity (P > 0.05). Compared to preoperative levels, the severity of pain, ASES scores and EQ-5D-3L scores were significantly lower at 3 and 6 months postoperatively and the final position (P < 0.05). However, there was no statistical difference in pain severity, ASES scores and EQ-5D-3L scores between repair group and non-repair group (P > 0.05). Similarly, compared to preoperative levels, the range of motion of shoulder joint was significantly improved after operation, including internal rotation, external rotation, forward flexion and elevation (P < 0.05). However, there was no statistical difference in range of motion of shoulder joint between repair group and non-repair group (P > 0.05). Operative treatment can effectively lessen severity of pain in the patients, improve shoulder joint function, increase the range of motion of the shoulder joint and enhance the QoL in treating anterosuperior rotator cuff injury. However, repair of subscapularis brings no benefit compared to debridement in treating supraspinatus tendon tear combined with Lafosse I subscapularis injury.


On the metabolism of the mycotoxin deoxynivalenol in the isolated perfused rat liver.
An isolated rat liver was perfused with deoxynivalenol (DON) at a dose of 3 mg in a recirculating perfusion system. To identify glucuronide conjugates equal amounts of bile samples, perfusate and liver homogenates were incubated with and without (control) a β-glucuronidase preparation and analyzed by thin layer chromatography and capillary gas liquid chromatography - chemical ionization mass spectrometry. A total of 40.4% of the administered dose of DON was found to be conjugated with glucuronic acid (perfusate 20.4%, bile 19.2%, liver 0.8%), while only 1.3% of the parent DON (perfusate 1.1%, bile 0.2%) was detected. The cleavage of DON-glucuronide was demonstrated by incubating DON-glucuronide containing bile samples with intestine contents under anaerobic conditions.


Separation of enantiomers on chiral stationary phase based on cellulase: Effect of preparation method and silica particle diameters on chiral recognition ability.
Cellulase (Cel) was immobilized onto aminopropyl-silica gels via its amino and carboxy groups, respectively, using N,N'-disuccinimidyl carbonate, and 1-ethyl-3-(3'-dimethylaminopropyl)carbodimide and N-hydroxysulfosuccinimide. They were termed N-Cel and C-Cel, respectively. Despite their smaller retention factors on a C-Cel column, the enantioseparation factors and resolution of β-blockers, propranolol, alprenolol, oxprenolol and pindolol, were similar with N- and C-Cel columns. In addition, C-Cel was prepared using aminopropyl-silica gels, whose nominal particle diameters were 5 and 3, and 2.1μm, respectively. A C-Cel column prepared with 2.1-μm aminopropyl-silica gels gave the highest enantioselectivity and column efficiency among three C-Cel columns. Furthermore, the influence of N,N-dimethyl-n-octylamine (DMOA) or cellobiose concentrations on the retentivity and enantioselectivity for β-blockers on a C-Cel column was investigated. The results indicate that single-site competition of β-blockers with DMOA or cellobiose on the catalytic binding site of Cel and the further bindings at the secondary site in a non-competitive fashion could occur. Furthermore, the enantioselective bindings of β-blockers could occur at the catalytic biding cite of Cel and at the secondary binding site.


Acclimatization in first-time hearing aid users using three different fitting protocols.
To study auditory acclimatization and outcome in first time hearing aid users fitted with state of the art hearing aids as a function of different hearing aid fitting protocols. Twenty-eight adult subjects participated in the study. Each subject was assigned to one of three study groups (named audiologist driven, AD; patient driven, PD; set-to-target, STT according to the fitting protocol used) and fitted with digital hearing aids (Bernafon Symbio). Speech recognition scores were measured in aided and unaided conditions over a 6-month period. Five subjects (three from the PD-group, two from the STT group) decided to withdraw from the study during the 6-month-study period, leaving a total of 23 complete data sets for analysis. Aided speech understanding increased significantly over this time period in all three groups. However, average hearing aid insertion gain changes were small over the same period. There were no statistically significant differences in aided or unaided speech recognition scores between the three groups after 2 weeks or after 6 months. On average, twice as many fine tunings of the hearing aids were requested by the patients in the AD and the STT group than in the PD group and subjects in the AD and STT group used their hearing aids approximately twice as much as subjects in the PD group. The substantial increase in speech intelligibility without significant changes of the insertion gain of the hearing aids over a 6-month period in all three groups suggests a significant acclimatization effect. Although the speech recognition with hearing aids did not differ significantly among the three study groups after 6 months, the lower average wearing time and the higher number of withdrawals from the study in the PD group suggest that the patients' needs are not adequately met. In terms of aided speech recognition scores and hearing aid wearing time the STT group and the AD group were very similar. However, comments of the patients and the higher rate of withdrawals in the STT group suggest an over-all advantage for the AD fitting protocol.


Gramine-derived Bromo-alkaloids Activating NF--kB-dependent Transcription from the Marine Hydroid Abietinaria abietina.
Two new natural products, 6-bromogramine (1) and bis-6-bromogramine (2) were isolated from the marine hydroid A bietinaria abietina and their structures were established using NMR and MS analysis. Compounds 1 and 2 activate NF-cB-dependent transcriptional activity in JB6 Cl 41 NF-KB cells at 1.6 AM concentrations.


Derivation and characterization of porcine vocal fold extracellular matrix scaffold.
To optimize decellularization of porcine vocal folds (VF) and quantify human bone marrow-derived mesenchymal stem cell (BM-MSC) interactions with this matrix to provide a foundation for regenerative approaches to VF repair. Vocal folds were dissected from porcine larynges and three decellularization protocols were compared, each consisting of washes and mechanical agitations with different combinations of reagents. DNA content was analyzed via Quant-iT Picogreen assay and hematoxylin and eosin staining. Bone marrow-derived MSCs were then seeded onto the decellularized VF matrices. Morphology, metabolic activity, DNA content, and gene expression were assessed using LIVE/DEAD Cell Viability, alamarBlue Cell Viability Assay, Quant-iT Picogreen assay, and quantitative polymerase chain reaction, respectively. The most successful decellularization protocol removed 95% DNA content within 1 day, compared to several days required for previously described protocols. Histology confirmed the retention of extracellular matrix (ECM) and its components, including glycosaminoglycans, collagen, and fibrin, while void of nuclear/cellular content. Decellularized scaffolds were then seeded with BM-MSCs. Similar DNA quantities were observed after 24 hours of seeding within the VF-ECM scaffold when compared to cells on tissue culture plastic (TCP). LIVE/DEAD staining of the seeded VF-ECM confirmed excellent cell viability, and the metabolic activity of BM-MSCs increased significantly on VF-ECM compared to TCP. Endoglin gene expression decreased, suggestive of differentiation. Porcine VFs can be efficiently decellularized within 5 hours using a combination of sodium deoxycholate and peracetic acid. Decellularized VF-ECM supported attachment and growth of human BM-MSCs, with evidence of differentiation. N/A.


Effect of ATP on liver function tests in experimental diabetes.
Liver function tests were performed in severe and mild diabetic rats and under the influence of ATP. In mild diabetics the serum cholesterol was significantly increased, while in severe diabetes the serum cholesterol was significantly lower than in mild diabetes. The decreased serum cholesterol in severe diabetes may be an indication for the development of fatty liver. The serum alkaline phosphatase and serum bilirubin were significantly increased in both the severe and mild diabetic states, while the thymol turbidity test was insignificantly changed in both states of diabetes. Serum albumin was significantly decreased in 10 days mild diabetes, while it was insignificantly changed in 48 hrs severe diabetic animals. The effect of ATP was investigated in mild diabetes. ATP resulted in a significant increase in serum albumin and a decrease in total globulins with the resultant increase in A/G ratio. The serum alkaline phosphatase exhibited a significant reduction under the influence of ATP. The elevated cholesterol of mild diabetic rats remained significantly elevated and was not reduced by ATP, though the fat content of the liver showed a significant reduction. This may be due to more rapid mobilisation of fat from the liver under the influence of ATP. ATP showed no significant effect on serum bilirubin and thymol turbidity test. the histopathological examination of the liver revealed that administration of ATP to alloxan diabetic rats had a beneficial effect. It resulted in disappearrance of the fat globules from the liver cells.


