Omicron breakthrough infections in wild-type SARS-CoV-2 vaccinees elicit high levels of neutralizing antibodies against pangolin coronavirus GX_P2V.
Omicron BF.7 became the predominant SARS-CoV-2 variant in Beijing after the abolishment of Zero-COVID policy in December 2022. The ability of antibodies elicited by BF.7 infection to cross-react with SARS-CoV-2-like viruses is unknown. This study aimed to investigate the cross-reactive neutralizing antibodies against SARS-CoV-2-related pangolin coronavirus GX_P2V in sera from vaccinated and/or SARS-CoV-2-infected individuals. All vaccinated individuals who recovered from Omicron BF.7 breakthrough infections exhibited substantially higher levels of neutralizing antibodies against GX_P2V, compared to other subject groups, with a geometric mean titer (GMT) of 362. Uninfected individuals who received four-mixed-dose vaccines also demonstrated higher levels of neutralizing antibodies (GMT = 44) against GX_P2V than those uninfected individuals who received two- or three-dose vaccines and those unvaccinated convalescents of wild-type SARS-CoV-2. This study highlights the significance of prior vaccinations with wild-type SARS-CoV-2 vaccines in generating potent cross-protective immunity against future spillovers of SARS-CoV-2-like viruses.


A comparison of medical and surgical termination of pregnancy: choice, emotional impact and satisfaction with care.
To investigate whether women having medical or surgical terminations of pregnancy differ in their emotional distress before or after the procedure. To evaluate whether choice of procedure occurs, the factors influencing type of procedure and the effect of choice on emotional responses and satisfaction with care. A prospective comparative study. A termination of pregnancy unit in a University Teaching Hospital. Two hundred and seventy-five women attending for medical or surgical first trimester termination of pregnancy. Interviews concerning choice and measures of emotional status were completed prior to terminations. Four weeks after termination emotional functioning was reassessed together with satisfaction with care. Women having a surgical termination waited longer for the procedure and were at more advanced gestation than those having the medical termination. There were no differences in emotional responses related to type of procedure or gestation. One-quarter remained highly anxious at four weeks. Medical and surgical groups did not differ in emotional status prior to termination. Those having the medical procedure rated it as marginally more stressful and experienced more post-termination physical problems and disruption to life. Seeing the fetus was associated with more intrusive events (nightmares, flashbacks, unwanted thoughts related to the experience). One-quarter of the medical and 67% of the surgical group reported having no choice in type of procedure. Only 53% of the medical group would choose the same procedure again compared with 77% of the surgical group. Termination method did not influence emotional adjustment. Many women were not offered genuine choice of procedure. Having choice was considered very important but was unrelated to emotional distress or satisfaction with care.


Down-regulation of the transcription factor snail in the placentas of patients with preeclampsia and in a rat model of preeclampsia.
Placental malfunction in preeclampsia is believed to be a consequence of aberrant differentiation of trophoblast lineages and changes in utero-placental oxygenation. The transcription factor Snail, a master regulator molecule of epithelial-mesenchymal transition in embryonic development and in cancer, is shown to be involved in trophoblast differentiation as well. Moreover, Snail can be controlled by oxidative stress and hypoxia. Therefore, we examined the expression of Snail and its downstream target, e-cadherin, in human normal term, preterm and preeclamptic placentas, and in pregnant rats that developed preeclampsia-like symptoms in the response to a 20-fold increase in sodium intake. Western blotting analysis was used for comparative expression of Snail and e- cadherin in total protein extracts. Placental cells expressing Snail and e-cadherin were identified by immunohistochemical double-labeling technique. The levels of Snail protein were decreased in human preeclamptic placentas by 30% (p < 0.01) compared to normal term, and in the rat model by 40% (p < 0.001) compared to control placentas. In preterm placentas, the levels of Snail expression varied, yet there was a strong trend toward statistical significance between preterm and preeclamptic placentas. In humans, e-cadherin protein level was 30% higher in preeclamptic (p < 0.05) placentas and similarly, but not significantly (p = 0.1), high in the preterm placentas compared to normal term. In the rat model of preeclampsia, e-cadherin was increased by 60% (p < 0.01). Immunohistochemical examination of human placentas demonstrated Snail-positive staining in the nuclei of the villous trophoblasts and mesenchymal cells and in the invasive trophoblasts of the decidua. In the rat placenta, the majority of Snail positive cells were spongiotrophoblasts of the junctional zone, while in the labyrinth, Snail-positive sinusoidal giant trophoblasts cells were found in some focal areas located close to the junctional zone. We demonstrated that human preeclampsia and the salt-induced rat model of preeclampsia are associated with the reduced levels of Snail protein in placenta. Down-regulation of the transcription factor Snail in placental progenitor cell lineages, either by intrinsic defects and/or by extrinsic and maternal factors, may affect normal placenta development and function and thus contribute to the pathology of preeclampsia.


Correction: Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis.
[This corrects the article DOI: 10.1371/journal.pgen.1006307.].


Middle-earth wasn't built in a day: How do we explain the costs of creating a world?
Dubourg and Baumard explain why fictional worlds are attractive to consumers. A complete account of fictional worlds, however, should also explain why some people create them. Creation is a costly and time-consuming process that does not resemble exploration but does resemble the culturally universal phenomenon of knowledge specialization.


Fixation beats: A novel marker for reaching the left bundle branch area during deep septal lead implantation.
One of the challenges of left bundle branch (LBB) pacing is placing the pacing lead deep enough in the septum to reach the LBB area, yet not too deep to avoid perforation. The purpose of this study was to investigate whether the occurrence of the ectopic beats with qR/rsR' morphology in lead V1 (fixation beats) during lead fixation would predict whether the desired intraseptal lead depth had been reached, whereas the lack of fixation beats would indicate a too-shallow position and the need for more lead rotations. Consecutive patients during LBB pacing device implantation were analyzed retrospectively and then prospectively with respect to the occurrence of fixation beats during each episode of lead rotation. We compared the presence of fixation beats during the lead rotation event directly before the LBB area depth was reached vs during the events before intermediate/unsuccessful positions. A total of 339 patients and 1278 lead rotation events were analyzed. In the retrospective phase, fixation beats were observed in 327 of 339 final lead positions and in 9 of 939 intermediate lead positions (P <.001). Sensitivity, specificity, and positive and negative predictive values of the fixation beats as a marker for reaching the LBB area were 96.4%, 97.3%, 97.3%, and 96.5%, respectively. In the prospective, fixation beats-guided implantation phase, fixation beats were observed in all patients and only at the LBB capture depth. Monitoring fixation beats during deep septal lead deployment can facilitate the procedure and possibly increase the safety of lead implantation.


A high-throughput colorimetric assay for glucose detection based on glucose oxidase-catalyzed enlargement of gold nanoparticles.
We developed a simple high-throughput colorimetric assay to detect glucose based on the glucose oxidase (GOx)-catalysed enlargement of gold nanoparticles (AuNPs). Compared with the currently available glucose kit method, the AuNP-based assay provides higher clinical sensitivity at lower cost, indicating its great potential to be a powerful tool for clinical screening of glucose.


The inhibition and disposition of intestinal alkaline phosphatase.
A primary mechanism of amino acid inhibition of intestinal alkaline phosphatase is postulated to be the formation of a dissociable enzyme-amino acid complex at an allosteric zinc site. The degree of inhibition was highly correlated with the Zn2+ stability constant of each amino acid and the inhibition was reversible by the addition of exogenous Zn2+ or by dialysis. This allosteric amino acid inhibition proved to be a useful probe of the membrane arrangement of the enzyme in the intact tissue. The catalytic site appears to face the lumen based on the poor permeability of the substrate, the accumulation of the coproducts in the luminal bath, and the response of the enzyme to luminal pH. Amino acid inhibition of alkaline phosphatase in the intact tissue was only effective in the presence of sodium; whereas sodium was not required in butanol extracted preparations which lacked the sidedness of the intact tissue. Since amino acid uptake from the intestine is sodium dependent, the allosteric inhibitory site is probably intracellular. The results suggest that the intestinal alkaline phosphatase spans the apical membrane with the catalytic site accessible from the lumen and the allosteric inhibitory site from the cytoplasm.


Similarities and Differences in Left Ventricular Size and Function among Races and Nationalities: Results of the World Alliance Societies of Echocardiography Normal Values Study.
The World Alliance Societies of Echocardiography (WASE) Normal Values Study evaluates individuals from multiple countries and races with the aim of describing normative values that could be applied to the global community worldwide and to determine differences and similarities among people from different countries and races. The present report focuses specifically on two-dimensional (2D) left ventricular (LV) dimensions, volumes, and systolic function. The WASE Normal Values Study is a multicenter international, observational, prospective, cross-sectional study of healthy adult individuals. Participants recruited in each country were evenly distributed among six predetermined subgroups according to age and gender. Comprehensive 2D transthoracic echocardiograms were acquired and analyzed following strict protocols based on recent American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. Analysis was performed at the WASE 2D core laboratory and included 2D LV dimensions, LV volumes, and LV ejection fraction (LVEF) by the biplane Simpson method and global longitudinal strain (GLS). Two thousand eight subjects were enrolled in 15 countries. The median age was 45 years (interquartile range, 32-65 years), 42.8% were white, 41.8% were Asian, and 9.7% were black. LV dimensions and volumes were larger in male subjects, while LVEF and GLS were higher in female subjects. Global WASE normal ranges for LV dimensions were smaller than those in the guidelines, but the upper limits of normal for LV volumes and the lower limits of normal for LVEF were higher in the WASE study. Significant intercountry variation was identified for all LV parameters reflecting LV size (dimensions, mass, and volumes) even after indexing to body surface area, with LV end-diastolic and end-systolic volumes having the highest variation. The largest volumes were noted in Australia, while the smallest were measured in India for both genders. This finding suggests that in addition to gender and body surface area, specific country should be considered when evaluating LV volumes. Intercountry variation for LVEF and GLS was smaller but still statistically significant (P < .05 for all). LV dimensions and volumes are larger in men, while LVEF and GLS are higher in women. Current guideline-recommended normal ranges for LV volumes and LVEF should be adjusted. Intercountry variability is significant for LV volumes, and therefore nationality should be considered for defining ranges of normality.


