Analysis of posterior mitral annular activation during entrainment and catheter ablation of mitral isthmus ventricular tachycardia using a coronary sinus catheter.
A detailed analysis of the ventricular activation along the posterior aspect of the mitral annulus was made using a multipolar catheter positioned in the coronary sinus in a patient with mitral isthmus ventricular tachycardia (VT) associated with a remote inferior myocardial infarction and prior cryosurgical ablation for the elimination of a different preexisting VT. A change in the timing and sequence of the ventricular activation along the isthmus could be observed during induction of the VT and entrainment pacing. A radiofrequency (RF) current application directed at the posterolateral region of the isthmus successfully eliminated this tachycardia. During the RF delivery, complete conduction block was confirmed by a sudden change in the activation sequence during sinus rhythm.


Economic efficiency of countries' clinical review processes and competitiveness on the market of human experimentation.
Clinical research is a specific phase of pharmaceutical industry's production process in which companies test candidate drugs on patients to collect clinical evidence about safety and effectiveness. Information is essential to obtain manufacturing authorization from the national drug agency and, in this way, make profits on the market. Considering this activity, however, the public stakeholder has to face a conflict of interests. On the one side, there is society's necessity to make advances in medicine and, of course, to promote pharmaceutical companies' investments in this specific phase (new generation). On the other side, there is the duty to protect patients involved in these experimental treatments (old generation). To abide by this moral duty, a protection system was developed through the years, based on two legal institutions: informed consent and institutional review board. How should an efficient protection system that would take human experimentation into account be shaped? Would it be possible for the national protection system of patients' rights to affect the choice of whether to develop a clinical trial in a given country or not? Looking at Europe and considering a protection system that is shaped around institutional review boards, this article is an empirical work that tries to give answers to these open questions. It shows how a protection system that can minimize the time necessary to start a trial can positively affect pharmaceutical clinical research, that is, the choice of pharmaceutical companies to start innovative medical treatments in a given country.


Evidence-Based Treatment Strategies in Youth Mental Health Services: Results from a National Survey of Providers.
Previous surveys indicate infrequent use of evidence-based treatment (EBT) manuals in usual care youth mental health, but the extent to which providers use core and common EBT strategies and what contextual factors impact EBT strategy implementation need further study. In a national, multidisciplinary survey of 1092 youth-serving providers, providers reported regular use of many EBT strategies. Provider learning theory orientation, more recent degree, more standardized and ongoing assessment use, more positive attitudes toward innovation and evidence, fewer low-income clients, and perceptions that their agency valued quality care and provided fewer training resources predicted more frequent EBT strategy use.


Liraglutide treatment causes upregulation of adiponectin and downregulation of resistin in Chinese type 2 diabetes.
To assess the effect of 16 weeks of liraglutide administration on the plasma levels of adiponectin and resistin in Chinese patients diagnosed with type 2 diabetes mellitus (T2DM). Forty-four subjects were recruited and randomly assigned to once-a-day dosage of either liraglutide, or glimepiride (4 mg) in a double-blinded double-dummy active-controlled study. All treatments were administered in combination with metformin (1 g, twice daily). The efficacy of liraglutide was estimated by measuring and comparing the levels of HbA1c, adiponectin and resistin in the plasma before and after the 16-week treatment. The plasma level of adiponectin was significantly increased (0.74±0.19 ng/ml, p<0.05) and resistin was significantly lowered (-1.34±0.34 pg/ml, p<0.05) in a dose-dependent manner in the liraglutide group when compared with the glimepiride group (-0.44±0.09 ng/ml of adiponectin and 0.14±0.41 pg/ml of resistin). In contrast, we found no differences in the decrease in HbA1c between the two groups (8.3±1.2% to 7.2±1.1% in NGSP units vs. 8.3±1.0% to 7.3±1.2% in NGSP units; 67±13 mmol/mol to 55±12 mmol/mol vs. 67±11 mmol/mol to 56±13 mmol/mol in IFCC units). In Chinese T2DM patients, liraglutide treatment led to increased adiponectin and decreased resistin levels compared to glimepiride-treated subjects, while inducing similar glycemic changes.


Efficiency of Measurements of Hepatitis C Virus RNA.
Hepatitis C virus loading was evaluated using modifications of PCR product detection: terminal point fluorescent detection, real time assay, and agarose gel electrophoresis. The advantages and flaws of the real time PCR and electrophoretic detection of amplification products for evaluation of the quantity of virus particle copies are evaluated.


Hormonal receptors in cutaneous vascular malformations: 51 cases.
Vascular malformations (VMs) are rare congenital anomalies that develop during embryogenesis in different types of vessels. Several triggering factors of cutaneous VMs include trauma, infections, or hormonal changes. We investigated the expression of hormonal receptors (androgen, estrogen, progesterone) in tissue samples of well-characterized VMs. A secondary objective was to identify self-reported triggering factors for these VMs, including hormonal changes, in the cohort of patients. We included patients with VM samples obtained in the tertiary center for vascular anomalies of the University Hospital Center of Tours, France, from January 1, 2007, to August 1, 2018. Immunohistochemistry was used to detect the expression of hormonal receptors (estrogen, progesterone, androgens). We obtained 51 samples from 51 patients: 13 cystic lymphatic malformations (CLMs), 16 venous malformations (VeMs), 11 arteriovenous malformations (AVMs), 4 combined VMs, 4 PIK3CA-related overgrowth spectrum, 1 Parkes-Weber syndrome, 1 Gorham syndrome, and 1 multiple lymphangioendotheliomatosis with thrombopenia. In total, 38 (74.5%) samples were positive for androgen receptor: 11 (84.6%) CLMs, 12 (75.0%) VeMs, 8 (72.2%) AVMs, and 7/11 (63.5%) other samples. All samples were negative for estrogen and progesterone receptors. Triggering factors were self-reported in 7 cases and were most frequently hormonal changes (n = 6, 18.2%). Hormonal triggers were frequent in AVMs (n = 4). Among patients with identified hormonal triggers, VM samples were positive for androgen receptor in 3 and negative in 3. Three-quarters of our VM samples expressed androgen receptor, and most CLM, VeM, and AVM samples were positive. Hormonal triggers were identified in 6/33 patients, mostly with AVMs.


Comparing adults who use cannabis medically with those who use recreationally: Results from a national sample.
Cannabis has been legalized for medical use in almost half of the states in the U.S. Although laws in these states make the distinction between medical and recreational use of cannabis, the prevalence of people using medical cannabis and how distinct this group is from individuals using cannabis recreationally is unknown at a national level. Data came from the 2013 National Survey on Drug Use and Health (NSDUH). All adults endorsing past year cannabis use who reported living in a state that had legalized medical cannabis were divided into recreational cannabis use only and medical cannabis use. Demographic and clinical characteristics were compared across these two groups. 17% of adults who used cannabis in the past year used cannabis medically. There were no significant differences between those who used medically versus recreationally in race, education, past year depression and prevalence of cannabis use disorders. In adjusted analyses, those with medical cannabis use were more likely to have poorer health and lower levels of alcohol use disorders and non-cannabis drug use. A third of those who reported medical cannabis use endorsed daily cannabis use compared to 11% in those who reported recreational use exclusively. Adults who use medical and recreational cannabis shared some characteristics, but those who used medical cannabis had higher prevalence of poor health and daily cannabis use. As more states legalize cannabis for medical use, it is important to better understand similarities and differences between people who use cannabis medically and recreationally.