Simulation vs. Understanding: A Tension, in Quantum Chemistry and Beyond. Part A. Stage Setting.
We begin our tripartite Essay with a triangle of understanding, theory and simulation. Sketching the intimate tie between explanation and teaching, we also point to the emotional impact of understanding. As we trace the development of theory in chemistry, Dirac's characterization of what is known and what is needed for theoretical chemistry comes up, as does the role of prediction, and Thom's phrase "To predict is not to explain." We give a typology of models, and then describe, no doubt inadequately, machine learning and neural networks. In the second part, we leave philosophy, beginning by describing Roald's being beaten by simulation. This leads us to artificial intelligence (AI), Searle's Chinese room, and Strevens' account of what a go-playing program knows. Back to our terrain-we ask "Quantum Chemistry, † ca. 2020?" Then move to examples of AI affecting social matters, ranging from trivial to scary. We argue that moral decisions are hardly to be left to a computer. At this point, we try to pull the reader up, giving the opposing view of an optimistic, limitless future a voice. But we don't do justice to that view-how could we? We return to questioning the ascetic dimension of scientists, their romance with black boxes. Onward: In the 3rd part of this Essay, we work our way up from pessimism. We trace (another triangle!) the special interests of experimentalists, who want the theory we love, and reliable numbers as well. We detail in our own science instances where theory gave us real joy. Two more examples-on magnetic coupling in inorganic diradicals, and the way to think about alkali metal halides, show us the way to integrate simulation with theory. Back and forth is how it should be-between painfully-obtained, intriguing numbers, begging for interpretation, in turn requiring new concepts, new models, new theoretically grounded tools of computation. Through such iterations understanding is formed. As our tripartite Essay ends, we outline a future of consilience, with a role both for fact-seekers, and searchers for understanding. Chemistry's streak of creation provides in that conjoined future a passage to art and to perceiving, as we argue we must, the sacred in science.


Cognitive-motivational determinants of fat food consumption in overweight and obese youngsters: the implicit association between fat food and arousal.
Cognitive-motivational accounts of fat food intake propose an association between fat food and action dispositions, which are according to the biphasic emotion theory of Lang [(1995). The emotion probe. Studies of motivation and attention. American Psychologist, 50, 372-385; Lang, P.J., Bradley, M.M., & Cuthbert, M.M. (1997). Motivated attention: Affect, activation and action. In P.J. Lang, R.F. Simons & M.T. Balaban (Eds.). Attention and orienting: Sensory and motivational processes (pp. 97-134). Hillsdale, NJ: Lawrence Erlbaum Associates, Inc.] characterized by high levels of arousal. In two experiments, this association was investigated in lean and overweight youngsters. In the first experiment, 29 overweight and 29 lean youngsters conducted two Implicit Association Tasks (IAT; Greenwald, A.G., McGhee, D.E., & Schwartz, J.L. (1998). Measuring individual differences in implicit cognition: The implicit association test. Journal of Personality and Social Psychology, 74, 1464-1480.). In a positive arousal IAT, implicit associations between fat vs. lean food, and high and low arousal words with a positive valence were assessed. In a negative arousal IAT, high and low arousal words with a negative valence were used. A second experiment was conducted to replicate Experiment 1 in 29 youngsters with severe obesity and 29 lean peers. The results revealed strong implicit associations between fat food and arousal in both the overweight and the control group. No differences were found between the groups, nor between the positive and the negative arousal task. These results are related to cognitive-motivational theories of fat food intake.


[Mechanism of inhibitory effect of angiostatin on plasminogen activation by its physiologic activators].
The influence of angiostatin K1-4.5--a fragment of the heavy chain of plasmin and a powerful inhibitor of angiogenesis--on kinetic parameters (k(Pg) and K(Pg)) of human Glu-plasminogen activation under the action of urokinase (uPA) not having affinity for fibrin and fibrin-specific tissue plasminogen activator (tPA) was investigated. Angiostatin does not affect the k(Pg) value, but increases the value K(Pg) urokinase plasminogen activation. A decrease in the k(Pg) value and an increase in the K(Pg) value were found for fibrin-stimulated plasminogen activation by tPA with increasing concentrations of angiostatin. The obtained results show that angiostatin is competitive inhibitor of the uPA activator activity, while it inhibits the activator activity of tPA by mixed type. Such an influence ofangiostatin on the kinetic constants ofthe urokinase plasminogen activation suggests that angiostatin dose dependent manner replaces plasminogen in the binary enzyme-substrate complex uPA-Pg. In case of fibrin-stimulated plasminogen activation by tPA, both zymogen and tPA are bound to fibrin with formation of the effective triple tPA-Pg-fibrin complex. Angiostatin replaces plasminogen both from the fibrin surface and from the enzyme-substrate tPA-Pg complex that leads to a decrease in k(Pg) and an increase in K(Pg) of plasminogen activation. Inhibition constants by angioststin (Ki) of plasminogen-activator activities of uPA and tPA determined by Dixon method were found to be 0.59 +/- 0.04 and 0.12 +/- 0.05 microM, respectively.


Automated Facial Acne Lesion Detecting and Counting Algorithm for Acne Severity Evaluation and Its Utility in Assisting Dermatologists.
Although lesion counting is an evaluation method that effectively analyzes facial acne severity, its usage is limited because of difficult implementation. We aimed to develop and validate an automated algorithm that detects and counts acne lesions by type, and to evaluate its clinical applicability as an assistance tool through a reader test. A total of 20,699 lesions (closed and open comedones, papules, nodules/cysts, and pustules) were manually labeled on 1213 facial images of 398 facial acne photography sets (frontal and both lateral views) acquired from 258 patients and used for training and validating algorithms based on a convolutional neural network for classifying five classes of acne lesions or for binary classification into noninflammatory and inflammatory lesions. In the validation dataset, the highest mean average precision was 28.48 for the binary classification algorithm. Pearson's correlation of lesion counts between algorithm and ground-truth was 0.72 (noninflammatory) and 0.90 (inflammatory), respectively. In the reader test, eight readers (100.0%) detected and counted lesions more accurately using the algorithm compared with the reader-alone evaluation. Overall, our algorithm demonstrated clinically applicable performance in detecting and counting facial acne lesions by type and its utility as an assistance tool for evaluating acne severity.


Synaptic connections between primary trigeminal afferents and accessory abducens motoneurons in the monitor lizard, Varanus exanthematicus.
We studied the anatomical pathway underlying the nictitating reflex in the monitor lizard Varanus exanthematicus by the anterograde degeneration technique combined with retrograde transport of horseradish peroxidase (HRP) and electron microscopy. After application of HRP to the abducens nerve, retrogradely labeled neurons were observed in the ipsilateral principal and accessory abducens motor nuclei. The transection, in the same experiments, of the root of the trigeminal nerve resulted in massive degeneration of myelinated fibers in the descending trigeminal tract. In the ipsilateral accessory abducens nucleus, we observed electron-dense degenerating axon terminals that formed asymmetric synaptic contacts with the primary and secondary dendrites of large neurons retrogradely labeled with HRP. A few of the degenerating terminals could be traced in serial sections to myelinated axons. No terminal degeneration was found in the contralateral accessory abducens nucleus or in the ipsilateral and contralateral principal abducens nuclei. The present results are complementary with the findings of previous light microscopic experimental tracing studies (Barbas-Henry, H.A., and A.H.M. Lohman, J. Comp. Neurol. 1986, 254:314-329; see also J. Comp. Neurol. 1988, 267:370-386), and strongly suggest the existence in Varanus of a monosynaptic, unilateral reflex pathway in which trigeminal fibers, presumably originating from the cornea, synapse with motoneurons of the bursalis and retractor bulbi muscles, which are located in the accessory abducens nucleus. This monosynaptic pathway may mediate a rapid unilateral eyeball retraction and nictitating membrane extension.