A three-dimensional organotypic assay to measure target cell killing by cytotoxic T lymphocytes.
Cytotoxic T lymphocytes (CTL) mediate antigen- and cell-cell contact dependent killing of target cells, such as cancer cells and virus-infected cells. In vivo, this process requires the active migration of CTL towards and away from target cells. We here describe an organotypic 3D collagen matrix assay to monitor CTL migration together with CTL-mediated killing of target cells. The assay supports both, time-lapse microscopy of killing dynamics as well as population analysis of killing after matrix digestion and flow cytometry. The assay was used to assess the detrimental effect of cyclosporine A (CsA) present during CTL activation, which caused an inhibition of CTL-target cell conjugation and strongly impaired CTL-mediated killing, particularly at low effector-target ratios. Thus, the organotypic assay is useful to monitor spatiotemporal control mechanisms of cytotoxic immune effector functions.


Effect of apomorphine on intracavernous pressure and blood pressure in conscious, spinalized rats.
Apomorphine, given subcutaneously (s.c.), induces erection and bladder overactivity in rats through stimulation of dopamine (D1- and D2-like) receptors in the central nervous system. In paraplegic patients, apomorphine was reported to cause bladder overactivity. This suggests that apomorphine may have a spinal site of action also for stimulation of erection. The present study was initiated to evaluate the effect of apomorphine on erectile function in spinalized rats. Apomorphine (100 microg/kg, s.c.) was given to awake, unrestrained male Sprague-Dawley rats (300 g) with or without spinal cord injury, made at the Th 8 level 2 weeks before the experiment. Intracavernous pressure changes from baseline were evaluated as time to first response to apomorphine (TFR; sec), number of phasic pressure changes in the first 30 min (PP30), duration (D; sec) of the phasic pressure changes, the amount of increase in tonic peak pressure (TPP; cmH2O), and burst peak pressure (BPP; cmH2O). Blood pressure (cmH2O) was recorded via an intra-arterial catheter. Apomorphine, 100 microg/kg, caused no significant differences in TFR (217.8 vs 271.2), PP30 (6.4 vs 6.5), D (38.9 vs 37.6.), TPP (51.0 vs 54.0) and BPP (128.9 vs 160.4) between normal (n=8) and spinalized rats (n=6). However, blood pressure decreased significantly more in spinalized than in normal animals (17.7 vs 43.3; P<0.05). The results suggest that both in normal rats, and in rats with spinal cord injury, apomorphine given s.c., can produce erection. This finding supports the use of apomorphine for treatment of erectile dysfunction in paraplegia patients. However, due consideration should be given to possible decreases in blood pressure.


Rotational diffusion tensor of nucleic acids from 13C NMR relaxation.
Rotational diffusion properties have been derived for the DNA dodecamer d(CGCGAATTCGCG)(2) from (13)C R(1rho) and R(1) measurements on the C(1'), C(3'), and C(4') carbons in samples uniformly enriched in (13)C. The narrow range of C-H bond vector orientations relative to the DNA axis make the analysis particularly sensitive to small structural deviations. As a result, the R(1rho)/R(1) ratios are found to fit poorly to the crystal structures of this dodecamer, but well to a recent solution NMR structure, determined in liquid crystalline media, even though globally the structures are quite similar. A fit of the R(1rho)/R(1) ratios to the solution structure is optimal for an axially symmetric rotational diffusion model, with a diffusion anisotropy, D(\|)/D(perpendicular), of 2.1+/-0.4, and an overall rotational correlation time, (2D(\|)+4D(perpendicular))(-1), of 3.35 ns at 35 degrees C in D(2)O, in excellent agreement with values obtained from hydrodynamic modeling.


Monitoring of decolorization kinetics of Reactive Brilliant Blue X-BR by online spectrophotometric method in Fenton oxidation process.
Online spectrophotometry method is employed to monitor simulated Reactive Brilliant Blue X-BR (RBB X-BR) in aqueous solution in Fenton oxidation process. The effects of initial dosage of FeSO(4) and H(2)O(2), pH value, initial concentration of dye and temperature have been studied. The results show that online spectrophotometric method is a quick, feasible and convenient technique to monitor color removal of RBB X-BR in Fenton process. The optimal dosage of H(2)O(2) and pH is 3.529 mM and 3, respectively. The optimal dosage of Fe(2+) for color removal is 0.1618 mM. The concentration of initial FeSO(4) against the reaction rate constant (k(ap)) for decolorizing is linear correlation as: k(ap)=0.1354[Fe(2+)](o) (R(2)>0.99). The apparent activation energies of reaction is 25.21 kJ mol(-1) (R(2)>0.99). The intrinsic reaction rate constant of OH with RBB X-BR in aqueous solution is 7.396 x 10(10)M(-1)s(-1). The molecule structure of RBB X-BR is decomposed and not mineralized by Fenton's reagent. The main intermediate products are 1,2-diacetylenzene and 2,5-diritrobenzoic acid. The probable mechanism of the decoloration of RBB X-BR is also discussed.


Ultrasonic Rhinoplasty and Septoplasty for Dorsum Preservation and for Dorsum Structural Reconstruction.
Ultrasonic rhinoplasty and ultrasonic septoplasty reshape the nasal bones using piezoelectric instruments specifically developed for these operations. They allow the realization of precise osteotomies under direct visual control after having performed first an open or closed extended approach, but also ostectomies and rhinosculpture. Piezoelectric instruments preserve bone stability by not damaging bone support structures and avoiding unwanted fractures. They allow precise control of nasal bone movements, their orientation, and their final position. The different inserts of ultrasonic rhinoplasty and ultrasonic septoplasty are detailed, with their scope of action. The applications to dorsum preservation and structural remodeling of dorsum are presented.


Tips and algorithms to get your patient's BP to goal.
Having diagnosed, treated, and studied hypertension for more than 3 decades, this author offers advice and 3 handy algorithms to help you optimize your care.


The Scottish RD survey 10 years on: the increasing incidence of retinal detachments.
The Scottish RD Survey reported an incidence of 12.05/100,000/yr in 2009. Data published from Denmark recently confirmed a 50% increase in RD presentations over the last 16 years. We set out to repeat the Scottish RD survey to determine if a similar trend has been observed in Scotland. All 16 Scottish VR surgeons, who make up the collaboration of Scottish VR Surgeons (SCVRs) were asked to prospectively record all primary RDs presenting from 12th August 2019 to 11th August 2020. For consistency, the case definitions were the same as for the 2009 Scottish RD Survey. Basic demographic and clinical features were recorded. Age specific incidence was calculated from mid-year population estimates for 2019 obtained from the National Records of Scotland. There were 875 RRDs recorded, which gives an updated incidence of 16.02/100,000/year in Scotland. 62.8% occurred in males and the greatest increases were seen in males aged 50-59 (p = 0.0094), 60-69 (p = 0.0395) and females aged 40-49 (p = 0.0312) and 50-59 (p = 0.0024). The proportion of pseudophakic RRDs in this study is 29.4% (253/860). Compared to the 21.6% in the 2010 study, this represents a 28% increase (χ2 = 11.03, p = 0.0009). The proportion of macula-off RRDs remained generally stable at 58%. Our study confirms that RRD is becoming more common in the UK, reflecting almost identical findings from Denmark. This trend is in part due to increasing myopia, increasing pseudophakia, and possibly other factors. This should be considered when planning VR services and allocating resources in the future.


In vitro protective and enhancing effects of interferons from several species on human lymphotoxin-induced target cell killing.
In a previous study it was reported that human alpha-interferons (IFN) caused a significant enhancement of human lymphotoxin (LT)-induced in vitro killing of human target cells. This synergistic effect was dose dependent and was demonstrable on normal and tumor cell targets. The effects of IFNs from human and several animal species on human LT-induced cell killing of human, mouse, and rabbit target cells are examined. In addition to enhancement of IFN, a new finding was made showing protective effects of IFN on human LT activity. IFN-induced enhancement or protection depended on the particular IFN:target cell combination, with the highest degree of enhancement being observed in the homologous human combination. In this latter case, IFN-induced enhancement was blocked by antiserum to IFN. While a role for other soluble factors cannot be ruled out, the results suggest that, in the homologous human system, enhancement of LT activity was mediated by IFN. These results are discussed in relationship to previously observed enhancing and protective effects of IFN in natural killer cell systems.


Intracardiac Electrogram Targets for Ventricular Tachycardia Ablation.
The pathogenesis of ventricular tachycardia (VT) in most patients with a prior myocardial scarring is reentry involving compartmentalized muscle fibers protected within the scar. Often the 12-lead ECG morphology of the VT itself is not available when treated with a defibrillator. Consequently, VT ablation takes on an interesting challenge of finding critical targets in sinus rhythm. High-density recordings are essential to evaluate a substrate based on whole electrogram voltage and activation delay, supplemented with substrate perturbation through alternate site pacing or introducing an extra stimulation. In this article, we discuss contemporary intracardiac electrogram targets for VT ablation, with explanation on each of their specific fundamental physiology.


Rodent population cycles: life history adjustments to age-specific dispersal strategies and intrinsic time lags.
Multi-annual population cycles can be generated by life history responses to density dependent changes in adult and pre-reproductive survival. The proximate mechanism linking population dynamics and demography of cycling rodents appears to be high pre-reproductive dispersal at peak density, or during periods of population increase. This model is similar to the Chitty hypothesis which can best be viewed as a special case of demographic control on population size. Normally, this control should be selfreinforcing and lead to damped oscillations toward a stable population density. Intrinsic time lags induced by variation in the length of the breeding season modify the dependence of demography on population size, and enable the cycles to persist.