Does Early Repair of Orbital Fractures Result in Superior Patient Outcomes? A Systematic Review and Meta-Analysis.
To date, no clear evidence-based guidelines exist pertaining to the ideal timing to perform surgical treatment of orbital fractures. The purpose of this study was to determine if early treatment of orbital fractures resulted in better patient outcomes. We designed and implemented a systematic review and meta-analysis to test the null hypothesis of no difference in outcomes between different time intervals between orbital injury and surgical intervention. PubMed, Embase, the Cochrane Library, the Elsevier text mining tool database, and clinicaltrials.gov trial registry were queried. The quality of evidence was based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The predictor variable was the timing of operative repair (early vs late). The outcome variable was complete recovery. Other variables of interest were diplopia, enophthalmos, and preoperative motility restriction. Meta-analyses were performed when definitions of active and control interventions and patient outcomes were deemed similar. In addition, χ2 tests were performed to determine differences in clinical outcomes between early and late operative repair. Of the 1,160 articles reviewed, 20 met the inclusion criteria. Surgery performed less than 2 weeks after injury was significantly associated with greater odds of complete recovery of symptoms (odds ratio [OR], 6.9 [95% confidence interval (CI), 1.35-35.06]), as well as a lower incidence of postoperative diplopia (OR, 0.3 [95% CI, 0.1-0.9]) and enophthalmos (OR, 0.2 [95% CI, 0.1-0.9]). Repair performed less than 30 days after injury was associated complete resolution of preoperative motility restriction (OR, 24.6 [95% CI, 1.30-462.34]) as well as diplopia. Differences in the timing of surgery and definition of patient outcomes, as well as variations in methods of evaluating postoperative outcomes, potentiate the risk of bias and warrant downgrading of the quality of evidence in a study. The timing of repair varied among 2, 4, and 8 weeks after injury. However, a short time to surgical intervention was significantly associated with resolution of vertical dystopia, postoperative enophthalmos, and motility restriction.


Evaluation of the quality of different endodontic obturation techniques by digital radiography.
This study was aimed to evaluate different endodontic obturation techniques (Thermafil, lateral condensation, and Tagger's hybrid technique) regarding the homogeneity of the obturation radiopacity. Seventy roots of human upper central incisors were filled using the Thermafil system, lateral condensation. and Tagger's hybrid technique. Radiopacity of the filling was evaluated based on mean of grey levels, and its homogeneity was assessed by the coefficient of variation (CV), analyzing the histograms obtained of digitized and digital radiographs. The increase in mean grey levels (p < 0.001) and reduction in the CV (p < 0.05) were higher for Tagger's hybrid technique compared with other methods. Tagger's hybrid technique provided better homogeneity of the obturation radiopacity and better apical sealing compared with lateral condensation technique. The results suggest that Tagger's hybrid technique provided the best compaction of the root canal filling material, an important factor for the sealing of obturations and, consequently, for the effectiveness of treatment.


The Myxococcus xanthus pilQ (sglA) gene encodes a secretin homolog required for type IV pilus biogenesis, social motility, and development.
The Myxococcus xanthus sglA1 spontaneous mutation was originally isolated because it allowed dispersed cell growth in liquid yet retained the ability to form fruiting bodies. Consequently, most of today's laboratory strains either contain the sglA1 mutation or were derived from strains that carry it. Subsequent work showed that sglA was a gene for social gliding motility, a process which is mediated by type IV pili. Here sglA is shown to map to the major pil cluster and to encode a 901-amino-acid open reading frame (ORF) that is homologous to the secretin superfamily of proteins. Secretins form a channel in the outer membrane for the transport of macromolecules. The closest homologs found were PilQ proteins from Pseudomonas aeruginosa and Neisseria gonorrhoeae, which are required for type IV pili biogenesis and twitching motility. To signify these molecular and functional similarities, we have changed the name of sglA to pilQ. The hypomorphic pilQ1 (sglA1) allele was sequenced and found to contain two missense mutations at residues 741 (G-->S) and 762 (N-->G). In addition, 19 independent social (S)-motility mutations are shown to map to the pilQ locus. In-frame deletions of pilQ and its downstream gene, orfL, were constructed. pilQ is shown to be essential for pilus biogenesis, S-motility, rippling, and fruiting body formation, while orfL is dispensable for these processes. The pilQ1 allele, but not the DeltapilQ allele, was found to render cells hypersensitive to vancomycin, suggesting that PilQ1 alters the permeability properties of the outer membrane. Many differences between pilQ1 and pilQ+ strains have been noted in the literature. We discuss some of these observations and how they may be rationalized in the context of our molecular and functional findings.


Endothelium-dependent vasorelaxations in response to aggregating platelets are impaired in reversed vein grafts.
The endothelium releases factor(s) that are potent vasodilators and inhibitors of platelet aggregation. Experiments were performed to determine whether the endothelium-dependent responses to aggregating platelets are altered in vein grafts. Segments of jugular veins were grafted in the reverse position into the carotid arteries in 16 rabbits. After 4 weeks the patent grafts (14 of 16) were removed, and the endothelium-dependent responses were examined in vitro. In control veins aggregating platelets, adenosine diphosphate, and serotonin caused endothelium-dependent relaxations. The platelet-induced relaxations were attenuated by apyrase (adenosine diphosphatase and adenosine triphosphatase) but not by methiothepin (serotonergic blocker). In vein grafts, endothelium-dependent relaxations in response to aggregating platelets were absent, and only contractions that could be attenuated by methiothepin were observed. In vein grafts, endothelium-dependent relaxations in response to adenosine diphosphate were reduced, and only endothelium-independent contractions were observed in response to serotonin. These contractions were attenuated by methiothepin. These results suggest that (1) the endothelium exerts an inhibitory effects mediated mainly by adenosine diphosphate in response to aggregating platelets in rabbit jugular veins and (2) endothelium-dependent relaxations in response to aggregating platelets are impaired in vein grafts because of reduced endothelium-independent contractions in response to serotonin. This impairment of endothelium-dependent responses in vein grafts may contribute to failure of the grafts.


What is necessary for next-generation atmospheric environmental standards? Recent research trends for PM2.5 -bound polycyclic aromatic hydrocarbons and their derivatives.
The air pollution associated with PM2.5 kills 7 million people every year in the world, especially threatening the health of children in developing countries. However, the current air quality standards depend mainly on particle size. PM2.5 contains many carcinogenic/mutagenic polycyclic aromatic hydrocarbons (PAHs) and their derivatives such as nitropolycyclic aromatic hydrocarbons and oxygenated PAHs. Among them, environmental standards and guidelines have been set for benzo[a]pyrene by few countries and international organizations. Recent research reports showed that these pollutants are linked to diseases other than lungs, and new methods have been developed for determining trace levels of not only PAHs but also their derivatives. It is time to think about the next-generation environmental standards. This article aims to (a) describe recent studies on the health effects of PAHs and their derivatives other than cancer, (b) describe new analytical methods for PAH derivatives, and (c) discuss the targets for the next-generation standards.


