Subjective cognitive dysfunction in patients with bipolar disorder: The prevalence, related factors and effects on predicting psychosocial functioning and suicidal ideation.
Persistent cognitive deficits are prevalent during all stages of bipolar disorder (BD). However, few studies have examined subjective cognitive complaints in patients with BD. This study aimed to investigate the prevalence and relevant factors of subjective cognitive functioning and its potential effects on predicting psychosocial functioning and suicidal ideation in BD. Ninety-two patients with BD type I (including 42 depressed patients and 50 euthymic patients) and 60 healthy individuals were recruited for this study. All participants were assessed with a battery of neuropsychological tests examining attention and processing speed, visual memory, working memory and executive functions, as well as the Cognitive Complaints in Bipolar Disorder Rating Assessment, the Global Assessment of Functioning scale and the Beck Scale for Suicide Ideation. Bipolar patients exhibited worse subjective cognitive dysfunction compared with healthy individuals, and depressed patients expressed more cognitive complaints than euthymic bipolar patients. In bipolar group, psychosocial functioning, suicidal ideation and occupational status were the main relevant factors of subjective cognitive functioning. Subjective cognitive functioning could also predict psychosocial functioning and suicidal ideation. Depressive symptoms moderated the associations between objective cognitive functioning and suicidal ideation, but could not moderate the correlations between cognitive functioning and psychosocial functioning. These findings suggest that subjective cognitive assessment should be further emphasized in clinical practice.


Intracerebroventricular administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridinium ion (MPP+) decrease dopamine and increase acetylcholine in the mouse neostriatum.
We found that both MPTP and its metabolite MPP+ decrease dopamine and increase acetylcholine content of mouse neostriatum when administered intracerebroventricularly (ICV). These observations support the notion that MPP+ may be the active neurotoxin formed in brain after MPTP administration. They also suggest that cholinergic mechanisms may be a target of the neurotoxin.


Manoeuvrability and biocompatibility of endodontic tricalcium silicate-based putties.
The present study evaluated the indentation depth, storage modulus and biocompatibility of an experimental endodontic putty designed for endodontic perforation repair and direct pulp-capping (NeoPutty). The results were compared with the properties associated with the commercially available EndoSequence BC RRM Putty (ES Putty). Indentation depth was measured by a profilometer following indentation with the 1/4 lb Gilmore needle. Elastic modulus was evaluated using a strain-controlled rheometer. The effects of eluents derived from these two putties were examined on the viability and proliferation of human dental pulp stem cells (hDPSCs) and human periodontal ligament fibroblasts (hPDLFs), before (1 st testing cycle) and after complete setting (2nd testing cycle). The ES Putty became more difficult to ident and acquired a larger storage modulus after exposure to atmospheric moisture. Biocompatibility results indicated that both putties were relatively more cytotoxic than the bioinert Teflon negative control, but much less cytotoxic than the zinc oxide-eugenol cement negative control. NeoPutty was less cytotoxic than ES putty in the 1st testing cycle, particularly with hDPSCs. Both putties exhibited more favourable cytotoxicity profiles after complete setting. NeoPutty has a better window of maneuverability after exposure to atmospheric moisture. From an in vitro cytotoxicity perspective, the NeoPutty may be considered more biocompatible than ES putty. The experimental NeoPutty is biocompatible and is capable of reducing the frustration of shortened shelf life when jar-stored endodontic putties are exposed to atmospheric moisture during repeated opening of the lid for clinical retrieval.


[Minocycline-induced autoimmune hepatitis].
Drug-induced autoimmune hepatitis is an acute and potentially severe side effect, particularly often reported after the long-term use of minocycline. The condition's characteristic biochemical findings are highly elevated transaminase levels, only mildly increased markers of cholestasis and bilirubin levels, an elevated IgG concentration and a high antinuclear antibody (ANA) titre. A 14-year-old girl developed autoimmune hepatitis due to the long-term use of minocycline for acne vulgaris. She presented with icterus and very high transaminase levels. The patient made a full recovery after the medication was discontinued. This type of autoimmune hepatitis can be differentiated from 'classic' autoimmune hepatitis by the patient's quick recovery after stopping the inducing drug and no relapse of the condition after the discontinuation of glucocorticoid therapy.


Erratum: Identifying factors associated with the discharge of male State patients from Weskoppies Hospital.
[This corrects the article DOI: 10.4102/sajpsychiatry.v23i0.1083.].


DSResSol: A Sequence-Based Solubility Predictor Created with Dilated Squeeze Excitation Residual Networks.
Protein solubility is an important thermodynamic parameter that is critical for the characterization of a protein's function, and a key determinant for the production yield of a protein in both the research setting and within industrial (e.g., pharmaceutical) applications. Experimental approaches to predict protein solubility are costly, time-consuming, and frequently offer only low success rates. To reduce cost and expedite the development of therapeutic and industrially relevant proteins, a highly accurate computational tool for predicting protein solubility from protein sequence is sought. While a number of in silico prediction tools exist, they suffer from relatively low prediction accuracy, bias toward the soluble proteins, and limited applicability for various classes of proteins. In this study, we developed a novel deep learning sequence-based solubility predictor, DSResSol, that takes advantage of the integration of squeeze excitation residual networks with dilated convolutional neural networks and outperforms all existing protein solubility prediction models. This model captures the frequently occurring amino acid k-mers and their local and global interactions and highlights the importance of identifying long-range interaction information between amino acid k-mers to achieve improved accuracy, using only protein sequence as input. DSResSol outperforms all available sequence-based solubility predictors by at least 5% in terms of accuracy when evaluated by two different independent test sets. Compared to existing predictors, DSResSol not only reduces prediction bias for insoluble proteins but also predicts soluble proteins within the test sets with an accuracy that is at least 13% higher than existing models. We derive the key amino acids, dipeptides, and tripeptides contributing to protein solubility, identifying glutamic acid and serine as critical amino acids for protein solubility prediction. Overall, DSResSol can be used for the fast, reliable, and inexpensive prediction of a protein's solubility to guide experimental design.


Fecal Microbiome Associated with Both Colon Adenomas and Lifetime Colorectal Cancer Risk.
Increasing data indicates the gut flora including bacteria and fungi combined with environmental factors are important in the pathogenesis of colorectal cancer (CRC). Understanding differences in the microbiome in patients with colon neoplasia will foster the development of biomarkers for early detection. Determine the association of microbiome with presence of adenomas and predicted CRC risk. In subjects referred for colonoscopy, the NCI CRC risk assessment tool was completed and stool for microbiome analysis as well as fecal immunochemical test (FIT) were collected. We calculated the microbiome alpha diversity using the Shannon index as well as individual bacterial and fungal species. Among 34 patients, we identified 10 with one or more adenomas. Only 2 patients were FIT positive. The median predicted lifetime CRC risk was 2.75% and the prevalence of adenoma was higher in the fourth quartile (P < 0.001). The measured alpha diversity was somewhat higher in patients with adenomas (P = 0.07). We identified 4 bacterial species with an increased relative abundance among patients with adenomas [P < 0.5]. Lifetime CRC risk was associated with 2 specific bacterial species, P. distasonis & E. hermannii [P = 0.05 & 0.09, respectively]. No associations were seen with fungal species and adenoma prevalence or lifetime CRC risk. In addition to a strong correlation of predicted CRC risk and adenoma prevalence, we also found important differences in specific bacterial species and both adenoma prevalence and CRC risk. Larger trials are needed to potentially implement further data in the clinical setting.


[Heterotopia of the third molar in the coronoid process. Clinical case].
The A.A. present an uncommon case of eterotopy of the wisdom-tooth placed in the coronoid process, examining etiopthogenesis of this pathology after an attentive analysis of the literature.


Frequency of the MSTN Lys(K)-153Arg(R) polymorphism among track & field athletes and swimmers.
The myostatin (MSTN) Lys(K)-153Arg(R) polymorphism may influence skeletal muscle phenotypes. Carrying the rare R allele was associated with greater muscle mass. The aim of the present study was to assess the frequency of the MSTN Lys(K)-153Arg(R) polymorphism among Israeli track and field athletes (n=185) and swimmers (n=80). Track and field athletes were divided into long distance runners (major event 5000 m-marathon, n=113) and power athletes (major event 100200 m sprints and long jump, n=72). Swimmers were divided into long-distance swimmers (major event: 800-1500 m, n=38), and short-distance swimmers (major event: 50-100 m, n=42). The control group included 118 non-athletes healthy participants. Twenty-seven track and field athletes (14.6%) and 7 swimmers (8.8%) were carriers of the rare MSTN R allele, and only two carried the 153RR genotype (0.8%). MSTN 153R allele frequency was significantly higher in top-compared to national-level among long-distance runners (26% versus 8%, p<0.05), short distance runners (16% versus 9%, p<0.05), and all runners combined (20% versus 8%, p<0.05), but not in top- compared to national-level swimmers. The frequency of arginine carriers was significantly greater among long compared to short-distance swimmers (16% versus 2%, p<0.03). In contrast to elite endurance and power track and field athletes, the MSTN 153RR genotype was not found in short distance-swimmers, and among the long distance-swimmers it was not associated with top level swimming performance. Whether evaluation of the MSTN K153R polymorphism can be used for sports selection in young athletes needs to be further studied.


Supraspinal fiber outgrowth and apparent synaptic remodelling across transected-reconstructed feline spinal cord.
Following complete transection of the spinal cord at T9, 12 cats were separated into two groups: Group 1 received a collagen matrix (CM) treated with a neuroactive agent or with saline to bridge the spinal cord stumps and an omental transposition which was placed on the dorsal surface of the matrix; Group 2 received spinal cord transection only. Two cats received no spinal cord transection. After 90 days, all animals were killed and their brains and spinal cords were removed for immunohistochemical examination. Two weeks prior to sacrifice, spinal cord blood flows (SCBF) were measured and the retrograde axonal tracer Fluoro-Gold was injected below the transection site. Results show that omental transposition to the CM bridge in Group 1 animals increased SCBF an average 59% (assessed by clamping the omental blood supply to the cord). Examination of the brain 90 days after cord transection revealed Fluoro-Gold accumulation in the cytoplasm and processes of neurons located in the brainstem, midbrain, and diencephalic region which are known to contribute pathways to the spinal cord. Immunohistochemical staining with antibodies against the catecholamine synthesizing enzymes tyrosine hydroxylase and dopamine-B-hydroxylase, indicated that only Group I treated cats developed dense bundles of dopaminergic and noradrenergic fibers within the CM bridge and distal spinal cord tissue. These fibers were seen to extend 90 mm below the transection site. In addition, the synaptogenic marker synaptophysin (SYN) was observed in association with dopaminergic and noradrenergic fibers distal to the collagen matrix bridge, an indication that synaptic remodelling (regeneration) by previously denervated supraspinal axons may have occurred. Immunostaining for glial fibrillary acidic protein (GFAP) showed little to none reactive astrocytosis near the transection site of cats treated with the CM and omentum transposition (Group 1). No catecholaminergic fibers or SYN expression below the transection site were observed in Group 2 treated cats. Group 2 treated cats also showed dense immunostaining of GFAP near the transection site indicating significant astrocytic proliferation. These findings indicate that following complete spinal cord transection in cats and reconstruction with a treated collagen matrix and omental transposition, disconnected supraspinal fibers have the ability to regenerate for long anatomic distances and seemingly engage in synaptic remodelling with distal target tissue.