Endothelium-dependent contractile actions of proteinase-activated receptor-2-activating peptides in human umbilical vein: release of a contracting factor via a novel receptor.
The contractile actions of the proteinase-activated receptor-2-activating peptides (PAR2APs), SLIGRL-NH2 (SL-NH2), SLIGKV-NH2 (KV-NH2), trans-cinnamoyl-LIGRLO-NH2 (tc-NH2), and the PAR1-AP. TFLLR-NH2 (TF-NH2) as well as trypsin and thrombin were studied in endothelium-denuded and intact human umbilical vein (HUV) ring preparations. In HUV rings with, but not without an intact endothelium, PAR2APs caused a concentration-dependent contractile response, whereas LSIGRL-NH2 trypsin and PAR1APs were inactive. The contractile response was not affected by the endothelin ETA receptor antagonist, BQ123, the cyclooxygenase inhibitor, indomethacin, the leukotriene synthesis inhibitor, MK886, or the epoxygenase/P450 inhibitor, SKF-525A. Other pharmacological antagonists (prazosin, Losartan") were similarly inactive. The order of potencies of the PAR2APs to cause a contraction in the endothelium-intact preparation was: SL-NH2 > > KV-NH2 > or = tc-NH2. Using an endothelium-free rat aorta ring as a reporter tissue, surrounded with endothelium-intact HUV as a donor tissue in a 'sandwich assay,' we also monitored the ability of SL-NH2, TF-NH2, trypsin and thrombin to release either contractile (EDCF) or relaxant (EDRF) factors. In the 'sandwich assay' done in the presence of L-NAME (0.1 mM), the endothelium-intact HUV tissue (but not endothelium-denuded HUV) released a contractile factor (EDCF) in response to SL-NH2 (50 microM) but not to trypsin or LSIGRL-NH2. The SL-NH2-mediated release/action of the EDCF was not affected by BQ123, indomethacin, MK886 or SKF-525A. In the 'sandwich assay', trypsin (4-10 nM), SL-NH2, KV-NH2 and tc-NH2 caused the release of a relaxant activity (EDRF) from the endothelium-intact (but not the denuded) HUV preparation. The release of EDRF was blocked by 0.1 mM (omega)nitro-L-arginine-methylester (L-NAME). Neither thrombin (10 u ml(-1), 100 nM) nor TF-NH2 (50 microM) were active in this EDRF-release assay. The relative potencies of the PAR2 agonists for causing the release of EDRF in the HUV sandwich assay were: trypsin> >SL-NH2> >tc-NH2>KV-NH2. This order of potencies differed from the one observed for the same agonists in the HUV contraction assay (above) and in an intracellular calcium signalling assay, conducted with cloned human PAR2 that was expressed in cultured rat kidney KNRK cells: trypsin > > SL-NH2 = tc-NH2 > KV-NH2. We conclude that PAR2APs (but not PAR1APs) via a receptor distinct from PAR2, can cause a contractile response in endothelium-intact HUV tissue via the release of a diffusable EDCF, that is different from previously recognized smooth muscle agonists (e.g. prostanoid metabolites, endothelin, noradrenaline, angiotensin-II, acetylcholine).


Complement factor H modulates the activation of human neutrophil granulocytes and the generation of neutrophil extracellular traps.
Factor H (FH) is a major inhibitor of the alternative pathway of complement activation in plasma and on certain host surfaces. In addition to being a complement regulator, FH can bind to various cells via specific receptors, including binding to neutrophil granulocytes through complement receptor type 3 (CR3; CD11b/CD18), and modulate their function. The cellular roles of FH are, however, poorly understood. Because neutrophils are important innate immune cells in inflammatory processes and the host defense against pathogens, we aimed at studying the effects of FH on various neutrophil functions, including the generation of extracellular traps. FH co-localized with CD11b on the surface of neutrophils isolated from peripheral blood of healthy individuals, and cell-bound FH retained its cofactor activity and enhanced C3b degradation. Soluble FH supported neutrophil migration and immobilized FH induced cell spreading. In addition, immobilized but not soluble FH enhanced IL-8 release from neutrophils. FH alone did not trigger the cells to produce neutrophil extracellular traps (NETs), but NET formation induced by PMA and by fibronectin plus fungal β-glucan were inhibited by immobilized, but not by soluble, FH. Moreover, in parallel with NET formation, immobilized FH also inhibited the production of reactive oxygen species induced by PMA and by fibronectin plus β-glucan. Altogether, these data indicate that FH has multiple regulatory roles on neutrophil functions. While it can support the recruitment of neutrophils, FH may also exert anti-inflammatory effects and influence local inflammatory and antimicrobial reactions, and reduce tissue damage by modulating NET formation.


Regional anesthesia in pediatrics.
The use of regional anesthetic techniques in infants and children has become increasingly accepted as standard care. The most commonly performed regional anesthetic techniques used in pediatric patients are the caudal and lumbar approaches to the epidural space, ilioinguinal/iliohypogastric, and penile nerve blockade. These and other techniques are reviewed, along with specific issues such as risks, benefits, drug dosage, and local anesthetic toxicity. The safety of regional anesthetic techniques in pediatric patients is addressed, with recommendations for prevention and treatment of complications.


Successful surgical procedure in a patient of aplastic anemia with platelet refractoriness, using cross-match compatible platelets.
This case marks the beginning of issuing cross-matched platelet products in Eastern India. A known case of aplastic anemia, on regular transfusion support, now presented with obstructed ventral periumbilical hernia requiring urgent surgical intervention. Platelet count at presentation was 13,000/μL. Platelet cross-matching was done by solid phase method. Ten units of random donor platelets were crossmatched. Five units were compatible and transfused. Counts rose to 84,000/μL after 1 h. Surgery was completed successfully. Thus, 50% units were compatible. This indicates possible underlying alloimmunization. Rapid count rise enabled completion of this urgent surgery. This rapid rise of platelet count would not have been possible without cross matching. We conclude that platelet cross matching is a powerful tool for alloimmunized patients.


Characterization of the supporting role of SecE in protein translocation.
SecYEG functions as a membrane channel for protein export. SecY constitutes the protein-conducting pore, which is enwrapped by SecE in a V-shaped manner. In its minimal form SecE consists of a single transmembrane segment that is connected to a surface-exposed amphipathic α-helix via a flexible hinge. These two domains are the major sites of interaction between SecE and SecY. Specific cleavage of SecE at the hinge region, which destroys the interaction between the two SecE domains, reduced translocation. When SecE and SecY were disulfide bonded at the two sites of interaction, protein translocation was not affected. This suggests that the SecY and SecE interactions are static, while the hinge region provides flexibility to allow the SecY pore to open.


Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases.
Rab27A is required for actin-based melanosome transport in mammalian skin melanocytes through its interaction with a specific effector, Slac2-a/melanophilin. Mutations that disrupt the Rab27A/Slac2-a interaction cause human Griscelli syndrome. The other Rab27 isoform, Rab27B, also binds all of the known effectors of Rab27A. In this study, we determined the crystal structure of the constitutively active form of Rab27B complexed with GTP and the effector domain of Slac2-a. The Rab27B/Slac2-a complex exhibits several intermolecular hydrogen bonds that were not observed in the previously reported Rab3A/rabphilin complex. A Rab27A mutation that disrupts one of the specific hydrogen bonds with Slac2-a resulted in the dramatic reduction of Slac2-a binding activity. Furthermore, we generated a Rab3A mutant that acquires Slac2-a binding ability by transplanting four Rab27-specific residues into Rab3A. These findings provide the structural basis for the exclusive association of Slac2-a with the Rab27 subfamily, whereas rabphilin binds several subfamilies, including Rab3 and Rab27.


Hypertrophy and hyperplasia of abdominal adipose tissues in women.
To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue. We obtained subcutaneous and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 47+/-5 years; BMI 27.9+/-5.3 kg/m(2)). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation and body fat distribution were obtained (dual-energy X-ray absorptiometry and computed tomography, respectively). Adipocyte size of both subcutaneous and omental fat were increased with higher body fat mass values, with similar regression slopes in each compartment. In contrast, with higher body fat mass values, fat accumulation was progressively higher in the subcutaneous than in the visceral fat compartment, suggesting hyperplasia in the subcutaneous fat compartment. Messenger RNA levels of CEBPalpha, PPARgamma2, SREBP1c and genes related to lipid metabolism (LPL, FABP4, DGAT1, DGAT2, PLIN and HSL) were significantly higher in subcutaneous than in omental fat tissue (P< or =0.001 for all). Only subcutaneous expression of these genes tracked with obesity levels as reflected by significant positive associations between subcutaneous fat CEBPalpha, SREBP1c and DGAT2 expression and total body fat mass (r=0.37, r=0.41, r=0.57, respectively, P< or =0,05), fat percentage (r=0.40, r=0.39, r=058, respectively, P< or =0,05) and subcutaneous adipose tissue area (r=0.36, r=0.38, r=0.58, respectively, P< or =0,05). Omental adipose tissue expression levels of these genes were not significantly related to adiposity measures. These results show that in obese women, hyperplasia is predominant in the subcutaneous fat depot, whereas fat cell hypertrophy is observed both in the omental and subcutaneous compartments.


Fetal weight estimation based on deep neural network: a retrospective observational study.
Improving the accuracy of estimated fetal weight (EFW) calculation can contribute to decision-making for obstetricians and decrease perinatal complications. This study aimed to develop a deep neural network (DNN) model for EFW based on obstetric electronic health records. This study retrospectively analyzed the electronic health records of pregnant women with live births delivery at the obstetrics department of International Peace Maternity & Child Health Hospital between January 2016 and December 2018. The DNN model was evaluated using Hadlock's formula and multiple linear regression. A total of 34824 live births (23922 primiparas) from 49896 pregnant women were analyzed. The root-mean-square error of DNN model was 189.64 g (95% CI 187.95 g-191.16 g), and the mean absolute percentage error was 5.79% (95%CI: 5.70%-5.81%), significantly lower compared to Hadlock's formula (240.36 g and 6.46%, respectively). By combining with previously unreported factors, such as birth weight of prior pregnancies, a concise and effective DNN model was built based on only 10 parameters. Accuracy rate of a new model increased from 76.08% to 83.87%, with root-mean-square error of only 243.80 g. Proposed DNN model for EFW calculation is more accurate than previous approaches in this area and be adopted for better decision making related to fetal monitoring.


Serum IL-1beta levels in health and disease: a population-based study. 'The InCHIANTI study'.
Interleukin-1 plays a role in normal homeostasis and in the inflammatory response which is deemed to be responsible for the development of major chronic diseases that are highly prevalent in the elderly. Aim of this study is to evaluate the factors influencing the serum levels of Interleukin-1 beta, in a large and representative population. Data were from the InCHIANTI project, a study of factors contributing to the decline of mobility in late life, which sampled people living in two sites in the surroundings of Florence. Blood samples were obtained from 1,292 participants and frozen aliquots were stored at -80 degrees C. The serum levels of several cytokines were measured by enzyme linked immunosorbent assay using an ultrasensitive commercial kit. Interleukin-1 beta serum levels were associated with congestive heart failure (p > 0.001) and angina (p = 0.02), with Ca2+ serum levels (p = 0.02), and with a history of dyslipidemia (p = 0.05). We found no association between serum IL-1beta level and age, sex, consumption of cardioactive drugs and serum levels of IL-1Ra, IL-6, sIL-6R, IL-10 and TNF-alpha. Our data could lend support to the hypothesis that IL-1beta is mainly involved in the functional alterations of cardiomyocytes under conditions marked by mononuclear cell infiltration and by downregulation of calcium.