Selective detection of dopamine in the presence of uric acid using a gold nanoparticles-poly(luminol) hybrid film and multi-walled carbon nanotubes with incorporated β-cyclodextrin modified glassy carbon electrode.
Gold nanoparticles-poly(luminol) (Plu-AuNPs) hybrid film and multi-walled carbon nanotubes with incorporated β-cyclodextrin modified glassy carbon electrode (β-CD-MWCNTs/Plu-AuNPs/GCE) was successfully prepared for simultaneous determination of dopamine (DA) and uric acid (UA). The surface of the modified electrode has been characterized by X-ray photo-electron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDS), field-emission scanning electron microscope (SEM) and transmission electron microscope (TEM). Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) have been used to investigate the β-CD-MWCNTs/Plu-AuNPs composite film. Gold nanoparticles anchored into poly(luminol) film exhibited catalytic activity for DA. MWCNTs with incorporated β-CD can greatly promote the direct electron transfer. In 0.10 M phosphate buffer solution (PBS, pH 7.0), the DPV response of the β-CD-MWCNTs/Plu-AuNPs/GCE sensor to DA is about 8-fold as compared with the Plu-AuNPs/GCE sensor, and the detection limit for DA is about one order of magnitude lower than the Plu-AuNPs/GCE sensor. The steady-state current response increases linearly with DA concentration from 1.0 × 10(-6) to 5.6 × 10(-5)M with a low detection limit (S/N=3) of 1.9 × 10(-7)M. Moreover, the interferences of ascorbic acid (AA) and uric acid (UA) are effectively diminished. The applicability of the prepared electrode has been demonstrated by measuring DA contents in dopamine hydrochloride injection.


Redesigning the rural health center: high tech, high touch, and low overhead.
To attract new physicians to rural primary care, new models of care are needed that are more effective, more sustainable, and replicable in smaller communities. This commentary provides a brief description of preliminary findings associated with a radically redesigned, low-overhead patient-centered medical-home practice model in North Carolina.


Time Course of Leg Edema after Endovenous Radiofrequency Ablation for Saphenous Varicose Veins.
The objectives of the study were to quantitatively evaluate leg edema in patients undergoing endovenous radiofrequency ablation (RFA) for saphenous varicose veins using bioelectrical impedance analysis (BIA) and to elucidate the time course of leg edema after RFA. The data of 87 patients with 128 limbs undergoing RFA for saphenous varicose veins in Eniwa Midorino Clinic from April 2018 to November 2019 were retrospectively analyzed. Saphenous vein reflux was evaluated by duplex scan. Extracellular water/total body water ratio (ECW/TBW) of the leg was measured by BIA. Moderate to severe leg edema (ECW/TBW ≥ 0.400) was defined as significant leg edema. Venous reflux was evaluated as a venous filling index (VFI) using air plethysmography. BIA revealed that 26 legs (20.3%) had significant edema and 102 legs (79.7%) did not before RFA. The proportion of patients with significant leg edema increased significantly from preoperative to 1 week after RFA (P < 0.05) and decreased 1 month after RFA (P < 0.01). The ECW/TBW increased significantly from preoperative (0.393 ± 0.008) to 1 week after RFA (0.394 ± 0.008, P < 0.05), whereas it decreased significantly before or 1 week to 1 month after RFA (0.391 ± 0.008, P < 0.05). There was a significant, moderate correlation between the decrease of the VFI and that of ECW/TBW (r = 0.34, P < 0.001). This is the first study to quantitatively elucidate the time course of leg edema after RFA. Leg edema worsens one week after RFA, but it is improved one month after RFA, compared with that preoperatively.


Cor triatriatum sinister: Long-term surgical outcomes in children and a proposal for a new classification.
Cor Triatriatum Sinister (CTS) is a rare congenital anomaly with an estimated incidence of 0.4%, resulting from abnormal left atrial septation. It may present in isolation or in association with other heart defects. High percentage of patients require surgery with low mortality and recurrence rates. CTS has been classified in the past however we aim to describe a case series with more comprehensive and inclusive classification. This was a single-center retrospective cohort study of 16 children with the diagnosis of CTS between 2000 and 2020. Medical records were reviewed for clinical presentations, hospital, and postoperative courses. Sixteen patients (63% female), with a median age at diagnosis of 4.3 months, five (31%) were neonates. Six (38%) had isolated CTS, two (13%) with functional single ventricle (SV), and the remaining eight patients (50%) had other associated heart defects (septal defects in three, coarctation of the aorta in another three, and anomalous pulmonary venous connections in three). Eight patients (50%) presented with obstructed CTS. Twelve patients (75%) underwent surgical intervention. Mortality occurred in three patients (19%) with two surgical (one with total anomalous pulmonary venous connection and another with SV) and one nonsurgical (septal defect with Fanconi anemia). The surgical median follow up was 4.7 years. Recurrence of the membrane occurred in two patients (17%). This study showed good long-term outcomes for patients with isolated and complex CTS. Complete and proper classification of CTS ensures appropriate diagnosis, surgical planning, and better family counseling which may correlate with outcomes.


Bone marrow aspirates as part of routine donor assessment for allogeneic blood and marrow transplantation can reveal presence of occult hematological malignancies in otherwise asymptomatic individuals.
Pre transplant screening work-up of donors for allogeneic blood and marrow transplantation is essential in an effort to minimize risks to the recipient and protect the donor. At Princess Margaret Hospital, every potential donor is screened with a bone marrow aspirate. The case histories of three asymptomatic potential donors who presented within 1 year with normal complete blood counts, history and physical examination are presented. A 65-year-old male patient was diagnosed with smouldering multiple myeloma, a 72-year-old male patient with chronic lymphocytic leukemia and a 42-year-old male patient with myelodysplastic syndrome. Bone marrow examination led to the diagnosis in each one of these cases. Of note is that each of the potential donors was discovered to have the same disease as the transplant recipient. In vitro clonogenic hemopoietic progenitor assays were compared to those of 20 normal volunteers. Inferior growth of hemopoietic progenitor colonies in all three was noted. In conclusion, particularly in older donors and donors with potential for familial malignancies, more screening investigations including bone marrow aspiration may be reasonable to investigate for occult hematological malignancies prior to stem cell donation. Clonogenic assays can contribute to detect hemopoietic abnormalities pre transplant.


