Antioxidative action of the beta-adrenoceptor antagonist bopindolol and its metabolite 18-502.
The antioxidative effects of beta-adrenoceptor antagonists and related compounds were investigated. Among the beta-adrenoceptor antagonists, the agents with a potent membrane-stabilizing activity such as bopindolol and propranolol strongly inhibited the hydrogen peroxide (H2O2)-induced lipid peroxidation of liver microsomes. Fifty percent inhibition concentration values for the lipid peroxidation of bopindolol, 18-502 (metabolite of bopindolol) and propranolol were calculated to be 1.8 microM, 10 microM and 2.3 microM, respectively. The same potency order of the agents for the inhibition of lipid peroxidation was observed in rat heart homogenates. Furthermore, cytochrome P-450-catalyzing lipid peroxidation in microsomes and H2O2-induced lipid peroxidation in coronary arteries or cardiac muscles of pigs were also inhibited by bopindolol, whereas propranolol was less effective. Bopindolol and 18-502, but not propranolol, scavenged a stable free radical 1,1-diphenyl-2-picrylhydrazyl. Thus it was concluded that bopindolol that has membrane-stabilizing and radical scavenging activities is a more potent antioxidant than propranolol and may produce a beneficial effect for the treatment of ischemic cardiac diseases.


Effect of breast- and bottle-feeding duration on the age of pacifier use persistence.
This study evaluated the effect of breast- and bottle-feeding duration on the age of pacifier use persistence. Questionnaires (n = 723) with information on nutritive and nonnutritive sucking habits of children aged 3-6 years were assessed. The sample was divided according to breastfeeding duration: G1 - non-breastfed, G2 - up to 3 months, G3 - discontinued between 4 and 6 months, G4 - discontinued between 7 and 12 months, and G5 - longer than 12 months. The children were also assigned to 4 groups by age of pacifier use persistence, as well as by age of bottle-feeding persistence: no habits, up to 2 years, 3-4 years and 5-6 years. Associations between nutritive sucking habits and pacifier use were analyzed using logistic regression. The larger breastfeeding groups were G2 (37.9%) and G4 (19.4%). Many children discontinued pacifier use and bottle-feeding at 3-4 years of age (24.9% and 40.1%, respectively). Chances of non-breastfed children (G1) with prolonged pacifier-sucking habits, in the three age ranges, were progressively higher in comparison with group G4 (OR: 4.0-7.5, p < 0.01). When comparing bottle-fed with non bottle-fed children, the age range at which bottle-feeding had been discontinued was significantly associated with that of pacifier use cessation: up to 2 years (OR = 6.2), 3-4 years (OR = 7.6) and 5-6 years (OR = 27.0), p < 0.01. It may be suggested that breastfeeding duration has an inversely proportional effect on the age of pacifier use persistence. Bottle-fed children who use pacifiers tend to discontinue these habits at the same period.


[Physical exertion tolerance and its determining factors in hypertrophic cardiomyopathy].
A contribution of specific features of myocardial hypertrophy and hypercontractility left ventricular diastolic dysfunction to decreased exercise tolerance and developed coronary failure is discussed on the basis of results obtained from a bicycle ergometric test performed in 40 patients with hypertrophic cardiomyopathy. Thallium-201 myocardial scintigraphy conducted at the maximum exercise in 17 patients revealed a reduction in coronary reserve with increased myocardial mass index that was higher than the critical value. An implication of severe myocardial hypertrophy in the presence with coexisting left ventricular posterior wall hypertrophy and impaired perfusion/mass ratios is considered as a risk factor for death of patients with hypertrophic cardiomyopathy.


A deep learning approach to automatic detection of early glaucoma from visual fields.
To investigate the suitability of multi-scale spatial information in 30o visual fields (VF), computed from a Convolutional Neural Network (CNN) classifier, for early-glaucoma vs. control discrimination. Two data sets of VFs acquired with the OCTOPUS 101 G1 program and the Humphrey Field Analyzer 24-2 pattern were subdivided into control and early-glaucomatous groups, and converted into a new image using a novel voronoi representation to train a custom-designed CNN so to discriminate between control and early-glaucomatous eyes. Saliency maps that highlight what regions of the VF are contributing maximally to the classification decision were computed to provide classification justification. Model fitting was cross-validated and average precision (AP) score performances were computed for our method, Mean Defect (MD), square-root of Loss Variance (sLV), their combination (MD+sLV), and a Neural Network (NN) that does not use convolutional features. CNN achieved the best AP score (0.874±0.095) across all test folds for one data set compared to others (MD = 0.869±0.064, sLV = 0.775±0.137, MD+sLV = 0.839±0.085, NN = 0.843±0.089) and the third best AP score (0.986 ±0.019) on the other one with slight difference from the other methods (MD = 0.986±0.023, sLV = 0.992±0.016, MD+sLV = 0.987±0.017, NN = 0.985±0.017). In general, CNN consistently led to high AP across different data sets. Qualitatively, computed saliency maps appeared to provide clinically relevant information on the CNN decision for individual VFs. The proposed CNN offers high classification performance for the discrimination of control and early-glaucoma VFs when compared with standard clinical decision measures. The CNN classification, aided by saliency visualization, may support clinicians in the automatic discrimination of early-glaucomatous and normal VFs.


Resonant inelastic X-ray scattering and X-ray absorption spectroscopy on the cathode materials LiMnPO4 and LiMn0.9Fe0.1PO4--a comparative study.
We present a study of the charge-state behavior of the Li-ion battery cathode materials Li(x)MnPO(4) and Li(x)Mn(0.9)Fe(0.1)PO(4) using X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS). A set of six identical battery cathodes for each material have been cycled and left in different charge states in the range of x = 0.2…1.0 before disassembly in an Ar glove box. Unexpectedly, we find that the Mn 3d-bands are almost inert to the delithiation process, suggesting that Mn ions participate to a very small extent in the charge compensation process. In Li(x)Mn(0.9)Fe(0.1)PO(4) the Fe 3d-band shows much more response to delithiation than the Mn 3d-band. The O 2p-band hybridizes with the bands of the other ions in Li(x)MnPO(4) and Li(x)Mn(0.9)Fe(0.1)PO(4) and thus, indirectly, carries useful information about the effects of delithiation at all ion sites. We conclude that the redox reactions during lithiation/delithiation of these materials are complex and involve repopulation of charges for all constituent elements.


Ullrich disease: collagen VI deficiency: EM suggests a new basis for muscular weakness.
Ullrich disease is a form of congenital muscular dystrophy characterized clinically by generalized muscle weakness, contractures of the proximal joints, and hyperflexibility of the distal joints from birth or early infancy. Recently, mutations of the collagen VI gene have been associated with Ullrich disease. The authors report on a boy with Ullrich disease who has complete deficiency of collagen VI and harbors compound heterozygous mutations in the collagen VI alpha 2 gene. Absence of microfibrils on EM, together with normal collagen fibrils and basal lamina, suggests that loss of a link between interstitium and basal lamina may be a new molecular pathomechanism of muscular dystrophy.


High density sickle cell erythrocyte core membrane skeletons demonstrate slow temperature dependent dissociation.
We have previously demonstrated that slow dissociation of HDSS membrane skeletons in high ionic strength Triton X-100 buffer was related to a posttranslational modification in beta-actin, in which a disulfide bridge was formed between cysteine 284 and cysteine 373[Shartava et al: J Cell Bio 128:805, 1995]. These previous dissociation assays were limited to two homozygous (SS) sickle cell patients and a single temperature (37 degrees C). In the current work, we have expanded the SS subjects to 9 and have carried out dissociation assays at 0, 24, 30, 34, and 37 degrees C. At 0 degrees C there was limited dissociation of spectrin and actin from normal(AA), low density sickle cell(LDSS), and high density sickle cell (HDSS) core skeleton up to 24 hr. The first order rate constants for dissociation of spectrin, at 0 degrees C, was 0.030-0.035 x 10-4 sec-1 for AA,LDSS, and HDSS core skeletons. However at 24, 30, 34, and 37 degrees C the rate of dissociation of spectrin from HDSS core skeletons was significantly slower than the rate of dissociation from AA core skeletons. Having determined the first order rate constants for spectrin dissociation at these specified temperatures, we then asked whether dithiothreitol (DTT) would hasten the dissociation of core skeletons. The presence of DTT caused the rate of dissociation of the HDSS membrane skeleton to become statistically indistinguishable from the rate of dissociation of AA membrane skeletons. This is consistent with the suggestion that reversible thiol oxidation is responsible for the slow dissociation of the HDSS membrane skeleton.


A Point Mutation R122C in RUNX3 Promotes the Expansion of Isthmus Stem Cells and Inhibits Their Differentiation in the Stomach.
RUNX transcription factors play pivotal roles in embryonic development and neoplasia. We previously identified the single missense mutation R122C in RUNX3 from human gastric cancer. However, how RUNX3R122C mutation disrupts stem cell homeostasis and promotes gastric carcinogenesis remained unclear. To understand the oncogenic nature of this mutation in vivo, we generated the RUNX3R122C knock-in mice. Stomach tissues were harvested, followed by histologic and immunofluorescence staining, organoid culture, flow cytometry to isolate gastric corpus isthmus and nonisthmus epithelial cells, and RNA extraction for transcriptomic analysis. The corpus tissue of RUNX3R122C/R122C homozygous mice showed a precancerous phenotype such as spasmolytic polypeptide-expressing metaplasia. We observed mucous neck cell hyperplasia; massive reduction of pit, parietal, and chief cell populations; as well as a dramatic increase in the number of rapidly proliferating isthmus stem/progenitor cells in the corpus of RUNX3R122C/R122C mice. Transcriptomic analyses of the isolated epithelial cells showed that the cell-cycle-related MYC target gene signature was enriched in the corpus epithelial cells of RUNX3R122C/R122C mice compared with the wild-type corpus. Mechanistically, RUNX3R122C mutant protein disrupted the regulation of the restriction point where cells decide to enter either a proliferative or quiescent state, thereby driving stem cell expansion and limiting the ability of cells to terminally differentiate. RUNX3R122C missense mutation is associated with the continuous cycling of isthmus stem/progenitor cells, maturation arrest, and development of a precancerous state. This work highlights the importance of RUNX3 in the prevention of metaplasia and gastric cancer.