Simultaneous quantification of eight hemoglobin adducts of genotoxic substances by isotope-dilution UHPLC-MS/MS.
Various genotoxic carcinogens ubiquitously present in the human environment or respective reactive metabolites form adducts in DNA and proteins, which can be used as biomarkers of internal exposure. For example, the mass spectrometric determination of Val adducts at the N-termini of hemoglobin (Hb) peptide chains after cleavage by an Edman degradation has a long tradition in occupational medicine. We developed a novel isotope-dilution UHPLC-MS/MS method for the simultaneous quantification of Val adducts of eight genotoxic substances in Hb after cleavage with fluorescein-5-isothiocyanate (FIRE procedure™). The following adducts were included [sources in square brackets]: N-(2,3-dihydroxypropyl)-Val [glycidol], N-(2-carbamoylethyl)-Val [acrylamide], N-(2-carbamoyl-2-hydroxyethyl)-Val [glycidamide], N-((furan-2-yl)methyl)-Val [furfuryl alcohol], N-(trans-isoestragole-3'-yl)-Val [estragole/anethole], N-(3-ketopentyl)-Val [1-penten-3-one], N-(3-ketooctanyl)-Val [1-octene-3-one], and N-benzyl-Val [benzyl chloride], each of which was quantified with a specific isotope-labeled standard. The limits of quantification were between 0.014 and 3.6 pmol/g Hb (using 35 mg Hb per analysis); other validation parameters were satisfactory according to guidelines of the U.S. Food and Drug Administration. The quantification in erythrocyte samples of human adults (proof of principle) showed that the median levels of Hb adducts of acrylamide, glycidamide, and glycidol were found to be significantly lower in six non-smokers (25.9, 12.2, and 4.7 pmol/g Hb, respectively) compared to those of six smokers (69.0, 44.2, and 8.6 pmol/g Hb, respectively). In summary, the method surpasses former techniques of Hb adduct quantification due to its simplicity, sensitivity, and accuracy. It can be extended continuously with other Hb adducts and will be used in epidemiological studies on internal exposure to carcinogens.


Sleep Disturbance during Infection Compromises Tfh Differentiation and Impacts Host Immunity.
Although the influence of sleep quality on the immune system is well documented, the mechanisms behind its impact on natural host immunity remain unclear. Meanwhile, it has been suggested that neuroimmune interactions play an important role in this phenomenon. To evaluate the impact of stress-induced sleep disturbance on host immunity, we used a murine model of rapid eye movement sleep deprivation (RSD) integrated with a model of malaria blood-stage infection. We demonstrate that sleep disturbance compromises the differentiation of T follicular helper cells, increasing host susceptibility to the parasite. Chemical inhibition of glucocorticoid (Glcs) synthesis showed that abnormal Glcs production compromised the transcription of Tfh-associated genes resulting in impaired germinal center formation and humoral immune response. Our data demonstrate that RSD-induced abnormal activation of the hypothalamic-pituitary-adrenal axis drives host susceptibility to infection. Understanding the impact of sleep quality in natural resistance to infection may provide insights for disease management.


Identification of novel therapeutic target genes in acquired lapatinib-resistant breast cancer by integrative meta-analysis.
Acquired resistance to lapatinib is a highly problematic clinical barrier that has to be overcome for a successful cancer treatment. Despite efforts to determine the mechanisms underlying acquired lapatinib resistance (ALR), no definitive genetic factors have been reported to be solely responsible for the acquired resistance in breast cancer. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets related to breast cancer with ALR, using the R-based RankProd package. From the meta-analysis, we were able to identify a total of 990 differentially expressed genes (DEGs, 406 upregulated, 584 downregulated) that are potentially associated with ALR. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs showed that "response to organic substance" and "p53 signaling pathway" may be largely involved in ALR process. Of these, many of the top 50 upregulated and downregulated DEGs were found in oncogenesis of various tumors and cancers. For the top 50 DEGs, we constructed the gene coexpression and protein-protein interaction networks from a huge database of well-known molecular interactions. By integrative analysis of two systemic networks, we condensed the total number of DEGs to six common genes (LGALS1, PRSS23, PTRF, FHL2, TOB1, and SOCS2). Furthermore, these genes were confirmed in functional module eigens obtained from the weighted gene correlation network analysis of total DEGs in the microarray datasets ("GSE16179" and "GSE52707"). Our integrative meta-analysis could provide a comprehensive perspective into complex mechanisms underlying ALR in breast cancer and a theoretical support for further chemotherapeutic studies.


Effects of the antioxidants Trolox, Tiron and Tempol on neutrophil extracellular trap formation.
Neutrophils can entrap and kill pathogens by releasing of neutrophil extracellular traps (NETs), in addition to their routine functions such as phagocytosis and degranulation. NETs consist of a DNA backbone supplemented by multiple bactericidal proteins from the nucleus, the cytoplasm and the granules. Neutrophils release NETs after their activation by a number of physiological and pharmacological stimuli. In addition to the antimicrobial function, NETs are involved in the pathogenesis of various autoimmune and inflammatory diseases. Since NET formation predominantly depends on the generation of reactive oxygen species (ROS), all substances that are capable of scavenging ROS or inhibiting the enzymes responsible for their synthesis should prevent ROS-associated NET release. The aim of this study was to test substances with an antioxidant activity, such as Trolox, Tiron, and Tempol, for their capacity to inhibit NET formation by primary human neutrophils in vitro. We revealed for the first time an inhibitory effect of Trolox on ROS-dependent NET release. We also established a suppressive effect of Tempol on NET formation that manifested itself in a wide range of concentrations. In this study, no inhibitory influence of Tiron on NET release was revealed. All tested substances exerted a significant dose-dependent antioxidative effect on ROS generation induced by phorbol 12-myristate 13-acetate (PMA). We suggest that the antioxidants Trolox and Tempol should be recommended for treating autoimmune and inflammatory diseases that implicate ROS-dependent NET release.


Quercitrin loaded cyclodextrin based nanosponge as a promising approach for management of lung cancer and COVID-19.
Lung cancer and pandemic acute respiratory disease, COVID-19, are examples of the most worldwide widespread diseases. The aim of the current study is to develop cyclodextrin based nanosponge (CD-NS) for loading the flavonoid drug, quercitrin (QCT). This is to improve its solubility in an attempt to enhance its activity against lung cancer as well as SARS-CoV-2 virus responsible for COVID-19. Preparation of CD-NS was performed by ultrasound-assisted synthesis method. Two CDs were employed, namely, β cyclodextrin (βCD) and 2-hydroxy propyl-β-cyclodextrin (2-HPβCD) that were crosslinked with diphenyl carbonate, one at a time. QCT loaded CD-NS revealed entrapment efficiency and particle size ranged between 94.17 and 99.03% and 97.10-325.90 nm, respectively. QCT loaded 2-HPβCD-NS revealed smaller particle size compared with that of QCT loaded βCD-NS. Zeta potential absolute values of the prepared formulations were >20 mV, indicating physically stable nanosystems. The selected formulations were investigated by Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscopy which proved the formation of QCT loaded CD-NS exhibiting porous structure. QCT exhibited partial and complete amorphization in βCD-NS and 2-HPβCD-NS, respectively. In vitro release revealed an improved release of QCT from CD-NS formulations. The biological activity of free QCT and QCT loaded CD-NS was investigated against lung cancer cell line A549 as well as SARS-CoV-2 virus. The results revealed that IC50 values of free QCT against lung cancer cell line A549 and SARS-CoV-2 were higher than those exhibited by QCT loaded CD-NS by 1.57-5.35 and 5.95-26.95 folds, respectively. QCT loaded 2-HPβCD-NS revealed enhanced in vitro release and superior biological activity compared with QCT loaded βCD-NS.


Improved nonclinical pharmacokinetics and biodistribution of a new PPAR pan-agonist and COX inhibitor in nanocapsule formulation.
We report the in vitro release profile and comparative pharmacokinetics and biodistribution of a new peroxisome proliferator-activated receptor-γ agonist and cyclooxygenase inhibitor (Lyso-7) free or associated to poly(D,L-lactic acid) nanocapsules (NC) after intravenous administration in mice. Lyso-7 pertains to the class of insulin-sensitizing agents that shows potential beneficial effects in diabetes therapy. Monodispersed Lyso-7 NC with a mean diameter of 273 nm with high encapsulation efficiency (83%) were obtained. Lyso-7 dissolution rate was reduced (2.6-fold) upon loading in NC. The pharmacokinetic parameters were determined using a non-compartmental approach. In comparison with Lyso-7 in solution, the plasma-AUC increased 14-fold, the mean residence time 2.6-fold and the mean half-life (t1/2) 1.5-fold for Lyso-7-NC; the Lyso-7 plasma clearance, distribution volume and elimination rate were reduced 13, 10 and 1.4 fold, respectively, which indicates higher retention of encapsulated Lyso-7 in the blood compartment. Upon association with NC, organ exposure to Lyso-7 was higher in the heart (3.6-fold), lung (2.8-fold), spleen (2.3-fold), kidney (2-fold) and liver (1.8-fold) compared to Lyso-7 in solution. The analysis of whole data clearly indicates that body exposure to Lyso-7 was enhanced and the general toxicity reduced upon nanoencapsulation, allowing further evaluation of Lyso-7 in nonclinical and clinical studies.