In-Depth Characterization of Protein Disulfide Bonds by Online Liquid Chromatography-Electrochemistry-Mass Spectrometry.
Disulfide bonds are an important class of protein post-translational modifications, yet this structurally crucial modification type is commonly overlooked in mass spectrometry (MS)-based proteomics approaches. Recently, the benefits of online electrochemistry-assisted reduction of protein S-S bonds prior to MS analysis were exemplified by successful characterization of disulfide bonds in peptides and small proteins. In the current study, we have combined liquid chromatography (LC) with electrochemistry (EC) and mass analysis by Fourier transform ion cyclotron resonance (FTICR) MS in an online LC-EC-MS platform to characterize protein disulfide bonds in a bottom-up proteomics workflow. A key advantage of a LC-based strategy is the use of the retention time in identifying both intra- and interpeptide disulfide bonds. This is demonstrated by performing two sequential analyses of a certain protein digest, once without and once with electrochemical reduction. In this way, the "parent" disulfide-linked peptide detected in the first run has a retention time-based correlation with the EC-reduced peptides detected in the second run, thus simplifying disulfide bond mapping. Using this platform, both inter- and intra-disulfide-linked peptides were characterized in two different proteins, ß-lactoglobulin and ribonuclease B. In order to prevent disulfide reshuffling during the digestion process, proteins were digested at a relatively low pH, using (a combination of) the high specificity proteases trypsin and Glu-C. With this approach, disulfide bonds in ß-lactoglobulin and ribonuclease B were comprehensively identified and localized, showing that online LC-EC-MS is a useful tool for the characterization of protein disulfide bonds.


Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.
The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.


First employment characteristics for the 2011 pediatric surgery fellowship graduates.
Information regarding initial employment of graduating pediatric surgery fellows is limited. More complete data could yield benchmarks of initial career environment. An anonymous survey was distributed in 2011 to 41 pediatric surgery graduates from all ACGME training programs interrogating details of initial positions and demographics. Thirty-seven of 41 (90%) fellows responded. Male to female ratio was equal. Graduates carried a median debt of $220,000 (range: $0-$850,000). The majority of fellows were married with children. 70% were university/hospital employees, and 68% were unaware of a business plan. Median starting compensation was $354,500 (range: $140,000-$506,000). Starting salary was greatest for >90% clinical obligation appointments (median $427,500 vs. $310,000; p=0.002), independent of geographic location. Compensation had no relationship to private practice vs. hospital/university/military position, coastal vs. inland location, and practice sites number. Median clinical time was 75% and research time 10%. 49% identified a formal mentor. Graduates covered 1-5 different offices (median 1) and 1-5 surgery sites (median 2). 60% were satisfied with their compensation. Recent pediatric surgery graduates are engaged mainly in clinical care. Research is not incentivized. Compensation is driven by clinical obligations. Graduates have limited knowledge of the business plan supporting their compensation, nature of malpractice coverage, and commitments to resources including research. Graduates have important fiscal and parenting obligations.


Effects of self-etching primers on dentin.
The effects of self-etching dentin primers on the hardness of dentin was evaluated by determination of the Vickers Hardness of both untreated dentin and dentin treated with different primers. Several experimental primers were prepared by dilution of dicarbonates or their esterified salts with different ratios of HEMA to obtain ratios of 5% and 35% by weight. Methacryloxyethyl succinate (MES) and Methacryloxyethyl phthalate (MEP) experimental primers caused less softening of dentin than did maleic acid diluted with HEMA or a commercial dentin primer (Scotchprep, 3M). A high correlation was observed between the pH of a primer and the hardness of dentin treated with the primer. A correlation was also observed between the hardness of treated dentin and the wall-to-wall polymerization contraction of a light-curing microfilled resin (Silux, 3M).


Highly accurate two-gene signature for gastric cancer.
Large amount of expression data were generated by high-throughput experimental techniques such as microarray. Single algorithm cannot be widely accepted as suitable method for mining of gene expression data. Therefore, integration of different algorithms and extraction of more useful information from the expression data are the key problems for identification of biomarkers. Here, we used three machine learning algorithms to select feature genes based on gene profiling data of gastric cancer (GC). Then, a common divisor was extracted as candidate feature genes aggregation for Tree Building and Tree Pruning analysis by Decision Tree (DT) algorithm. Real-time quantitative PCR and immunohistochemistry (IHC) staining were used to validate the relative expression levels of the candidate feature genes. Receiver operating characteristic curves were used to analyse the classification sensitivity and specificity of the feature genes. A total of 174, 202, 149 feature genes were selected by Class Information Index, Information Gain Index and Relief algorithms, with a common divisor consisting of 32 genes. Using a DT algorithm to contribute to the classification rule sets, we identified COL2A1 and ATP4B as candidate biomarkers of GC. The expression levels of these two genes were validated by real-time PCR and IHC with high sensitivity (>90 %) and specificity (>90 %) in both training and test samples. We first introduced an integral and systematic data-mining model for identification of biomarkers based on gene expression data. The two-gene signature obtained by our predictive model could be used for recognizing the biological characteristic of GC.


[Sensomotor learning and heart rhythm dynamics under the conditions of monocular vision].
According to P. K. Anokhin's general functional system theory, integral behavior is considered to be realization of processes directed towards achieving a useful result. The subjects of the study were a number of students, whose ECG was recorded while they were trained to fulfill a visual-motor task. Successfulness of learning was estimated. The study demonstrated a connection between the heart rhythm dynamics and the level of learning to fulfill visual-motor tasks.


Physicians' attitudes and perceived barriers to adherence to the national breast cancer clinical practice guidelines in Mexico: a survey study.
Adherence to clinical practice guidelines improves outcomes for patients with breast cancer. However, their implementation may not be feasible in low- and middle-income countries. This study aimed to evaluate physicians' adherence, attitudes, and barriers towards the Colima Consensus, which is the Mexican national breast cancer clinical practice guideline. A cross-sectional, 31-item survey was e-mailed to Consensus attendees and members of the Mexican Society of Oncology and Mexican Mastology Association. Descriptive statistics, univariate, and multivariate analysis were used to analyze the associations between participants' characteristics, adherence, attitudes, and barriers. Of 439 respondents, 78% percent adhered to Consensus recommendations and 94% believed it was applicable to their clinical practice. Forty percent reported using the Consensus as their sole breast cancer guideline. This was associated with being a surgical oncologist (OR 3.3, 95% CI 2.0-5.3) and practicing at a public hospital (OR 2.1, 95% CI 1.2-3.7). The most common barriers to adherence were lack of resources and logistical problems. Regarding attitudes towards the Consensus, 90% considered it a good educational tool, 89% considered it a reliable source of information, and 90% thought it improved quality of care. We showed high levels of adherence and positive attitudes towards the Colima Consensus, with a significant proportion of physicians using it as their only guideline. Lack of resources and logistical issues were the main barriers to adherence. Our results highlight the relevance of local breast cancer guidelines and suggest a need for the creation of resource-stratified guidelines.


TV shearography: quantitative measurement of shear-magnitude fields by use of digital speckle photography.
Digital speckle photography combined with TV shearography is developed for precise measurement of the magnitude of the shear field in a linear shear configuration. As an application the method is implemented to determine the slope-change variations of a three-dimensional object with TV shearography in which the shear magnitude is obtained with the digital speckle photography technique.