Release Mechanism Between Ion Osmotic Pressure and Drug Release in Ionic-Driven Osmotic Pump Tablets (I).
The objective of this study was to develop an authentic ionic-driven osmotic pump system and investigate the release mechanism, simultaneously exploring the in vitro and in vivo correlation of the ionic-driven osmotic pump tablet. A comparison of the ionic-driven and conventional theophylline osmotic pump, the influence of pH and the amount of sodium chloride on drug release, the relationship between the ionic osmotic pressure and the drug release, and the pharmacokinetics experiment in beagle dogs were investigated. Consequently, the similarity factor (f 2 ) between the novel and conventional theophylline osmotic pump tablet was 60.18, which indicated a similar drug-release behavior. Also, the release profile fitted a zero-order kinetic model. The relative bioavailability of the ionic-driven osmotic pump to the conventional osmotic pump calculated from the AUC (0-∞) was 93.6% and the coefficient (R = 0.9945) confirmed that the ionic-driven osmotic pump exhibited excellent IVIVC. The driving power of the ionic-driven osmotic pump was produced only by ions, which was strongly dependent on the ion strength, and a novel formula for the ionic-driven osmotic pump was derived which indicated that the drug-release rate was proportional to the ionic osmotic pressure and the sodium chloride concentration. Significantly, the formula can predict the drug-release rate and release characteristics of theophylline ionic-driven osmotic pumps, guiding future modification of the ionic osmotic pump.


Dosimetric performance of an enhanced dose range radiographic film for intensity-modulated radiation therapy quality assurance.
Film-based quality assurance (QA) is an important element of any intensity modulated radiation therapy (IMRT) program. XV2 film is often used for IMRT QA, however, it has saturation and energy response limitations which hinder accurate film dosimetry. A new commercially released ready-pack film has been introduced that has an extended dose range (EDR2), reportedly allowing measured doses above 600 cGy without saturation. Also, this film may have less energy dependence due to its composition. The purpose of this paper is to study and compare the two types of film with respect to absolute dose accuracy for IMRT plans, percent depth dose accuracy for square fields between 2 and 20 cm, ability to measure composite plan isodoses and single beam fluence maps for IMRT cases, and sensitivity to processor variations over time. In 19 IMRT patient QA tests, the EDR2 film was able to achieve an absolute dose accuracy of better than 2% vs over 4% for XV2 film. The EDR2 film was able to reproduce ionization chamber and diode-measured percent depth doses to 20 cm depth generally to within 1% over the range of field sizes tested compared to about 10% for the XV2 film. When compared to calculations, EDR2 film agreed better than XV2 film for both composite plan isodoses and single beam fluence intensity maps. The EDR2 film was somewhat more resistant to processor changes over time than the XV2 film, with a standard deviation of dose reproducibility of less than 2% compared to 6%, respectively.


Thyroid gland diseases in adult patients with diabetes mellitus.
This review concerns the relation between most frequent thyroid gland diseases and diabetes mellitus in adult patients. Special attention is paid to autoimmune thyroiditis, Graves' disease, thyroid autoimmunity in pregnant diabetic women, and iodine metabolism. We focused on mechanisms leading to coexistence of both endocrine disorders, and on distinctions in the prevalence, diagnosis, clinical course and treatment of thyroid diseases in diabetic patients. The prevalence of thyroid diseases in diabetic patients is 2-3 times higher than in nondiabetic subjects; it raises with age, and is strongly influenced by female gender and autoimmune diabetes. Clinical relevance of thyroid diseases, especially in diabetic patients, significantly increases if it is associated with deteriorated function, which always cause a number problems with metabolic compensation of diabetes. Most serious consequences are increased frequency of hypoglycaemia in hypothyroidism and development of potentially life-threatening ketoacidosis in thyrotoxicosis. In spite of that, little attention is paid to the diagnosis of thyroid diseases in diabetics, as they are diagnosed in only about half of the patients. At the end, we provide recommendations for the thyroid disease screening and diagnosis in patients with diabetes mellitus based on our experience.


Which roads lead to depression in Latinas? A network analysis of prenatal depressive symptoms, discrimination, acculturative stress, and low birth weight.
Although immigrant mothers from some Latinx subgroups initially achieve healthy birth outcomes despite lower socioeconomic status, this advantage deteriorates across generations in the United States. Interpersonal discrimination and acculturative stress may interact with economic hardship to predict an intergenerational cascade of emotional and biological vulnerabilities, particularly perinatal depression. Network analyses may elucidate not only how and which psychosocial experiences relate to depressive symptoms, but which symptom-to-symptom relationships emerge. This study aims to understand (1) how economic, acculturative, and discrimination stressors relate to prenatal depression and low birth weight and (2) how Latinas may respond to and cope with stressors by exploring symptom-symptom and symptom-experience relationships. A sample of 151 pregnant Latinas (predominantly foreign-born and Mexican and Central American descent) completed the EPDS and psychosocial questionnaires (discrimination, acculturation, acculturative stress, economic hardship) during pregnancy (24-32 weeks). Birth weights were recorded from postpartum medical records. We created network models using the Extended Bayesian Information Criterion Graphical Least Absolute Shrinkage and Selection Operator to estimate the relationship between variables. Discrimination exposure connected psychosocial stressors to depressive symptoms, particularly worry, crying, sadness, and self-blame. Discrimination also revealed a connection between acculturation and low birth weight. Furthermore, younger age of migration and greater acculturation levels were correlated to greater discrimination stress and low birth weights. Perinatal research in Latinas must account not only for measures of cultural adaptation but recognize how developmental exposures across the life span, including discrimination, may be associated with adverse health trajectories for a mother and her child.


[Effect of Gantry Speed on Image Quality of Four-dimensional Cone-beam Computed Tomography Using a Dynamic Phantom of Lung].
The purpose of this paper was to determine the optimal imaging conditions for four-dimensional cone-beam computed tomography (4D-CBCT) using an X-ray tube and a flat-panel detector mounted on a radiotherapy device. The optimal imaging conditions were examined by changing the gantry speed (GS) parameter that affected the exposure time. Exposed dose during imaging and image quality of moving phantom were compared between examined conditions. The weighted computed tomography dose index (CTDIW) decreased linearly with increasing GS. However, when GS was 180°/min or faster, the image quality degraded, and errors of 1 mm or more were observed regarding the size of mock tumor in the moving phantom. The accuracy of automatic image matching was within 0.1 mm when GS of 120°/min or slower was chosen. From the results of this study, we concluded that GS of 120°/min is the optimum imaging condition. Under this imaging condition, the exposure time and CTDIW can be reduced by about 50% without compromising the accuracy of image registration, compared to the conventional GS of 70°/min. In addition, it has been clarified that there is an event that image reconstruction is not performed correctly due to the influence of phantom artifacts without depending on GS.


Electrochemical study of reversible hydrogenase reaction of Desulfovibrio vulgaris cells with methyl viologen as an electron carrier.
An electrode modified with immobilized whole cells of Desulfovibrio vulgaris (Hildenborough) produces an S-shaped voltammogram with both cathodic- and anodic-catalytic-limiting currents in a methyl viologen-containing buffer saturated with H2. Methyl viologen penetrates into the bacterial cells to serve as an electron carrier in the reversible reaction of hydrogenase in the cells and functions as an electron-transfer mediator between the bacterial cells and the electrode, thus producing the catalytic currents for the evolution and consumption of H2. An equation for the catalytic current that takes into account the reversible hydrogenase reaction explains well the shape of the voltammogram. The potential at null current on the voltammogram agrees with the potential determined by potentiometry with the same electrode, which is equal to the redox potential of the H+/H2 couple in the solution--the standard potential of a hydrogen electrode at the pH of the solution. When D. vulgaris cells are suspended in an argon-saturated buffer containing methyl viologen, the suspension produces a catalytic current at a bare glassy carbon electrode for the evolution of H2. Analysis of the current by a theory for a catalytic current for a unidirectional nonlinear enzyme catalysis allows us to determine the kinetic parameters of the reaction between methyl viologen and hydrogenase in intact D. vulgaris cells. Thus we obtain the apparent Michaelis constant for methyl viologen cation radical, K'MV.+ = 0.16 mM, and the apparent catalytic constant (that is, the turnover number per D. vulgaris cell), zkcat,H+ = 1.2 x 10(7) s-1, for the H2 evolution reaction at pH 5.5 and at 25 degrees C, z being the number of hydrogenases contained in a D. vulgaris cell. The bimolecular reaction rate constant, kcat,H+/K'MV.+, of the reaction between methyl viologen cation radical and oxidized hydrogenase in intact D. vulgaris cells is estimated as 4.2 x 10(7) M-1 s-1. Similarly, the bimolecular reaction rate constant, kcat,H2/K'MV2+, of the reaction between methyl viologen and reduced hydrogenase is estimated to be 1.2 x 10(7) M-1 s-1 at pH 9.5 and 25 degrees C. Both rate constants are large enough for the reactions to be diffusion-limited processes.


Nerve growth factor and Alzheimer's disease.
Clinical trials with cholinergic agents suggest that cholinergic hypertrophy may be beneficial in the treatment of Alzheimer's disease (AD). Recent findings substantiate the view that nerve growth factor (NGF) selectively acts on cholinergic neurons. In adult rats and primates, intraventricular administration of nerve growth factor produces trophic actions on cholinergic neurons and prevents age related neuronal atrophy. These findings suggest the possibility of the eventual development of pharmacological applications of nerve growth factor for the treatment of AD.


Sulfhydryl modification induces calcium entry through IP₃-sensitive store-operated pathway in activation-dependent human neutrophils.
As the first line of host defense, neutrophils are stimulated by pro-inflammatory cytokines from resting state, facilitating the execution of immunomodulatory functions in activation state. Sulfhydryl modification has a regulatory role in a wide variety of physiological functions through mediation of signaling transductions in various cell types. Recent research suggested that two kinds of sulfhydryl modification, S-nitrosylation by exogenous nitric oxide (NO) and alkylation by N-ethylmaleimide (NEM), could induce calcium entry through a non-store-operated pathway in resting rat neutrophils and DDT₁MF-2 cells, while in active human neutrophils a different process has been observed by us. In the present work, data showed that NEM induced a sharp rising of cytosolic calcium concentration ([Ca²⁺](c)) without external calcium, followed by a second [Ca²⁺](c) increase with readdition of external calcium in phorbol 12-myristate 13-acetate (PMA)-activated human neutrophils. Meanwhile, addition of external calcium did not cause [Ca²⁺](c) change of Ca²⁺-free PMA-activated neutrophils before application of NEM. These data indicated that NEM could induce believable store-operated calcium entry (SOCE) in PMA-activated neutrophils. Besides, we found that sodium nitroprusside (SNP), a donor of exogenous NO, resulted in believable SOCE in PMA-activated human neutrophils via S-nitrosylation modification. In contrast, NEM and SNP have no effect on [Ca²⁺](c) of resting neutrophils which were performed in suspension. Furthermore, 2-Aminoethoxydiphenyl borate, a reliable blocker of SOCE and an inhibitor of inositol 1,4,5-trisphosphate (IP₃) receptor, evidently abolished SNP and NEM-induced calcium entry at 75 µM, while preventing calcium release in a concentration-dependent manner. Considered together, these results demonstrated that NEM and SNP induced calcium entry through an IP₃-sensitive store-operated pathway of human neutrophils via sulfhydryl modification in a PMA-induced activation-dependent manner.