An unusual cause of obstruction in the anesthesia circuit.
A near accident is described caused by a protection cap of an infusionset which accidentally clogged the swivel-connector in the anesthesia circuit.


Post-dispersal predation and scatterhoarding of Dipteryx panamensis (Papilionaceae) seeds by rodents in Panama.
In tropical rain forests of Central America, the canopy tree Dipteryx panamensis (Papilionaceae) fruits when overall fruit biomass is low for mammals. Flying and arboreal consumers feed on D. panamensis and drop seeds under the parent or disperse them farther away. Seeds on the ground attract many vertebrate seed-eaters, some of them potential secondary seed dispersers. The fate of seeds artificially distributed to simulate bat dispersal was studied in relation to fruitfall periodicity and the visiting frequency of diurnal rodents at Barro Colorado Island (BCI), Panama. The frequency of visits by agoutis is very high at the beginning of fruitfall, but in the area close (<50 m) to fruiting trees (Dipteryx-rich area) it declines throughout fruiting, whereas it remains unchanged farther (>50 m) away (Dipteryx-poor and Gustavia-rich area). Squirrels were usually observed in the Dipteryx-rich area. Along with intense post-dispersal seed predation by rodents in the Dipteryx-rich area, a significant proportion of seeds were cached by rodents in the Dipteryx-poor area. Post-dispersal seed predation rate was inversely related to hoarding rate. A significantly greater proportion of seeds was cached in March, especially more than 100 m from the nearest fruiting tree. This correlates with the mid-fruiting period, i.e. during the height of D. panamensis fruiting, when rodents seem to be temporarily satiated with the food supply at parent trees. Hoarding remained high toward April, i.e. late in the fruiting season of D. panamensis. Low survival of scatterhoarded seeds suggests that the alternative food supply over the animal's home-ranges in May-June 1990 was too low to promote survival of cached seeds. Seedlings are assumed to establish in the less-used area of the rodents' home-range when overall food supply is sufficient to satiate post-dispersal predators.


Development of NADPH-diaphorase/nitric oxide synthase in the brain of the urodele amphibian Pleurodeles waltl.
In the present study, the ontogenesis of nitrergic neurons has been studied in the urodele amphibian Pleurodeles waltl by means of NADPH-diaphorase (NADPHd) histochemistry and neuronal nitric oxide synthase (NOS) immunohistochemistry. Embryonic and larval stages were studied. Except for the olfactory fibers and glomeruli, both methods were equally suitable to reveal nitrergic structures in the brain. The earliest positive neurons were observed in the inferior reticular nucleus (Ri) in the caudal rhombencephalon at embryonic stage 30. At stage 33b, weakly reactive cells appeared in the tegmentum of the mesencephalon and isthmus, in the ventral hypothalamus (VH), and in the proximity of the solitary tract (sol). At initial larval stages (stages 34-38), two new groups appeared in the caudal telencephalon (future amygdaloid complex (Am)) and in the middle reticular nucleus (Rm) of the rhombencephalon. During the active larval life (stages 39-55c) the nitrergic system developed progressively both in number of cells and fiber tracts. At stages 39-42 reactive cells were found in the inner granular layer (igl) of the olfactory bulb, the telencephalic pallium, the pretectal region, the optic tectum (OT) and retina. New populations of nitrergic cells appear during the second half of the larval period (stages 52-55). Rostrally, reactive cells were found in the telencephalic diagonal band (DB) nucleus, medial septum and in the thalamic eminence (TE), whereas caudally cells appeared in the raphe (Ra) and the descending trigeminal nucleus (Vd). The last changes occurred during the juvenile period (metamorphic climax), when cells of the spinal cord (sc) and the preoptic area became positive. The sequence of appearance of nitrergic cells revealed a first involvement of this system in reticulospinal control, likely influencing locomotor behavior. As development proceeds, cells in different sensory systems expressed progressively nitric oxide synthase in a pattern that shows many similarities with amniotes.


Role of distress in delusion formation.
Contemporary cognitive psychological theories suggest that distress plays a mediating role in delusion formation. To study the amplifying role of distress from early perceptual intrusions to delusion formation. A general population sample of 7076 individuals was interviewed with the Composite International Diagnostic Interview (CIDI) in 1996 (baseline), 1997 (T1) and 1999 (T2). At T2, clinicians also scored the Brief Psychiatric Rating Scale (BPRS) item "unusual thought content". Analyses compared hallucinatory experiences with and without subjective distress at baseline for risk of delusion formation at follow-up. Individuals experiencing hallucinations with distress, compared with those without distress had a fourfold increased risk of subsequent delusion formation. This finding corroborates the hypothesis that distress associated with early perceptual intrusions serves as a catalyst in the development of delusions.


Four-fold increased mortality rate in patients with Wilson's disease: A population-based cohort study of 151 patients.
Few studies have investigated mortality rates in patients with Wilson's disease and compared these to the general population. Here, we examined several clinical outcomes (including cardiovascular, psychiatric, neurologic conditions) in a population-based study of patients with Wilson's disease. We used nationwide registers to identify all patients with a first diagnosis of Wilson's disease between 2002 and 2020 in Sweden. Each patient was matched by age, sex, and municipality with up to 10 reference individuals from the general population. Validated registers were used to investigate outcomes up to 19 years after baseline in patients and reference individuals. We identified 151 patients with Wilson's disease matched with 1441 reference individuals. Median age at baseline was 26 years (IQR 17-42) and 50% were males. During a median follow-up of 6.6 years (IQR 2.9-12.9), 10 (6.6%) patients with Wilson's disease died compared with 31 (2.2%) reference individuals. This translated to a hazard ratio (HR) of 3.8 (95%CI = 1.8-8.1). Mortality was higher among Wilson's disease patients with baseline neuropsychiatric diagnoses (HR 7.9, 95%CI = 2.9-21.8). Cumulative mortality over 10 years was 9.3% (95%CI = 5.0-16.8) in Wilson's disease, compared to 2.4% (95%CI = 1.6-3.6) in reference individuals. We observed significantly elevated risks in the Wilson's disease group for incident cardiovascular disease, and incident psychiatric and neurological conditions when considering liver transplantation or death from other causes as competing events. In this large population-based cohort study, patients with Wilson's disease had an almost four-fold increased mortality rate compared with matched individuals from the general population.


Zebrafish models: Gaining insight into purinergic signaling and neurological disorders.
Zebrafish (Danio rerio) has been considered a complementary model for biomedical studies, especially due to advantages such as external and rapid development, and genetic manipulation. There is growing interest in this model in neuroscience research since the species has morphological and physiological similarities to mammals and a complex behavioral repertoire. The purinergic signaling has been described in zebrafish, and purinoceptors and nucleotide- and nucleoside-metabolizing enzymes have already been identified in the central nervous system (CNS) of this species. The involvement of the purinergic system in several models of neurological disorders, such as Alzheimers disease, Parkinson's disease, epilepsy, schizophrenia, and autism has been investigated in zebrafish. This mini review presents several studies describing purinergic signaling in the zebrafish CNS and the action of this neurotransmitter system in models of neurological disorders using this species as a biological model. The use of pharmacological approaches at different stages of development may be a useful tool for preclinical assays and the testing of purinergic compounds as new alternatives for the treatment of neurological disorders.


Alkaloids from Hippeastrum morelianum Lem. (Amaryllidaceae).
The Amaryllidaceae family has proven to be a rich source of active molecules. As part of an ongoing project, we report a phytochemical study of Hippeastrum morelianum (Amaryllidaceae), from which we have isolated two homolycorine-type alkaloids, the new 2α,7-dimethoxyhomolycorine (1) and the poorly described candimine (2), as well as six known alkaloids: tazettine, pretazettine, 3-epimacronine, haemanthamine, hamayne and trisphaeridine. For reference purposes, the NMR of the isolated compounds was unequivocally described, based on 2D NMR measurements including (1)H-(1)H COSY, (1)H-(1)H NOESY, HSQC and HMBC.