Surgical aortic valvuloplasty in children and adolescents with aortic regurgitation: acute and intermediate effects on aortic valve function and left ventricular dimensions.
Surgical aortic valvuloplasty is increasingly employed in the management of children and adolescents with aortic regurgitation, but the durability of this approach and factors associated with outcome are not well defined. From 1989 to 2005, a total of 81 patients younger than 19 years with moderate or severe aortic regurgitation underwent surgical aortic valvuloplasty. Aortic regurgitation was congenital in 20 cases, after treatment of aortic stenosis in 30, from other injuries to the aortic valve in 12, and from other causes in 19. Eighteen patients had moderate or severe aortic stenosis. Preoperative left ventricular end-diastolic dimension z score was 4.9 +/- 2.7. After surgical aortic valvuloplasty with various techniques, including pericardial leaflet augmentation in 80%, aortic regurgitation was improved in 77 patients and was mild or less in 68. Ten of 18 patients with moderate or severe aortic stenosis before repair had a decrease to mild, whereas 2 had progression from mild to moderate. Left ventricular end-diastolic dimension z score decreased by 2.9 +/- 2.1 (P < .001). During follow-up (median 4.7 years), 33 patients underwent aortic valve reinterventions, including aortic valve replacement in 25. Estimated freedoms from aortic valve replacement were 72% +/- 6% at 5 years and 54% +/- 9% at 7.5 years and were shorter in patients with moderate or severe aortic stenosis before surgical aortic valvuloplasty. Among surviving patients who did not undergo aortic valve replacement, aortic regurgitation at follow-up was moderate in 21 and trivial or mild in 34; left ventricular and aortic root dimensions were preserved. Surgical aortic valvuloplasty is a valid option with good intermediate results for children and adolescents with aortic regurgitation from a variety of causes, particularly for patients with less than moderate aortic stenosis.


CT of the spine.
The level of CT section in the lumbosacral region may be correlated with routine AP views of the spine using a reference plane constructed according to the distance between the iliac crests. CT scans of the spine in 100 patients have been analyzed. The majority of these cases consisted of primary or secondary bone or soft-tissue tumors. CT examination was valuable to supplement plain films and/or myelograms in evaluation of the extent of pathology. It was also useful in the work-up of patients with malignant tumors whose other studies were equivocal.


The Mechanism of Hyperoxia-Induced Neonatal Renal Injury and the Possible Protective Effect of Resveratrol.
With recent advances in neonatal intensive care, preterm infants are surviving into adulthood. Nonetheless, epidemiological data on the health status of these preterm infants have begun to reveal a worrying theme; prematurity and the supplemental oxygen therapy these infants receive after birth appear to be risk factors for kidney disease in adulthood, affecting their quality of life. As the incidence of chronic kidney disease and the survival time of preterm infants both increase, the management of the hyperoxia-induced renal disease is becoming increasingly relevant to neonatologists. The mechanism of this increased risk is currently unknown, but prematurity itself and hyperoxia exposure after birth may predispose to disease by altering the normal trajectory of kidney maturation. This article reviews altered renal reactivity due to hyperoxia, the possible mechanisms of renal injury due to hyperoxia, and the role of resveratrol in renal injury. KEY POINTS: · Premature infants commonly receive supplementary oxygen.. · Hyperoxia can cause kidney damage via signal pathways.. · We should reduce the occurrence of late sequelae..


Effect of subtle positioning flaws on measured bone mineral density of the hip.
Careful hip positioning is necessary for accurate and precise measurement of bone mineral density (BMD) by dualenergy X-ray absorptiometry (DXA). Large, intentional rotational deviations from best hip position reportedly increase measured BMD at the femoral neck. The aim of this study is to determine the effect of unintentional, subtle deviations from best hip position ("flaws") on expected and measured BMD of the hip and its subregions. Two hundred DXA scans (GE/Lunar Prodigy) performed in the dual-femur mode were randomly selected and scrutinized for hip-positioning flaws. Hips were sorted by side (right/left), positioning quality (flawless/flawed), and specific positioning flaw (under/over-rotation and adduction/abduction). Individual hip pairs in which at least one hip was flawlessly positioned were further sorted as flawless/flawless, flawless/vertically flawed, flawless/rotationally flaw, and flawless/dually flawed. Differences and direction of difference in BMD between sorted groups and within individual hip pairs were analyzed by univariate analysis (t-test for equal samples). Two hundred hip pairs (400 individual hip scans) were analyzed. Overall, there was no significant difference in BMD between all right and all left hips or between all flawlessly positioned and all flawed hips. In hip pairs in which one hip was flawlessly positioned and the contralateral hip position was flawed (vertically, rotationally, or both), the measured BMD of the latter hip was not predictably greater than the former. Average absolute intrapair BMD difference between hip subregions was 0.038+/-0.001 g/cm2 and was unaffected by the presence or type of positioning flaw. Net intrapair difference between sorted hip groups and within hip pairs was negligible, indicating that the direction of the variance was equally positive and negative. In the practice of clinical densitometry, subtle positioning flaws do not generate predictable changes in measured BMD at any hip region of interest. The current teaching that rotational deviations from best hip position results in a greater measured BMD needs to be reconsidered when comparing a rotationally flawed hip with a contralateral flawlessly positioned hip.


PmiRtarbase: A positive miRNA-target regulations database.
MicroRNAs (miRNAs) are ~22 nt small non-coding RNA segments that are widely involved in the regulation of gene expression. Accumulating evidences show that miRNAs not only inhibit the expression of some targeted genes but also promote that of some targeted genes in specific conditions. Over the past decades, many miRNA-target databases have been developed from computational prediction and/or experimental validation perspectives. However, there is no database available to systematically collect positive miRNA-target associations that are essential in deciphering the miRNA regulation mechanism. To promote the miRNA study, we developed a new database: PmiRtarbase that acquires validated positive miRNA-target interactions by mining published literature. It includes 312 curated associations between 119 miRNAs and 169 genes in 8 species from 130 studies and summarizes the conditions and detailed descriptions of the miRNA-target associations. We also constructed a database named PmiRtarbase, a user-friendly interface to conveniently search and download all related entries. This elaborate database aims to serve as a beneficial resource for studying the miRNA positive regulation mechanism and miRNA-based therapeutics. DATA AVAILABILITY: The full positive miRNA-target data can be accessed through the link http://www.lwb-lab.cn/PmiRtarbase. Users of this dataset should acknowledge the contributions of the original authors and properly cite this article.