Living Donor Liver Transplantation vs. Split Liver Transplantation Using Left Lateral Segment Grafts in Pediatric Recipients: An Analysis of the UNOS Database.
Split and LDLT in pediatric patients have the potential to decrease wait times and waitlist mortality. Using UNOS-STAR data, we compared outcomes of pediatric patients undergoing LDLT and SLT using LLS grafts. The baseline characteristics and post-operative outcomes were compared between groups. Actuarial graft and patient survival were analyzed with Kaplan-Meier curves. Between 2010 and 2019, 911 pediatric LT were included in the analysis (LD graft group, n = 508, split graft group, n = 403). LD graft recipients spent more time on the waitlist vs. the split graft group (60 (22-138) days vs. 46 (16-108) days; p = 0.007). LD recipients had a lower rate of graft failure, found in 9.8% of patients compared with 14.6% in the split graft group (p = 0.02). HAT was the most common graft failure cause, with similar rates. Graft and patient survival at 1-, 3-, and 5-years was comparable between LDLT and SLT. In subgroup analyses, patients with biliary atresia, those ≤10 kg or ≤10 years old receiving an LD graft showed improved graft survival. In conclusion, LDLT is associated with a lower rate of graft failure in pediatric patients. The use of LLS regardless of the type of donor is a safe way to facilitate access to transplantation to pediatric patients with acceptable short and long-term outcomes.


Prevention of F-actin assembly switches the response to SCF from chemotaxis to degranulation in human mast cells.
Following antigen/IgE-mediated aggregation of high affinity IgE-receptors (FcεRI), mast cells (MCs) degranulate and release inflammatory mediators leading to the induction of allergic reactions including anaphylaxis. Migration of MCs to resident tissues and sites of inflammation is regulated by tissue chemotactic factors such as stem cell factor (SCF (KIT ligand)). Despite inducing similar early signaling events to antigen, chemotactic factors, including SCF, produce minimal degranulation in the absence of other stimuli. We therefore investigated whether processes regulating MC chemotaxis are rate limiting for MC mediator release. To investigate this issue, we disrupted actin polymerization, a requirement for MC chemotaxis, with latrunculin B and cytochalasin B, then examined chemotaxis and mediator release in human (hu)MCs induced by antigen or SCF. As expected, such disruption minimally affected early signaling pathways, but attenuated SCF-induced human mast cell chemotaxis. In contrast, SCF, in the absence of other stimuli, induced substantial degranulation in a concentration-dependent manner following actin disassembly. It also moderately enhanced antigen-mediated human mast cell degranulation which was further enhanced in the presence of SCF. These observations suggest that processes regulating cell migration limit MC degranulation as a consequence of cytoskeletal reorganization.


Using domain adaptation for classification of healthy and disease conditions from mobile-captured images of standard 12-lead electrocardiograms.
12-lead electrocardiogram (ECG) recordings can be collected in any clinic and the interpretation is performed by a clinician. Modern machine learning tools may make them automatable. However, a large fraction of 12-lead ECG data is still available in printed paper or image only and comes in various formats. To digitize the data, smartphone cameras can be used. Nevertheless, this approach may introduce various artifacts and occlusions into the obtained images. Here we overcome the challenges of automating 12-lead ECG analysis using mobile-captured images and a deep neural network that is trained using a domain adversarial approach. The net achieved an average 0.91 receiver operating characteristic curve on tested images captured by a mobile device. Assessment on image from unseen 12-lead ECG formats that the network was not trained on achieved high accuracy. We further show that the network accuracy can be improved by including a small number of unlabeled samples from unknown formats in the training data. Finally, our models also achieve high accuracy using signals as input rather than images. Using a domain adaptation approach, we successfully classified cardiac conditions on images acquired by a mobile device and showed the generalizability of the classification using various unseen image formats.


Risk Factors Associated With Failure to Reach Minimal Clinically Important Difference After Correction Surgery in Patients With Degenerative Lumbar Scoliosis.
A retrospective study. The aim of this study was to evaluate the factors affecting health-related quality of life (HRQOL) after surgery in patients with degenerative lumbar scoliosis (DLS) by minimum clinically important difference (MCID). MCID has been introduced in the adult spinal deformity to quantify the absolute minimum change that can be considered a success. There are limited data available to identify factors affecting reaching MCID after DLS surgery. This study reviewed a cohort of 123 DLS patients after correction surgery and with a minimum 2-year follow-up (FU). Inclusion criteria included age ≥40 and minimum five vertebrae fused and the availability of Scoliosis Research Society (SRS)-22 scores and radiographic data at baseline (BL) and FU. Using a multivariate analysis, two groups were compared to identify possible risk factors: those who reached MCID in the all four SRS domains (N = 65) at the last FU and those who missed MCID (N = 58). At baseline, patients differed significantly from matched normative data in all SRS-22 domains. The baseline HRQOL was comparable in reached MCID and missed MCID group patients (P > 0.05). The HRQOL scores at FU were significantly higher than those at baseline. Of 123 included patients, 77.2% (N = 95), 72.4% (N = 89), 76.4% (N = 94), and 89.4% (N = 110) reached MCID in SRS pain, activity, appearance, and mental domain, respectively. Pelvic incidence (PI) >55°, lumbar lordosis (LL) loss >4.65°, coronal imbalance at FU, sagittal vertical axis (SVA) at FU >80 mm, and presence of proximal junctional kyphosis (PJK) and distal junctional problem (DJP) had negative effects on the recovery process. Factors affecting reaching MCID after surgery for DLS were higher PI, LL loss, coronal imbalance, severe sagittal imbalance, and the occurrence of PJK and DJP. 4.


Identification and functional analysis of cation-efflux transporter 1 from Brassica juncea L.
Brassica juncea behaves as a moderate-level accumulator of various heavy metal ions and is frequently used for remediation. To investigate the roles of metal ion transporters in B. juncea, a cation-efflux family gene, BjCET1, was cloned and functionally characterized. BjCET1 contains 382 amino acid residues, including a signature motif of the cation diffusion facilitator protein family, six classic trans-membrane-spanning structures and a cation-efflux domain. A phylogenetic analysis showed that BjCET1 has a high similarity level with metal tolerance proteins from other Brassica plants, indicating that this protein family is highly conserved in Brassica. BjCET1 expression significantly increased at very early stages during both cadmium and zinc treatments. Green fluorescence detection in transgenic tobacco leaves revealed that BjCET1 is a plasma membrane-localized protein. The heterologous expression of BjCET1 in a yeast mutant increased the heavy-metal tolerance and decreased the cadmium or zinc accumulations in yeast cells, suggesting that BjCET1 is a metal ion transporter. The constitutive expression of BjCET1 rescued the heavy-metal tolerance capability of transgenic tobacco plants. The data suggest that BjCET1 is a membrane-localized efflux transporter that plays essential roles in heavy metal ion homeostasis and hyper-accumulation.


PIWI-interacting RNAs (piRNAs) - a mouse testis perspective.
Over the past decade, PIWI-interacting RNAs (piRNAs) have emerged as the most intriguing class of small RNAs. Almost every aspect of piRNA biology defies established rules of the RNA interference world while the scope of piRNA functional potential spans from transcriptional gene silencing to genome defense to transgenerational epigenetic phenomena. This review will focus on the genomic origins, biogenesis, and function of piRNAs in the mouse testis - an exceptionally robust experimental system amenable to genetic, cell-biological, molecular, and biochemical studies. Aided and frequently guided by knowledge obtained in insect, worm, and fish germ cells, mouse spermatogenesis has emerged as the primary model in understanding the role of this conserved pathway in mammals.


Use of cigarettes and heated tobacco products during pregnancy and maternal-fetal outcomes: a retrospective, monocentric study.
To compare the effects of using heated tobacco products (HTP) or traditional cigarettes (C) on maternal and neonatal outcomes. This is a retrospective, monocentric study conducted at San Marco Hospital from July 2021 to July 2022. We compared a cohort of pregnant patients who smoked HTP (HS), with pregnant women smoking cigarettes (CS), ex-smoker (ES) and non-smoker (NS) pregnant women. Biochemistry, ultrasound, and neonatal evaluations were performed. In total, 642 women were enrolled, of which 270 were NS, 114 were ES, 120 were CS, and 138 were HS. CS had the greatest weight gain and had more difficulty getting pregnant. Smokers and ES experienced more frequently threats of preterm labor, miscarriages, temporary hypertensive spikes, and higher rates of cesarean sections. Preterm delivery was more associated with CS and HS groups. CS and HS had lower awareness of the risks to which the mother and the fetus are exposed. CS were more likely to be depressed and anxious. Biochemical parameters did not show significant differences between the groups. CS had the greatest difference in days between the gestational age calculated based on the last menstrual period and the one based on the actual ultrasound age. The average percentile newborn weight range of CS was lower, as well as the mean 1st minute and the 5th minute Apgar scores. The comparison of the data obtained between CS and HS underlines the greater danger of C. Nevertheless, we do not recommend HTP because the maternal-fetal outcomes are not superimposable to the NS outcomes.


New operation for "krummerik" (penile curvature).
A corrective operation for penile curvature using plication of the tunica albuginea on the opposite side of the angulation is described. The operation is fast, easy to perform, and complications are rare.