Chemical and physical drivers of beryllium retention in two soil endmembers.
Meteoric 10Be and 7Be produced in the atmosphere from high-energy spallation reactions are deposited onto the Earth's surface through wet and dry deposition and are sorbed onto the surfaces of particles. On land, the sorbed concentrations scale with the residence time of sediments in a landscape-offset by slow (10Be) and fast (7Be) radioactive decay. Additionally, the amount of native 9Be, leached from minerals, correlates with the chemical weathering of soils. However, previous work has shown that chemical and physical properties of soils and river sediments affects sorption of beryllium. Therefore, the magnitude of sorbed beryllium concentrations may be more representative of the sorption capacity of the system rather than its erosional or weathering history. Although previous work has examined the physical and chemical properties of soil that influence beryllium sorption, these studies either lack consensus or exclude potentially important variables. In this work, we provide a thorough examination of variables previously reported to have influence on beryllium chemistry as well as new variables such as nitrogen, phosphorus and sulfur concentrations in order to determine which factors best predict beryllium sorption. We selected two soil endmembers with differing compositions, separated them into different size fractions, and characterized the surface area, cation exchange capacity (CEC), mineralogy, sulfur, carbon, nitrogen and phosphorus concentrations. We determined that the inverse percent abundance of quartz and the CEC best predict beryllium sorption potential in these soils. By deriving a model that relates these two variables to the percent sorbed beryllium, we were able to predict the sorption capacity of our system and reduced the error in sorbed beryllium amounts due to differences in soil properties by about 42%. From these results, we provide insight as to why there is inconsistency in the literature with regards to the physio-chemical controls on the environmental behavior of beryllium.


Molecular epidemiology of plasmid-mediated high-level mupirocin resistance in methicillin-resistant Staphylococcus aureus in four Spanish health care settings.
Mupirocin is used for the decolonization of methicillin-resistant Staphylococcus aureus (MRSA). High-level mupirocin resistance (Hi-Mup(R)) is of concern, having been associated with therapeutic failure. Our main objective was to assess the emergence and mode/s of spread of Hi-Mup(R) in the MRSA population recovered between 2002 and 2009 in four health care settings in the Pontevedra province, northwest Spain. Five hundred and fifty consecutive clinical MRSA isolates were obtained and screened for antimicrobial susceptibility. Isolates were stratified into multidrug-resistant (MDR) and non-MDR. High-level mupirocin resistant MRSA were characterized by genotyping and plasmid analysis. Thirty-one MRSA (5.6%) exhibited Hi-Mup(R). No association was detected between Hi-Mup(R) and MDR but isolates displaying Hi-Mup(R) were more likely to be resistant to gentamicin and tobramycin. Four main MRSA clones were identified: ST125/t067/PFGE A, ST36/t018/PFGE D, ST8/t008/PFGE B, and ST72/t148 or t3092/PFGE B. Each isolate carried the Hi-Mup(R)ileS2-encoding gene on plasmids and ten plasmid types were distinguished based on unique IS257-ileS2 configurations. Some plasmid types were successfully disseminated among the MRSA clones. Remarkably, six plasmid types were acquired by the predominant genotype ST125/t067/PFGE A. In conclusion, molecular characterization of MRSA isolates combined with the rapid typing of ileS2-encoding plasmids through determination of IS257-ileS2 configurations have proved to be a powerful strategy to address the molecular epidemiology of Hi-Mup(R). The transmission of a diverse set of ileS2-carrying plasmids promoted the emergence of the resistance, with a limited role of clonal expansion in its dispersion.


Effect of testosterone administration on rates of ethanol elimination in hypogonadal patients.
Rates of ethanol elimination were determined in four hypogonadal subjects at one week and again at eight weeks after the administration of one dose of 200 mg of testosterone cypionate (Depo-testosterone). Ethanol elimination was unchanged in two patients, slightly decreased in one, and markedly increased in one patient at eight weeks as compared to one week after testosterone administration. In the three patients with little or no change in ethanol elimination, initial high levels of plasma-free testosterone, ranging from 445.0 to 3.8 ng/dl did not decrease to abnormally low levels, but ranged between 1.6 and 7.7 ng/dl (normal, 1.20-2.10 ng/dl). In the fourth patient, an increase in ethanol elimination from 86.6 to 107.4 mg/kg body weight/hr was associated with a decrease in plasma-free testosterone from a high level of 4.7 to 0.8 ng/dl. These results indicate that pharmacological plasma concentration of testosterone do not affect the rate of ethanol elimination. A suppressing effect of testosterone on rate of ethanol elimination may occur at levels of plasma-free testosterone which extend from abnormally low up into the normal physiologic range.


The balance between NANOG and SOX17 mediated by TET proteins regulates specification of human primordial germ cell fate.
Human primordial germ cells (hPGCs) initiate from the early post-implantation embryo at week 2-3 and undergo epigenetic reprogramming during development. However, the regulatory mechanism of DNA methylation during hPGC specification is still largely unknown due to the difficulties in analyzing early human embryos. Using an in vitro model of hPGC induction, we found a novel function of TET proteins and NANOG in the hPGC specification which was different from that discovered in mice. Using the CRISPR-Cas9 system, we generated a set of TET1, TET2 and TET3 knockout H1 human embryonic stem cell (hESC) lines bearing a BLIMP1-2A-mKate2 reporter. We determined the global mRNA transcription and DNA methylation profiles of pluripotent cells and induced hPGC-like cells (hPGCLCs) by RNA-seq and whole-genome bisulfite sequencing (WGBS) to reveal the involved signaling pathways after TET proteins knockout. ChIP-qPCR was performed to verify the binding of TET and NANOG proteins in the SOX17 promoter. Real-time quantitative PCR, western blot and immunofluorescence were performed to measure gene expression at mRNA and protein levels. The efficiency of hPGC induction was evaluated by FACS. In humans, TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) impaired the NODAL signaling pathway and impeded hPGC specification in vitro, while the hyperactivated NODAL signaling pathway led to gastrulation failure when Tet proteins were inactivated in mouse. Specifically, TET proteins stimulated SOX17 through the NODAL signaling pathway and directly regulates NANOG expression at the onset of hPGCLCs induction. Notably, NANOG could bind to SOX17 promoter to regulate its expression in hPGCLCs specification. Furthermore, in TKO hESCs, DNMT3B-mediated hypermethylation of the NODAL signaling-related genes and NANOG/SOX17 promoters repressed their activation and inhibited hPGCLC induction. Knockout of DNMT3B in TKO hESCs partially restored NODAL signaling and NANOG/SOX17 expression, and rescued hPGCLC induction. Our results show that TETs-mediated oxidation of 5-methylcytosine modulates the NODAL signaling pathway and its downstream genes, NANOG and SOX17, by promoting demethylation in opposition to DNMT3B-mediated methylation, suggesting that the epigenetic balance of DNA methylation and demethylation in key genes plays a fundamental role in early hPGC specification.


The involvement of immunoglobulin E isotype switch in scleroderma skin tissue.
The involvement of mast cell, which is activated by immunoglobulin E (IgE), has been reported in the formation of systemic sclerosis (SSc) abnormality. IgE is generated with isotype switch. During isotype switch, switch circles resulting from direct mu to epsilon, or from sequential mu to gamma via epsilon switching will be created. We studied whether switching occurs in SSc. We used nested polymerase chain reaction to analyze the S fragments from switch circles. Fifty-two patients with SSc, and 62 healthy women were studied. Neither of 62 normal skin tissues showed direct switch, nor sequential switch. Neither of seven normal whole blood cells showed direct switch, nor sequential switch. In 52SSc skin tissues, three (5.8%) showed direct switch, and two (3.8%) showed sequential switch. As a result, five (9.6%) of SSc skin tissue showed immunogobulin E class switch. These results were confirmed by DNA sequencing. These results demonstrated that isotype switch to the epsilon locus achieved by direct and/or sequential switch are involved in SSc skin.


Tissue Engineering for Tracheal Replacement: Strategies and Challenges.
The critical feature in trachea replacement is to provide a hollow cylindrical framework that is laterally stable and longitudinally flexible, facilitating cartilage and epithelial tissue formation. Despite advanced techniques and sources of materials used, most inherent challenges are related to the complexity of its anatomy. Limited blood supply leads to insufficient regenerative capacity for cartilage and epithelium. Natural and synthetic scaffolds, different types of cells, and growth factors are part of tissue engineering approaches with varying outcomes. Pre-vascularization remains one of the crucial factors to expedite the regenerative process in tracheal reconstruction. This review discusses the challenges and strategies used in tracheal tissue engineering, focusing on scaffold implantation in clinical and preclinical studies conducted in recent decades.