Efficacy of modified time of flight magnetic resonance venography in diagnosis of iliac vein compression syndrome.
We investigated the diagnostic efficacy of modified time of flight magnetic resonance venography (mTOF-MRV) for iliac vein compression syndrome diagnosis by optimizing the scanning parameters and improving image quality. A retrospective study was conducted on 69 patients who underwent routine time of flight magnetic resonance venography (TOF-MRV) and 85 patients who received mTOF-MRV. Assessment of image quality of the two methods was performed by two radiologists using a four-point method. The sensitivity, specificity, positive and negative predictive values of TOF-MRV and mTOF-MRV in the diagnosis of significant iliac vein compression (stenosis >50%) were analyzed by calculating the iliac vein stenosis rates of the two methods and using digital subtraction angiography (DSA) as the gold standard. Inter-observer assessment of objective data measurement revealed excellent agreement {ICC [95% confidence interval (CI)]: 0.972 (0.953 to 0.983) for TOF-MRV and 0.979 (0.965 to 0.988) for m-TOF MRV, 0.976 (0.960 to 0.986) for DSA}. The mean error of stenosis rate of mTOF-MRV was markedly smaller than that of TOF-MRV (p < 0.05). Sensitivity, specificity, positive and negative predictive values of TOF-MRV in the diagnosis of significant stenosis were 100%, 95%, 67% and 100%, respectively. The sensitivity, specificity, positive and negative predictive values of mTOF-MRV were 100%. The mean image score for the mTOF-MRV was 3.63 ± 0.59, which was significantly higher compared with that of TOF-MRV (2.19 ± 0.42). mTOF-MRV has better image quality and can accurately diagnose venous stenosis. Therefore, it can be used for the detection of iliac vein compression syndrome and further assessment after endovascular interventions.


T-tubule remodeling in human hypertrophic cardiomyopathy.
The highly organized transverse T-tubule membrane system represents the ultrastructural substrate for excitation-contraction coupling in ventricular myocytes. While the architecture and function of T-tubules have been well described in animal models, there is limited morpho-functional data on T-tubules in human myocardium. Hypertrophic cardiomyopathy (HCM) is a primary disease of the heart muscle, characterized by different clinical presentations at the various stages of its progression. Most HCM patients, indeed, show a compensated hypertrophic disease ("non-failing hypertrophic phase"), with preserved left ventricular function, and only a small subset of individuals evolves into heart failure ("end stage HCM"). In terms of T-tubule remodeling, the "end-stage" disease does not differ from other forms of heart failure. In this review we aim to recapitulate the main structural features of T-tubules during the "non-failing hypertrophic stage" of human HCM by revisiting data obtained from human myectomy samples. Moreover, by comparing pathological changes observed in myectomy samples with those introduced by acute (experimentally induced) detubulation, we discuss the role of T-tubular disruption as a part of the complex excitation-contraction coupling remodeling process that occurs during disease progression. Lastly, we highlight how T-tubule morpho-functional changes may be related to patient genotype and we discuss the possibility of a primitive remodeling of the T-tubule system in rare HCM forms associated with genes coding for proteins implicated in T-tubule structural integrity, formation and maintenance.


Failure of selective termination and dexamethasone rescue therapy to arrest HELLP syndrome in a midtrimester triplet gestation with one triploid fetus.
We present a case of a patient with a triplet pregnancy at 22 weeks with one triploid fetus (69XXX) who developed severe preeclampsia that did not reverse with dexamethasone rescue therapy and selective termination. With multiple gestations on the rise and the early diagnosis of abnormal pregnancies being accomplished through ultrasound, serum markers, and invasive procedures, the question remains if there is a point in gestation before which selective termination of an abnormal fetus would allow the pregnancy to continue without preeclampsia developing or progressing. Appropriate counseling as to the maternal risk in cases of trisomy 13 or triploidy is essential as early in pregnancy as possible.


Epidemiological investigation of cerebrovascular disease in Iceland, 1958-1968 (ages 0-35 years): a total population survey.
This study was undertaken to estimate the incidence of cerebrovascular disease in the age group 0-35 years in the population of Iceland during the 11 year period 1958 through 1968. The incidence for the whole country was 7.9/100,000-- males 7.5 and females 8.4. The incidence in Reykjavik, 8.3/100,000, was not significantly different from the rest of the country (7.2/100,000)nor was there any significant difference between the sexes. Comparison is made with similar studies.


Severe or Profound Sensorineural Hearing Loss Caused by Novel USH2A Variants in Korea: Potential Genotype-Phenotype Correlation.
We, herein, report two novel USH2A variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL). Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. We conducted the whole exome sequencing and subsequent pathogenicity prediction analysis. We identified the following variants of USH2A from the two probands manifesting more than severe SNHL and retinitis pigmentosa (RP): compound heterozygosity for a nonsense (c.8176C>T: p.R2723X) and a missense variant (c.1823G>A: p.C608Y) in SB237, and compound heterozygosity for two frameshift variants (c.14835delT: p.S4945fs & c.13112_13115delAAAT: p.G4371fs) in SB354. Based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, two novel variants, c.1823G>A: p.C608Y and c.14835delT: p.Ser4945fs, can be classified as "uncertain significance" and "pathogenic," respectively. The audiogram exhibited more than severe SNHL and a down-sloping configuration, necessitating cochlear implantation. The ophthalmic examinations revealed typical features of RP. Interestingly, one proband (SB 354-692) carrying two truncating compound heterozygous variants exhibited more severe hearing loss than the other proband (SB 237-461), carrying one truncation with one missense variant. Our results provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring USH2A variants, suggesting that USH2A should also be included in the candidate gene of cochlear implantation. A specific combination of USH2A variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of USH2A variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with USH2A will be helpful for genetic counseling and treatment starategy.


Optimizing community and stakeholder engagement in a merger of community health centres.
Community Health Centres (CHCs) are grounded in a model of care that includes engagement with the community and have a history of working with communities to respond to emerging needs. Although most CHCs consider themselves to be integrated, mergers in this sector are uncommon. In Ontario, the first voluntary merger of CHCs showed the importance of community engagement to realize the intended benefits of the integration and to effectively manage change.


3-[Substituted]-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitriles: identification of highly potent and selective metabotropic glutamate subtype 5 receptor antagonists.
Structure-activity relationship studies on the phenyl ring of 3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile 2 led to the discovery that small, non-hydrogen bond donor substituents at the 3-position led to a substantial increase in in vitro potency. In particular, 3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile (7) is a highly potent and selective mGlu5 receptor antagonist with good rat pharmacokinetics, brain penetration, and in vivo receptor occupancy.


The chemical peel.
The spectrum of chemical peeling encompasses a diverse group of peeling agents with the ability to produce a wide range of cutaneous burns. The most spectacular peels are produced by the phenol formulas. The physician, however, is restricted in the number of potential candidates as determined by skin color and potential toxicity. While not as impressive, trichloroacetic acid peels are an excellent modality for treatment of actinic keratoses, actinic dermatitis and lentigoes. Improvement of rhytides, skin tone, and texture can be impressive. Utilization of TCA may require repetitive peeling to obtain the desired result. With the alarming increase in the incidence of severe facial solar radiation as manifested by multiple premalignant and in situ malignant lesions, therapeutic chemical peeling has become an increasingly important procedure. The dermatologic surgeon can not only eradicate the multitude of facial lesions present but also markedly diminish the incidence of new lesions.


SNARE Dance: a musical interpretation of Atg9 transport to the tubulovesicular cluster.
There is little doubt that humans rely on vision as their primary sensory input. However, various studies indicate that audiovisual combinations of data presentation actually enhance the ability of the learner to comprehend the information. We present an example of a musical-biological interface that provides an audible demonstration of SNARE protein function in the process of macroautophagy.