The effect of neutrophil extracellular traps in venous thrombosis.
Neutrophil extracellular traps (NETs) as special release products of neutrophils have received extensive attention. They are composed of decondensed chromatin and coated with nucleoproteins, including histones and some granulosa proteins. NETs can form a network structure to effectively capture and eliminate pathogens and prevent their spread. Not only that, recent studies have shown that NETs also play an important role in venous thrombosis. This review provides the most important updated evidence regarding the mechanism of NETs formation and the role of NETs in the process of venous thrombosis. The potential prophylactic and therapeutic value of NETs in venous thrombotic disease will also be discussed.


Comparative effectiveness of cardiovascular, renal and safety outcomes of second-line antidiabetic drugs use in people with type 2 diabetes: A systematic review and network meta-analysis of randomised controlled trials.
To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes. MEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second-line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non-cardiovascular adverse events. Risk ratios (RRs) and corresponding confidence intervals (CI) or credible intervals (CrI) were reported within pairwise and network meta-analysis. The quality of evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Number needed to treat (NNT) and number needed (NNH) to harm were calculated at 5 years using incidence rates and RRs. PROSPERO (CRD42020168322). We included 38 trials from seven classes of glucose-lowering therapies. Both sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) showed moderate to high certainty in reducing risk of 3-point major adverse cardiovascular events, 3P-MACE (network estimates: SGLT2i [RR 0.90; 95% CrI 0.84-0.96; NNT, 59], GLP1RA [RR 0.88; 95% CrI 0.83-0.93; NNT, 50]), cardiovascular death, all-cause mortality, renal composite outcome and macroalbuminuria. SGLT2i also showed high certainty in reducing risk of hospitalization for heart failure (hHF), ESRD, acute kidney injury, doubling in serum creatinine and decline in eGFR. GLP1RA were associated with lower risk of stroke (high certainty) while glitazone use was associated with an increased risk of hHF (very low certainty). The risk of developing ESRD was lower with the use of sulphonylureas (low certainty). For adverse events, sulphonylureas and insulin were associated with increased hypoglycaemic events (very low to low certainty), while GLP1RA increased the risk of gastrointestinal side effects leading to treatment discontinuation (low certainty). DPP-4i increased risk of acute pancreatitis (low certainty). SGLT2i were associated with increased risk of genital infection, volume depletion (high certainty), amputation and ketoacidosis (moderate certainty). Risk of fracture was increased with the use of glitazones (moderate certainty). SGLT2i and GLP1RA were associated with lower risk for different cardiorenal end points, when used as an adjunct to metformin in people with type 2 diabetes. Additionally, SGLT2i demonstrated benefits in reducing risk for surrogate end points in kidney disease progression. Safety outcomes differ among the available pharmacotherapies.


Determining patients' suitability for thrombolysis: coronary care nurses' agreement with an expert cardiological 'gold standard' as assessed by clinical and electrocardiographic 'vignettes'.
Thrombolytic therapy is an established treatment for acute myocardial infarction, the benefits of which are time-dependent. Coronary care nurses are often the first professionals to assess patients with suspected myocardial infarction on hospital admission, and there are a number of reports of nurseled practices for immediate assessment and 'cardiac triage'. To assess coronary care nurses' ability to determine patients' suitability for thrombolysis as judged by an expert cardiological 'gold standard'. Ten coronary care units in the Northern and Yorkshire region of England were sent packs comprising 10 sets of 10 'vignettes' and accompanying electrocardiograms together with a questionnaire regarding treatment decisions. An expert 'gold standard' for correct responses to the questionnaire was derived following independent assessment of the vignettes by three nurse specialists and three consultant cardiologists. Respondents' treatment decisions were subsequently compared with the 'gold standard'. Of 42 (42%) completed sets of questionnaires returned for analysis, 37 (87%) of respondents indicated management decisions in absolute agreement with the 'gold standard'. Where there was not absolute agreement, most treatment decisions were acceptable as safe practice. The majority of nurses indicated safe and appropriate management decisions. These limited data provide further support for ongoing developments of nurse-initiated thrombolysis, although there is a need for further, larger trials to determine the safety and efficacy of such an approach to patient care.


Management Patterns for Benign Prostatic Hyperplasia: Impact of a Patient Decision Aid.
Decision aids aimed at men with benign prostatic hyperplasia used in clinical trials have decreased the use of procedures and affected elements of decisional quality. We employed an online, interactive decision aid for men with benign prostatic hyperplasia as a routine part of care with a urologist and tracked subsequent treatment choice. We further evaluated the role of patient preferences on treatment selection. Men scheduled for a new patient visit with a urologist for benign prostatic hyperplasia at a single tertiary care center were invited to use a decision aid prior to their visit. We compared treatment patterns in men who used the decision aid to a usual care group identified prior to the decision aid's introduction. Latent class analysis identified clusters of patients by their treatment preferences, which were then compared to their treatment choice. The rate of procedures in the decision aid group was significantly lower than in the usual care group (6% vs 15%; p=0.0250), matching the rates reporting a procedure as their preferred treatment choice in the post-consult questionnaire (5% vs 15%; p=0.0082). Of the patients in our project 36% had never tried an alpha blocker prior to their urology consult. Latent class analysis found 2 clusters of patient preferences but without a significant association with final treatment selection. Use of a decision aid was associated with a significant decrease in procedural management of benign prostatic hyperplasia. A high proportion of patients were evaluated by urologists without exhausting primary care management options.


CineECG: A novel method to image the average activation sequence in the heart from the 12-lead ECG.
The standard 12-lead electrocardiogram (ECG) is a diagnostic tool to asses cardiac electrical activity. The vectorcardiogram is a related tool that represents that activity as the direction of a vector. In this work we investigate CineECG, a new 12-lead ECG based analysis method designed to directly estimate the average cardiac anatomical location of activation over time. We describe CineECG calculation and a novel comparison parameter, the average isochrone position (AIP). In a model study, fourteen different activation sequences were simulated and corresponding 12-lead ECGs were computed. The CineECG was compared to AIP in terms of location and direction. In addition, 67-lead body surface potential maps from ten patients were used to study the sensitivity of CineECG to electrode mispositioning and anatomical model selection. Epicardial activation maps from four patients were used for further evaluation. The average distance between CineECG and AIP across the fourteen sequences was 23.7 ± 2.4 mm, with significantly better agreement in the terminal (27.3 ± 5.7 mm) versus the initial QRS segment (34.2 ± 6.1 mm). Up to four cm variation in electrode positioning produced an average distance of 6.5 ± 4.5 mm between CineECG trajectories, while substituting a generic heart/torso model for a patient-specific one produced an average difference of 6.1 ± 4.8 mm. Dominant epicardial activation map features were recovered. Qualitatively, CineECG captured significant features of activation sequences and was robust to electrode misplacement. CineECG provides a realistic representation of the average cardiac activation in normal and diseased hearts. In particular, the terminal segment of the CineECG might be useful to detect pathology.


Hybrid zeolite-based ion-exchange and sulfur oxidizing denitrification for advanced slaughterhouse wastewater treatment.
The discharge of slaughterhouse wastewater (SWW) is increasing and its wastewater has to be treated thoroughly to avoid the eutrophication. The hybrid zeolite-based ion-exchange and sulfur autotrophic denitrification (IX-AD) process was developed to advanced treat SWW after traditional secondary biological process. Compared with traditional sulfur oxidizing denitrification (SOD), this study found that IX-AD column showed: (1) stronger ability to resist NO3- pollution load, (2) lower SO42- productivity, and (3) higher microbial diversity and richness. Liaoning zeolites addition guaranteed not only the standard discharge of NH4+-N, but also the denitrification performance and effluent TN. Especially, when the ahead secondary biological treatment process run at the ultra-high load, NO3--N removal efficiency for IX-AD column was still ~100%, whereas only 64.2% for control SOD column. The corresponding average effluent TN concentrations for IX-AD and SOD columns were 5.89 and 65.55 mg/L, respectively. Therefore, IX-AD is a promising technology for advanced SWW treatment and should be widely researched and popularized.


Clinical characteristics of patients with COVID-19 harboring detectable intracellular SARS-CoV-2 RNA in peripheral blood cells.
Although SARS-CoV-2 RNAemia has been reported to strongly impact patients with severe COVID-19, the clinical characteristics of patients with COVID-19 harboring detectable intracellular SARS-CoV-2 RNA remain unknown. We included adult patients who had developed COVID-19 between February and September 2020. Total white blood cells derived from the buffy coat of peripheral whole blood were used to detect SARS-CoV-2 RNA using the Illumina COVIDSeq test. We compared the clinical characteristics between patients with and without detected viral RNA (detected and undetected groups). Among the 390 patients included, 17 harbored SARS-CoV-2 RNA in peripheral white blood cells. All 17 patients required oxygen support during the disease course and had higher intensive care unit admission (52.9% vs 28.9%, P = 0.035), mortality (17.7% vs 3.5%, P = 0.004), kidney dysfunction (severe, 23.5% vs 6.4%, P = 0.029), and corticosteroid treatment rates (76.5% vs 46.5%, P = 0.016) than those of patients in the undetected group. We propose that patients with circulating intracellular SARS-CoV-2 RNA in the peripheral blood exhibited the most severe disease course.


Luminance Thresholds and Their Correlation With Retinal Structure in X-Linked Retinoschisis.
To provide a comprehensive analysis of light- and dark-adapted luminance thresholds and their associations with retinal structure in X-linked retinoschisis (XLRS). Nine subjects with XLRS and 10 visually-normal individuals participated. Threshold was measured at 15 locations along the horizontal meridian of the visual field at several adaptation levels (5 × 10-5 to 50 cd/m2) after dark-adaptation. The relationship between threshold and adaptation level across the field was described using a standard "threshold-versus-illuminance" model. Optical coherence tomography images were obtained and segmented to quantify outer nuclear layer (ONL+) and outer segment (OS+) thickness. A linear structure-function model was used to describe the relationship between threshold and the product of ONL+ and OS+ thickness. For peripheral field measurements, thresholds were generally normal for most subjects with XLRS. All subjects had perifoveal and parafoveal threshold elevations under dark-adapted and high illuminance conditions, with thresholds at moderate illuminances being closer to normal. For foveal measurements, seven of nine subjects with XLRS had normal dark-adapted thresholds, and all had abnormally elevated high illuminance thresholds. Threshold-versus-illuminance curves in the fovea, parafovea, and perifovea were abnormally steep for subjects with XLRS, appearing similar to the normal peripheral field shape. Under both dark- and light-adapted conditions, threshold was predicted by ONL+ × OS+ thickness at nearly all field locations. Threshold elevation in XLRS is complex, depending on both the adaptation level and the visual field location. The pattern of threshold-versus-illuminance suggests that macular function in XLRS is similar to the periphery of controls.