Purification and characterization of C1, the catalytic subunit of Saccharomyces cerevisiae cAMP-dependent protein kinase encoded by TPK1.
In the yeast Saccharomyces cerevisiae, three genes TPK1, TPK2, and TPK3 encode catalytic subunits of cAMP-dependent protein kinase. We have purified and characterized the catalytic subunit, C1, encoded by the TPK1 gene. In order to purify C1 completely free of C2 and C3, a strain was constructed that contained only the TPK1 gene and genetic disruptions of the other two TPK genes. The cellular level of C1 was increased by expressing the genes for C1 (TPK1) and yeast regulatory subunit (BCY1) on multiple copy plasmids within this strain. Purification was accomplished by a two-column procedure in which holoenzyme was chromatographed on Sephacryl-200, then bound to an anti-regulatory subunit immunoaffinity column. Pure C1 was released from the antibody column by addition of cAMP. The protein migrated on a sodium dodecyl sulfate-polyacrylamide gel with an Mr of 52,000. Kinetic analysis showed that the apparent Km for ATP and Leu-Arg-Arg-Ala-Ser-Leu-Gly was 33 and 101 microM, respectively. The kcat was determined to be 640 min-1. The protein weakly autophosphorylated, incorporating less than 0.1 mol of phosphate/mol of catalytic subunit. NH2-terminal sequencing revealed that the protein was blocked.


[Cardiovascular ultrahigh field magnetic resonance imaging : challenges, technical solutions and opportunities].
This involves high spatial resolution cardiac imaging with ultrahigh magnetic fields (7 T) and clinically acceptable image quality. Cardiovascular magnetic resonance imaging (MRI) at a field strength of 1.5 T using a spatial resolution of (2 × 2 × 6-8) mm(3). Cardiac MRI at ultrahigh field strength makes use of multitransmit/receive radiofrequency (RF) technology and development of novel technology that utilizes the traits of ultrahigh field MRI. Enhanced spatial resolution which is superior by a factor of 6-10 to what can be achieved by current clinical cardiac MRI. The relative spatial resolution (pixels per anatomical structure) comes close to what can be accomplished by current cardiac MRI in small rodents. Feasibility studies demonstrate the gain in spatial resolution at 7.0 T due to the sensitivity advantage inherent to ultrahigh magnetic fields. Please stay tuned and please put further weight behind the solution of the remaining technical problems of cardiac MRI at 7.0 T.


Similarity of the swine vasculature to the human carotid bifurcation: analysis of arterial diameters.
We assessed the similarities of the iliac bifurcation in two breeds of swine to the known human carotid bifurcation, in order to assess its applicability as a preclinical model of the human carotid bifurcation. Mixed-Landrace crossbreed (domestic; n = 66) and Yucatan miniswine (Yucatan; n = 13) were studied. The diameters of the iliac bifurcation arteries were measured from angiographic pictures, the relations between the arterial diameters and the animal's weight assessed, and diametrical ratios calculated. Findings were compared with the known human carotid bifurcation. The external iliac diameter (approximately 6-7mm) in the lower weight swine was similar to the known human common carotid artery. The best similarity was found between the diametrical ratios of the human internal to common carotid artery (mean 0.63) to the swine profunda to external iliac (means 0.68 and 0.65 for the domestic and Yucatan, respectively). The arterial diameters of the domestic swine were highly correlated with their weight that increased considerably with time, while in the Yucatan group, arterial diameters did not change with increasing weight and the average weight increase rate was low. Thus, the estimated arterial diameter increase rate over time was high in the domestic while minor in the Yucatan group. Similarities were found between the swine iliac bifurcation arteries to the human carotid bifurcation in terms of diameters, diametrical ratios and angle. The swine iliac bifurcation may be used for preclinical endovascular research of devices intended to the human carotid bifurcation, with miniswine strains a preferable model for long-term studies.


Cryptosporidium parvum infects human cholangiocytes via sphingolipid-enriched membrane microdomains.
Cryptosporidium parvum attaches to intestinal and biliary epithelial cells via specific molecules on host-cell surface membranes including Gal/GalNAc-associated glycoproteins. Subsequent cellular entry of this parasite depends on host-cell membrane alterations to form a parasitophorous vacuole via activation of phosphatidylinositol 3-kinase (PI-3K)/Cdc42-associated actin remodelling. How C. parvum hijacks these host-cell processes to facilitate its infection of target epithelia is unclear. Using specific probes to known components of sphingolipid-enriched membrane microdomains (SEMs), we detected aggregation of host-cell SEM components at infection sites during C. parvum infection of cultured human biliary epithelial cells (i.e. cholangiocytes). Activation and membrane translocation of acid-sphingomyelinase (ASM), an enzyme involved in SEM membrane aggregation, were also observed in infected cells. Pharmacological disruption of SEMs and knockdown of ASM via a specific small interfering RNA (siRNA) significantly decreased C. parvum attachment (by approximately 84%) and cellular invasion (by approximately 88%). Importantly, knockdown of ASM and disruption of SEMs significantly blocked C. parvum-induced accumulation of Gal/GalNAc-associated glycoproteins at infection sites by approximately 90%. Disruption of SEMs and knockdown of ASM also significantly blocked C. parvum-induced activation of host-cell PI-3K and subsequent accumulation of Cdc42 and actin by up to 75%. Our results suggest an important role of SEMs for C. parvum attachment to and entry of host cells, likely via clustering of membrane-binding molecules and facilitating of C. parvum-induced actin remodelling at infection sites through activation of the PI-3K/Cdc42 signalling pathway.


Heavy metal distribution in marine sediments from the southwest coast of Spain.
The latest version (1999) of the BCR-sequential extraction technique was used to determine the distribution of metals (Cu, Zn, Cd, Pb, Fe, Ni, Cr, and Mn) with major sedimentary phases (acid-soluble, reducible, oxidisable and residual) in samples from the southwest coast of Spain. The total metal content was also determined. The results showed that an extensive area along the coast (35 km long), near the joint mouth of the Tinto and Odiel Rivers, contains sediments with high concentrations of metals, with maximums of 649 mg/kg of Zn, 336 mg/kg of Cu, 197 mg/kg of Pb and 2.5 mg/kg of Cd. The values found for Cr, Ni and Mn are comparable to those in unpolluted areas. Based on the chemical distribution of metals, we found that Zn is the most mobile (i.e., it can pass easily into the water under changing environmental conditions). This metal showed the highest percentages in the acid-soluble fraction (the most labile), especially in the central coastal area, where the samples contained over 50% of this element associated with this fraction. This area close to the Tinto and Odiel river mouths also shows a significant increase in the mobility of Cd and Cu. In both cases the amount present in the residual fraction is lower, and the acid-soluble fraction is increased for Cd and the oxidisable fraction for Cu. However, the highest percentages of Fe, Cr and Ni are found in the residual fraction (84%, 89% and 75%, respectively), which implies that these metals are strongly bound to the sediments.


Different in vivo reactivity profile in health care workers and patients with spina bifida to internal and external latex glove surface-derived allergen extracts.
Allergy to natural rubber latex is a well-recognized health problem, especially among health care workers and patients with spina bifida. Despite latex sensitization being acquired in health institutions in both health care workers and patients with spina bifida, differences in allergen sensitization profiles have been described between these two risk groups. To investigate the in vivo reactivity of health care workers and patients with spina bifida to extracts of internal and external surfaces of latex gloves and also to specific extracts enriched in major allergens for these risk groups. Gloves from different manufacturers were used for protein extraction, and salt precipitation and hydrophobic interaction chromatography (HIC) were applied to obtain the enriched latex extracts. The major latex allergens were quantified by an enzyme immunoassay. The extracts obtained were tested in 14 volunteers using skin prick tests (SPT). Latex glove extracts enriched in the hydrophobic allergens that are most often seen in patients with spina bifida were obtained by selective precipitation, whereas HIC produced extracts enriched in the hydrophilic allergens commonly found in health care workers. The health care workers had positive SPTs to glove extracts from internal surfaces and to the hydrophilic allergen-enriched extracts. By contrast, patients with spina bifida had larger skin reactions both to external glove extracts and to the extracts enriched with the hydrophobic major allergens for this risk group. Despite the protein concentration of these extracts being less than half the concentration of the commercial extract, the weal-and-flare reactions were of similar magnitude. Using novel latex extracts, our study showed a different in vivo reactivity pattern in health care workers and in patients with spina bifida to extracts of the internal and external surfaces of gloves, which suggests that sensitization may occur by different routes of exposure, and that this influences the allergen reactivity profiles of these risk groups.


Synergistic neuroprotection by epicatechin and quercetin: Activation of convergent mitochondrial signaling pathways.
In view of evidence that increased consumption of epicatechin (E) and quercetin (Q) may reduce the risk of stroke, we have measured the effects of combining E and Q on mitochondrial function and neuronal survival following oxygen-glucose deprivation (OGD). Relative to mouse cortical neuron cultures pretreated (24h) with either E or Q (0.1-10μM), E+Q synergistically attenuated OGD-induced neuronal cell death. E, Q and E+Q (0.3μM) increased spare respiratory capacity but only E+Q (0.3μM) preserved this crucial parameter of neuronal mitochondrial function after OGD. These improvements were accompanied by corresponding increases in cyclic AMP response element binding protein (CREB) phosphorylation and the expression of CREB-target genes that promote neuronal survival (Bcl-2) and mitochondrial biogenesis (PGC-1α). Consistent with these findings, E+Q (0.1 and 1.0μM) elevated mitochondrial gene expression (MT-ND2 and MT-ATP6) to a greater extent than E or Q after OGD. Q (0.3-3.0μM), but not E (3.0μM), elevated cytosolic calcium (Ca(2+)) spikes and the mitochondrial membrane potential. Conversely, E and E+Q (0.1 and 0.3μM), but not Q (0.1 and 0.3μM), activated protein kinase B (Akt). Nitric oxide synthase (NOS) inhibition with L-N(G)-nitroarginine methyl ester (1.0μM) blocked neuroprotection by E (0.3μM) or Q (1.0μM). Oral administration of E+Q (75mg/kg; once daily for 5days) reduced hypoxic-ischemic brain injury. These findings suggest E and Q activate Akt- and Ca(2+)-mediated signaling pathways that converge on NOS and CREB resulting in synergistic improvements in neuronal mitochondrial performance which confer profound protection against ischemic injury.