[Effect of dekaris and sodium nucleinate on the blood antioxidant system of guinea pigs exposed to paprin inhalation].
The changes of lipid peroxidation, thiol disulfide equilibrium, glucoso-6-phosphate dehydrogenase, catalase and superoxide dismutase activity under influence of immunostimulants during paprin inhalation were studied. Pro-oxidant effect of dekaris has been established. The conclusion on the necessity to estimate the level of antioxidant system under immunocorrection has been made.


Determination of arsenic(III) by flow injection solid phase extraction coupled with on-line hydride generation atomic absorption spectrometry using a PTFE turnings-packed micro-column.
A novel flow injection (FI) solid phase extraction method for the determination of arsenic(III) at trace levels was developed, using on-line hydride generation atomic absorption spectrometry (HG-AAS). Selective determination of As(III) was achieved by on-line formation and retention of the pyrrolidine dithiocarbamate arsenic complex As(III)-PDC on the PTFE turnings which are packed in the preconcentration micro-column. The retained complex was eluted by 2 ml 2 mol l(-1) HCl and subsequently introduced on-line into the integrated reaction chamber/gas-liquid separator (RC-GLS). A 1.5% (m/v) NaBH4 solution was used for arsine generation, while a gas stream of N2 was employed for flash release and transportation towards the atomic absorption flow through cell (AAC) for atomization and measurement. The excellent performance of PTFE turnings as sorbent material and the compact design of the RC-GLS result to high sensitivity, selectivity and sampling frequency. For 60s preconcentration time and sample consumption 10.4 ml a sampling frequency of 25 h(-1) and a detection limit of c(L)=0.02 microg l(-1) were obtained. The repeatability, expressed as relative standard deviation (R.S.D.), at 1.0 microg l(-1) As(III), was s(r)=2.8%. The proposed method was successfully applied to the selective determination of As(III) in natural waters and total arsenic determination in certified reference material.


Constitutive Activity of Serotonin Receptor 6 Regulates Human Cerebral Organoids Formation and Depression-like Behaviors.
Serotonin receptor 6 (5-HT6R), a typical G protein-coupled receptor (GPCR) mainly expressed in the neurogenic area with constitutive activity, is of particular interest as a promising target for emotional impairment. Here, we found that 5-HT6R was highly expressed in human NSCs and activation of the receptor promoted self-renewal of human NSCs, and thus induced the expansion and folding of human cerebral organoids; dysfunction of receptor or inhibition of its constitutive activity resulted in the premature differentiation of NSCs, which ultimately depleted the NSC pool. The following mechanistic study revealed that EPAC-CREB signaling was involved in 5-HT6R regulation. Furthermore, we showed that mice with genetic deletion of 5-HT6R or knockin A268R mutant presented depression-like behaviors and impaired hippocampal neurogenesis for progressive decrease of the NSC pool. Thus, this study indicates that the modulation of 5-HT6R and its constitutive activity may provide a therapeutic alternative to alleviate depression.


The effects of ciprofloxacin on early life stages of common carp (Cyprinus carpio).
The authors performed a toxicity test with ciprofloxacin in fertilized eggs of common carp according to guideline 210 of the Organisation for Economic Co-operation and Development. The tested concentrations were 1 μg L(-1) , 100 μg L(-1) , 500 μg L(-1) , 1000 μg L(-1) , and 3000 μg L(-1) . Accelerated hatching was found in all groups exposed to ciprofloxacin, but significant growth reduction was found only in the group exposed to the highest concentration (3000 μg L(-1) ). Increased numbers of macroscopic morphological anomalies were observed on day 6 of the test (after hatching). The highest numbers of macroscopic morphological anomalies were observed in the groups of free embryos and larvae exposed to ciprofloxacin concentrations of 100 μg L(-1) , 500 μg L(-1) , 1000 μg L(-1) , and 3000 μg L(-1) (20-23% of tested samples). A gradual decrease in glutathione S-transferase activity was detected in all experimental groups exposed to ciprofloxacin, but significant differences (p < 0.01) were found only in groups treated with 500 μg L(-1) and 3000 μg L(-1) . Glutathione peroxidase and catalase exhibited increased activity in most of the tested concentrations (p < 0.01 and <0.05, respectively), whereas decreased glutathione reductase activity was found in the groups exposed to ciprofloxacin concentrations of 500 μg L(-1) and 3000 μg L(-1) (p < 0.05). The concentration of thiobarbituric acid-reactive substances was significantly lower (p < 0.01) in all experimental groups exposed to ciprofloxacin. The lowest-observed-effect concentration of ciprofloxacin was 1 μg L(-1) . These results suggest that hatching, early ontogeny, occurrence of morphological anomalies, antioxidant and biotransformation enzyme activity, and lipid peroxidation in fish can be affected by ciprofloxacin. Environ Toxicol Chem 2016;35:1733-1740. © 2015 SETAC.


Relationship of prostate-specific antigen and prostate volume in Korean men with biopsy-proven benign prostatic hyperplasia.
To investigate the relationship between prostate-specific antigen (PSA) and prostate volume in a histologically defined subset of Korean men confirmed to have benign prostatic hyperplasia (BPH) only from multicore biopsy of prostate. A total of 707 Korean men with a PSA level of 10 ng/mL or lower who were shown to have stromoglandular hyperplasia only from transrectal ultrasound (TRUS)-guided multicore biopsy of prostate were included in the study. We analyzed PSA and total prostate volume (TV) measured through TRUS by stratified age cohorts. We used Pearson correlation coefficient (r) and linear regression model to describe the relationship between variables. Serum PSA level significantly correlated with TV in all stratified age cohorts, with r ranging from 0.29 to 0.47 (all P <0.001). Meanwhile, the degree of correlation appeared to increase with age. The slope of linear regression showing an association of PSA and TV was 3.68. The PSA increase per unit prostate volume decreased with the advancing cohort of age when we excluded subjects 70 years or older. Although PSA was significantly correlated with TV, the exact nature of the relationship between PSA and TV in Korean men with biopsy-proven BPH may be different from that in other races. Further basic research on the pathophysiology of BPH is needed to explain such a racial difference.


Inflammation as a Pathophysiologic Pathway to Anhedonia: Mechanisms and Therapeutic Implications.
Anhedonia, characterized by a lack of motivation, interest, or ability to experience pleasure, is a prominent symptom of depression and other psychiatric disorders and has been associated with poor response to standard therapies. One pathophysiologic pathway receiving increased attention for its potential role in anhedonia is inflammation and its effects on the brain. Exogenous administration of inflammatory stimuli to humans and laboratory animals has reliably been found to affect neurotransmitters and neurocircuits involved in reward processing, including the ventral striatum and ventromedial prefrontal cortex, in association with reduced motivation. Moreover, a rich literature including meta-analyses describes increased inflammation in a significant proportion of patients with depression and other psychiatric illnesses involving anhedonia, as evident by elevated inflammatory cytokines, acute phase proteins, chemokines, and adhesion molecules in both the periphery and central nervous system. This endogenous inflammation may arise from numerous sources including stress, obesity or metabolic dysfunction, genetics, and lifestyle factors, many of which are also risk factors for psychiatric illness. Consistent with laboratory studies involving exogenous administration of peripheral inflammatory stimuli, neuroimaging studies have further confirmed that increased endogenous inflammation in depression is associated with decreased activation of and reduced functional connectivity within reward circuits involving ventral striatum and ventromedial prefrontal cortex in association with anhedonia. Here, we review recent evidence of relationships between inflammation and anhedonia, while highlighting translational and mechanistic work describing the impact of inflammation on synthesis, release, and reuptake of neurotransmitters like dopamine and glutamate that affects circuits to drive motivational deficits. We will then present insight into novel pharmacological strategies that target either inflammation or its downstream effects on the brain and behavior. The meaningful translation of these concepts through appropriately designed trials targeting therapies for psychiatric patients with high inflammation and transdiagnostic symptoms of anhedonia is also discussed.