An introduction to quality improvement in paediatrics and child health.
Quality improvement is a focus on changing the way in which patient care is delivered. Central to this is developing a more rounded, patient-focused approach to the design and delivery of care. Here, in the first of a series, we introduce the concepts of quality improvement, explain why quality improvement should matter to paediatricians and give some pointers as to where and how paediatricians can learn and do more.


Glucomannan Biosynthesis Catalyzed by Pisum sativum Enzymes.
The results of molecular weight studies, structural analysis of the [(14)C]polysaccharides, and enzymic properties indicate that the Pisum sativum guanosine diphosphosphate glucose: glucosyltransferase is an enzymic component involved in the biosynthesis of glucomannan chains. The properties of the Pisum sativum particulate enzyme are essentially identical to the glucomannan synthetase obtained from Phaseolus aureus. Also present in the particulate preparation is an enzyme which catalyzes the formation of a [(14)C]mannolipid, using guanosine diphosphate-[(14)C]mannose as a substrate. The [(14)C]mannolipid is hydrolyzed by treatment with 0.012 m HCl, but is stable to treatment with 0.09 m NaOH. The formation of the [(14)C]mannolipid is apparently reversed by guanosine diphosphate, but not by guanosine monophosphate. The chromatographic mobility of the [(14)C]mannolipid is identical to that of a similar mannolipid synthesized by a Phaseolus aureus enzyme.


Viral Hepatitis E and Chronicity: A Growing Public Health Concern.
Hepatitis E viral infection recently emerges as a global health concern. Over the last decade, the understanding of hepatitis E virus (HEV) had changed with the discovery of new genotypes like genotype-7 and genotype-8 with associated host and mode of infection. Diversification in the mode of hepatitis E infection transmission through blood transfusion, and organ transplants in contrast to classical feco-oral and zoonotic mode is the recent medical concern. The wide spectrum of infection ranging from self-limiting to acute liver failure is now overpowered by HEV genotype-specific chronic infection especially in transplant patients. This concern is further escalated by the extra-hepatic manifestations of HEV targeting the central nervous system (CNS), kidney, heart, and pancreas. However, with the development of advanced efficient cell culture systems and animal models simulating the infection, much clarity toward understanding the pathogenetic mechanism of HEV has been developed. Also this facilitates the development of vaccines research or therapeutics. In this review, we highlight all the novel findings in every aspect of HEV with special emphasis on recently emerging chronic mode of infection with specific diagnosis and treatment regime with an optimistic hope to help virologists and/or liver specialists working in the field of viral hepatitis.


Neoehrlichiosis: A Case Study of the Tick-Borne Pathogen That Can Cause Thromboembolic Events.
Candidatus Neoehrlichia mikurensis is a gram-negative bacterium carried and spread by Ixodes ricinus ticks often found in Europe and Asia. It causes a disease process called neoehrlichiosis, which can result in vasculitis and thromboembolic events. This pathogen does not grow in typical culture medium, and most laboratories do not carry the specific polymerase chain reaction (PCR) test needed to detect neoehrlichiosis. If a patient presents to an emergency department complaining of a recent tick bite and symptoms of a deep vein thrombosis or pulmonary embolism, consider that these symptoms may be related. Treat the tick bite with doxycycline for 3 weeks and manage the thromboembolic event according to standard treatment of care.


Neuroimmunogastroenterology: At the Interface of Neuroimmunology and Gastroenterology.
The central nervous system (CNS) is an important regulator of the gastrointestinal tract, and CNS dysfunction can result in significant and disabling gastrointestinal symptom manifestation. For patients with neuroimmunologic and neuroinflammatory conditions, the recognition of gastrointestinal symptoms is under-appreciated, yet the gastrointestinal manifestations have a dramatic impact on quality of life. The current treatment strategies, often employed independently by the neurologist and gastroenterologist, raise the question of whether such patients are being treated optimally when siloed in one specialty. Neuroimmunogastroenterology lies at the borderlands of medical specialties, and there are few resources to guide neurologists in this area. Here, we provide an overview highlighting the potential mechanisms of crosstalk between immune-mediated neurological disorders and gastrointestinal dysfunction.


EEG bands during wakefulness, slow-wave, and paradoxical sleep as a result of principal component analysis in the rat.
Rat EEG has been empirically divided in bands that frequently do not correspond with EEG generators nor with the functional meaning of EEG rhythms. Power spectra from wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS) of Wistar rats were submitted to Principal Component Analyses (PCA) to investigate which frequencies are covariant. Three independent eigenvectors were identified for SWS: a band between 1-6, an intermediate band between 7-15, and a fast band between 16-32 Hz (90.74% of the variance); two independent eigenvectors were extracted for PS: slow frequencies between 1-6 covarying together with frequencies between 11-16 Hz, and activity between 6-10 covarying together with fast frequencies between 17-32 Hz (80.38% of the variance); four eigen-vectors were obtained for W: 3-7, 8-9, 10-21 and 21-32 Hz (81.47% of the variance). Vigilance states showed significant differences in AP from 1 to 22 Hz. PCA extracted broad bands different for each vigilance state, which included the most representative EEG activities characteristic of them. These results indicate that during SWS, slow oscillations include frequencies up to 6 Hz, and spindle oscillations frequencies down to 7 Hz. No alpha frequencies were identified as an independent band. Frequencies within theta and beta were gathered in the same eigenvector during PS and in different eigenvectors during W suggesting coordinated activation of hippocampal and cortical systems during PS. These bands are consistent with the underlying neurophysiological mechanisms of sleep and wakefulness and with firing frequencies of generators of rhythmic activity obtained in cellular studies in animals.


How long are the ends of polyene chains?
In this work we study conjugation in all-trans polyene chains H[Single Bond](HC[Double Bond]CH)(n)[Single Bond]H with a view to establishing the length scale for the interaction between conjugated double bonds. As a polyene oligomer is made longer, bond length alternation between formal carbon-carbon single and double bonds diminishes toward the middle of the chain, eventually reaching a constant value characteristic of an "infinite" chain. However those bonds near the end of the chain continue to be influenced by the end, even in the long-chain limit. We have determined optimized geometries for polyene oligomers with up to n=11 repeat units at the MP2/cc-pVTZ level. At this length the central-most bonds are almost converged to the long chain limit, for which we estimate R(C[Double Bond]C)=1.3652 A and R(C[Single Bond]C)=1.4238 A. In contrast, the endmost double bond has a length of 1.3442 A and the endmost single bond has a length of 1.4425 A. We find that a given bond is significantly influenced by conjugation paths through up to six neighboring conjugated double bonds. End effects can also be monitored by examining the energy increment per added monomer as the oligomer length is increased. This analysis also indicates that significant conjugation effects extend out through approximately six neighboring double bonds. From the energy per monomer of the longest chains we extract a value of about 8 kcal/mol for the extra stabilization energy per monomer due to conjugation in long chains.


Polycarbonate Masters for Soft Lithography.
Fabrication of microfluidic devices by soft lithography is by far the most popular approach due to its simplicity and low cost. The approach relies on casting of elastomers, such as polydimethylsiloxane (PDMS), on masters fabricated from photoresists on silicon substrates. These masters, however, can be expensive, complicated to fabricate, and fragile. Here we describe an optimized replica molding approach to preserve the original masters by heat molding of polycarbonate (PC) sheets on PDMS molds. The process is faster and simpler than previously reported methods and does not result in a loss of resolution or aspect ratio for the features. The generated PC masters were used to successfully replicate a wide range of microfluidic devices, including rectangular channels with aspect ratios from 0.025 to 7.3, large area spiral channels, and micropost arrays with 5 µm spacing. Moreover, fabrication of rounded features, such as semi-spherical microwells, was possible and easy. Quantitative analysis of the replicated features showed variability of <2%. The approach is low cost, does not require cleanroom setting or hazardous chemicals, and is rapid and simple. The fabricated masters are rigid and survive numerous replication cycles. Moreover, damaged or missing masters can be easily replaced by reproduction from previously cast PDMS replicas. All of these advantages make the PC masters highly desirable for long-term preservation of soft lithography masters for microfluidic devices.


Head and neck mucosal melanoma: experience with 42 patients, with emphasis on the role of postoperative radiotherapy.
Treatment of head and neck mucosal melanoma remains a challenge. Surgery has traditionally been the main therapeutic approach. The role of postoperative radiotherapy has never been clearly established. The experience with a group of 42 patients (16 males, 26 females) with a primary head and neck mucosal melanoma is reported. Eleven of 19 patients (57.9%) receiving surgery alone developed a regional lymphatic metastasis. For patients receiving postoperative radiotherapy (19 patients), regional metastatic spread occurred in 4 patients (21%). Percentages of local failure were 57.9% (11/19) and 26.3% (5/19) for patients treated with surgery alone and for those treated with surgery and radiotherapy, respectively. Distant metastases occurred in 10 of 19 patients (52.6%) receiving surgery alone and in 9 of 19 patients (47.3%) receiving both therapies. The present evaluation confirms a poor prognosis for patients with head and neck mucosal melanoma, independent of the treatment modality.


Intronic mutation in the growth hormone (GH) receptor gene from a girl with Laron syndrome and extremely high serum GH binding protein: extended phenotypic study in a very large pedigree.
Laron syndrome (LS) is a hereditary form of GH resistance due to molecular defects in the GH receptor (GHR). Most of the identified mutations are located in the extracellular domain of the receptor, resulting in a lack of serum GHBP in the majority of LS patients. We present an LS patient with supranormal levels of serum GHBP, in addition to 35 of her relatives. The proband is a 3.5 year-old Druse girl with severe short stature (height SDS -5.1), high GH (250 micrograms/l), low IGF-I (2.7 nmol/l) and IGFBP-3 (410 micrograms/l), both unresponsive to exogenous GH. The binding capacity of the serum GHBP was 22 nM (adult reference serum, 0.7 nM), with an affinity constant Ka = 1.9 x 10(9) M-1 comparable to that of normal sera (Ka = 1.7-2.1 x 10(9) M-1). The apparent MW of the GHBP was approximately 60-80 kDa, similar to that of control sera. In the proband's sister, parents, grandparents and uncles, extremely high GHBP values were observed (43.0 +/- 4.8 RSB, n = 10) compared with normal adults (0.81 +/- 0.06 RSB) (p << 0.001). The remaining subjects had normal or moderately elevated GHBP levels. Serum GH in adults with high GHBP was significantly elevated above control values (6.0 +/- 0.9 micrograms/l vs 0.76 +/- 0.13 microgram/l, p < 0.001). Serum IGF-I and IGFBP-3 levels were normal in all the subjects, with the exception of an aunt (IGF-I 3.9 nmol/l) and the proband's sister (IGFBP-3 460 micrograms/l). All the subjects' heights were within the normal range. Analysis of the GHR gene performed in the proband revealed an as yet undescribed homozygous intronic point mutation. It consists of a G-->T substitution at nucleotide 785-1 preceding exon 8, a sequence that encodes the transmembrane domain. This mutation, which destroys the invariant dinucleotide of the splice acceptor site, is expected to alter GHR mRNA splicing and to be responsible for skipping exon 8. The resulting truncated protein that retains GH binding activity is probably no longer anchored in the cell membrane, affecting signal transmission in the homozygous patient and causing high GHBP levels in the heterozygous relatives.