Impact of Residual Lesion Severity on Neurodevelopmental Outcomes Following Congenital Heart Surgery in Infancy and Childhood.
Children with congenital heart disease are at increased risk of neurodevelopmental delay throughout their lifespan. This risk is exacerbated following congenital heart surgery (CHS) in infancy. However, there are few modifiable risk factors for postoperative neurodevelopmental delay. In this study, we assessed the Residual Lesion Score (RLS), a quality assessment metric that evaluates residual lesion severity following CHS, as a predictor of neurodevelopmental delay. This was a single-center, retrospective review of patients who underwent CHS from 01/2011 to 03/2021 and post-discharge neurodevelopmental evaluation from 12 to 42 months of age using the Bayley Scales of Infant Development, 3rd Edition (BSID-III). RLS was assigned per published criteria: RLS 1, no residua; RLS 2, minor residua; and RLS 3, major residua or pre-discharge reintervention. Associations between RLS and BSID-III scores, as well as trends in neurodevelopmental outcomes over time, were evaluated. Of 517 patients with median age at neurodevelopmental testing of 20.0 (IQR 18.0-22.7) months, 304 (58.8%), 146 (28.2%), and 67 (13.0%) were RLS 1, 2, and 3, respectively. RLS 3 patients had significantly lower scaled scores in the cognitive, receptive, and expressive communication, and fine and gross motor domains, compared with RLS 1 patients. Multivariable models accounted for 21.5%-31.5% of the variation in the scaled scores, with RLS explaining 1.4-7.3% of the variation. In a subgroup analysis, RLS 3 patients demonstrated relatively fewer gains in cognitive, expressive communication, and gross motor scores over time (all p < 0.05). In conclusion, RLS 3 patients are at increased risk for neurodevelopmental delay, warranting closer follow-up and greater developmental support for cognitive, language, and motor skills soon after surgery.


Early assessment of ventricular synchronization and function after left bundle-branch-area pacing with right bundle-branch block.
To evaluate ventricular synchronization and function in patients with right bundle-branch block after left bundle-branch-area pacing (LBBAP) by echocardiography. Forty patients who successfully received LBBAP were selected and divided into the right bundle-branch block group (RBBB group) and the non-RBBB group by pre-operation ECG. Echocardiography and follow-up were performed 1 month after operation. Interventricular synchronization was evaluated by tissue Doppler (TDI), tissue mitral annular displacement (TMAD), and interventricular mechanical delay. The tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), tricuspid annulus sidewall systolic velocity (TV-s'), left ventricular global ventricular longitudinal strain (GLS), right ventricular free wall longitudinal strain (LS-RV), standard deviation of left ventricular 18 segments peak time difference (SDt-L) and standard deviation of right ventricular free wall 3 segments peak time difference (SDt-R) were applied to evaluate intraventricular synchronization and ventricular function. The difference of displacement peak time of the tricuspid and mitral valves, namely ΔPTTV-MV measured by TMAD, the difference of systolic time to peak of the tricuspid and mitral valves, namely ΔTsTV-MV measured by TDI, were statistically different between the two groups (P < 0.05). Compared with the non-RBBB group, there were no statistically significant differences in the GLS, RVFAC, LS-RV, TAPSE, TV-s', SDt-L, SDt-R (P > 0.05). Echocardiography technology including two-dimensional speckle tracking imaging (2D-STI), TDI, and TMAD can effectively analyze interventricular synchronization, intraventricular synchronization, and ventricular function. Although the movement of the right ventricular myocardium in the RBBB group was slightly later than that of the left ventricular myocardium after LBBAP, LBBAP could still be applied in RBBB patients with pacing indication.


What Does the APP Family Do in the Brain?
Amyloid-β precursor protein (APP) is overshadowed by its degradation product, the Alzheimer protein Aβ. Lee et al. now find a role for the APP family in neuronal excitability, synaptic plasticity, and memory in adulthood, despite the lack of requirement for neuronal survival.


A higher correlation of the antibody activities against the calcium-dependent epitopes of desmoglein 3 quantified by ethylenediaminetetraacetic acid-treated enzyme-linked immunosorbent assay with clinical disease activities of pemphigus vulgaris.
Nonpathogenic anti-desmoglein (Dsg) 3 antibodies can be found in pemphigus vulgaris (PV) patients' sera. Previously, ethylenediaminetetraacetic acid (EDTA)-treated enzyme-linked immunosorbent assay (ELISA) was found to detect only nonpathogenic anti-Dsg3 antibodies against the non-calcium (Ca(2+))-dependent epitopes. We examined whether the calculated anti-Dsg3 antibody titer for Ca(2+)-dependent epitopes, using the conventional and EDTA-treated ELISAs, correlated better with the disease activity of PV. We analyzed 123 serum samples from 19 PV patients. Of these samples, there were 52 samples from 15 PV patients obtained in asymptomatic phases. The difference between conventional Dsg3 ELISA index and EDTA-treated Dsg3 ELISA index was calculated as the anti-Dsg3 antibody activity for Ca(2+)-dependent conformational epitopes (conformational Dsg3 ELISA index). We analyzed the correlation between Dsg3 ELISA index values and the pemphigus disease area index (PDAI). Moreover, we examined whether the conformational Dsg3 ELISA index fluctuated in parallel with the disease activity during clinical courses of 6 PV patients. We evaluated the pathogenicity of anti-Dsg3 antibodies detected in remission phases using a dissociation assay. The conventional Dsg3 ELISA index showed a high positive rate in the asymptomatic phase of PV. By contrast, the conformational Dsg3 ELISA index showed a much closer correlation to the disease activity when monitored in individual cases. Nonpathogenic anti-Dsg3 antibodies were detected in these cases. The conformational Dsg3 ELISA index reflected the pathogenicity of anti-Dsg3 antibodies more accurately than the conventional Dsg3 ELISA index. Using both conventional and EDTA-treated ELISAs would be useful in monitoring the disease activity of PV.


Studying the effect of weather conditions on daily crash counts using a discrete time-series model.
In previous research, significant effects of weather conditions on car crashes have been found. However, most studies use monthly or yearly data and only few studies are available analyzing the impact of weather conditions on daily car crash counts. Furthermore, the studies that are available on a daily level do not explicitly model the data in a time-series context, hereby ignoring the temporal serial correlation that may be present in the data. In this paper, we introduce an integer autoregressive model for modelling count data with time interdependencies. The model is applied to daily car crash data, metereological data and traffic exposure data from the Netherlands aiming at examining the risk impact of weather conditions on the observed counts. The results show that several assumptions related to the effect of weather conditions on crash counts are found to be significant in the data and that if serial temporal correlation is not accounted for in the model, this may produce biased results.


Inhaled salbutamol and doping control: effects of dose on urine concentrations.
The present study was designed to examine the dose-response relationship of inhaled salbutamol and its concentration in the urine while resting at various times after inhalation, and to compare these values against the current World Anti-Doping Code limits. An interventional, repeated-measures design. Sport Medicine Clinic, University of British Columbia (Vancouver, Canada). Eight healthy, nonasthmatic males participated in this study (age = 28 +/- 6 years, height = 179.4 +/- 5.1 cm, and weight = 77.4 +/- 5.4 kg). Administration of three different doses of inhaled salbutamol (800, 400, and 200 microg) in a randomized fashion separated by at least 72 hours. Urine concentration of nonsulphated salbutamol Urine concentrations were highly variable between subjects and increased as dose increased, with a significant difference noted between 800 and 200 microg at 30, 60, and 120 minutes after inhalation. Urine concentrations of salbutamol peaked at 60 minutes for all doses. No samples exceeded the doping criterion of 1000 ng/mL, and the maximum value observed was 904 ng/mL. These results indicate that after inhalation of doses up to 800 microg, urinary concentrations of salbutamol are well below the limits used in doping control.


On the site and mechanism of action of the anti-obesity effects of interleukin-6.
We conducted an experimental study examining the site and mechanism of action of the anti-obesity effect of interleukin-6 (IL-6) in mice and rats. We used dual energy X-ray absorptiometry (DEXA) and computerized tomography to investigate the body composition of mice with knockout of the IL-6 gene and wild-type control mice. Rats were treated with IL-6 or vehicle through intracerebroventricular (ICV) cannulae. Energy expenditure was measured as oxygen consumption by indirect calorimetry in metabolic chambers. Results showed that the mice lacking IL-6 increased in body weight compared with wild-type mice from 6 months of age onward, although there was no marked difference in food intake between the pre-obese IL-6 knockout mice and the wild-type mice. IL-6 given as a single ICV injection to rats stimulated oxygen consumption; whereas, the same doses were ineffective when given peripherally. Chronic ICV IL-6 treatment decreased body weight and fat mass in rodents. Administration of IL-6 may decrease fat mass in mice and rats by stimulating energy expenditure at the CNS level, possibly in the hypothalamus.


Steroid hormones of the octopus self-destruct system.
Among all invertebrates, soft-bodied cephalopods have the largest central nervous systems and the greatest brain-to-body mass ratios, yet unlike other big-brained animals, cephalopods are unusually short lived.1-5 Primates and corvids survive for many decades, but shallow-water octopuses, such as the California two-spot octopus (Octopus bimaculoides), typically live for only 1 year.6,7 Lifespan and reproduction are controlled by the principal neuroendocrine center of the octopus: the optic glands, which are functional analogs to the vertebrate pituitary gland.8-10 After mating, females steadfastly brood their eggs, begin fasting, and undergo rapid physiological decline, featuring repeated self-injury and leading to death.11 Removal of the optic glands completely reverses this life history trajectory,10 but the signaling factors underlying this major life transition are unknown. Here, we characterize the major secretions and steroidogenic pathways of the female optic gland using mass spectrometry techniques. We find that at least three pathways are mobilized to increase synthesis of select sterol hormones after reproduction. One pathway generates pregnane steroids, known in other animals to support reproduction.12-16 Two other pathways produce 7-dehydrocholesterol and bile acid intermediates, neither of which were previously known to be involved in semelparity. Our results provide insight into invertebrate cholesterol pathways and confirm a remarkable unity of steroid hormone biology in life history processes across Bilateria.