Stereospecific high-performance liquid chromatographic assay of ibuprofen: improved sensitivity and sample processing efficiency.
A high-performance liquid chromatographic (HPLC) assay suitable for the analysis of the enantiomers of the non-steroidal anti-inflammatory drug ibuprofen (IB) in plasma was developed. Following the addition of racemic fenoprofen as internal standard (I.S.), samples are acidified and extracted with a mixture of isooctane-isopropanol (95:5, v/v). After evaporation of the organic layer, the drug and I.S. are derivatized with S-(-)-1(1-naphthyl)ethylamine (S-NEA) after addition of ethyl chloroformate as the coupling reagent. Ethanolamine is added 3 min after the addition of S-NEA to react with the excessive ethyl chloroformate. The resultant diastereomers corresponding to IB and I.S. were chromatographed at ambient temperature on a 100 mm x 4.6 mm I.D. C18 reversed-phase column using acetonitrile-water-acetic acid-triethylamine (60:40:0.1:0.02) as the mobile phase pumped at a flow-rate of 1.2 ml/min. Detection of the fluorescent chromophore was at 280 and 320 nm for excitation and emission, respectively. The suitability of the assay for clinical pharmacokinetic studies of IB was determined by the analysis of plasma samples obtained from a healthy volunteer, following administration of a single 400-mg oral dose of racemic IB.


Effects of a strong static magnetic field on bacterium Shewanella oneidensis: an assessment by using whole genome microarray.
The effect of a strong static 14.1 T magnetic field on log phase cells of bacterial strain Shewanella oneidensis MR-1 was evaluated by using whole genome microarray of this bacterium. Although differences were not observed between the treatment and control by measuring the optical density (OD), colony forming unit (CFU), as well as post-exposure growth of cells, transcriptional expression levels of 65 genes were altered according to our microarray data. Among these genes, 21 were upregulated while other 44 were downregulated, compared with control.


(S029) Managing therapeutic anticoagulation in bariatric surgery patients.
Patients that undergo bariatric surgery are at risk of bleeding. Some obesity-related comorbidities including venous thromboembolism and heart disease can often require therapeutic anticoagulation. Previous small institutional studies have demonstrated that bariatric surgery can be performed in this patient population. This study attempts to identify best practices in stopping and restarting therapeutic anticoagulation in patients undergoing bariatric surgery. A retrospective analysis was completed of our institution's database using anticoagulant medications to identify patients on therapeutic anticoagulation. Patients not on therapeutic anticoagulation were excluded, as well as patients that were started on therapeutic anticoagulation only in the post-operative period or those whose anticoagulation was stopped and not restarted. Indications for anticoagulation were recorded, as well as patient demographics and comorbid conditions. The patient chart was examined for when anticoagulation was stopped before surgery, when it was restarted after surgery, and whether or not the patient was therapeutically bridged. Baseline and post-operative hemoglobin values were recorded, as well as bleeding events, transfusions, reoperation, length of stay, and readmissions. Binary variables were compared across groups using Chi-square and Fisher's exact tests, and continuous variables were analyzed using T test. There were 2933 bariatric operations performed between January 1, 2012 and August 31, 2019. Of these patients, 64 were on therapeutic anticoagulation before and after the operation for one or more indications, including history of VTE (39), atrial fibrillation (27), clotting disorder (6), ventricular assist device (5), previous PCI (4), or mechanical valve (2). There were 4 (6.2%) patients that experienced bleeding events. All four patients were on Coumadin pre-operatively. Three patients experienced extraluminal bleeding, and one patient had intraluminal bleeding, and all events occurred within 72 h of the operation. All four patients had their anticoagulation restarted prior to the bleeding event becoming evident, with anticoagulation in these patients restarted an average of 1.25 days after surgery. There were no conditions that predisposed a patient to bleeding. There was no significant difference in amount of time anticoagulation was stopped before surgery in bleeding versus non-bleeding patients, and there appeared to be no increased risk of bleeding in patients that were on therapeutic bridging therapy. There were no thrombotic complications from the interruption in anticoagulation therapy. Bariatric surgery can be safely performed in patients on therapeutic anticoagulation, though this population is at greater risk for bleeding complications in the perioperative period. Meticulous hemostasis in the operating room is the most important aspect of preventing bleeding complications.


Identification of three different types of smokers who are not motivated to quit: Results from a latent class analysis.
The majority of smokers are not motivated to quit within 30 days. We examined whether these smokers are a homogeneous group, hypothesizing that subtypes of unmotivated smokers could be identified. Included were 500 smokers not ready to quit within 30 days who completed an online survey assessing variables known to be associated with quitting. Latent Class Analysis revealed 3 unmotivated smoker subtypes. "Health-Concerned Smokers," (HCS; n = 166) had a significantly greater proportion of previous smoking-related illness and high risk perceptions. "Smokers with Psychosocial Barriers" (SPB; n = 192) had a significantly greater proportion of younger smokers, partners who smoked, other household smokers, and children. "Unconvinced Smokers" (UCS; n = 142) had the lowest proportion of those who: were motivated and confident to quit, had smoking-related illnesses, and perceived the risks of smoking and benefits of quitting. UCS had the highest proportion with optimistic bias, and no prior quit attempts. A greater proportion of HCS had high motivation to quit versus SPB and UCS. In model validation, 60.6% of UCS said they "never plan to quit" versus 31.8% of SPB and 22.3% of HCS; SPB and HCS had lower odds of never planning to quit versus UCS. Of those who plan on quitting at some point, 75.2% of HCS and 62.6% of SPB plan on quitting within 1 year, versus 46.4% of UCS; the cumulative odds of planning to quit later were higher among UCS. Smokers who are not motivated to quit are not a homogeneous group; tailored intervention approaches and targeted messages might be needed to motivate quitting. (PsycINFO Database Record


Do financial incentives trump clinical guidance? Hip Replacement in England and Scotland.
Following devolution in 1999 England and Scotland's National Health Services diverged, resulting in major differences in hospital payment. England introduced a case payment mechanism from 2003/4, while Scotland continued to pay through global budgets. We investigate the impact this change had on activity for Hip Replacement. We examine the financial reimbursement attached to uncemented Hip Replacement in England, which has been more generous than for its cemented counterpart, although clinical guidance from the National Institute for Clinical Excellence recommends the later. In Scotland this financial differential does not exist. We use a difference-in-difference estimator, using Scotland as a control, to test whether the change in reimbursement across the two countries had an influence on treatment. Our results indicate that financial incentives are directly linked to the faster uptake of the more expensive, uncemented Hip Replacement in England, which ran against the clinical guidance.


Immunocytochemical localization of a kallikrein-like serine protease (esterase A) in rat salivary glands.
Light and electron microscopic (EM) immunocytochemical methods have been used to localize arginine esterase A, a kinin-generating enzyme immunologically similar to tissue kallikrein, in rat salivary glands. Both polyclonal and monoclonal antibodies to arginine esterase A were used in these studies. By means of a polyclonal antiserum, esterase A was found in granular tubules of submandibular glands and in striated ducts of all three major salivary glands, in a distribution similar to that of tissue kallikrein. With recently developed specific monoclonal antibodies to esterase A, this enzyme was localized in the granules of some (but not all) granular convoluted tubule cells (GCT) and along the basal membranes (but not in apical granules) of striated ducts. By an EM immunoperoxidase method, esterase A was localized subcellularly in granules of some GCT cells and along the basal cell membranes of the tubule and duct system. Thus, this enzyme is found in some sites (GCT granules) shared with tissue kallikrein, but in some unique sites, i.e., basal membranes of striated ducts. The polyclonal antibody used in the present study cross-reacted with tissue kallikrein, but when absorbed with kallikrein, it gave the staining pattern characteristic of monoclonal antibody to esterase A.


Sutimlimab provides clinically meaningful improvements in patient-reported outcomes in patients with cold agglutinin disease: Results from the randomised, placebo-controlled, Phase 3 CADENZA study.
Cold agglutinin disease (CAD) is a rare chronic autoimmune haemolytic anaemia, driven mainly by classical complement pathway activation, leading to profound fatigue and poor quality of life. In the Phase 3 CADENZA trial, sutimlimab-a C1s complement inhibitor-rapidly halted haemolysis, increased haemoglobin levels and improved fatigue versus placebo in patients with CAD without a recent history of transfusion. Patient-reported outcomes (PROs) included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), 12-Item Short Form Health Survey (SF-12), EuroQol visual analogue scale (EQ-VAS), Patient Global Impression of Change (PGIC) and Patient Global Impression of (fatigue) Severity (PGIS). Sutimlimab resulted in significant rapid and meaningful improvements versus placebo in PROs. From Week 1, the FACIT-Fatigue mean score increased >5 points above baseline (considered a clinically important change [CIC]). Least-squares (LS) mean change in FACIT-Fatigue score from baseline to treatment assessment timepoint was 10.8 vs. 1.9 points (sutimlimab vs. placebo; p < 0.001). Improvements in physical (PCS) and mental (MCS) component scores of the SF-12 were also considered CICs (LS mean changes from baseline to Week 26: PCS 5.54 vs. 1.57 [p = 0.064]; MCS 5.65 vs. -0.48 [p = 0.065]). These findings demonstrate that in addition to improving haematologic parameters, sutimlimab treatment demonstrates significant patient-reported benefits. Study registered at www.clinicaltrials.gov: NCT03347422.