Spin-Enhanced Reverse Intersystem Crossing and Electroluminescence in Copper Acetate-Doped Thermally Activated Delayed Fluorescence Material.
Thermally activated delayed fluorescence (TADF) materials are attractive for next-generation organic light-emitting diodes (OLEDs) because of their utilization of nonradiative triplets via reverse intersystem crossing (RISC), which requires not only a small singlet-triplet energy splitting but also the conservation of spin angular momentum. Here we use copper acetate as a spin sensitizer to facilitate RISC and thus enhance electroluminescence in TADF-exciplex OLEDs. Copper acetate is involved in the radiative decay process due to its coordination interaction with exciplex molecules having intermolecular charge-transfer characteristics, which causes significant changes in the photoluminescence intensity and lifetime. Meanwhile, magneto-photoluminescence reveals that the addition of copper acetate promotes spin conversion in the RISC process. It allows the enhancement of the electroluminescence (∼80%) from spin-sensitized OLEDs, accompanied by the suppression of magneto-electroluminescence upon the doping of copper acetate. These results illustrate that using a spin sensitizer may overcome the limitation of harvesting nonradiative triplets in organic luminescent materials and devices.


Endoscopic sclerotherapy of oesophageal varices due to hepatosplenic schistosomiasis. A randomized controlled trial evaluating the effect of adjuvant propranolol therapy.
The relative high incidence of rebleeding during the course of injection sclerotherapy requires attempts at its improvement. Forty consecutive patients with bleeding oesophageal varices underwent either injection sclerotherapy only or injection sclerotherapy with an adjuvant fixed daily dose of propranolol (40 mg tds) in a single-blind randomized controlled trial. They were injected on a weekly basis until varices were eradicated at which time propranolol was withdrawn. Patients were then followed-up for a period of two years. The results showed that ad to a decline in resting pulse rate by a median of 23.9%. Patients undergoing injection sclerotherapy with adjuvant propranolol required fewer injection sessions for variceal eradication than patients undergoing injection sclerotherapy alone (8 versus 11: p > 0.05). Patients undergoing injection sclerotherapy with adjuvant propranolol experienced more variceal recurrences than those undergoing injection sclerotherapy alone (25% versus 13.3%, p > 0.05). Five of 20 patients undergoing sclero-therap with adjuvant propranolol rebleed as compared to 6 of 20 y patients undergoing injection sclerotherapy only (p > 0.05). The probability of rebleeding and survival was similar in both groups (p > 0.05).


Identification of an immunodominant drug efflux pump in Burkholderia cepacia.
Burkholderia cepacia, a major pathogen amongst individuals with cystic fibrosis (CF), is intrinsically resistant to most clinically available antibiotics. We report the identification of an immunodominant antigen in CF patients infected with B. cepacia, a multidrug-resistance efflux pump called BcrA. The bcrA gene encodes a 46 kDa peptide with 14 potential alpha-helices that belongs to the major facilitator superfamily of drug transporters. A recombinant Escherichia coli strain was constructed containing the bcrA gene, which resulted in a four-fold increase in resistance to tetracycline and an eight-fold increase in resistance to nalidixic acid. These results demonstrate that the bcrA gene is part of a drug efflux system that is potentially a major contributor to the high-level antibiotic resistance observed in B. cepacia and thus a potential target for novel therapeutics.


Characteristics and age-related injury patterns of maxillofacial fractures in children and adolescents: A multicentric and prospective study.
Paediatric maxillofacial trauma accounts for 15% of all maxillofacial trauma but remains a leading cause of mortality. The aim of this prospective, multicentric epidemiological study was to analyse the characteristics of maxillofacial fractures in paediatric patients managed in 14 maxillofacial surgery departments on five continents over a 1-year period. The following data were collected: age (preschool [0-6 years], school age [7-12 years], and adolescent [13-18 years]), cause and mechanism of the maxillofacial fracture, alcohol and/or drug abuse at the time of trauma, fracture site, Facial Injury Severity Scale score, associated injuries, day of the maxillofacial trauma, timing and type of treatment, and length of hospitalization. Statistical analyses were performed using SPSS software. Between 30 September 2019 and 4 October 2020, 322 patients (male:female ratio, 2.3:1) aged 0-18 years (median age, 15 years) were hospitalized with maxillofacial trauma. The most frequent causes of the trauma were road traffic accidents (36%; median age, 15 years), followed by falls (24%; median age, 8 years) and sports (21%; median age, 14 years). Alcohol and/or drug abuse was significantly associated with males (p < .001) and older age (p < .001). Overall, 474 fractures were observed (1.47 per capita). The most affected site was the mandibular condyle in children <13 years old and the nose in adolescents. The proportion of patients who underwent open reduction and internal fixation increased with age (p < .001). The main cause of paediatric maxillofacial fractures was road traffic accidents, with the highest rates seen in African and Asian centres, and the frequency of such fractures increased with age. Falls showed an inverse association with age and were the leading cause of trauma in children 0-6 years of age. The choice of treatment varies with age, reflecting anatomical and etiological changes towards patterns more similar to those seen in adulthood.


HIV-related characteristics of migrant workers in rural South Carolina.
After finding human immunodeficiency virus (HIV) infection in a migrant worker named as a syphilis contact, the South Carolina Department of Health and Environmental Control offered HIV counseling and testing and syphilis screening to migrant workers in the surrounding two-county area. In addition, a brief questionnaire was administered to document demographics and risk behavior. Of the 265 workers aged 16 and older in 15 migrant camps, 198 (75%) consented to the survey and testing. Of the 198 tested, 85% were male and 75% single. The median age was 39, with a range of 16 to 69 years. Twenty-five (13%) were HIV antibody positive, and 32 (16%) had reactive serologic tests for syphilis. Of the 166 workers who reported the frequency of condom use, 77 (46%) indicated they never use condoms. We conclude that there is a relatively high rate of HIV infection in these rural South Carolina migrant workers, whose behavior puts them at risk for HIV infection and other sexually transmitted diseases.


[Benign gastric tumors. Unusual forms. Therapeutic considerations].
The authors present a study preformed on 38 patients with benign gastric tumours, representing 8.4% of the total number of gastric neoformations. Aspects related to the site of the tumours are discussed, as well as data concerning frequency, clinical and radiologic aspects, histologic characteristics, and the possible relationship with gastric cancers. A series of cases are described, the particularities of which may lead to diagnosis errors, and aspects are discussed in relation to surgical treatment of benign gastric tumours. The authors have mostly performed the excision of the tumours or a limited gastric resection, and obtained good results with this conservative attitude.


Centrally administered mu- and delta-opioid agonists increase operant responding for saccharin.
In previous reports, ICV administration of selective mu- or delta-opioid receptor agonists was found to stimulate the intake of saccharin and salt solutions in nondeprived rats. In the present study, we measured the effects of selective mu-, delta-, and kappa-agonists on operant responding for saccharin. The selective mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and the selective delta-agonist [D-Thr2]-leucine enkephalin-Thr (DTLET) increased responding, whereas the kappa-agonist dynorphin A analog kappa ligand (DAKLI) had no significant effect. These results agree with previous studies on saccharin and salt intake and are consistent with the possibility that the effects of opioids on the intake of these fluids are mediated via enhancement of activity in brain reward pathways.


Development and characterization of sponge-like acyclovir ocular minitablets.
For the treatment of ocular keratitis acyclovir, as a highly specific inhibitor of herpes virus replication, is applied topically into the eye. The objective of this study was to design and evaluate freeze-dried, bioadhesive and biodegredable acyclovir ocular minitablets for prolonged local drug action. The sponge-like nature of the lyophilized ocular minitablets ensures rapid hydration and gelation of these tablets in the eye and thus would reduce the foreign body sensation. The polymers used were sodium carboxymethylcellulose (NaCMC), hydroxypropylmethylcellulose (HPMC), xanthan gum, chitosan and Carbopol 943P. The minitablets were evaluated for drug content, weight variation, bioadhesion, water uptake and in vitro drug release. In addition, the rheological characteristics of the polymers solutions were investigated. Rheological data revealed that all tested polymers exhibited pseudoplastic behaviour which is required to minimize interference with blinking. Drug release was found to be affected by the type and concentration of polymer. The order of sustainment was chitosan > xanthan > HPMC > Carbopol > NaCMC. Water uptake study, dissolution rate of the polymers and viscosity measurements could explain the different release profiles of the drug from the polymers. Chitosan minitablet was chosen for its significant sustained release and good bioadhesive property for in vivo study in rabbits. The tablet showed a good permeation into the cornea in comparison to the commercially available Zovirax(®) eye ointment. In conclusion, chitosan ocular minitablets containing acyclovir could be considered as a promising sustained drug delivery system for ocular keratitis treatment.


Utilization of macrophages in anticancer therapy: the macrophage network theory.
Appropriate and rational modulation of innate immunity may enhance the therapeutic efficacy of emerging immune therapies for treating cancer. One of the crucial cells of innate immunity is the macrophage. The purpose of this article was to review those issues that suggest ways of exploiting macrophage local functions in immune therapy, and to discuss the suitability of low molecular-weight lipopolysaccharides as potent modulators of macrophage functions for immune therapy of cancer.