Exploring the potential of microRNA as a diagnostic tool for gestational diabetes.
MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating host gene expression. Recent studies have indicated a role of miRNAs in the pathogenesis of gestational diabetes mellitus (GDM), a common pregnancy-related disorder characterized by impaired glucose metabolism. Aberrant expression of miRNAs has been observed in the placenta and/or maternal blood of GDM patients, suggesting their potential use as biomarkers for early diagnosis and prognosis. Additionally, several miRNAs have been shown to modulate key signaling pathways involved in glucose homeostasis, insulin sensitivity, and inflammation, providing insights into the pathophysiology of GDM. This review summarizes the current knowledge on the dynamics of miRNA in pregnancy, their role in GDM as well as their potential as diagnostic and therapeutic targets.


Minor salivary gland tumors: the role of radiotherapy.
Previous analyses of minor salivary gland tumors (MSGTs) have not clearly established the role of radiotherapy in their treatment. The following is a retrospective review of 44 patients treated from 1956 to 1984 with MSGT of the maxillary sinus (15 of 44), nasal cavity/ethmoid complex (six of 44), or hard palate (23 of 44). Histological findings included adenocarcinoma (18), adenoid cystic (17), high-grade mucoepidermoid (six), and mixed malignant (three). Treatment was by surgery (18 of 44), radiotherapy (eight of 44), or a combination of both (18 of 44). Patients treated with radiotherapy, either alone or combined with surgery, had disease that was inoperable, marginally resectable, or residual after surgery. Despite this handicap, 3-year local control rates for all treatment modalities were similar (surgery, 78%; radiotherapy, 63%; and combined treatment, 83%). Absolute 3-year survival rates were 94% for surgery, 63% for radiotherapy, and 78% for combined therapy, with death attributable to distant metastases a significant factor in the advanced cases treated with radiotherapy. A dose response relationship was apparent in those patients whose treatment involved radiotherapy. Clearly, MSGTs are radioresponsive lesions and radiotherapy can play an important role in their management.


Increased ammonium in culture medium may promote cellular apoptosis and negatively affect pluripotency of human blastocysts.
To determine the association between ammonium concentration in culture medium and blastocyst development and to assess the influence of increased ammonium concentration on the expression of Bax, Bcl-2 and Oct4. A total of 254 cleavage-stage embryos were individually cultured in 30μL G2-plus medium on Day 3, and then culture media samples were collected on Day 5 for ammonium concentration determination immediately after evaluating the embryos morphology. Poor-quality blastocysts (combined score of CC) were used for gene expression analysis. The blastocyst formation rate, good-quality blastocyst rate and relative expression levels of Bax, Bcl-2 and Oct4 were analyzed. Based on receiver operating characteristic curve, the cutoff value of ammonium concentration produced by embryos was 16.07 μmol/L (AUC = 0.722, 95% CI 0.637-0.807; P = 0.000), so all embryos were assigned to two groups according to the cutoff value: normal group (< 16.07 μmol/L) and increased group (≥ 16.07 μmol/L). There was a significant difference in blastocyst formation rate (80.5% vs 59.0%, P < 0.01) between normal group and increased group, as well as for good-quality blastocyst rate (21.0% vs 3.4%, P < 0.01). A significantly higher expression level of Bax (P < 0.05) and considerably lower expression level of Oct4 (P < 0.01) were observed in increased group compared to normal group. Our data demonstrated for the first time that increased ammonium concentration in culture medium may promote cellular apoptosis and negatively affect pluripotency of human blastocyst.


A combined open and laparoscopic technique for the management of De Garengeot's hernia with acute appendicitis: A case report.
De Garengeot's hernia is a rare type of femoral hernia which describes the vermiform appendix incarcerated within the hernia sac. In this case report we present our case and review the surgical approaches described in the literature. We present the case of an 84-year-old female with a background of Parkinson's Disease who presented to the emergency department with a five day history of a right-sided groin lump with worsening pain, nausea and reduced appetite. Computed tomography of the abdomen and pelvis revealed an inflamed appendix herniating through the right femoral canal. She had a two staged surgical approach involving an open repair of her femoral hernia followed by laparoscopic appendicectomy. Due to its rarity, there is no standard surgical approach to the appendicectomy and femoral hernia repair. Multiple approaches have been described in the literature, however most reports describe a simultaneous femoral hernia repair and appendicectomy. If an additional abdominal incision is required to complete the appendicectomy safely, we advocate the consideration of a hybrid open-laparoscopic approach, particularly in patients such as this with a history of Parkinson's disease. Here we highlight the usefulness of combining an open low inguinal approach followed by a laparoscopic appendicectomy.


Peroxisomes in the head of Drosophila melanogaster.
Peroxisomes were localized in the head of wild-type and mutant strains of Drosophila melanogaster by use of a cytochemical method for the demonstration of D-amino acid oxidase activity. With similar techniques we had found previously that vertebrate photoreceptors have few, if any, bodies with cytochemically demonstrable oxidase activity, but that the pigment epithelial cells adjacent to the photoreceptors have a substantial population of such bodies. Peroxisomes in Drosophila were very abundant in the fat body. Probable peroxisomes were also present in the peripheral retina of the eye, including in retinular (retinula) and pigment cells, but there were very few of them. Thus, our results suggest that the fat body, which lies adjacent to the eye, is the principal site of peroxisomal function in the head. Peroxisome functions in the Drosophila head may include participation in the genesis of eye pigments.


Ti and its alloys as examples of cryogenic focused ion beam milling of environmentally-sensitive materials.
Hydrogen pick-up leading to hydride formation is often observed in commercially pure Ti (CP-Ti) and Ti-based alloys prepared for microscopic observation by conventional methods, such as electro-polishing and room temperature focused ion beam (FIB) milling. Here, we demonstrate that cryogenic FIB milling can effectively prevent undesired hydrogen pick-up. Specimens of CP-Ti and a Ti dual-phase alloy (Ti-6Al-2Sn-4Zr-6Mo, Ti6246, in wt.%) were prepared using a xenon-plasma FIB microscope equipped with a cryogenic stage reaching -135 °C. Transmission electron microscopy (TEM), selected area electron diffraction, and scanning TEM indicated no hydride formation in cryo-milled CP-Ti lamellae. Atom probe tomography further demonstrated that cryo-FIB significantly reduces hydrogen levels within the Ti6246 matrix compared with conventional methods. Supported by molecular dynamics simulations, we show that significantly lowering the thermal activation for H diffusion inhibits undesired environmental hydrogen pick-up during preparation and prevents pre-charged hydrogen from diffusing out of the sample, allowing for hydrogen embrittlement mechanisms of Ti-based alloys to be investigated at the nanoscale.


Revisiting definition and assessment of intestinal trans-epithelial passage.
This study aims to remind that Intestinal Passage (IP) measurement is a complex task that cannot be achieved by a unique measure of an orally given exogenous marker in blood or urine. This will be illustrated in the case of NOD mice. Indeed, various methods have been proposed to measure IP. Among them ex vivo measurement in Ussing chambers of luminal to serosal fluxes of exogenous markers and in vivo measurement of exogenous markers in blood or urine after oral gavage are the more commonly used. Even though they are commonly used indifferently, they do not give the same information and can provide contradictory results. Published data showed that diabetic status in female Non Obese Diabetic (NOD) mice increased FD4 concentration in blood after gavage but did not modify FD4 fluxes in Ussing chamber. We observed the same results in our experimental conditions and tracked FD4 concentrations in blood over a kinetic study (Area Under the Curve-AUC). In vivo measurements are a dynamic process and address not only absorption (IP and intestinal surface) but also distribution, metabolism and excretion (ADME). Diabetic status in NOD mice was associated with an increase of intestinal length (absorptive surface), itself positively correlated with AUC of FD4 in blood. We concluded that increased intestinal length induced by diabetic status will extend the absorptive surface and increase FD4 concentration in plasma (in vivo measurement) despite no modification on IP of FD4 (ex vivo measurement). In addition, this study characterized intestinal function in diabetic NOD mice. Diabetic status in NOD female mice increases intestinal length and decreases paracellular IP (FSS) without affecting transcellular IP (HRP, FD4). Histological studies of small and large intestine did not show any modification of intestinal circumference nor villi and crypt size. Finally, diabetic status was not associated with intestinal inflammation (ELISA).


Management practices for West syndrome in South Asia: A survey study and meta-analysis.
Considering the dearth of literature on West syndrome (WS) from South Asian countries, this study aimed to evaluate the management practices in South Asia by an online survey and meta-analysis. An online questionnaire was sent to 223 pediatric neurologists/pediatricians in India, Pakistan, Myanmar, Sri Lanka, Bhutan, Nepal, and Bangladesh. Their responses were evaluated and supplemented by a meta-analysis. Of 125 responses received (response rate: 56%), around 60% of responders observed male preponderance and an approximate lead-time-to-treatment (LTTT) of 4-12 weeks. The commonest etiology observed was a static structural insult (88.6% of responders). Most commonly used first-line drug (country-wise) was as follows: India-adrenocorticotropin hormone (ACTH, 50%); Pakistan-oral steroids (45.5%); Myanmar, Sri Lanka, and Nepal-oral steroids (94.4%); Bangladesh-ACTH (2/2); Bhutan-vigabatrin (3/5). ACTH and vigabatrin are not available in Myanmar and Nepal. The most commonly used regime for ACTH was maximal-dose-at-initiation-regime in India, Sri Lanka, and Bangladesh and gradually escalating-regime in Pakistan. Maximum dose of prednisolone was variable-most common response from India: 3-4 mg/kg/d; Pakistan, Bhutan, and Bangladesh: 2 mg/kg/d; Sri Lanka, Nepal, and Myanmar: 5-8 mg/kg/d or 60 mg/d. The total duration of hormonal therapy (including tapering) ranged from 4 to 12 weeks (67/91). Most responders considered cessation of spasms for four weeks as complete response (54/111) and advised electroencephalography (EEG; 104/123) to check for hypsarrhythmia resolution. Difficult access to pediatric EEG in Bhutan and Nepal is concerning. More than 95% of responders felt a need for more awareness. The meta-analysis supported the preponderance of male gender (68%; confidence interval [CI]: 64%-73%), structural etiology(80%; CI 73%-86%), longer LTTT (2.4 months; CI 2.1-2.6 months), and low response rate to hormonal therapy(18% and 28% for ACTH and oral steroids respectively) in WS in South Asia. This study highlights the practices and challenges in the management of WS in South Asia. These include a preponderance of male gender and structural etiology, a longer LTTT, difficult access to pediatric EEG, nonavailability of ACTH and vigabatrin in some countries, and low effectiveness of hormonal therapy in this region.