Comparison of antibody titers using conventional tube technique versus column agglutination technique in ABO blood group incompatible renal transplant.
Measurement of alloantibody titer to a red cell antigen (ABO titers) is an integral part of management of ABO incompatible kidney transplants (ABOiKT). There are different methods of titer estimation. Alloantibody detection by tube titration and Gel agglutination columns are accepted methodologies. It is essential to find the difference in titers between the two methods so as to set the 'cut-off' titer accordingly, depending upon the method used. We did a prospective observational study to compare and correlate the ABO titers using these two different techniques - conventional tube technique (CTT) and the newer column agglutination technique (CAT). A total of 67 samples were processed in parallel for anti-A/B antibodies by both tube dilution and column agglutination methods. The mean titer by conventional tube method was 38.5 + 96.6 and by the column agglutination test was 96.4 + 225. The samples correlated well with Spearman rho correlation coefficient of 0.94 (P = 0.01). The column agglutination method for anti A/B titer estimation in an ABO incompatible kidney transplant is more sensitive, with the column agglutination results being approximately two and half fold higher (one more dilution) than that of tube method.


Genome‑wide characterization of the Gα subunit gene family in Rosaceae and expression analysis of PbrGPAs under heat stress.
The Gα subunit is an important component of the heterotrimeric G-protein complex and an integral component of several signal transduction pathways. It plays crucial roles in the diverse processes of plant growth and development, including the response to abiotic stress, regulation of root development, involvement in stomatal movement, and participation in hormone responses, which have been well investigated in many species. However, no comprehensive analysis has identified and explored the evolution, expression pattern characteristics and heat stress response of the Gα subunit genes in Rosaceae. In this study, 52 Gα subunit genes were identified in eight Rosaceae species; these genes were divided into three subfamilies (I, II, and III) based on their phylogenetic, conserved motif, and structural characteristics. Whole genome and dispersed duplication events were found to have contributed significantly to the expansion of the Gα subunit gene family, and purifying selection to have played a key role in the evolution of Gα subunit genes. An expression analysis identified some PbrGPA genes that were highly expressed in leaf, root, and fruit, and exhibited diverse spatiotemporal expression models in pear. Under abiotic stress conditions, the mRNA transcript levels of PbrGPA genes were up-regulated in response to high temperature treatment in leaves. Furthermore, three Gα subunit genes were shown to be located in the plasma membrane and nucleus in pear. In conclusion, the study of the Gα subunit gene family will help us to better understand its evolutionary history and expression patterns, while facilitating further investigations into the function of the Gα subunit gene in response to heat stress.


Movements of attention in the three spatial dimensions and the meaning of "neutral" cues.
Six experiments were conducted to examine the effect of various attentional manipulations on reaction time to visual stimuli. The first three experiments compared the responses to stimuli presented in the depth (Experiment 1), along the horizontal (Experiment 2), and vertical (Experiment 3) meridians in a valid condition (stimulus presented in the cued position), an invalid condition (stimulus presented in the alternative position to the cued position) and a neutral condition (no information on stimulus position). The most interesting result was the demonstration that attention can be moved along the sagittal plane in the absence of vergence eye movements and that when attention is focused on a certain point, unattended points between this point and the observer (i.e. near points) are responded faster than unattended points beyond it (i.e. far points). In the frontal plane no asymmetry was found between the responses to unattended points above or below the fixation, whereas a certain, albeit non-constant, advantage was present for unattended stimuli on the right of the fixation point in respect to those on the left of it. The second series of experiments was similar to the first one, except that a new situation was introduced in which the fixation point was cued and stimuli could appear either in correspondence to it or in a peripheral position (invalid condition with attention at the fixation point). The results showed that in this new situation the responses to unattended stimuli are much longer than they are under neutral conditions, and as long as they are under conventional invalid condition. It is suggested that the so called neutral condition is a condition of diffuse attention and an attempt is made to explain it in terms of a premotor theory of attention.


Locked intramedullary nailing of diaphyseal femur fractures without intraoperative fluoroscopy, fracture table and power reaming: retrograde affords greater procedural efficiency than antegrade approach.
To compare the intraoperative procedural efficiency of antegrade and retrograde locked intramedullary nailing of diaphyseal femur fractures without intraoperative fluoroscopy, power reaming devices and fracture tables. A secondary analysis of prospectively collected data was conducted on 238 isolated diaphyseal femur fractures fixed with SIGN Standard and Fin nails within three weeks of injury. The data included baseline patient and fracture characteristics, nail type and diameter, fracture reduction methods, operative times and outcome measures. There were 84 and 154 fractures in the antegrade and retrograde groups respectively. Both groups were similar vis-a-vis baseline patient and fracture characteristics. Closed reduction of the fractures was significantly easier for retrograde than an antegrade approach. The retrograde approach more readily permitted the use of Fin nails. The mean nail diameter used for retrograde was significantly larger than that for antegrade. The time taken to achieve retrograde nailing was significantly lesser than that of antegrade. There was no statistically significant difference between the outcomes of the two groups. In the absence of expensive fracture-surgery gadgets, retrograde nailing offers many procedural advantages over antegrade, such as easier closed reduction and canal reaming, the greater possibility of using the Fin nail with fewer interlocking screws and shorter operative times. However, we acknowledge the lack of randomisation and the presence of an unequal number of fractures in the two groups as limitations of this study.


REIN: a tool at the service of health monitoring, exemple of the SARS-Cov-2
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of its role in health monitoring, the following key messages were retained. The recent health crisis showed the adaptability and agility of the registry. Thanks to a human network that has been established and organised for many years, and the possibility of rapidly developing the collection system, the registry was able to provide information about the number of dialysis patients infected with the new SARS-Cov-2 from 30 March 2020. The use of REIN as a decision support and health monitoring tool in these times of empirical decisions has emerged as a strategic issue.


Insulin injection practice and health related quality of life among individuals with diabetes at Tikur Anbessa Specialized Hospital, Ethiopia: a cross-sectional study.
Insulin therapy can be inconvenient, painful, burdensome, and restrict patients' daily activities and health related quality of life (HRQOL) due to improper injection techniques or the nature of administration. This study aimed to assess insulin injection practice, HRQOL and predictors among patients treated with insulin at Tikur Anbessa Specialized Hospital (TASH). An institutional-based cross-sectional study was conducted among diabetes patients on insulin therapy from May to June 2022. A structured questionnaire was used to collect patient characteristics and insulin injection practice. The validated Amharic version of an EQ-5D-5L tool was used to assess the HRQOL. The data was analyzed using SPSS version 26. The patient data were summarized using descriptive statistics. One-way ANOVA using Kruskal-Wallis H tests was used to assess factors that predict insulin handling practice scores. Multivariate linear regression analysis was used to assess factors affecting HRQOL among diabetes patients treated with insulin. The EQ5D-5L utility scores of the patients were calculated using disutility coefficients taken from the Ethiopian general population. Statistical significance was declared at p-value < 0.05. Of 319 patients who agreed and completed the survey, 51.1% of them were males. Almost half of the participants (n = 158) were > 50 years of age. Among the study participants, 62.1% were only on intermediate acting insulin. A significantly higher proportion of participants 291(91.2%) in this study were taking insulin two times per day. Most of the participants 234(73.4%) had fair practice with a median insulin handling practice score of 38 out of 56. Patient characteristics such as age, educational status, occupation, disease duration, and type of diabetes were significantly association with insulin injection practice (p < 0.05). The mean ± SD utility score of patients were 0.89 ± 0.19 (ranged from -0.04 to 1). Being female (β = -5.42, 95%CI:-8.63,-2.21, p = 0.001) and treated for type-I diabetes mellitus (β = + 9.04, 95%CI: 4.23,13.85, p-value < 0.0001) were significantly associated with HRQOL of patients on insulin therapy. The study participants had fair practices in insulin handling, storage, and administration techniques, and it was seen that male and type one diabetes patients have a better quality of life compared to their counterparts.