Resuscitation from hemorrhagic shock with Ringer's ethyl pyruvate solution improves survival and ameliorates intestinal mucosal hyperpermeability in rats.
We previously showed that pretreatment with a solution of ethyl pyruvate in a calcium-containing balanced salt solution, Ringer's ethyl pyruvate solution (REPS), ameliorates gut mucosal damage in rats subjected to mesenteric ischemia/reperfusion. Herein, we sought to test the hypothesis that REPS would be beneficial as a post-treatment (i.e., resuscitation fluid) for hemorrhagic shock. Anesthetized Sprague-Dawley rats were bled to a mean arterial pressure (MAP) of 40 mmHg until 40% of shed blood was returned. The animals then were resuscitated over 60 min with the remaining shed blood plus twice the shed blood volume as either Ringer's lactate solution (RLS) or REPS. In Experiment 1, RLS or REPS was then infused for 3 h more (or until death) at 3 mL/kg/h. Read-outs were post-resuscitation ileal mucosal permeability to fluorescein-labeled Dextran with an average molecular mass of 4000 Da (FD4) and survival. Permeability, determined just before death (MAP < 40 mmHg) or after 4 h of resuscitation, was assessed using an ex vivo everted gut sac technique and is expressed as a clearance (nL/cm/min). In Experiment 2, the read-outs were ileal FD4 permeability measured at 60 min after starting resuscitation and gut and liver malondialdehyde (MDA) formation. FD4 clearance data were logarithmically transformed prior to performing statistical analyses. In Experiment 1, 4/8 (50%) of RLS-treated rats survived 4 h after resuscitation whereas 7/7 (100%) of REPS-treated rats survived (P< 0.05). Ileal FD4 clearances were 105 +/- 30*, 85 +/- 34*, and 38 +/- 7 for all rats treated with RLS, surviving rats treated with RLS, and rats treated with REPS, respectively (the asterisk indicates P < 0.05 vs. REPS). In Experiment 2, ileal FD4 clearances were 71 +/- 13* and 34 +/- 8 for rats treated with RLS and REPS (n = 5 each), respectively. Post-resuscitation levels of MDA in the ileum and liver were significantly lower in rats treated with REPS as compared with RLS. Resuscitation with REPS, a stable and nontoxic antioxidant solution, improves survival and ameliorates ileal mucosal permeability in a rat model of severe hemorrhagic shock.


[Plasma technology in the practice of orthodontics. 1].
The paper describes the technique of plasma spraying used to fortify the coating of permanent dentures. This method helps improve the quality of permanent dentures and strengthen the adhesion of coatings on retention layers. Hence, dentures with very thin retention layer and vary strong coating adhesion can be made by traditional methods of denture making, thus improving the quality of prosthetic treatment. Traditional plastic may be used as coating material.


Ultrasound-amplified immunohistochemistry.
We describe a novel technique for improving the sensitivity of immunofluorescence staining by use of ultrasonic irradiation. Free-floating vibratome sections from rat cerebellum were incubated with primary antiserum and simultaneously were briefly exposed to ultrasound (US) in a conventional ultrasound bath. After the US treatment, a conventional immunohistochemical method was employed. Two different antisera and two conventional immunohistochemical detection systems were tested. In all cases a 10-20-sec US treatment strengthened immunoreactivity considerably. Irradiated samples showed a good morphology compared with non-irradiated sections. Our results demonstrate that with ultrasonic treatment the dilutions of primary antibodies can be increased and the incubation times of primary antisera can be reduced. The ultrasonic method described here requires no special equipment. It is easy, reproducible, and it can be considered a new method for the enhancement at immunohisto- and cytochemical staining of free-floating vibratome sections.


The effect of child development on the components of the Frequency Following Response: Child development and the Frequency Following Response.
During childhood, neuronal modifications occur so that typical childhood communicative development occurs. This work aims to contribute to the understanding of differences in the speech encoding of infants and school-age children by assessing the effects of child development, in different phases of early childhood, on the encoding of speech sounds. There were 98 subjects of both sexes, aged from 1 day to 8 years and 9 months who participated in the study. All subjects underwent a Frequency Following Response (FFR) assessment. A regression and linear correlation showed the effects of age in the FFR components, i.e., significant decrease in the latency and increased amplitude of all FFR waves with age. An increase in the slope measure was also observed. Younger infants require more time and show less robust responses when encoding speech than their older counterparts, which were shown to have more stable and well-organized FFR responses.


[Phytotherapy in Primary Health Care: perspectives of managers and professionals in the Family Health Program of Teresina, Piauí, Brazil].
Since 2006, thanks to experiments and the inclusion of norms, phytotherapy has become an integral and complementary practice in the Unified Health System, duly increasing the options in Primary Health Care. This study sought to identify the qualitative and quantitative perceptions of 8 managers and 68 health professionals in family health strategy (36 nurses, 18 physicians and 14 dentists) in Teresina in the State of Piauí, regarding the inclusion of phytotherapy in Primary Health Care. A semi-structured questionnaire was used In the interviews with questions regarding the interviewees' personal details, their knowledge about phytotherapy and their opinions about the potential of its inclusion in Primary Health Care. In general, the interviewees accept the institutionalization of phytotherapy, use this therapeutic measure personally and acknowledge that it is a popular form of medication. Technical training of phytotherapy health professionals, as well as knowledge of policies involving the issue is lacking. The managers revealed that they are open to discuss the issue, albeit listing justifications, strategies and difficulties of a political and structural nature. Thus, they acknowledged the importance of disseminating the discussion on phytotherapy to broaden the options in Primary Health Care.


Doppler echocardiography in diagnosis of mitral insufficiency.
By means of pulsed Doppler echocardiography (PDE) the authors investigated 53 patients who subsequently underwent heart catheterization and left ventriculography. The results of PDE examination agreed with ventriculography in 29 out of 31 patients with mitral regurgitation (PDE sensitivity = 94%). In 22 patients with no angiographic evidence of mitral regurgitation PDE exhibited two false positive results (PDE specificity = 91%). A semi-quantitative assessment of regurgitation by predetermined PDE criteria was successful in differentiating a group of severe mitral insufficiency (MI) from less significant MI (= mild and moderate MI angiographically). The agreement with ventriculographic classification of MI was 87 and 86%, respectively. The presented results clearly indicate that PDE, as a non-invasive methods, is precise enough in detecting mitral regurgitation and can be recommended for application in adult cardiology.


Insecticides and their use in the dog and cat.
With such a variety of insecticides available, the veterinary surgeon will need to assess each case on its history, the owner, the patient and the severity of parasitical infestation. Without such an assessment there is more likelihood of problems, either failure to eradicate parasites or toxicity from incorrect use of the product. It must be remembered that two methods of application of insecticides should not be used together, eg, a collar and a spray.


Limited beneficial effects of perfluorocarbon emulsions on encapsulated cells in culture: experimental and modeling studies.
Due to the high solubility of oxygen in perfluorocarbons (PFCs), these compounds have been explored for improved cell and tissue oxygenation. The goal of this study is to investigate the effects of a PFC emulsion on cellular growth and function in a tissue engineered construct. A perfluorotributylamine (PFTBA) emulsion was co-encapsulated at 10 vol% with mouse βTC-tet insulinoma cells in calcium alginate beads and cultured under normoxic and severely hypoxic conditions. The number of metabolically active cells and the induced insulin secretion rate were measured over time for up to 16 days. Results showed no significant effect of PFTBA relative to the PFTBA-free control. The alginate-PFC-cell system was also modeled mathematically, and simulations tracked the number of viable cells over time under the same conditions used experimentally. Simulations revealed only a small, likely experimentally undetectable difference in cell density between the PFC-containing and PFC-free control beads. It is concluded that PFTBA up to 10 vol% has no significant effect on the growth and function of encapsulated βTC-tet cells under normoxic and hypoxic conditions.


[Lung cancer screening is not the right answer, a ban on smoking is].
The Minister of Health, Welfare and Sport of the Netherlands has asked the Dutch Health Council an advice on lung cancer screening. But even the target group will gain little: yearly approximately 90 fewer lung cancer deaths of over 8,000 due to smoking, and most if not all of them will die as quickly from other consequences of smoking. Moreover, lung cancer screening harms the population screened, as well as our society and health care providers. So how to stop this public health problem? Ban smoking. The health effects are much wider than lung cancer and start immediately. After 10 years, lung cancer risk of ex-smokers will be halved. After a few decades, over 8,000 people would not die from lung cancer anymore each year and, on top of that, over 10,000 less persons would die from the many other consequences of smoking. So only banning smoking is the answer -starting lung cancer screening is not a healthy answer.


Reduced glycosaminoglycan sulfation diminishes the agrin signal transduction pathway.
Proteoglycans consist of a protein core complexed to glycosaminoglycan (GAG) side chains, are abundant in skeletal muscle cell membranes and basal lamina, and have important functions in neuromuscular synapse development. Treatment with chlorate results in the undersulfation of heparan sulfate and chondroitin sulfate GAGs in cell culture. In addition, chlorate treatment decreases the frequency of spontaneous acetylcholine receptor (AChR) clustering in skeletal muscle cell culture. AChRs and other molecules cluster to form the postsynaptic component of neuromuscular synapses. Chlorate treatment is shown here to decrease the frequency of agrin-induced AChR clustering and agrin-induced tyrosine phosphorylation of the AChR beta-subunit. These data suggest that reduced GAG chain sulfation decreases the frequency of AChR clustering by diminishing the agrin signal transduction pathway.


[Progress in diagnosis and treatment of gangrenous cholecystitis].
Gangrenous cholecystitis is a kind of acute cholecystitis, whose course of disease progresses rapidly, early diagnosis is difficult and mortality is high, and clinicians are prone to misdiagnosis and missed diagnosis in clinical work.However, gangrenous cholecystitis has been ignored in various guidelines.This paper systematically summarized the pathogenesis, pathological manifestations, epidemiology, clinical diagnosis and treatment of gangrenous cholecystitis, hoping to provide a complete and clear diagnosis and treatment process for clinicians.


Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant.
Hypovitaminosis D is common in India. In the present prospective partially randomised study of vitamin D (D₃) supplementation during pregnancy, subjects were randomised in the second trimester to receive either one oral dose of 1500 μg vitamin D₃ (group 1, n 48) or two doses of 3000 μg vitamin D₃ each in the second and third trimesters (group 2, n 49). Maternal 25-hydroxyvitamin D (25(OH)D) at term, cord blood (CB) alkaline phosphatase (ALP), neonatal serum Ca and anthropometry were measured in these subjects and in forty-three non-supplemented mother-infant pairs (usual care). Median maternal 25(OH)D at term was higher in group 2 (58·7, interquartile range (IQR) 38·4-89·4 nmol/l) v. group 1 (26·2, IQR 17·7-57·7 nmol/l) and usual-care group (39·2, IQR 21·2-73·4 nmol/l) (P = 0·000). CB ALP was increased (>8.02 μkat/l or >480 IU/l) in 66·7 % of the usual-care group v. 41·9 % of group 1 and 38·9 % of group 2 (P = 0·03). Neonatal Ca and CB 25(OH)D did not differ significantly in the three groups. Birth weight, length and head circumference were greater and the anterior fontanelle was smaller in groups 1 and 2 (3·08 and 3·03 kg, 50·3 and 50·1 cm, 34·5 and 34·4 cm, 2·6 and 2·5 cm, respectively) v. usual care (2·77 kg, 49·4, 33·6, 3·3 cm; P = 0·000 for length, head circumference and fontanelle and P = 0·003 for weight). These differences were still evident at 9 months. We conclude that both 1500 μg and two doses of 3000 μg vitamin D₃ had a beneficial effect on infant anthropometry, the larger dose also improving CB ALP and maternal 25(OH)D.