Qualitative and quantitative analyses of a 'lock and key' hypothesis of depression.
We examine a 'lock and key' ('L-K') hypothesis to depression which posits that early adverse experiences establish locks that are activated by keys mirroring the earlier adverse experience to induce depression. Two-hundred and seventy clinically depressed patients were examined with open-ended and pre-coded interview questions to ascertain both early adverse experiences and precipitating life events. Qualitative and quantitative data analyses examined for any associations between developmental 'locks' and precipitating 'keys'. Qualitative assessment suggested 'L-K' links in almost one-third of the sample, and examples are provided. While quantitative analyses indicated significant associations between several identical 'lock' and 'key' constructs, evidence of specificity was rare. When individual 'locks' and 'keys' were consolidated into three higher-order constructs, variable models were suggested, including a non-specific link, a specific link and absence of any link. 'L-K' links appeared more likely in those with 'non-melancholic' (versus 'melancholic') depression, with the seemingly greater relevance to 'reactive' (versus 'neurotic') depression in the quantitative analyses inviting speculation that that 'disorder' may be more a reaction to a salient rather than a severe stressor. This exploratory study suggests that early adverse experiences may variably establish specific and non-specific patterns of vulnerability to having depression triggered by exposure to salient mirroring life event stressors.


Use of tramadol and the risk of bleeding complications in patients on oral anticoagulants: a systematic review and meta-analysis.
This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants. This systematic review was registered on PROSPERO, CRD42022327230. We searched PubMed and Embase up to 14 April 2022, and references and citations of included studies were screened. Comparative and non-comparative studies exploring bleeding complications among adult patients on oral anticoagulants and tramadol were included. Risk of bias was assessed using an adaptation of the Drug Interaction Probability Scale for case reports and case series and the Newcastle-Ottawa Scale for comparative studies. A meta-analysis was performed for the risk of serious bleeding (leading to hospitalisation or death) associated with tramadol in patients on vitamin K antagonists. A total of 17 studies were included: 1 case series, 12 case reports, 2 case-control studies and 2 cohort studies. Most of the studies described tramadol-vitamin K antagonists' concomitant use; one case-control study also assessed dabigatran and rivaroxaban; one case report involved dabigatran. Among case reports/series, a total of 33 patients had a bleeding complication while using tramadol and an oral anticoagulant. The 4 comparative studies reported an increased bleeding risk during tramadol and vitamin K antagonist intake which was statistically significant in one study; the pooled risk ratio of serious bleeding was 2.68 [95% CI: 1.45 to 4.96; p < 0.001]. This systematic review confirms an association between tramadol use and risk of bleeding in patients on vitamin K antagonists. Evidence is too limited to assess whether this risk extends to patients on direct oral anticoagulants, and further studies are needed.


Can Shunt Response in Patients with Idiopathic Normal Pressure Hydrocephalus Be Predicted from Preoperative Brain Imaging? A Retrospective Study of the Diagnostic Use of the Normal Pressure Hydrocephalus Radscale in 119 Patients.
The Normal Pressure Hydrocephalus Radscale is a combined scoring of 7 different structural imaging markers on preoperative brain CT or MR imaging in patients with idiopathic normal pressure hydrocephalus: callosal angle, Evans Index, Sylvian fissure dilation, apical sulcal narrowing, mean temporal horn diameter, periventricular WM lesions, and focal sulcal dilation. The purpose of this retrospective study was to assess the performance of the Normal Pressure Hydrocephalus Radscale in distinguishing idiopathic normal pressure hydrocephalus shunt responders from nonresponders. The preoperative MR imaging and CT scans of 119 patients with idiopathic normal pressure hydrocephalus were scored using the Normal Pressure Hydrocephalus Radscale. A summary shunt-response score assessed within 6 months from ventriculoperitoneal shunt surgery, combining the effect on cognition, gait, and urinary incontinence, was used as a reference. The difference between the mean Normal Pressure Hydrocephalus Radscale for responders and nonresponders was tested using the Student t test. The area under the curve was calculated for the Normal Pressure Hydrocephalus Radscale to assess shunt response. To ascertain reproducibility, we assessed the interobserver agreement between the 2 independent observers as intraclass correlation coefficients for the Normal Pressure Hydrocephalus Radscale for 74 MR imaging scans and 19 CT scans. Ninety-four (79%) of 119 patients were shunt responders. The mean Normal Pressure Hydrocephalus Radscale score for shunt responders was 8.35 (SD, 1.53), and for nonresponders, 7.48 (SD, 1.53) (P = .02). The area under the curve for the Normal Pressure Hydrocephalus Radscale was 0.66 (range, 0.54-0.78). The intraclass correlation coefficient for the Normal Pressure Hydrocephalus Radscale was 0.86 for MR imaging and 0.82 for CT. The Normal Pressure Hydrocephalus Radscale showed moderate discrimination for shunt response but cannot, on its own, be used for selecting patients with idiopathic normal pressure hydrocephalus for shunt surgery.


Morphology and rheology of the rectum in patients with chronic idiopathic constipation.
To evaluate whether there is a relationship between the viscoelastic properties of the rectum and its surface, barium enema and rectal accommodation studies were performed under standard conditions in 46 subjects (25 adults, 21 children) with chronic idiopathic constipation. In adults, a significant correlation was found between rectal surface at barium enema and the minimum radius of rectal distention with a balloon necessary to higher wall tension changes (r = 0.68; P less than 0.01). In both adults (r = 0.48; P less than 0.05) and children (r = 0.57; P less than 0.01), negative correlations were found between the surface of the rectum and its elasticity. It is concluded that rectal accommodation studies produce data comparable to those of radiologic examinations and may therefore be used repetitively, and without fear of radiation, as follow-up studies on constipated patients.


Sidestream bio-P and mainstream anammox in a BNR process with upstream carbon capture.
The integration of biological phosphorus removal (bio-P) and shortcut nitrogen removal (SNR) processes is challenging because of the conflicting demands on influent carbon: SNR allows for upstream carbon diversion, but this reduction of influent carbon (especially volatile fatty acids [VFAs]) prevents or limits bio-P. The objective of this study was to achieve SNR, either via partial nitritation/anammox (PNA) or partial denitrification/anammox (PdNA), simultaneously with biological phosphorus removal in a process with upstream carbon capture. This study took place in a pilot scale A/B process with a sidestream bio-P reactor and tertiary anammox polishing. Despite low influent rbCOD concentrations from the A-stage effluent, bio-P occurred in the B-stage thanks to the addition of A-stage WAS fermentate to the sidestream reactor. Nitrite accumulation occurred in the B-stage via partial denitrification and partial nitritation (NOB out-selection), depending on operational conditions, and was removed along with ammonia by the tertiary anammox MBBR, with the ability to achieve effluent TIN less than 2 mg/L. PRACTITIONER POINTS: A sidestream reactor with sufficient fermentate addition enables biological phosphorus removal in a B-stage system with little-to-no influent VFA. Enhanced biological phosphorus removal is not inhibited by intermittent aeration and is stable at a wide range of process SRTs. Partial nitritation and partial denitrification are viable routes to produce nitrite within an A/B process with sidestream bio-P, for downstream anammox in a polishing MBBR.


Impact of consumption frequency on generations of sensory product profiles using CATA questions: Case studies with two drink categories.
Check-All-That-Apply (CATA) is a very popular tool for rapid sensory profiling in consumer research. Yet, consumers' dietary habits, such as consumption frequency, has been neglected in regard to the impact, if any, on CATA question responses. The present work aimed to fill this gap, by focusing on the effect of different consumption frequencies with four studies (N = 686). Two categories of drink products were involved, chrysanthemum tea and instant coffee. For each category, two sets of products were prepared to constitute two levels of difference between samples (larger vs. smaller). Consumers were classified into high- and low-consumption groups according to their consumption frequencies of each focal product; the size of these subgroups ranged from 54 to 130. Overall, the two groups did not produce large discrepancies from each other when constructing sensory profiling of the tested samples with CATA questions as well as the stability of sample configurations. However, there were some nuances between them. In the evaluation of chrysanthemum tea samples, the higher-consumption group of consumers presented better discrimination than the lower-consumption group while this was reversed for coffee samples. This might be mainly attributed to the fact infrequent consumers were more sensitive to such negative attributes as "strong chrysanthemum smell for chrysanthemum samples, earthy for coffee samples". Further, despite the higher stability obtained with larger sizes of difference between samples in Studies 3 and 4, in general, the effect of size of differences within sample sets was not significant between different consumption groups. To more effectively contribute to refinement of methodological guidelines for CATA questions, more validation work is needed.


Fetal blood volume responses to intravenous saline solution and dextran.
The purpose of this study was to determine to what extent the volume of blood circulating in the fetus can be increased by intravascular infusions of either isotonic saline solution or high-molecular weight dextran in saline solution. Unanesthetized, chronically catheterized fetal sheep that averaged 130 days' gestation were studied. In seven fetuses, 50 to 100 ml of warm saline solution (i.e., an average of 19.5% of the initial fetal blood volume) was infused into a vein over 5 minutes, and changes in blood volume were determined 10, 20, and 30 minutes after the infusion was begun. At these times, an average of only 15%, 9%, and 7%, respectively, of the infused volume remained in the fetal circulation. A second infusion of saline solution into these fetuses gave intravascular retentions that averaged 17%, 6%, and 6% at 10, 20, and 30 minutes, respectively. In five fetuses, a 6% solution of dextran 70 that averaged 14.9% of the initial fetal blood volume was infused over 5 minutes. The intravascular retentions averaged 80%, 63%, and 55%, respectively, at 10, 20, and 30 minutes after the infusions were started. Under comparable conditions in the adult, blood volume expansion 30 minutes after rapid infusions averages 20% to 40% of the infused volume for saline solution and 150% to 200% for 6% dextran 70. Thus, the present study suggests that intravascular infusions of crystalloid solutions have very little effect on fetal blood volume, whereas oncotic solutions cause only moderate blood volume expansion.


A novel motion detection method for improving the quality of two-dimensional echocardiographic images.
Two-dimensional echocardiographic pictures from elderly patients are often technically unsatisfactory. It may be helpful or even necessary to improve the signal-to-noise ratio of these images before interpreting them. A novel picture-averaging method for obtaining the improved image is described here. The procedure may be performed with either live video or video taped two-dimensional echocardiograms and does not require an electrocardiogram signal for triggering images from the same cardiac phase of successive heart beats. Instead, the triggering is performed by comparing video frames with a reference image, automatically selecting only the frames that are most nearly equivalent to the reference picture and averaging the selected images to obtain an enhanced, time-averaged picture. Frames that are rejected by the method are those in which motion has been detected relative to the reference image, often caused by slight beat-to-beat image changes that accompany breathing. This enhancement may facilitate the interpretation and measurement of echocardiographic data, thus improving the diagnosis and management of heart disease in these patients.