Inflammatory mediators expressed in human islets of Langerhans: implications for islet transplantation.
Expression of immune modulating mediators in human Islets of Langerhans could have important implications for development of autoimmunity in type 1 diabetes and influence the outcome of clinical islet transplantation. Islets obtained from five donors were analyzed at various times after isolation using cDNA array technology. The Atlas Human Cytokine/Receptor and Hematology/Immunology nylon membranes representing 268 genes and 406, respectively, were used and the relative expression of each gene analyzed. Of the 51 gene products identified, high mRNA expression of MCP-1, MIF, VEGF, and thymosin beta-10 was detected in all islet samples. IL-8, IL-1-beta, IL-5R, and INF-gamma antagonist were expressed in islets cultured for 2 days. IL-2R was expressed in islets cultured for more than 6 days. In conclusion, several inflammatory mediators were expressed in isolated islets, particularly at an early stage after isolation, indicating that a few days of culture could be beneficial for the outcome of islet transplantation.


The impact of coping strategies on weight control in the aftermath of dietary lapses in a high impulsivity group.
Individuals with high impulsivity tend to overeat on impulse. The objective of this study was to examine methods of weight control, focusing on coping with the aftermath of dietary lapses, among those who have high impulsivity. Eight hundred adults aged 20-59 years, who were registered with a research company completed a self-reported cross-sectional questionnaire. They were classified into low and high impulsivity groups using the median impulsivity score measured with the Barratt Impulsiveness Scale. We compared coping strategies in the aftermath of dietary lapses between the two groups. We also examined the correlation between coping methods and body mass index (BMI) using multiple regression analysis in the low and high impulsivity groups. The high impulsivity group used more coping strategies, such as self-monitoring, self-reflective thoughts, and positive thoughts. The main finding of this study was that compensation by healthy eating was negatively correlated with BMI in the high impulsivity group. Additionally, positive thoughts were positively correlated with BMI. The results suggest that compensation with healthy eating in the aftermath of dietary lapses is important to control weight in those with high impulsivity.


Patterns of Time Use among 12-Year-Old Children and Their Life Satisfaction: A Gender and Cross-Country Comparison.
Despite the importance of children's time use to their quality of life, relatively few international comparative studies have focused on the patterns of children's time use and their relationship with quality of life. This study, therefore, aimed to examine the typologies of time use among 12-year-old children by gender and their relationship with their quality of life. We used the second wave of data from the International Survey of Children's Well-Being collected from 16 countries. Children's time use, gender, satisfaction with time use, and life satisfaction were included as the key variables. Latent class analysis using MPLUS 7.0 was utilized. Gender differences in the classification of time-use patterns were identified. Three latent classes (G1, G2, and G3) were identified for girls. Overall high activity group (G1) had the highest level of satisfaction, whereas family helpers (G3) had the lowest level of satisfaction with their time use and life in general. Boys, however, were classified into four classes (B1, B2, B3, and B4). Overall high activity group (B4) had the highest levels of satisfaction with their time use and life in general. The results show that children who actively engage in various activities experience the most satisfaction with their lives and time. Substantial gender differences in time use, particularly around typical gender roles (e.g., housework and family caring), are noteworthy. Programs and policies that encourage children to reduce digital time and enhance activities in other areas are also discussed.


Common rodenticide toxicoses in small animals.
This article focuses on the 3 most commonly used rodenticide types: anticoagulants, bromethalin, and cholecalciferol. It is important to verify the active ingredient in any rodenticide exposure. Many animal owners may use the term "D-con" to refer to any rodenticide regardless of the actual brand name or type of rodenticide. The EPA released their final ruling on rodenticide risk mitigation measures in 2008 and all the products on the market had to be compliant by June 2011, changing to consumer products containing either first-generation anticoagulants or nonanticoagulants including bromethalin and cholecalciferol. These regulations are likely to cause an increase in the number of bromethalin and cholecalciferol cases.


Thermal Resistance Variations of Fly Ash Geopolymers: Foaming Responses.
This paper presents a comparative study of the characteristic of unfoamed and foamed geopolymers after exposure to elevated temperatures (200-800 °C). Unfoamed geopolymers were produced with Class F fly ash and sodium hydroxide and liquid sodium silicate. Porous geopolymers were prepared by foaming with hydrogen peroxide. Unfoamed geopolymers possessed excellent strength of 44.2 MPa and degraded 34% to 15 MPa in foamed geopolymers. The strength of unfoamed geopolymers decreased to 5 MPa with increasing temperature up to 800 °C. Foamed geopolymers behaved differently whereby they deteriorated to 3 MPa at 400 °C and increased up to 11 MPa at 800 °C. Even so, the geopolymers could withstand high temperature without any disintegration and spalling up to 800 °C. The formation of crystalline phases at higher temperature was observed deteriorating the strength of unfoamed geopolymers but enhance the strength of foamed geopolymers. In comparison, foamed geopolymer had better thermal resistance than unfoamed geopolymers as pores provide rooms to counteract the internal damage.


Movements of radioactive potassium in isolated rat ganglia.
1. Isolated rat superior cervical ganglia were continuously superfused with (42)K (or (86)Rb) solution and the amount of radioactivity taken up was monitored using scintillation counting.2. Entry of (42)K into the ganglia could be resolved into two components, one amounting to 83% of the total (42)K uptake, with a rate constant of 0.015 min(-1), and the other of 17% of the total, with a rate constant of 0.15 min(-1).3. With 6 mM-K in the bathing solution, the equilibrium uptake of (42)K after 4 hr corresponded to an intracellular concentration of 147 mM-K. Changes in the K concentration of the bathing solution (0.5-20 mM) had little effect on this value.4. Carbachol or nicotine caused a rapid net loss of (42)K. (42)K was recaptured on washing out the depolarizing agents, with a rate constant of about 0.3 min(-1). This recapture rate was slowed by ouabain, dinitrophenol, cyanide, mersalyl and by reducing the K concentration in the bathing solution.5. Efflux of (42)K from preloaded ganglia occurred with a rate constant of 0.017 min(-1). This rate was increased about sixfold by 180 muM carbachol in 6 mM-K but not in 150 mM-K suggesting that the increase in efflux was mainly a consequence of the depolarization caused by carbachol.6. (86)Rb fluxes and the effects of carbachol thereon were similar.


Familial Factors Associated With Symptom Severity in Children and Adolescents With ADHD: A Meta-Analysis and Supplemental Review.
Both genetic and environmental factors contribute to the development of ADHD, but associations between risk factors and ADHD symptom severity in affected children remain unclear. This systematic review and meta-analysis synthesizes evidence on the association between familial factors and symptom severity in children with ADHD (PROSPERO CRD42020076440). PubMed and PsycINFO were searched for eligible studies. Forty-three studies (N = 11,123 participants) were meta-analyzed. Five additional studies (N = 2,643 participants) were considered in the supplemental review. Parenting stress (r = .25), negative parenting practices (r = .19), broken parental partnership (r = .19), critical life events (r = .17), parental psychopathologies (r = .14-.16), socioeconomic status (r = -.10), and single-parent family (r = .10) were significantly associated with ADHD symptom severity. These results suggest that psychosocial familial factors show small but significant associations with symptom severity in children with ADHD. Implications are discussed.