Clinical and 3-Dimensional Analyses of Nasal Forms After Secondary Correction of Cleft Lip-Nose Deformities Using Extended Spreader Cartilage Graft With a Cross-Lap Joint Technique.
A surgical strategy for definitive cleft lip-nasal correction that stably provides symmetric and natural nasal forms has not been established to date. The purpose of this study was to describe our surgical techniques and 3-dimensional (3D) assessment results after the definitive correction of cleft lip-nose deformity using an extended spreader cartilage graft with a cross-lap joint technique to achieve a rigid strut for lower lateral cartilage repositioning to obtain a desirable nasal tip projection. This study enrolled 14 patients with unilateral cleft lip (UCL) with or without cleft palate and 8 patients with bilateral cleft lip (BCL) with or without cleft palate who underwent definitive nose correction and were followed for 1 to 3 years. All patients were treated by open rhinoplasty, repositioning of the lower lateral cartilage, use of an extended spreader cartilage graft with a cross-lap joint technique for nasal tip support, and medial-upward advancement of nasolabial components with vestibular expansion by a free mucosal graft. For the BCL nose, pedicle flaps from rim skin were used for columella lengthening. Preoperative and postoperative nasal forms were 3-dimensionally analyzed by use of 3D images serially obtained in 12 patients. The postoperative nasal forms were satisfactorily improved in all patients, without any serious postoperative complications. Preoperative and postoperative 3D analyses showed a significantly projected nasal tip in the postoperative noses of patients in both the UCL group and the BCL group (P < .01 and P < .05, respectively) and a sharper nasal tip angle in the BCL group (P < .05). Lateral deviation of the nasal tip was significantly improved in the center of the face in patients in the UCL group (P < .01). The results of this study suggest that the extended spreader cartilage graft using the cross-lap joint graft technique is useful to provide a desirable projection of the nasal tip in the center of the face on definitive correction of both UCL and BCL nose deformities.


Ergonomics & retention.
The Visiting Nurse Association of Texas found that the impact of repetitive motion injuries on their office staff was costing them almost $200,000 a year. They formed a committee to design a cumulative trauma disorder prevention program. Since that time repetitive motion injuries have decreased dramatically and the program has assisted in staff retention.


Cardiopulmonary bypass, rewarming, and central nervous system dysfunction.
During cardiopulmonary bypass a nasopharyngeal temperature greater than 38 degrees C at the end of rewarming may indicate cerebral hyperthermia. This could exacerbate an ischemic brain injury incurred during cardiopulmonary bypass. In a cohort of 150 aortocoronary bypass patients neuropsychologic test scores of 66 patients whose rewarming temperature exceeded 38 degrees C were compared with those who did not. There were no differences between groups with respect to demographic and intraoperative variables. A trend was seen for hyperthermic patients to do worse on all neuropsychologic tests in the early postoperative period but not at 3-month follow-up. By analysis of covariance hyperthermic patients did worse on the visual reproduction subtest of the Weschler memory scale at 3 months (p = 0.02), but this difference was not found by linear regression (p = 0.10). We were unable to demonstrate any significant deterioration in patients rewarmed to greater than 38 degrees C in the early postoperative period. The poorer performance in the visual reproduction subtest of the Wechsler memory scale at 3 months in the group rewarmed to more than 38 degrees C is interesting but far from conclusive. Caution with rewarming is still advised pending more in-depth study of this issue.


Pregnancy associated breast cancer.
Treatment of pregnancy associated breast cancer (PABC) is usually compromised as both foetal and maternal health has to be taken into consideration. We have identified on our database twelve patients with PABC and twenty-four age-matched controls diagnosed in the same time-frame. The mean age was 36 and 38 years respectively. There was no difference in time to presentation between the two groups. The mean tumour size was 48.72 mm and 26.30 mm respectively (p = 0.001). Lymphovascular invasion and lymph node involvement were more common in the PABC group. In the PABC group, 5 patients (42%) were treated with neo-adjuvant chemotherapy including one patient in first trimester. All patients underwent surgery. Adjuvant chemotherapy was given to seven (58.3%) of the PABC patients. At median follow up of 36 months, there was a single mortality and two patients (17%) had developed recurrent disease. All children are healthy with no deformity or learning disability.


Characterization and pharmacological studies of an octopamine-sensitive adenylate cyclase from nerve cord of Locusta migratoria.
An octopamine-sensitive adenylate cyclase that is insensitive to stimulation by dopamine (DA) and 5-hydroxytryptamine (5-HT), was studied in a homogenized nerve cord preparation of the migratory locust, Locusta migratoria. The enzyme complex is similar to catecholamine-sensitive cyclases from mammals with respect to pH-optimum, requirement for Mg++ and GTP, and sensitivity to forskolin. The octopamine-mediated elevation of adenylate cyclase activity is antagonized by a variety of drugs with the following order of potency: mianserin greater than phentolamine greater than promethazine greater than gramine greater than cyproheptadine greater than cis-flupenthixol greater than chlorpromazine greater than metoclopramide.


Early migration of uncemented porous coated anatomic femoral component related to aseptic loosening.
Primary total hip arthroplasties were performed in 108 patients (116 hips) using a porous coated anatomic (PCA) hip system. Nineteen (22 hips) of 108 patients (116 hips) who had a subsidence of a PCA femoral stem more than 3 mm were studied for the time onset, the amount of stem subsidence, and outcomes. A minimum follow-up period was seven years. The average age of the patients at operation was 37.4 years. The operative diagnosis was avascular necrosis of femoral head in seven hips; osteoarthrosis secondary to childhood septic hip joint in six; fracture of femoral neck in three; and miscellaneous in six hips. The average preoperative Harris hip score was 57 points, which improved to 82 points at the seven-year follow-up examination. Overall, there was a 79% prevalence of thigh pain (15 patients). Six patients had occasional, nondisabling, activity-related thigh pain. The remaining nine patients had persistent and disabling thigh pain at the final follow-up examination. All stems had an undersized component in one or both planes. One hip was stabilized by bone ingrowth. Twelve hips were fixed by fibrous tissue ingrowth and had occasional clinical symptoms. Nine hips had component loosening at the final follow-up examination, of which four were revised and five were pending revision. Early instability of the femoral component measured by radiographs was correlated with and predictive of late radiographic loosening of the femoral component.


[Patient satisfaction with the work of the hospital medical personnel].
The article presents the data of patient's satisfaction with the work of nurses and physicians in the hospitals, which belong to Lithuanian Health promotion hospitals network. All nine hospitals of the Lithuanian health promotion hospitals network took part in this study. Altogether 1300 questionnaires were handed out. They have been completed and returned by 1271 patients, i.e. 97.8%. Patients were asked to complete uniform anonymous questionnaire and evaluate the work, behavior and educational activity of nurses and physicians. The majority of respondents assessed the work of nurses and physicians positively, respectively 96.1% and 95.5%. The evaluation of nurses' work depended on patients' sex and the size of the hospital in which they were treated. Male patients and the ones who were treated in big hospitals assessed the work of nurses better than females and patients in smaller hospitals. The evaluation of physicians' work was related to the patients' education and extra payment for health services. Patients, who had higher education and indicated that they had paid additionally, assessed the work of physicians more critically. The majority of patients assessed the behavior of nurses and physicians as very good or excellent, respectively 86.0% and 90.5%. The work of nurses was better evaluated by elderly people and patients treated in big hospitals and as well as in the departments of internal medicine. Patients' satisfaction with the behavior of physicians was associated with patients' education. Better-educated people were more critical in assessing the behavior of physicians. The results of this study have shown that patients' satisfaction depends on many factors. To improve the quality of health care services in hospitals it is necessary to study patients' needs, expectations and factors associated with patients' satisfaction.


1-Methyl-1H-imidazo[4,5-f]quinolin-6-ium chloride monohydrate.
The title compound, C(11)H(10)N(3)(+) x Cl(-) x H(2)O, belongs to the N1-methyl-substituted imidazo[4,5-f]quinoline family, in which the heterocyclic ring is protonated at the pyridine rather than at the imidazole N atom. The molecule as a whole is almost exactly planar. The molecular structure has been compared with that of the 2-amino analogue described in the literature, and it was found that the extra amino group of the latter is involved in conjugation with the adjacent double bond, i.e. the conjugation does not extend over the entire heterocyclic system. The cation of the title compound forms a strong hydrogen bond with the Cl(-) anion and the anions are interconnected by the water solvent molecule.


Reactivity of an oxoboryl complex toward fluorinated aryl boron reagents.
X-Ray and IR data of unprecedented oxoboryl species indicate a significant alteration in the B[triple bond]O bond strength underlining the novel oxoboryl complexes' close relationship with the well investigated and important class of carbonyl complexes.


Mercury-Tolerant Ensifer medicae Strains Display High Mercuric Reductase Activity and a Protective Effect on Nitrogen Fixation in Medicago truncatula Nodules Under Mercury Stress.
Mercury (Hg) is extremely toxic for all living organisms. Hg-tolerant symbiotic rhizobia have the potential to increase legume tolerance, and to our knowledge, the mechanisms underlying Hg tolerance in rhizobia have not been investigated to date. Rhizobial strains of Ensifer medicae, Rhizobium leguminosarum bv. trifolii and Bradyrhizobium canariense previously isolated from severely Hg-contaminated soils showed different levels of Hg tolerance. The ability of the strains to reduce mercury Hg2+ to Hg0, a volatile and less toxic form of mercury, was assessed using a Hg volatilization assay. In general, tolerant strains displayed high mercuric reductase activity, which appeared to be inducible in some strains when grown at a sub-lethal HgCl2 concentration. A strong correlation between Hg tolerance and mercuric reductase activity was observed for E. medicae strains, whereas this was not the case for the B. canariense strains, suggesting that additional Hg tolerance mechanisms could be playing a role in B. canariense. Transcript abundance from merA, the gene that encodes mercuric reductase, was quantified in tolerant and sensitive E. medicae and R. leguminosarum strains. Tolerant strains presented higher merA expression than sensitive ones, and an increase in transcript abundance was observed for some strains when bacteria were grown in the presence of a sub-lethal HgCl2 concentration. These results suggest a regulation of mercuric reductase in rhizobia. Expression of merA genes and mercuric reductase activity were confirmed in Medicago truncatula nodules formed by a sensitive or a tolerant E. medicae strain. Transcript accumulation in nodules formed by the tolerant strain increased when Hg stress was applied, while a significant decrease in expression occurred upon stress application in nodules formed by the Hg-sensitive strain. The effect of Hg stress on nitrogen fixation was evaluated, and in our experimental conditions, nitrogenase activity was not affected in nodules formed by the tolerant strain, while a significant decrease in activity was observed in nodules elicited by the Hg-sensitive bacteria. Our results suggest that the combination of tolerant legumes with tolerant rhizobia constitutes a potentially powerful tool in the bioremediation of Hg-contaminated soils.