Interlaboratory survey of enzymatic analyses. II. Intermediate studies.
A set of six interrelated specimens was analyzed for creatinine, urea, and five enzyme constituents by about 10 laboratories on two occasions. The results from each laboratory were subjected to linear regression analysis and the correlation coefficients, X and Y intercepts, and slopes were calculated. These parameters then were used in various ways to (a) evaluate the composition, linearity and stability of the specimens, (b) assess the analytic precision of each laboratory, (c) assess the accuracy of the laboratories relative to their peer group, and (d) identify systematic differences among peer groups. The results suggest that this technic is a viable approach to the evaluation of laboratory performance in enzymatic analyses.


Type 2 Diabetes: A Risk Factor for Hospital Readmissions and Mortality in Australian Patients With Cirrhosis.
Although there is evidence that type 2 diabetes mellitus (T2D) impacts adversely on liver-related mortality, its influence on hospital readmissions and development of complications in patients with cirrhosis, particularly in alcohol-related cirrhosis (the most common etiological factor among Australian hospital admissions for cirrhosis) has not been well studied. This study aimed to investigate the association between T2D and liver cirrhosis in a population-based cohort of patients admitted for cirrhosis in the state of Queensland, Australia. A retrospective cohort analysis was conducted using data from the Queensland Hospital Admitted Patient Data Collection, which contains information on all hospital episodes of care for patients with liver cirrhosis, and the Death Registry during 2008-2017. We used demographic, clinical data, and socioeconomic characteristics. A total of 8,631 patients were analyzed. A higher proportion of patients with T2D had cryptogenic cirrhosis (42.4% vs. 27.3%, respectively; P < 0.001) or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (13.8% vs. 3.4%, respectively; P < 0.001) and an admission for hepatocellular carcinoma (18.0% vs. 12.2%, respectively; P < 0.001) compared to patients without T2D. Patients with liver cirrhosis with T2D compared to those without T2D had a significantly increased median length of hospital stay (6 [range, 1-11] vs. 5 [range, 1-11] days, respectively; P < 0.001), double the rate of noncirrhosis-related admissions (incidence rate ratios [IRR], 2.03; 95% confidence interval [CI], 1.98-2.07), a 1.35-fold increased rate of cirrhosis-related admissions (IRR, 1.35; 95% CI, 1.30-1.41), and significantly lower survival (P < 0.001). Conclusion: Among hospitalized patients with cirrhosis, the cohort with T2D is at higher risk and may benefit from attention to comorbidities and additional support to reduce readmissions.


Introduction: women, health, and healing in early modern Europe.
Women played substantial roles in health and healing in medieval and early-modern Europe. They have been undercounted in studies that rely upon occupational labels, but when we look at caregiving and bodywork, we can see women providing a broad range of services. Although women often healed in domestic settings, neither female patients nor practitioners should be considered in isolation from larger market forces that shaped men's healing work.


Initial diagnosis of chronic myelogenous leukemia based on quantification of M-BCR status using droplet digital PCR.
Formed from a reciprocal translocation t(9:22)(q34;q11) of genetic material between the long arms of human chromosomes 9 and 22, the constitutively active breakpoint cluster region (BCR) Abelson 1 (ABL) tyrosine kinase BCR-ABL is known to be causative of chronic myelogenous leukemia (CML). In 98% of CML patients harboring the t(9:22)(q34;q11) translocation, known as the Philadelphia chromosome, the chimeric BCR-ABL oncogene is created through cleavage of the BCR gene within its major breakpoint region (M-BCR) and breakage of the ABL gene within a 100-kbp region downstream of exon 2a. Clinical detection of the fused BCR-ABL oncogene currently relies on direct visualization by fluorescence in situ hybridization (FISH), a relatively tedious assay that typically offers a detection limit of ca. 2%. Here, we describe a novel assay that uses droplet digital PCR (ddPCR) technology to reliably measure M-BCR status and the presence of BCR-ABL. When applied to cell-line models of CML, the assay accurately quantifies BCR-ABL frequency to a detection limit of 0.25%. It therefore offers improved specificity relative to FISH, and may allow identification of variant translocation patterns, including derivative chromosome 9 deletions.


Safety and effectiveness of cupric oxide particles for increasing liver copper stores in sheep.
Five groups of four, housed Cheviot ewes (mean live-weight 50 kg) were given single doses of 0, 2.5, 5, 10 or 20 g cupric oxide particles in gelatin capsules while receiving a diet of marginal copper content based on pelleted oats. After 65 days liver copper concentrations had increased curvilinearly in relation to dose and all ewes given 10 or 20 g cupric oxide particles showed increases of at least 13.4 mmol kg-1 dry matter (850 ppm). Liver copper concentrations had generally declined after 85 days but biochemical and histological evidence of copper toxicity was recorded in one ewe which had received 20 g cupric oxide particles. Despite marked variations between individual sheep a dose of 0.1 g kg-1 liveweight (5 g) was considered to be safe and did not induce clinical copper toxicity in five sheep of the susceptible North Ronaldsay breed given the same basal diet.


Optimization of enzyme-mediated peptide bond formation.
Enzyme-catalyzed peptide bond formation requires thorough examination and optimization of each coupling step. In order to identify factors influencing the selectivity between aminolysis and hydrolysis, a systematic study was carried out for the kinetically controlled peptide synthesis. The reaction temperature, the type of C-terminal protecting group, and different organic cosolvents showed little influence on the selectivity. The enzyme, excess nucleophile, pH, N-terminal protecting group, and ionic strength of the solution were identified as major factors controlling the selectivity and, therefore, the yield of the dipeptide synthesis. Under optimized conditions, the selectivity of the chymotrypsin-catalyzed synthesis of PheSer could be increased from 35 to 100%.


Age- and gender-related variations in hematology, clinical biochemistry, and hormones in Spanish fillies and colts.
In order to assess which laboratorial parameters need specific age- and/or gender-related reference values, hematological and biochemical profiles (including hormones) were performed in 205 Spanish foals of 5 groups: A (1-2 months; 20 fillies, 10 colts), B (2-3 months; 24 fillies, 18 colts), C (3-6 months; 25 fillies, 16 colts), D (6-9 months; 20 fillies, 23 colts) and E (9-12 months; 25 fillies, 15 colts). Additionally, 120 adult horses were sampled in order to establish baseline data for this breed in our laboratory. Group E had lower red blood cell number and mean cell volume than B, C and D, and neutrophil count was lower in A. Albumin was lower in A than in D, lactate was higher in B, C and D, CK, AST and K were higher in C. In D and E, cortisol was lower and adrenaline was higher. Urea progressively increases, whereas ALP decreases with age. Packed cell volume was higher in fillies of group A, creatinine was higher in colts of group E and fillies of groups B, C, and D had higher aldosterone than colts. In comparison to Spanish adult horses, mean cell volume, albumin, urea, CK, AST, LDH, and ALP requires specific ranges for foals.


A ten-color tube with dried antibody reagents for the screening of hematological malignancies.
The workflow in clinical flow cytometry laboratories must constantly be reviewed to develop technical procedures that improve quality and productivity and reduce costs. Using the Beckman Coulter dry coating technology, we customized a ten-color tube with dried antibody reagents, designated the Duraclone screening tube (DST), for screening hematological malignancies. Here, we compared the applicability, clinical and numerical equivalence, and cost and time required for the technical procedures between the liquid reagents and the DST. The DST contains CD4 + Kappa-FITC, CD8 + Lambda-PE, CD3 + CD14-ECD, CD33-PE-Cy5.5, CD20 + CD56-PE-Cy7, CD34-APC, CD19-APC-AlexaFluor700, CD10-APC-AlexaFluor750, CD5-Pacific Blue, and CD45-Krome Orange. We evaluated 20 bone marrow samples, 13 peripheral blood samples, 6 lymph node biopsy samples, 5 fine-needle aspirate samples, 5 cerebrospinal fluid samples, and 1 pleural fluid sample. The DST was useful for more than 60% of our samples. It was able to enumerate the majority of the populations in all types of samples with a statistically acceptable correlation with the liquid reagents. The use of the DST translated into significant time and cost savings of 15.8% and 12.3%, respectively, compared with the use of the liquid reagent. The cost was reduced by $14.36 per sample. The DST is an efficient solution for screening hematological malignancies with improved quality, productivity, standardization, and sustainability. These improvements could benefit patients by providing faster diagnoses using a higher quality and lower cost reagent.


Thyroid function and morphology in patients affected by Williams syndrome.
To evaluate the prevalence of abnormalities of thyroid function and morphology in a cohort of patients with Williams syndrome (WS). Serum concentrations of free-T3, free-T4, TSH, thyroperoxidase antibodies (TPOA) and thyroglobulin antibodies (TgA), as well as ultrasonographic data, of 20 patients with WS (12 females and eight males), aged 1.7-34.9 years, were evaluated. Three cases (15%) of subclinical hypothyroidism were identified. Overt hypothyroidism was diagnosed in two cases (10%). Thyroid antibodies were negative in all patients. Fourteen patients (70%) showed thyroid hypoplasia involving the entire gland. In these patients, the left thyroid lobe appeared usually, but not significantly, reduced compared with the right thyroid lobe. One patient (5%) showed thyroid hemiagenesis. Only five patients (25%) showed a thyroid with normal volume, and of these five, one patient showed marked thyroid hypoplasia of the left lobe. In all WS patients with diagnosis of subclinical or overt hypothyroidism, thyroid hypoplasia was detected. No cases of subclinical or overt hypothyroidism were found in WS with normal thyroid volume. This study confirms the presence of alterations of thyroid function in WS and also suggests the frequent occurrence of abnormalities of thyroid morphology in these patients. Patients with WS should be monitored for thyroid function and a thyroid ultrasound screening should be considered, especially in those patients with changes in thyroid function.