Changes in corneal aberrations after cataract surgery.
To study the changes in corneal aberrations after cataract surgery. This study comprised 36 eyes of 36 patients (mean age, 67.3 years) who underwent cataract surgery through a 2.2-mm superior sclerocorneal incision. The anterior, posterior, and total corneal wavefront aberrations for the 6.0-mm pupillary diameter were measured preoperatively and 1 month postoperatively. The postoperative changes in corneal aberrations were evaluated for individual Zernike terms (Z 2 (-2) , Z 2 (0) , Z 2 (2) , Z 3 (-1) , Z 3 (1) , and Z 4 (0) ) and the root mean squares of the third, fourth, and total higher-order aberrations (S3, S4, and THOA). No significant postoperative changes were observed in S3 and S4 of the total and anterior cornea, although significant changes were observed in S4 and THOA of the posterior cornea. Regarding the preoperative and postoperative Zernike terms of the total cornea, the oblique astigmatism (Z 2 (-2) ) changed significantly (P = 0.02). Significant positive correlations were observed in the Z 2 (-2) , Z 2 (0) , Z 2 (2) Z 3 (-1) , Z 3 (1) and Z 4 (0) between the changes in the total and the anterior cornea (P < 0.001 for all comparisons). However, no correlations were observed in the changes in the Zernike terms between the total and the posterior cornea, except for the Z 2 (0) . The oblique astigmatism (Z 2 (-2) ) of the total cornea significantly changed after 2.2-mm-incision cataract surgery. The changes in the lower- and higher-order aberrations of the anterior cornea mainly contributed to the changes in the total cornea.


Teaching Ear Examination Skill to Undergraduate Students Using Check List.
For examination of ear, proper illumination is a pre requisite. Diseases related to ear may lead to altered sense of hearing and may affect normal balance system. If students are taught to examine ear using a check list, they may perform better. To teach ear examination to undergraduate students using a check list. Total 50 undergraduate students of M.B.B.S. attending E.N.T. clinic in Chirayu Medical College and Hospital were included in the study. They were given enrolment no. 1 to 50 and were divided into two groups. Group 1, enroll. no. 1 to 25 and group 2, enroll. no. 26 to 50. Group 1 was taught using check list and the Group 2 was taught without use of checklist. Both the groups were evaluated using check list. The group B students were again taught, using check list and were again evaluated using check list. Use of check list showed that there was statistically significant improvement in learning by students using check list in group 1 students compared to group 2 students who were taught without use of check list. The group 2 students also had improvement on evaluation, after they were taught using check list. Study suggests that use of check list for ear examination skill to undergraduate students has significant role and students learn better than when taught without use of checklist. Inclusion of checklist for teaching ear examination to undergraduate students may be considered.


Treatment of chronic myelomonocytic leukaemia by allogeneic marrow transplantation.
We evaluated the outcome of allogeneic bone marrow transplantation (BMT) in 21 patients with chronic myelomonocytic leukaemia (CMML) who were treated at the Fred Hutchinson Cancer Research Center between 1990 and 1998. There were 11 male and 10 female patients with a median age of 47.4 years (range 1.0-62.9). Patients were conditioned either with total body irradiation (TBI) and chemotherapy, with or without antithymocyte globulin (n = 19), or with chemotherapy alone (n = 2). The marrow donor was an HLA-identical sibling in 12 patients, an HLA-non-identical related donor in three patients and an unrelated volunteer donor in six patients. All evaluable patients achieved sustained engraftment. Fifteen patients developed grades II-IV acute graft-versus-host disease (GVHD). Nine patients (43.0%) are surviving disease free at 0.7-8.1 years (median 6.9) after transplantation. Five patients relapsed 75-660 d after transplant and all died. Five patients died with organ failure and two died with GVHD and associated infections. The Kaplan-Meier estimates of disease-free survival and relapse at 3 years were 39% and 25% respectively. The probability of survival was improved in patients with shorter disease duration compared with those with a long interval from diagnosis to BMT. Thus, as with other myeloproliferative diseases or myelodysplastic syndromes, BMT offers curative therapy for a proportion of patients with CMML. We suggest that patients with CMML who have a suitable donor should be considered for transplantation, probably early in their disease course. However, it will be important to develop new regimens with enhanced antileukaemic efficacy without further increasing regimen-related toxicity and mortality.


Association of a functional RAD52 genetic variant locating in a miRNA binding site with risk of HBV-related hepatocellular carcinoma.
As an important member in homologous recombination repair, RAD52 plays a crucial part in maintaining genomic stability and prevent carcinogenesis. Several cancer susceptibility RAD52 single nucleotide polymorphisms (SNPs) have been identified previously. However, little or nothing has been known about the RAD52 SNPs and their functional significance in hepatitis B viruses (HBV)-related hepatocellular carcinoma (HCC). Therefore, we investigated the association between five RAD52 SNPs (rs1051669, rs10774474, rs11571378, rs7963551, and rs6489769) and HBV-related HCC risk as well as its biological function in vivo. Genotypes were determined in two independent case-control sets from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The allele-specific regulation on RAD52 expression by the functional genetic variant was examined with normal liver tissues. We found that only the RAD52 rs7963551 SNP was significantly associated with HCC risk, with the odds of having the rs7963551 CC genotype in patients was 0.59 (95% CI = 0.45-0.78, P = 1.5 × 10(-4), HCC cases versus chronic HBV carriers) or 0.65 (95% CI = 0.52-0.81, P = 1.1 × 10(-4), HCC cases versus healthy controls) compared with the AA genotype. In the genotype-phenotype correlation analyses of 44 human liver tissue samples, rs7963551 CC or AC was associated with a statistically significant increase of RAD52 mRNA expression, which are consistent to functional relevance of allelic regulation of RAD52 expression by rs7963551 SNP and miRNA let-7 in cancer cells. Our data demonstrated that RAD52 functional rs7963551 SNP contributes to susceptibility to developing HCC.


Comparison of a needleless system with conventional heparin locks.
Despite the improvements in needle disposal systems, needlesticks to health care workers continue to occur at unacceptably high rates. Needleless systems have been shown to reduce the risk of needlesticks. This pilot study examined the safety of such a system for patients by comparing the rates of intravenous infection-related indicators between a conventional heparin lock and a needleless system. Patients (n = 97) were categorized on the basis of the duration of intravenous placement into 24-, 48-, and 72-hour groups. Within each group, half of the patients received conventional heparin locks and half received the needleless system. Intravenous infection-related indicators included catheter tip culture, adaptor fluid culture, intravenous site erythema, induration and tenderness, and elevated oral temperature. Prevalence of one or more indicators was 48% for the conventional and 40% for the needleless system, a difference that was not statistically significant. The needleless system appeared to pose no greater risk of infection to patients and nurses preferred it for its reduced risk of potential needlesticks.


Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients.
Reduced phospholipase A2 (PLA2) activity and increased phosphorylation of glycogen synthase kinase 3B (GSK3B) participate in the production of beta-amyloid plaques and of neurofibrillary tangles, which are two neuropathological hallmarks of Alzheimer's disease (AD). Experimental evidences suggest a neuroprotective effect of the cholinesterase inhibitor donepezil in the treatment the disease. The aims of the present study were to evaluate in AD patients the effects of treatment with donepezil on PLA2 activity and GSK3B level. Thirty patients with AD were treated during 6 months with 10 mg daily of donepezil. Radio-enzymatic assays were used to measure PLA2 activity and Elisa assays for GSK3B level, both in platelets. Before treatment and after 3 and 6 months on donepezil, AD patients underwent a cognitive assessment and platelet samples were collected. Values were compared to a healthy control group of 42 sex- and age-matched elderly individuals. Before treatment, iPLA2 activity was lower in patients with AD as compared to controls (p < 0.001). At baseline, no differences were found in GSK3B level between both groups. After 3 and 6 months of treatment, we found a significant increase in iPLA2 activity (p = 0.015 and p < 0.001, respectively). iPLA2 increment was related to the cognitive improvement during treatment (p = 0.037). After 6 months, we found an increase in phosphorylated GSK3B (p = 0.02). The present findings suggest two possible mechanisms by which donepezil delays the progression of AD. The increment of iPLA2 activity may reduce the production of beta-amyloid plaques, whereas the phosphorylation of GSK3B inactivates the enzyme, reducing thus the phosphorylation of tau protein.


Determination of the enantiomeric composition of ibuprofen in human plasma by high-performance liquid chromatography.
A normal-phase high-performance liquid chromatographic method, using a hexane-ethyl acetate solvent system, for the determination of the enantiomeric composition of ibuprofen in human plasma is described. The method is based on the resolution of the diastereoisomeric amides formed on reaction of the ibuprofen enantiomers with S-1-(naphthen-1-yl)ethylamine using p-chlorophenoxy-acetic acid as internal standard. The application of the method for the determination of the enantiomeric composition of ibuprofen in human plasma following the repeated oral administration of the drug to two volunteers is reported. The plasma concentrations of the S-(+) enantiomer were always greater than that of the R-(-), the ratio of the areas under the enantiomer plasma concentration-time curves (S/R) being 1.8 and 1.6.


"Excess" electrons in LuGe.
The monogermanide LuGe is obtained via high-pressure high-temperature synthesis (5-15 GPa, 1023-1423 K). The crystal structure is solved from single-crystal X-ray diffraction data (structure type FeB, space group Pnma, a=7.660(2) Å, b=3.875(1) Å, and c=5.715(2) Å, RF =0.036 for 206 symmetry independent reflections). The analysis of chemical bonding applying quantum-chemical techniques in position space was performed. It revealed-beside the expected 2c-Ge-Ge bonds in the germanium polyanion-rather unexpected four-atomic bonds between lutetium atoms indicating the formation of a polycation by the excess electrons in the system Lu3+ (2b)Ge2- ×1 e- . Despite the reduced VEC of 3.5, lutetium monogermanide is following the extended 8-N rule with the trend to form lutetium-lutetium bonds utilizing the electrons left after satisfying the bonding needs in the anionic Ge-Ge zigzag chain.


Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: possible implications for heroin neurotoxicity.
Heroin is one of the most dangerous drugs of abuse, which may exert various neurotoxic actions on the brain (such as gray matter loss, neuronal apoptosis, mitochondrial dysfunction, synaptic defects, depression of adult neurogenensis, as well as development of spongiform leucoencephalopathy). Some of these toxic effects are probably mediated by the gas nitric oxide (NO). We studied by morphometric analysis the numerical density of neurons expressing neuronal nitric oxide synthase (nNOS) in cortical and hypothalamic areas of eight heroin overdose victims and nine matched controls. Heroin addicts showed significantly increased numerical densities of nNOS immunoreactive cells in the right temporal cortex and the left paraventricular nucleus. Remarkably, in heroin abusers, but not in controls, we observed not only immunostained interneurons, but also cortical pyramidal cells. Given that increased cellular expression of nNOS was accompanied by elevated NO generation in brains of heroin addicts, these elevated levels of NO might have contributed to some of the known toxic effects of heroin (for example, reduced adult neurogenesis, mitochondrial pathology or disturbances in synaptic functioning).


Multilevel small area estimation for county-level prevalence of colorectal cancer screening test use in the United States using 2018 data.
National screening estimates mask county-level variations. We aimed to generate county-level colorectal cancer (CRC) screening prevalence estimates for 2018 among adults aged 50-75 years and identify counties with low screening prevalence. We combined individual-level county data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS) (n = 204,947) with the 2018 American Community Survey county poverty data as a covariate, and the 2018 U.S. Census county population count data to generate county-level prevalence estimates for being current with any CRC screening test, colonoscopy, and home stool blood test. Because BRFSS is a state-based survey, and because some counties did not have samples for analysis, we used correlation coefficients to test internal consistency between model-based and BRFSS state estimates. Correlation coefficients tests were ≥0.97. Model-based national prevalence for any test was 69.9% (95% CI, 69.5% -70.4%) suggesting 30% are not current with screening test use. State mean estimates ranged from 62.1% in Alaska and Wyoming to 76.6% in Maine and Massachusetts. County mean estimates ranged from 42.2% in Alaska to 80.0% in Florida and Rhode Island. Most tests were performed with colonoscopy. Estimates across all U.S. counties showed large variations. Estimates may be informative for planning by states and local screening programs.


High-risk cutaneous squamous cell carcinoma.
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and its incidence has increased in recent decades. Most cSCCs are successfully treated by surgery, but local and distant metastases develop in approximately 5% of cases; this proportion is higher in certain forms of cSCC with high-risk factors, namely: tumor size >2cm, depth >2mm, Clark level ≥IV, perineural invasion, lymphovascular invasion, poor differentiation, certain histologic subtypes (desmoplastic or adenosquamous carcinoma, invasive Bowen disease, or a cSCC arising in areas of chronic inflammation), immunosuppression, human papillomavirus infection, high-risk anatomic location (pinna of the ear, labial mucosa), expression of certain tumor genes, and inadequate tumor resection. The latest TNM (tumor, lymph node, metastasis) classification of cSCC published by the American Joint Committee on Cancer (AJCC) in the seventh edition of its Cancer Staging Manual now incorporates several of these risk factors to improve disease staging. We review all the factors currently considered to be markers of poor prognosis in cSCC and analyze the new AJCC classification and the different treatment options for high-risk cSCC.


[A bio-psycho-social approach to acute hypertensive disease in pregnancy].
In this paper, the approach to the genesis of the acute hypertension of pregnancy, uses a conceptual and methodological perspective adjusted to its multifactorial nature; a set of questions with epidemiologic focus is proposed, in order to vinculate psychosocial factors with the biologic processes characteristic of this health problem.


Inheritance of the duration of fertility in chickens and its correlation with laying performance.
Duration of fertility (DF) is an important economic trait in poultry production because it has a strong effect on chick output. Various criteria or traits to assess DF on individual hens have been reported but they are affected by many nongenetic factors. Thus, a reliable definition and associated genetic parameters are needed. Because egg production is also vital in chicken breeding, knowledge of the relationship between DF and laying performance is needed for designing selection programs. We used five traits that consider both fertility and embryonic livability to delineate DF. Phenotypic and genetic analyses were completed for 2094 hens, with measurements of DF at 35 and 60 weeks of age and hatching egg production at 400 days of age (HEP400). The selection differentials for DF and HEP400 were evaluated. DF is largely independent of the number of oviposited eggs in the peak laying period but both egg production and DF naturally decline with age. The heritability of the five DF traits ranged from 0.11 to 0.13 at 35 weeks of age and increased slightly in the later laying period, ranging from 0.14 to 0.17 (except for efficient duration, time between insemination and the first unhatched egg). Estimates of the genetic correlation for a given trait measured at the two ages were moderate (0.37-0.44), except for efficient duration. However, number of viable embryos depends strongly on egg production. Estimates of genetic correlations of fertility duration day (FDD) at both ages with HEP were weak. Selection for FDD improved DF but without a significant change in laying performance. Selection for increased HEP400 did not contribute to DF improvement. Although estimates of heritability of the five traits related to DF were low, selection to improve DF based on any one of them is possible. Among these, FDD is an effective selection criterion when the eggs are collected for approximately two weeks after insemination. The best selection procedure for DF improvement would involve multiple measurements at various ages. FDD is independent of laying performance and can be incorporated into a breeding program with egg production to improve reproductive efficiency.


Micro triboelectric ultrasonic device for acoustic energy transfer and signal communication.
As a promising energy converter, the requirement for miniaturization and high-accuracy of triboelectric nanogenerators always remains urgent. In this work, a micro triboelectric ultrasonic device was developed by integrating a triboelectric nanogenerator and micro-electro-mechanical systems technology. To date, it sets a world record for the smallest triboelectric device, with a 50 µm-sized diaphragm, and enables the working frequency to be brought to megahertz. This dramatically improves the miniaturization and chip integration of the triboelectric nanogenerator. With 63 kPa@1 MHz ultrasound input, the micro triboelectric ultrasonic device can generate the voltage signal of 16.8 mV and 12.7 mV through oil and sound-attenuation medium, respectively. It also achieved the signal-to-ratio of 20.54 dB and exhibited the practical potential for signal communication by modulating the incident ultrasound. Finally, detailed optimization approaches have also been proposed to further improve the output power of the micro triboelectric ultrasonic device.


The mitogen-activated protein kinase homolog HOG1 gene controls glycerol accumulation in the pathogenic fungus Candida albicans.
The Candida albicans HOG1 gene (HOG1CA) was cloned by functional complementation of the osmosensitive phenotype associated with Saccharomyces cerevisiae hog1 delta mutants. HOG1CA codes for a 377-amino-acid protein, 78% identical to S. cerevisiae Hog1p. A C. albicans hog1 null mutant was found to be sensitive to osmotic stress and failed to accumulate glycerol on high-osmolarity media.


Systematic review of specialist palliative day-care for adults with cancer.
To inform future practice, research and policy in specialist palliative day-care by systematically reviewing the evidence for how the structure and process of this form of care relate to outcomes for adults with cancer. Medical, nursing and social science computerized databases were searched up until December 2003 for studies of palliative day-care reporting information on service structure, care processes or outcomes including symptom control, quality of life, social and psychological support, and patient and relative satisfaction with care. Qualitative and quantitative studies were assessed for methodological quality and graded, and the findings synthesized into the review. Twelve observational studies were found that showed the difficulties of evaluating a service already operating and of recruiting a vulnerable population of patients as they deteriorated. Most services are nurse-led, but varied in the facilities, staff mix, care models, activities and places they offered. Patients attending seemed a selected group of those already receiving palliative care who were mostly white, aged over 60 years and retired, with needs for emotional and social support and pain control. There were insufficient studies to provide conclusive evidence of improved symptom control or health-related quality of life, but all qualitative studies found patients valued the social support and opportunity to take part in activities that day-care provided. There is evidence for high satisfaction among patients selected into day-care, but not yet sufficient to judge whether this improves symptom control or health-related quality of life. Further research should explore selection and access into care, the most effective models of care, its cost, and potential benefits for relatives and carers. Comparison with models of care for older adults and those with mental illness would also be informative.


Design of Near-Infrared Nonfullerene Acceptor with Ultralow Nonradiative Voltage Loss for High-Performance Semitransparent Ternary Organic Solar Cells.
Semitransparent organic solar cells (ST-OSCs) are considered as one of the most valuable applications of OSCs and a strong contender in the market. However, the optical band gap of current high-performance ST-OSCs is still not low enough to achieve the optimal balance between power conversion efficiency (PCE) and average visible transmittance (AVT). An N-substituted asymmetric nonfullerene acceptor SN with over 40 nm bathochromically shifted absorption compared to Y6 was designed and synthesized, based on which the device with PM6 as donor obtained a PCE of 14.3 %, accompanied with a nonradiative voltage loss as low as 0.15 eV. Meanwhile, ternary devices with the addition of SN into PM6 : Y6 can achieve a PCE of 17.5 % with an unchanged open-circuit voltage and improved short-circuit current. Benefiting from extended NIR absorption and lowered voltage loss, ST-OSCs based on PM6 : SN : Y6 were fabricated and the optimized device demonstrated a PCE of 14.0 % at an AVT of 20.2 %, which is the highest PCE at an AVT over 20 %.


Effect of adrenalectomy on the slimming activity of liposome-carried oleoyl-estrone in the rat.
To determine the extent of glucocorticoid counter-regulatory control in the slimming action of oleoylestrone. Control and adrenalectomized rats were subjected to a seven-day treatment with 3.5 micromol/kg/d oleoylestrone in liposomes injected i.v. continuously by implanted osmotic minipumps. Sham-operated control and adrenalectomized lean Zucker rats. Body weight and food intake; plasma glucose, urea, insulin, leptin and corticosterone; liver glycogen. Treatment with oleoyl-estrone resulted in decreases in body weight and in food intake, as well as in circulating glucose, insulin and leptin. Combined adrenalectomy and oleoyl-estrone treatment resulted in a loss of almost 15% body weight in only seven days, with a severe drop in circulating glucose and insulin, almost total disappearance of plasma leptin and liver glycogen and a 3-fold rise in circulating urea. Food intake decreased sharply, which resulted in the exhaustion of energy reserves. The results presented here, strongly support the hypothesis that glucocorticoids play an important role in the modulation of oleoyl-estrone-induced imbalance of energy intake and expenditure. The large effect of oleoyl-estrone on glucose, glycogen- and protein-derived (urea levels) energy in adrenalectomized rats, provides more evidence for the assumed protective role of glucocorticoids against the oleoyl-estrone-induced net loss of energy reserves. The results also show the powerful destabilizing effects of unchecked oleoyl-estrone on energy balance.