[General therapeutic approaches in systemic vasculitides].
The paper presents general therapeutic principles applied in systemic vasculitis. Several factors may help to contain the clinical activity, such as the location and extent of the inflammatory process affecting the vascular system, the ultimate narrowing of the vascular lumen with subsequent ischemia of the affected tissue and organ. Treatment of vasculitis involves besides glucocorticoids not only cytotoxic drugs (cyclophosphamide, chlorambucil, methotrexate), and immunomodulatory therapeutic agents with immunosuppressive action (cyclosporin A) but also other immunomodulatory drugs, as e.g. dialyzed homogenate of leukocytes (DHL), pentoxyphylline, hydrolytic enzymes, and monoclonal antibodies. The authors emphasize the importance of a complex approach in the management of systemic vasculitis. (Tab. 1, Ref. 36.).


The effects of enhanced recovery after surgery on wound infection, complications, and postoperative hospital stay in patients undergoing colorectal surgery: A systematic review and meta-analysis.
This study aimed to systematically evaluate the effects of enhanced recovery after surgery (ERAS) on surgical site infections, postoperative complications, and length of hospital stay in patients undergoing colorectal surgery. A comprehensive search was conducted of PubMed, Web of Science, Ovid, EMBASE, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data from database inception to April 2023 to identify relevant studies on the application of ERAS in colorectal surgery. Studies were screened, and data were extracted based on predetermined inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. A total of 22 studies, including 3702 patients (ERAS group: 1906; control group: 1796), were included in the final analysis. ERAS significantly reduced the incidence of surgical site infection (odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.34-0.69, p < 0.001), postoperative complications (OR: 0.33, 95% CI: 0.27-0.41, p < 0.001), and length of hospital stay (standardised mean difference: -1.22 days, 95% CI: -1.66 to -0.77 days, p < 0.001). These findings suggest that ERAS reduces the incidence of surgical site infections and postoperative complications and shortens the length of hospital stay in patients undergoing colorectal surgery. Therefore, ERAS should be promoted and applied in clinical practice.


[Modification of psychic, autonomic and metabolic reactions during examinations by a single dose of beta-receptor blockers].
18 students of human medicine were checked during their state examinations when they were or were not administered the beta-receptor blocker Propranolol. In the present examinations under psychic stress Propranolol has no ascertaining influence on the experience parameters, but on somatic reactions in the cardio-circulatory system, the haematological system as well as in the influence on a series of laboratory-chemical parameters. While slighter heart rate, lower blood pressure, a slighter decrease of the absolute number of lymphocytes and a lower plasma cortisol level refer to less distinct reactions of demand under influence of Propranolol, in the region of the lipid parameters HDL-cholesterol and LDL-cholesterol changes develop in the sense of an at least situational increased atherogenic risk.


Assessment of the Effects of Graded Doses of Polyphenolic-Rich Fraction of Garcinia kola Seeds on Pituitary-Testicular Axis of Male Wistar Rats.
This study evaluated the ameliorative and prophylactic effects of 2 different doses of polyphenolic-rich fraction of Garcinia kola (PPRFGk) seeds on the histology and hormones of pituitary-testicular axis of male Wistar rats. Thirty-five male Wistar rats (150-200 g) were divided into 7 groups of 5 rats each. Groups I and II were given distilled water (0.5 mL/day) for 8 days followed by propylene glycol (0.2 mL/d) and 600 mg/kg of PPRFGk, respectively, for 21 days. Group III received sodium arsenate (8 days), left untreated for 21 days. Groups IV and V received sodium arsenate (20 mg/kg) for 8 days followed by PPRFGk (300 and 600 mg/kg, respectively) for 21 days. Groups VI and VII received PPRFGk (300 and 600 mg/kg, respectively) for 21 days followed by sodium arsenate (20 mg/kg) for 8 days. Rats were killed by cervical dislocation 24 hours after the last dose and their blood collected through cardiac puncture. Blood sera were assayed for the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone using immunoassay techniques. Histology of the pituitary gland and testes was carried out. A significant reduction was observed in the concentration of FSH in groups IV, V, VI, and VII in comparison with groups I and II. The concentrations of both LH and testosterone showed significant decreases in groups IV, V, VI, and VII in comparison with group I. Group III presented with the lowest serum hormonal concentrations. Photomicrographs of the pituitary gland revealed greatly reduced basophils in group III and mildly reduced basophils in groups IV, VI, and VII in comparison with groups I and II. Group V revealed hypercellularized and distorted basophils. Photomicrographs of the testes showed detachment of the seminiferous tubules from the basement membrane and disruption of the interstitial space which was worse in group III, moderate in groups V and VI, and mild in group VII. In conclusion, PPRFGk effected a dose-dependent reversal and prevention of the perturbations caused by arsenate in rats.


MicroRNA-630 may confer favorable cisplatin-based chemotherapy and clinical outcomes in non-small cell lung cancer by targeting Bcl-2.
MicroRNA-630 (miR-630) plays dual roles in tumor progression in various human cancers. However, the role of miR-630 in chemoresistance and prognosis in non-small cell lung cancer (NSCLC) remains to be elucidated. This retrospective study enrolled 114 surgically resected patients with NSCLC who experienced tumor relapse and underwent cisplatin-based chemotherapy. The aim was to examine the possible association between miR-630 (and its targeting of Bcl-2 expression) and the response to cisplatin-based chemotherapy. Patients with tumors expressing low miR-630, high Bcl-2, and a combination of both were more likely than their counterparts to show unfavorable responses to cisplatin-based chemotherapy. Kaplan-Meier and Cox regression analysis indicated that low miR-630, high Bcl-2, and a combination of both may independently predict poor overall survival and short relapse-free survival in patients with NSCLC. Six types of NSCLC cells were collected to determine the inhibitory concentration of cisplatin yielding 50% viability (IC50) by the MTT assay. The IC50 value for cisplatin was negatively correlated with miR-630 expression levels among these cell types, except for A549 cells. Mechanistically, low miR-630 expression conferred cisplatin resistance and colony formation by de-targeting Bcl-2 in NSCLC cells. We therefore suggest that low miR-630, high Bcl-2, and a combination of both may potentially predict an unfavorable chemotherapeutic response and poor outcome in patients with NSCLC.


ZntR is a Zn(II)-responsive MerR-like transcriptional regulator of zntA in Escherichia coli.
We have identified the promoter/operator region of the zntA gene of Escherichia coli and shown that Zn(II) is the primary inducer of expression of this Zn(II)/Cd(II) export gene. The promoter PzntA shows sequence similarities to the promoters of mercury resistance (mer) operons, including a long spacer region containing an inverted repeat sequence. The gene encoding the transcriptional regulator of PzntA, designated zntR, has been identified from genome sequence data, by expression of the gene product and by insertional inactivation/complementation. The ZntR product is a member of the MerR family of transcriptional regulators and appears to act as a hypersensitive transcriptional switch. A hybrid MerR/ZntR protein has been constructed and indicates that the C-terminal region of ZntR recognizes Zn(II).


Long-term results of porous-coated cementless total knee arthroplasty with screw fixation.
The aim of this study was to evaluate the long-term results of porous-coated, cementless total knee arthroplasty with screw fixation. This study included 68 knees of 54 patients (43 female, 11 male; mean age: 56.9 years, range 46 to 70 years). Cruciate-retaining cementless total knee prostheses were implanted in all patients diagnosed with primary osteoarthritis. Clinical, functional and radiological evaluations were performed according to the Knee Society's Knee Scoring System (KSS). Prosthesis survival was analyzed using Kaplan-Meier curves. Mean follow-up time was 9.2 (range: 8 to 12) years. Preoperative mean knee and function scores were 42.3 (range: 32 to 61) and 39.1 (range: 35 to 66), respectively, while they were 88.6 (range: 54 to 96) and 82.8 (range: 50 to 100), respectively at the final follow-up (p<0.05). Mean preoperative knee flexion was 98° (range: 80° to 110°) and 112° (range: 85° to 130°) at the final follow-up (p<0.05). Preoperative and postoperative mean alignments were 9.2° varus and 5.4° valgus, respectively. Revisions were performed due to aseptic loosening of the tibial component in one patient, periprosthetic fracture in one and dislocation of the patella in one. Two superficial infections (3%) were observed. There was no osteolysis around the screws during the follow-up period. The overall rate of implant survival was 95.6% (range: 91.56% to 99.60%; 95% CI) at 12 years. Long-term outcomes of porous-coated, cementless total knee arthroplasty with screw fixation were successful in terms of clinical and radiological evaluation and yielded a high survival rate.


A possible attenuation of stress-induced increases in striatal dopamine metabolism by the expression of non-functional masticatory activity in the rat.
It is thought that the expression of oral parafunctions may provide an outlet for stress or aggressiveness in man. Stress-induced increases in central noradrenergic neurotransmission are attenuated in rats which are allowed to bite during stress. Striatal dopaminergic neurotransmission is involved in the genesis of parafunctional oral movements in rodents. As tail pinch is the stressor which most clearly provokes non-functional masticatory activity (NFMA), and also increases striatal dopamine (DA) activity in rats, we investigated whether the expression of NFMA during tail pinch could modify the changes in striatal dopaminergic neurotransmission induced by this stressor. Rats were subjected to tail pinch for 5 min, and the duration of the NFMA displayed was recorded. As an index of dopaminergic activity, 3,4-dihydroxyphenylalanine (DOPA) accumulation and DA and 3,4-dihydroxyphenylacetic (DOPAC) contents in both striata were determined by high-performance liquid chromatography. Striatal DOPA accumulation was similarly increased in relation to control, both in rats which did and did not display NFMA during tail pinch. However, the increases in striatal DOPAC contents, reported 24 min after the stress session, were lower in animals which had displayed NFMA. These results provide further evidence in support of the assumption that the expression of parafunctional masticatory activity attenuates the effects of stress on central catecholaminergic neurotransmission.