Brain Signatures During Reward Anticipation Predict Persistent Attention-Deficit/Hyperactivity Disorder Symptoms.
Children experiencing attention-deficit/hyperactivity disorder (ADHD) symptoms may retain symptoms into adulthood, but little is known about the underlying mechanism. To identify biomarkers of persistent ADHD symptom development, we carried out whole-brain analyses of neuroimaging data during the anticipation phase of the Monetary-Incentive-Delay (MID) task in 1,368 adolescents recruited by the IMAGEN Consortium at age 14 years, whose behavioral measurements were followed up longitudinally at age 16. In particular, we focused on comparing individuals with persistent high ADHD symptoms at both ages 14 and 16 years to unaffected control individuals, but also exploring which individuals demonstrating symptom remission (with high ADHD symptoms at age 14 but much reduced at age 16). We identified reduced activations in the medial frontal cortex and the thalamus during reward anticipation as neuro-biomarkers for persistent ADHD symptoms across time. The genetic relevance of the above findings was further supported by the associations of the polygenic risk scores of ADHD with both the persistent and control status and the activations of both brain regions. Furthermore, in an exploratory analysis, the thalamic activation might also help to distinguish persons with persistent ADHD from those remitted in both an exploratory sample (odds ratio = 9.43, p < .001) and an independent generalization sample (odds ratio = 4.64, p = .003). Using a well-established and widely applied functional magnetic resonance imaging task, we have identified neural biomarkers that could discriminate ADHD symptoms that persist throughout adolescence from controls and potentially those likely to remit during adolescent development as well.


Determination of polychlorinated biphenyls in biosolids using continuous ultrasound-assisted pressurized solvent extraction and gas chromatography-mass spectrometry.
An efficient continuous pressurized solvent extraction (PSE) method assisted by ultrasound energy was developed for the extraction of polychlorinated biphenyls (PCBs) from biosolids. Analytes were determined in the extracts by gas chromatography-mass spectrometry in selected ion monitoring (SIM) mode. A screening-type experimental design pointing to dynamic extraction time as the only significant variable in the extraction process was carried out to optimize PCB extraction from the biosolids. Final selected conditions for PSE were extraction temperature, 50 degrees C; static extraction time, 0 min; and dynamic extraction time, 30 min. Recovery of the PSE method was 73%, which was significantly improved (103%) when PSE was assisted with 30-min ultrasound (US-PSE). Precision of the overall method, expressed as relative standard deviation, was 3.6% and the detection limit was 0.037 mg/kg. The method was applied to the determination of PCBs in biosolids from different water treatment plants from central Chile.


Relationship between effort sense and ventilatory response to intense exercise performed with reduced muscle glycogen.
The purpose of the present study was to examine the effects of muscle glycogen reduction on surface electromyogram (EMG) activity and effort sense and ventilatory responses to intense exercise (IE). Eight subjects performed an IE test in which IE [100-105% of peak O(2) uptake ([Formula: see text]), 2 min] was repeated three times (IE(1st), IE(2nd) and IE(3rd)) at 100-120-min intervals. Each interval consisted of 20-min passive recovery, 40-min submaximal exercise at ventilatory threshold intensity (51.5 ± 2.7% of [Formula: see text]), and a further resting recovery for 40-60 min. Blood pH during IE and subsequent 20-min recovery was significantly higher in the IE(3rd) than in the IE(1st) (P < 0.05). Effort sense of legs during IE was significantly higher in the IE(3rd) than in the IE(1st) and IE(2nd). Integrated EMG (IEMG) measured in the vastus lateralis during IE was significantly lower in the IE(3rd) than in the IE(1st). In contrast, mean power frequency of the EMG was significantly higher in the IE(2nd) and the IE(3rd) than in the IE(1st). Ventilation ([Formula: see text]) in the IE(3rd) was significantly higher than that in the IE(1st) during IE and the first 60 s after the end of IE. These results suggest that ventilatory response to IE is independent of metabolic acidosis and at least partly associated with effort sense elicited by recruitment of type II fibers.


Insight into the neuroendocrine basis of signal evolution: a case study in foot-flagging frogs.
A hallmark of sexual selection is the evolution of elaborate male sexual signals. Yet, how the physiology of an animal changes to support a new or modified signal is a question that has remained largely unanswered. Androgens are important in regulating male reproductive behavior, therefore, selection for particular signals may drive the evolution of increased androgenic sensitivity in the neuro-motor systems underlying their production. Studies of the neuroendocrine mechanisms of anuran sexual signaling provide evidence to support this idea. Here, we highlight two such cases: first, a large body of work in Xenopus frogs demonstrates that sexually dimorphic androgen receptor (AR) expression in the laryngeal nerves and muscles underlies sexually dimorphic vocal behavior, and second, our own work showing that the recent evolution of a hind limb signal (known as the "foot flag") in Staurois parvus is accompanied by a dramatic increase in androgenic sensitivity of the thigh muscles that control limb movement. Together, these examples illustrate that the evolutionary modification or gain of a sexual signal is linked with a novel pattern of AR expression in the tissues that support it. We suggest that such co-evolution of AR expression and sex-specific or species-specific signaling behavior exists across vertebrates.


TreeToReads - a pipeline for simulating raw reads from phylogenies.
Using phylogenomic analysis tools for tracking pathogens has become standard practice in academia, public health agencies, and large industries. Using the same raw read genomic data as input, there are several different approaches being used to infer phylogenetic tree. These include many different SNP pipelines, wgMLST approaches, k-mer algorithms, whole genome alignment and others; each of these has advantages and disadvantages, some have been extensively validated, some are faster, some have higher resolution. A few of these analysis approaches are well-integrated into the regulatory process of US Federal agencies (e.g. the FDA's SNP pipeline for tracking foodborne pathogens). However, despite extensive validation on benchmark datasets and comparison with other pipelines, we lack methods for fully exploring the effects of multiple parameter values in each pipeline that can potentially have an effect on whether the correct phylogenetic tree is recovered. To resolve this problem, we offer a program, TreeToReads, which can generate raw read data from mutated genomes simulated under a known phylogeny. This simulation pipeline allows direct comparisons of simulated and observed data in a controlled environment. At each step of these simulations, researchers can vary parameters of interest (e.g., input tree topology, amount of sequence divergence, rate of indels, read coverage, distance of reference genome, etc) to assess the effects of various parameter values on correctly calling SNPs and reconstructing an accurate tree. Such critical assessments of the accuracy and robustness of analytical pipelines are essential to progress in both research and applied settings.


Effect of anticoagulants on the measurement of pregnancy-associated plasma protein-A (PAPP-A).
The level of pregnancy-associated plasma protein-A (PAPP-A) in blood measured by rocket immunoelectrophoresis is affected by the addition of anticoagulants. When compared with levels in serum, those in heparin and sequestrene plasmas were higher, while those in sodium citrate, acid citrate dextrose and fluoride oxalate plasmas were lower. Similar results were obtained when the anticoagulants were added to serum and the effect on the measured level was dose-dependent within limits. Addition of anticoagulants to serum affected the mobility of PAPP-A in crossed immunoelectrophoresis, but this was not necessarily in keeping with the effect on rocket height. Addition of sodium chloride to serum did not influence the measured levels of PAPP-A.


Two-dimensional 1H NMR study of two cyclobutane type photodimers of thymidylyl-(3'----5')-thymidine.
2D NMR spectroscopy and J coupling constant analysis are applied to resolve the structure of two photoproducts of thymidylyl-(3'----5')-thymidine. These products are cyclobutane type thymine dimers possessing the cis-syn (the predominant one) and trans-syn geometry. The cis-syn is formed in an ANTI-ANTI conformation about the N-glycosyl linkages and resembles the normal base-stacked configuration. The glycosidic conformation in solution of the 5' terminal fragment differs from the crystal in which the less common SYN conformation is observed. In this isomer only the sugar pucker of the 3' terminal fragment is changed substantially with respect to the dinucleotide. The trans-syn isomer is formed in a SYN-ANTI glycosidic conformation. In this isomer the sugar puckers of both deoxyribose rings are affected and a preference for a pure 2'-endo conformation is observed.


Handgrip strength in older adults with chronic diseases from 27 European countries and Israel.
Understanding the association of deconditioned strength with the most prevalent chronic diseases in older adults and inferring possible interventional strategies is of utmost importance. We aimed to investigate the association between handgrip strength and chronic diseases in a large representative European population of adults over the age of 50 years. Individuals aged 50 or older residing in 27 European countries and Israel participated in this cross-sectional study. Data on prior or current chronic disease and handgrip strength were retrieved from the 7th wave of Survey of Health, Ageing and Retirement in Europe (SHARE). We tested associations using binary logistic regression adjusted for potential confounders. Based on data from 73,463 participants, the examined diseases showed a negative association with handgrip strength in the fully adjusted model. Participants from the highest tertile of handgrip strength had particularly lower odds for Parkinson ((Adjusted odds ratio (AOR) = 0.42 [95% Confidence Interval = 0.32-0.56])), stroke (AOR = 0.51 [95% Confidence Interval = 0.44-0.59], and emotional disorders ((Adjusted odds ratio (AOR) = 0.51 [95% Confidence Interval = 0.45-0.58])) compared with participants with the lowest level of handgrip strength in the fully adjusted model. There is a negative association between handgrip strength and a wide range of chronic diseases. Evaluating handgrip strength in this population may provide a valuable clinical measure and a simple preventive strategy in relation to these diseases. The present findings support the use of resistance training for the prevention of specific chronic conditions, particularly Parkinson, stroke and emotional disorders.


Autoantibodies testing in autoimmunity: Diagnostic, prognostic and classification value.
Diagnosis of autoimmune diseases is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the conditions. This review focused on the current knowledge of the role of autoantibodies' testing in various diseases, such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, undifferentiated connective tissues disease, primary biliary cholangitis and primary sclerosing cholangitis. Similarly, the prognostic and diagnostic values of autoantibodies testing in patients with interstitial lung disease have been reviewed. In-depth research on the molecular action of these autoantibodies on immune regulation and diseases pathogenesis has been explored beyond their correlation with disease phenotypes, highlighting the impact of autoantibodies targeting on disease outcomes and etiopathogenesis.


Differentiation inhibiting activity is produced in matrix-associated and diffusible forms that are generated by alternate promoter usage.
The differentiation of embryonic stem (ES) cells is controlled by the regulatory factor differentiation inhibiting activity/leukemia inhibitory factor (DIA/LIF). Examination of feeder cell-mediated suppression of ES cell differentiation revealed that DIA/LIF is produced both as a diffusible protein and in an immobilized form associated with the extracellular matrix. This alternative localization arises from the expression of alternate transcripts that diverge throughout exon 1. The effect of alternate first exon usage is to change the amino terminus of the primary translation product and to direct incorporation of mature, biologically active DIA/LIF into the extracellular matrix. The production of a potent regulatory factor in both diffusible and immobilized forms may be an important element of developmental control mechanisms.