How Has American Constitutional Law Influenced Medical School Admissions and Thwarted Health Justice?
Medical schools have sought to diversify their classes to motivate inclusion, to draw upon the educational benefits of diversification, to promote educational opportunity, to facilitate representation of persons with minoritized identities in the US physician workforce, and to advance racial and ethnic equity in health status and access to health services regionally and nationally in the United States. The US Supreme Court has allowed schools' race-conscious admissions when their purpose is to diversify an incoming class but not to remediate inequity. This article explains why this limit to affirmative action laws' implementation blunts medical schools' capacity to do their part to secure health justice for all in the United States. Since the Supreme Court is poised to rule more narrowly on affirmative action law again, this article also considers key threats to health justice posed by further limiting or eliminating race-conscious admissions.


Transcriptomics of Parental Care in the Hypothalamic-Septal Region of Female Zebra Finch Brain.
(1) Background: The objective of this study was to uncover genomic causes of parental care. Since birds do not lactate and, therefore, do not show the gene expressional changes required for lactation, we investigate gene expression associated with parenting in caring and non-caring females in an avian species, the small passerine bird zebra finch (Taeniopygia guttata). Here, we compare expression patterns in the hypothalamic-septal region since, previously, we showed that this area is activated in parenting females. (2) Methods: Transcriptome sequencing was first applied in a dissected part of the zebra finch brain related to taking care of the nestlings as compared to a control group of social pairs without nestlings. (3) Results: We found genes differentially expressed between caring and non-caring females. When introducing a log2fold change threshold of 1.5, 13 annotated genes were significantly upregulated in breeding pairs, while 39 annotated genes were downregulated. Significant enrichments of dopamine and acetylcholine biosynthetic processes were identified among upregulated pathways, while pro-opiomelanocortin and thyroid hormone pathways were downregulated, suggesting the importance of these systems in parental care. Network analysis further suggested neuro-immunological changes in mothers. (4) Conclusions: The results confirm the roles of several hypothesized major pathways in parental care, whereas novel pathways are also proposed.


The distribution of carbonic anhydrase and ribulose diphosphate carboxylase in maize leaves.
Extraction of maize (Zea mays) leaves by progressive grinding under suitably protective conditions yields total carbonic anhydrase activities (4800 units per milligram chlorophyll) comparable to the activity in spinach (Spinacia oleracea) leaves. The total ribulose diphosphate carboxylase activity was also equal to or greater than the best literature values for maize. Of the total leaf carbonic anhydrase, 72.5% on a chlorophyll basis was present in the mesophyll cells and 14.2% in the bundle-sheath cells. The distribution of the total leaf ribulose diphosphate carboxylase between the mesophyll and bundle-sheath cells was 42.0 and 48.7% respectively. There was three times as much total chlorophyll in extracts of the mesophyll cells compared with the bundle-sheath cells of maize. Similar results for the above distribution of the two enzymes were found using a differential grinding technique. The possible function of carbonic anhydrase in photosynthesis is discussed. The equal distribution of ribulose diphosphate carboxylase activity between the mesophyll and bundle-sheath cells casts doubt upon the hypothesis that a rigid biochemical compartmentation exists between these cell types in maize.


His majesty's subjects: from laboratory to human experiment in pneumatic chemistry.
Experiments in pneumatic chemistry paved the way for medical innovation in the last quarter of the eighteenth century. Thomas Beddoes and James Watt were instrumental in the spread of the use of new gas chemistry in pneumatic therapy, but they were far from alone. There was no shortage of experimental subjects, as the practice was quickly taken up by medics throughout Britain.


The neonatal energy triangle. Part 1: Metabolic adaptation.
The first part of this two part series on the neonatal energy triangle gives a general overview of the transition period during the first six to ten hours of life. Although all elements of the triangle, hypothermia, hypoglycaemia and hypoxia, are interlinked this first part of the series describes the normal metabolic adaptation at birth and the difficulties involved in recognising and treating hypoglycaemia. In the second part of the series the two other elements of the triangle, hypoxia and hypothermia, will be addressed.


The implications of pain and physical symptoms in depression.
Patients with major depression often have painful physical symptoms. The synergy of co-occurring depression and pain impacts patients' mental and physical well-being as well as their occupational and social functioning. The presence of painful physical symptoms in patients with depression also lessens the ability of patients to achieve remission, which is the clinical standard for patient outcomes. Clinicians should be aware that depression often co-occurs with painful physical symptoms and that this relationship has a negative impact on patients' functional outcomes, remission, and recovery.


The Transcriptome of Exophiala dermatitidis during Ex-vivo Skin Model Infection.
The black yeast Exophiala dermatitidis is a widespread polyextremophile and human pathogen, that is found in extreme natural habitats and man-made environments such as dishwashers. It can cause various diseases ranging from phaeohyphomycosis and systemic infections, with fatality rates reaching 40%. While the number of cases in immunocompromised patients are increasing, knowledge of the infections, virulence factors and host response is still scarce. In this study, for the first time, an artificial infection of an ex-vivo skin model with Exophiala dermatitidis was monitored microscopically and transcriptomically. Results show that Exophiala dermatitidis is able to actively grow and penetrate the skin. The analysis of the genomic and RNA-sequencing data delivers a rich and complex transcriptome where circular RNAs, fusion transcripts, long non-coding RNAs and antisense transcripts are found. Changes in transcription strongly affect pathways related to nutrients acquisition, energy metabolism, cell wall, morphological switch, and known virulence factors. The L-Tyrosine melanin pathway is specifically upregulated during infection. Moreover the production of secondary metabolites, especially alkaloids, is increased. Our study is the first that gives an insight into the complexity of the transcriptome of Exophiala dermatitidis during artificial skin infections and reveals new virulence factors.


Cutaneous carcinosarcoma with metastasis to the parotid gland.
Cutaneous carcinosarcoma is a rare malignancy that exhibits both mesenchymal and epithelial components. It is similar to nonmelanoma skin cancers in terms of risk and prognostic factors. However, these malignancies are known to have a propensity for local recurrence and metastasis, even with adequate resection margins. Here we report a case of metastatic cutaneous carcinosarcoma to the parotid gland and review the relevant literature.


Photo-Imprinting of the Helical Organization in Liquid-Crystal Networks Using Achiral Monomers and Circularly Polarized Light.
Control over molecular motion is facilitated in materials with highly ordered nanoscale structures. Here we report on the fabrication of cholesteric liquid-crystal networks by circularly polarized light irradiation, without the need for chiral dopant or plasticizer. The polymer network is obtained by photopolymerization of a smectic achiral diacrylate mesogen consisting of an azobenzene core and discrete oligodimethylsiloxane tails. The synchronous helical photoalignment and photopolymerization originate from the cooperative movement of the mesogens ordered in well-defined responsive structures, together with the flexibility of the oligodimethylsiloxane blocks. The resulting thin films show excellent thermal stability and light-induced memory features with reversible responses. Additionally, we demonstrate the fabrication of photo-patterned films of liquid-crystal networks with opposite helical senses. These findings provide a new method to make light-controllable chiroptical materials with exciting applications in optics and photonics.


Efficacy of oral isotretinoin in the control of skin and nasal colonization by antibiotic-resistant propionibacteria in patients with acne.
Skin colonization by antibiotic-resistant propionibacteria is commonplace among acne patients globally. Increasing attention is now being paid to how resistance rates might be reduced to preserve the future efficacy of antibiotics, especially erythromycin and clindamycin in acne therapy. To assess the efficacy of oral isotretinoin in the control of antibiotic-resistant propionibacteria. Acne patients (72 in the U.K., 62 in the U.S.A.) colonized with high numbers of antibiotic-resistant propionibacteria were sampled before, during and 12 weeks after oral isotretinoin therapy. Propionibacterial samples were collected from five acne-prone skin surface sites using a detergent scrub method and from the anterior nares using moistened swabs. Total and antibiotic-resistant propionibacteria were enumerated by viable counting on media with and without selective antibiotics. After 16 weeks of oral isotretinoin therapy, mean population densities of viable propionibacteria and variants resistant to erythromycin, clindamycin or tetracycline had fallen by more than 90% at all skin sites and in the nares. The sole exception was a smaller reduction in tetracycline-resistant strains on the lower back. In general, greater reductions were observed on skin than in the nares. By the end of the treatment period only three patients (all in Philadelphia) yielded no antibiotic-resistant strains from any site. Post-treatment, propionibacterial counts remained well below pretreatment levels but had begun to recover on the face and in the nares. The recovering propionibacterial population included both susceptible and resistant strains. Changes during and post-treatment at the two centres were similar but not identical. Oral isotretinoin effectively reduced skin and nasal colonization by antibiotic-resistant propionibacteria. However, viable populations of resistant isolates persisted post-treatment at multiple sites. Novel methods are required to eradicate antibiotic-resistant propionibacteria completely, especially from the nasal reservoir.


Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, a novel putative endocannabinoid.
The endogenous cannabinoids N-arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) are known to decrease intraocular pressure (IOP). Recently, a novel putative endogenous cannabinoid, noladin ether, was isolated in porcine and rat brains. In the present study, both the degradation of endogenous cannabinoids in ocular tissues and the effect on IOP of 2-AG and noladin ether were compared. The rates of enzymatic degradation for AEA, 2-AG, and noladin ether were determined in bovine cornea and iris-ciliary body homogenates. 2-AG and noladin ether were dissolved in either hydroxypropyl-beta-cyclodextrin (HP-beta-CD) or propylene glycol and administered unilaterally to the rabbit eye. IOPs were measured in the treated and untreated eyes. The CB1 receptor antagonist AM251 was administered topically 15 minutes before the cannabinoids to investigate whether CB1 receptors mediate the effect on IOP produced by 2-AG and noladin ether. Noladin ether degraded more slowly than either 2-AG or AEA in the iris-ciliary body and cornea homogenates. The effect on IOP of 2-AG was biphasic (i.e., an initial increase in IOP followed by a reduction in the treated eye). Noladin ether decreased IOP immediately after topical administration, and no initial IOP increase was observed in the treated eye. The CB1 receptor antagonist AM251 (25 micro g) blocked the effect on IOP of noladin ether but did not affect the action of 2-AG. Topical administration of the novel putative endogenous cannabinoid noladin ether decreased IOP in rabbits. This IOP reduction was most probably mediated through the CB1 receptor. The effect on IOP of noladin ether differed from those of the known endogenous cannabinoids AEA and 2-AG, probably because of its more stable chemical structure.