Isolation and characterization of related substances in alogliptin benzoate by LC-QTOF mass spectrometric techniques.
A highly specific and efficient LC-QTOF mass spectrometric method was developed for the separation and characterization of process related substances and the major degradation products in alogliptin benzoate and its tablets. The separation was performed on Phenomenex Gemini-NX C18 column (250mm×4.6mm, 5μm) using 0.2% formic acid-0.2% ammonium acetate in water as mobile phase A, acetonitrile and methanol (60:40, v/v) as mobile phase B in linear gradient elution mode. Forced degradation studies were also conducted under ICH prescribed stress conditions. Alogliptin benzoate and its tablets were tending to degrade under acid, alkaline, oxidative and thermal stresses, while relatively stable to photolytic stress. A total of seven related substances were detected and characterized through liquid chromatography-high resolution QTOF mass spectrometry techniques, including process related substances and degradation products, and two of them were further synthesized and characterized by NMR spectroscopy. Based on the related substances elucidation and the plausible formation mechanisms, efficient approaches were proposed to reduce or eliminate related substances, and in consequence the quality of alogliptin benzoate and its tablets have been promoted obviously. Therefore, the impurity profiles obtained are critical to the quality control and manufacturing processes optimization and monitoring of alogliptin benzoate and its tablets.


Defective Kin28, a subunit of yeast TFIIH, impairs transcription-coupled but not global genome nucleotide excision repair.
The essential Saccharomyces cerevisiae KIN28 gene encodes a subunit of general transcription factor TFIIH, a multiprotein complex required for RNA polymerase II transcription initiation and nucleotide excision repair (NER). Kin28 is implicated in the transition from transcription initiation to transcription elongation by phosphorylation of the carboxy-terminal domain (CTD) of the largest subunit of the RNA polymerase II complex. Here, we explore the possibility that Kin28 like the other subunits of TFIIH is involved in NER in vivo, using yeast cells carrying either a wildtype or a thermosensitive KIN28 allele. The removal of UV induced cyclobutane pyrimidine dimers (CPDs) was monitored at base resolution from both strands of the RNA polymerase II transcribed genes RPB2 and URA3. Cells carrying the thermosensitive KIN28 allele display a transcription-coupled repair (TCR) defect at the non-permissive temperature, which was most pronounced directly downstream of transcription initiation, probably as an indirect result of a general decrease in the level of RNA polymerase II transcription. The fact that CPD removal in non-transcribed DNA is completely unaffected in these cells indicates that Kin28 is not essential for general NER in vivo, providing the first example of a TFIIH subunit that is required for TCR but not for NER in general.


Type A monoamine oxidase regulates life and death of neurons in neurodegeneration and neuroprotection.
In Parkinson's disease, type B monoamine oxidase (MAO-B) is proposed to play an important role in the pathogenesis through production of reactive oxygen species and neurotoxins from protoxicants, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In addition, inhibitors of MAO-B protect neurons in the cellular and animal models of Parkinson's and Alzheimer's diseases. However, the role of type A MAO (MAO-A) in neuronal death and neuroprotection by MAO-B inhibitors has been scarcely elucidated. This chapter presents our recent results on the involvement of MAO-A in the activation of mitochondrial death signal pathway and in the induction of prosurvival genes to prevent cell death with MAO-B inhibitors. The roles of MAO-A in the regulation of neuronal survival and death are discussed in concern to find a novel strategy to protect neurons in age-associated neurodegenerative disorders and depression.


Discovery of novel indane derivatives as liver-selective thyroid hormone receptor β (TRβ) agonists for the treatment of dyslipidemia.
Thyromimetics that specifically target TRβ have been shown to reduce plasma cholesterol levels and avoid atherosclerosis through the promotion of reverse cholesterol transport in an animal model. We designed novel thyromimetics with high receptor (TRβ) and organ (liver) selectivity based on the structure of eprotirome (3) and molecular modeling. We found that indane derivatives are potent and dual-selective thyromimetics expected to avoid hypothyroidism in some tissues as well as heart toxicity. KTA-439 (29), a representative indane derivative, showed the same high human TRβ selectivity in a binding assay as 3 and higher liver selectivity than 3 in a cholesterol-fed rat model.


n-3 fatty acids: antiatherosclerotic effects.
The low incidence of cardiovascular disease associated epidemiologically with high consumption of food rich in n-3 fatty acids suggests the possibility that part of the beneficial cardiovascular effects of these natural substances may be due to a reduction of atherosclerosis. This has been recently confirmed in autoptic data and in at least one prospective trial evaluating the progression of coronary atherosclerosis in humans. This paper reviews published literature on n-3 fatty acids and atherosclerosis in animal models and in humans and in vitro experimental data yielding suport to the hypothesis of antiatherosclerotic effects of these substances.


Circular, circular-linear and branched herpes simplex virus DNA molecules from arginine deprived cells.
Analysis of the virus DNA isolated from arginine deprived cells revealed that the majority of DNA molecules are linear, with some molecules having one or more short branches. In addition, circular and circular-linear DNA molecules of genome size and smaller were observed.


Identification of the interaction sites of Inhibitor-3 for protein phosphatase-1.
Inhibitor-3 is a potent inhibitor of protein phosphatase-1, with an IC(50) in the nanomolar range for the inhibition of the dephosphorylation of phosphorylase a. Human Inhibitor-3 possesses a putative protein phosphatase-1 binding motif, (39)KKVEW(43). We provide direct evidence that this sequence is involved in PP1 interaction by examining the effects of site-directed mutations of Inhibitor-3 on its ability to inhibit protein phosphatase-1. A second interaction site whose deletion led to loss of inhibitory potency was identified between residues 65 and 77. The existence of two interaction sites is consistent with the high inhibitory potency of Inhibitor-3, and with current models for other inhibitor and targeting proteins that interact with protein phosphatase-1 with high affinity.


Stentless valves versus stented bioprostheses at the aortic position: midterm results.
Our aim was to compare stentless and stented bioprostheses. Clinical outcomes, hemodynamic performance, and postoperative left ventricular mass regression were the principal outcomes assessed. Sixty-two patients were recruited for the study. Our protocol was to consider all patients older than 55 years for bioprostheses, and also younger patients were implanted with a bioprosthesis if they wanted to avoid anticoagulation. Patients selected for bioprostheses were randomly assigned to receive stentless (group A) and stented (group B) bioprostheses, depending on the treating unit. Patients in groups A and B were further divided into subgroups I and II based on left ventricular ejection fractions of 50% or greater and less than 50%, respectively. At 18 +/- 3 months postoperatively, the effective orifice area was greater in group A versus group B. Left ventricular ejection fraction, left ventricular mass index, functional class, and mean gradient were similar in patients of subgroup I (left ventricular ejection fraction >50%) from both groups. However, there was a significant difference between all except mean gradient in patients of subgroup II (left ventricular ejection fraction <50%) from both groups. Also, in the patient subgroup implanted with valves of less than 19 mm (group A, 4 patients; group B, 3 patients), there was a significant difference in left ventricular mass index and mean gradient. In patients with left ventricular impairment or a small aortic annulus, stentless bioprostheses might allow for greater improvement in left ventricular function postoperatively.


Calretinin and FMRFamide immunoreactivity in the nervus terminalis of prenatal tree shrews (Tupaia belangeri).
The distribution and development of FMRFamide- and calretinin-immunoreactive neurons were investigated in the nervus terminalis of prenatal tree shrews from gestation day 19 onwards. The first FMRFamide-immunoreactive cells were observed medially in the olfactory epithelium on gestation day 20. From gestation day 23 onwards, the migrating nervus terminalis ganglion cells showed FMRFamide calretinin immunoreactivity. The distribution pattern of FMRFamide- and calretinin-immunoreactive cells was similar along the migratory route and in the ganglion of the terminal nerve. However, most probably calretinin and FMRFamide were expressed in separate neuronal populations. For the first time in a mammal, FMRFamide and calretinin are reported to occur in the migrating perikarya and neuronal processes of the nervus terminalis during prenatal development. The results suggest (i) an early activation of the rostral FMRFamide-immunoreactive migratory stream comparable to that described for the GnRH-immunoreactive part of the terminal nerve in other mammals and possibly (ii) an involvement of calretinin in mechanisms of cell migration and outgrowth of neuronal processes in the terminal nerve during the studied period.


Heat priming effects on anthesis heat stress in wheat cultivars (Triticum aestivum L.) with contrasting tolerance to heat stress.
The incidence of heat episodes during the phase of reproductive development in crops is accountable for great yield losses worldwide. Plants subjected to stress events during vegetative stages (primed) are reported be more resistant to future stress exposure during the reproductive phases. We aimed to test if repeated early abiotic stresses could improve heat tolerance during anthesis in wheat cultivars. Two wheat cultivars (Triticum aestivum L.), 'Gladius' and 'Paragon', were subjected to a heat priming process consisting of two periods with heat at the developmental stages of three and five completely developed leaves, respectively. The primed and non-primed plants were later subjected to either a heat stress or non-heat stress (control) temperature for seven days during anthesis. Gas exchange and chlorophyll fluorescence were used to investigate the physiological performance of the plants. No difference in assimilation rate was observed between treatments for 'Gladius'. Measurements were not possible to obtain for heat stressed 'Paragon' plants due to premature senescence. We did not observe strong evidence to prove our hypothesis of early heat stress (priming) being accountable for improving heat tolerance. However, a significant difference between cultivars in response to heat stress was observed. The yield parameters of 'Gladius' primed plants did not differ from their respectively control treatment. A distinct result was observed for the heat sensitive cultivar 'Paragon', suggesting a cumulative deleterious effect caused by the repeated heat stress.


Novel chromosomes and genomes provide new insights into evolution and adaptation of the whole genome duplicated yeast-like fungus TN3-1 isolated from natural honey.
Aureobasidium melanogenum TN3-1 strain and A. melanogenum P16 strain were isolated from the natural honey and the mangrove ecosystem, respectively. The former can produce much higher pullulan from high concentration of glucose than the latter. In order to know what happened to their genomes, the PacBio sequencing and Hi-C technologies were used to create the first high-quality chromosome-level reference genome assembly of A. melanogenum TN3-1 (51.61 Mb) and A. melanogenum P16 (25.82 Mb) with the contig N50 of 2.19 Mb and 2.26 Mb, respectively. Based on the Hi-C results, a total of 93.33% contigs in the TN3-1 strain and 92.31% contigs in the P16 strain were anchored onto 24 and 12 haploid chromosomes, respectively. The genomes of the TN3-1 strain had two subgenomes A and B. Synteny analysis showed that the genomic contents of the two subgenomes were asymmetric with many structural variations. Intriguingly, the TN3-1 strain was revealed as a recent hybrid/fusion between the ancestor of A. melanogenum CBS105.22/CBS110374 and the ancestor of another unidentified strain of A. melanogenum similar to P16 strain. We estimated that the two ancient progenitors diverged around 18.38 Mya and merged around 10.66-9.98 Mya. It was found that in the TN3-1 strain, telomeres of each chromosome contained high level of long interspersed nuclear elements (LINEs), but had low level of the telomerase encoding gene. Meanwhile, there were high level of transposable elements (TEs) inserted in the chromosomes of the TN3-1 strain. In addition, the positively selected genes of the TN3-1 strain were mainly enriched in the metabolic processes related to harsh environmental adaptability. Most of the stress-related genes were found to be related to the adjacent LTRs, and the glucose derepression was caused by the mutation of the Glc7-2 in the Snf-Mig1 system. All of these could contribute to its genetic instability, genome evolution, high stress resistance, and high pullulan production from glucose.


Potential of astrocytes in targeting therapy for Alzheimer's disease.
As the most common neurodegenerative disease, Alzheimer's disease (AD) exhibits an incomprehensible pathogenesis, which has led to the continuous failure of drug development in recent years. Although neuronal damage is considered a pathological feature of AD, treatment strategies targeting β-amyloid (Aβ) have not achieved beneficial effects. In-depth research on glial cells has revealed the strong importance and application prospects of astrocytes in the recovery of cognitive functions. This review summarizes the role of astrocytes in AD and the possibility of therapeutic strategies targeting astrocytes. Astrocytes are involved in brain lipid metabolism and can regulate the synthesis and degradation of Aβ to affect the pathology of AD. The tau protein is phosphorylated by astrocytes, and this phosphorylation leads to the formation of neurofibrillary tangles (NFTs). Astrocytes can express a variety of receptors and inflammatory factors and participate in the neuroinflammatory process and the release of proinflammatory mediators. When the glutamate produced by the neurons is not cleared by astrocytes, neurons undergo apoptosis due to blocked cell metabolism. Therapies for astrocytes are highly efficient, and these include stem cell therapy, gene editing technology, astrocyte transformation and chemical drugs. Here, we discuss the advantages and disadvantages of animal and cell models applied to the study of targeted astrocyte therapies. This study helps elucidate the mechanism of astrocytes in AD and promotes the clinical application of potential therapeutic strategies targeting astrocytes.


Anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: vertical distribution of cases in apartment blocks.
Owing to the civil war, the inhabitants of Kabul in Afghanistan are suffering a major epidemic of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica. Surveys conducted among children in 2 high-rise apartment blocks in the city revealed that the prevalence of active lesions was much lower on upper stories: 84% lower in one block (chi 2 = 7.13, d.f. = 1, P = 0.008) and 54% lower in the other (chi 2 = 6.17, d.f. = 1, P = 0.01). Similar trends were apparent with regard to scars from old lesions. These results suggest that in Kabul most transmission of ACL takes place in the home. In addition, the results imply that there must be limited vertical movement of the vector within apartment blocks. Together, these findings suggest that indoor spraying should be an effective means of control and that insecticidal applications could probably be restricted to lower stories.


An Ultrathin, Triple-Band Metamaterial Absorber with Wide-Incident-Angle Stability for Conformal Applications at X and Ku Frequency Band.
An ultrathin and flexible metamaterial absorber (MA) with triple absorption peaks is presented in this paper. The proposed absorber has been designed in such a way that three absorption peaks are located at 8.5, 13.5, and 17 GHz (X and Ku bands) with absorption of 99.9%, 99.5%, and 99.9%, respectively. The proposed structure is only 0.4 mm thick, which is approximately 1/88, 1/55, and 1/44 for the respective free space wavelengths of absorption frequency in various bands. The MA is also insensitive due to its symmetric geometry. In addition, the proposed structure exhibits minimum 86% absorption (TE incidence) within 60° angle of incidence. For TM incidence, the proposed absorber exhibits more than 99% absorptivity up to 60° incidence. Surface current and electric field distributions were investigated to analyze the mechanism governing absorption. Parameter analyses were performed for absorption optimization. Moreover, the performance of the MA was experimentally demonstrated in free space on a sample under test with 20 × 30 unit cells fabricated on a flexible dielectric. Under normal incidence, the fabricated MA exhibits near perfect absorption at each absorption peak for all polarization angles, and the experimental results were found to be consistent with simulation results. Due to its advantages of high-efficiency absorption over a broad range of incidence angles, the proposed absorber can be used in energy harvesting and electromagnetic shielding.


[Preparation of capillary electrophoresis column physically coated with hyperbranched polyesters and its application in the separation of basic proteins].
Two series of hyperbranched polyesters were synthesized using pentaerythritol as the core by one-step and pseudo-step procedures. The molecular structures of the hyperbranched polyesters were characterized using infrared spectrum and hydroxyl value. Due to their low viscosity, the hyperbranched polyesters were easily coated on the inner surface of the fused-silica capillary by physical adsorption. The adsorption behavior of this capillary electrophoresis column coated with polyesters was investigated by the separation of three basic proteins. The electro-osmotic flow and the capability for the separation of the basic proteins were studied. It was found that the coatings of hyperbranched polyesters could significantly reduce the electroosmotic flow and suppress the protein adsorption onto the inner surface of the fused-silica capillaries in the pH range of 3.0-7.0. Three basic proteins were effectively separated at pH=5 on the column coated with the hyperbranched polyesters, with the separation efficiency being 10(5) plates/m. The experimental results also showed that the separation efficiency and the resolution on columns coated with hyperbranched polyesters by pseudo-step procedure were much better than those by one-step procedure.


Stem photosynthesis in Psorothamnus spinosus (smoke tree) in the Sonoran desert of California.
Stem photosynthetic responses to environmental parameters were investigated with Psorothamnus spinosus in the Sonoran Desert of California. Light saturation of stem photosynthesis was equal to maximum midday summer irradance (1600-2000 μmol·m-2·s-1). The optimum temperature for stem photosynthesis was 39°C, and lower stem temperatures (27-35°C) caused significant decreases (up to 50%) in stem photosynthesis. Positive stem photosynthesis was maintained up to 51°C. Stem photosynthesis was relatively insensitive to increasing vpd up to 5 kPa; However, stem conductance decreased by 25% at a vpd of 5 kPa. At vpd greater than 5 kPa stem photosynthesis decreased relatively more than that of stem conductance causing a decrease in water use efficiency and an increase an intercellular carbon dioxide concentration. Maximum stem photosynthetic rates were low (6.2-10.6 μmol·m-2·s-1) on a stem surface area, but, stem photosynthetic rates of young shoots were substantially higher (19.5-33.3 μmol· m-2·s-1) on a projected area basis.


Nimbolide ameliorates fibrosis and inflammation in experimental murine model of bleomycin-induced scleroderma.
Clinical manifestations of skin fibrosis are very variable and ambiguous, making its management quite critical and challenging. The lack of appropriate established pharmacological interventions make its treatment even more complicated. Intricate details of the underlying pathogenesis are thus imperative to further explore different treatment possibilities. Of note, the TGF-β/Smad signaling axis and epithelial to mesenchymal transition (EMT) are the principal offenders in this fibrotic disorder. Our current study is aimed at demonstrating the antifibrotic and anti-inflammatory potential of nimbolide, a triterpene derived from Indian traditional plant neem, in a murine model of Bleomycin-induced scleroderma. Male C57BL/6 mice were administered with Bleomycin injections subcutaneously, daily for 28 days, at a constant site on the dorsum of the mice. Treatment with nimbolide lasted from day 1 to day 28. At the time of study termination, the injected sites were collected and stored suitably to conduct further molecular experiments and protein expression studies. The results of our study show that nimbolide can significantly intervene in the TGF-β/Smad signaling axis and the consequent EMT process, thus attenuating deposition of extracellular matrix. Nimbolide also profoundly caused the regression of established inflammation-driven fibrosis, thus demonstrating both antifibrotic and anti-inflammatory activities. Another commendable finding of this study is that nimbolide was able to decrease the levels of LOXL2, a collagen cross-linker, which is aberrantly expressed in scleroderma. Although further mechanistic studies are required, our study displays nimbolide for the first time as a potent antifibrotic agent which can be used as a pharmacological intervention for the treatment of scleroderma.


Racial and ethnic differences in breastfeeding, maternal knowledge, and self-efficacy among low-income mothers.
The purpose of this secondary analysis was to examine racial and ethnic differences in the propensity to engage in breastfeeding, maternal knowledge, and self-efficacy in infant feeding among three groups of low-income mothers: non-Hispanic (NH) White, NH African American, and Hispanic. While racial and ethnic differences in infant feeding practices are substantial, these differences have not been broadly examined in relation to breastfeeding, maternal knowledge, and self-efficacy in infant feeding among low-income mothers. This secondary analysis used baseline data from a randomized clinical trial with a sample of 540 low-income, mother-infant dyads from Michigan and Colorado. All data were collected when infants were approximately one month old via self-report questionnaires. After adjusting for mothers' age, education, marital and working status, the odds of engaging in any form of breastfeeding among Hispanic mothers remained significantly higher than among NH African-American mothers (OR=2.5, 95% CI:1.59-3.96) and NH White mothers (OR=1.7, 95% CI:1.08-2.81). However, Hispanic mothers had significantly lower maternal knowledge and self-efficacy in infant feeding than the other two groups. No significant correlations were found between maternal knowledge, self-efficacy in infant feeding, and the propensity to breastfeed. Racial and ethnic variations were evident in the propensity to breastfeed, maternal knowledge, and self-efficacy in infant feeding suggesting the importance of tailoring breastfeeding programs to improve breastfeeding, and associated positive health outcomes. Further investigation is needed to find a better way to address breastfeeding disparity in relation to race and ethnicity, maternal knowledge, and self-efficacy in infant feeding.