Effect of acupressure in nausea and vomiting treatment during pregnancy: A meta-analysis.
Many women experience nausea and vomiting in early pregnancy. Regardless of the disease severity, it affects the work and life of pregnant women. However, drug treatment may potentially impact the foetus; thus, alternative safe and effective measures are essential. We aimed to evaluate the effect of acupressure, a non-drug treatment for nausea and vomiting, during pregnancy. PubMed, EMBASE, Cochrane, Web of Science, CNKI, CBM, VIP, and Wanfang databases were searched using 'pregnancy', 'nausea', 'vomiting', and 'acupressure' as keywords. The search period was from database inception to 30 November 2022. Two researchers independently screened articles, extracted data, and used RevMan 5.4 software for statistical analysis. We included 33 trials and 3 390 patients in this meta-analysis. Acupressure was effective for women with nausea and vomiting during pregnancy (odds ratio (OR)= 4.81, 95% confidence interval (CI) [3.47, 6.68]; p<0.0001); it significantly reduced the nausea score of the Rhodes index (mean square deviation (MD): -3.21, 95% CI [-4.85, -1.57], Z = 3.83, p = 0.0001), modified Pregnancy Unique Quantification of Emesis and Nausea score (MD: -2.18, 95% CI [-3.21, -1.15], Z = 4.15, p<0.0001), and hospital stay (OR=-3.27, 95% CI [-6.18, -0.36]; p = 0.03) and improved quality of life (MD: -14.06,95% CI [- 17.31, -10.18], Z = 8.48, p<0.00001). However, no significant difference was observed in nursing satisfaction and anxiety scores (OR=4.13, 95% CI [0.89, 19.15]; p = 0.07) (MD: -13.26,95% CI [-32.04,5.53], Z = 1.38, p = 0.17). This meta-analysis provides evidence of a non-drug intervention for women with nausea and vomiting during pregnancy; acupressure effectively reduces nausea and vomiting during pregnancy.


A modular approach for cytosolic protein delivery: metal ion-induced self-assembly of gold nanoclusters as a general platform.
We developed a versatile and modular method for cytosolic protein delivery through metal ion-induced co-assembly of gold nanoclusters and proteins into supramolecular assemblies. The versatility and high efficiency of this strategy to assemble and deliver various proteins into living cells were demonstrated. Importantly, the activity of proteins was maintained during the delivery. This modular approach provides an exciting and promising new nano-platform for cytosolic protein delivery.


Perceptions of Multidisciplinary Renal Team Members toward Home Dialysis Therapies.
Patients with ESKD are encouraged to pursue home dialysis therapy with the aims of improving quality of life, increasing patient autonomy, and reducing cost to health care systems. In a multidisciplinary team setting, patients interact with nephrologists, nurses, and allied health staff, all of whom may influence a patient's modality choice. Our objective was to evaluate the perceptions of all renal team members toward home dialysis therapies. We performed a cross-sectional survey of multidisciplinary renal team members across five renal programs in British Columbia, Canada. The survey contained questions regarding primary work area, modality preference, patient and system factors that may influence modality candidacy, perceived knowledge of home therapies, and need for further education. A total of 334 respondents (22 nephrologists, 172 hemodialysis nurses, 49 home nurses, 20 predialysis nurses, and 71 allied health staff) were included (48% response rate). All respondents felt that home dialysis was beneficial for patients who work or study, improved patients' quality of life, and provided cost savings to the system. Compared with in-center hemodialysis nurses, home therapies nurses were between five and nine times more likely to favor a home therapy for patients of older age, lower socioeconomic status, lower educational level, higher burden of comorbidities, and those lacking social supports. Nephrologists and patients were felt to have the most influence on modality choice, whereas dialysis nurses were seen as having the least effect on modality choice. Most respondents felt the need for further education in home therapies. The majority of multidisciplinary team members, including allied health staff, acknowledged the benefits of home therapies. There were significant discrepancies among team members regarding patient-/system-level factors that may affect the candidacy of home therapies. Structured, focused, and repeated education sessions for all renal team members may help to address misperceptions around factors that influence modality candidacy.


MicroRNA-146a and microRNA-146b deficiency correlates with exacerbated disease activity, and their longitude increment relates to etanercept response in psoriasis patients.
MicroRNA (miR)-146a and miR-146b regulate autoimmunity, inflammation, and keratinocytes proliferation to engage in psoriasis pathology. The current study aimed to investigate their correlation with disease risk and clinical features, and the linkage of their longitudinal changes with clinical response to etanercept in psoriasis patients. Plasma samples were collected from 84 moderate-to-severe psoriasis patients who underwent etanercept treatment (at baseline (M0), 1 month (M1), 3 months (M3), and 6 months (M6)), 80 disease controls and 80 health controls (both after enrollment); afterward, miR-146a and miR-146b expressions were detected by RT-qPCR. Furthermore, PASI75 and PASI90 responses were assessed in psoriasis patients. Both miR-146a and miR-146b were decreased in psoriasis patients compared with disease controls and health controls (all p < 0.001), which also distinguished psoriasis patients from disease controls and health controls by receiver-operating characteristic analyses. Furthermore, miR-146a positively correlated with miR-146b in psoriasis patients (p < 0.001) and disease controls (p = 0.005) but not in healthy controls (p = 0.062). In psoriasis patients, miR-146a negatively related to psoriatic body surface area (p = 0.011) and PASI score (p = 0.003); miR-146b negatively linked with PASI score (p = 0.020). At M1, M3, and M6 after etanercept treatment, PASI75 response rate was 14.3%, 32.1%, and 69.0%, respectively; PASI90 response rate was 1.2%, 17.9%, and 36.9%, respectively. During etanercept treatment, both miR-146a and miR-146b elevated gradually over time and their longitude increments were associated with PASI75 response (all p < 0.001). MiR-146a and miR-146b might serve as indicators for optimizing etanercept application and improving treatment outcomes in psoriasis patients.


Fetal liver hematopoietic stem cell niches associate with portal vessels.
Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver niche is not yet elucidated. We show that Nestin(+)NG2(+) pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin(+)NG2(+) cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1(+)Ephrin-B2(+) artery to EphB4(+) vein phenotype, associated with a loss of periportal Nestin(+)NG2(+) cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a periportal vascular niche with a fractal-like organization enabled by placental circulation.


Molecular evolution of plants as deduced from changes in free energy of 5S ribosomal RNAs.
The nucleotide sequence of Pinus silvestyris 5S rRNA was determined using two independent methods and compared with other plant 5S rRNAs. It shows more than 90% sequence homology with gymnosperm 5S RNAs. The free energy (delta G) analysis of 5S rRNAs from gymnosperms, angiosperms and the other higher plants revealed that the free energy of this ribosomal RNA decreases with evolution.


Is antibiotic treatment effective in the management of chronic low back pain with disc herniation? Study protocol for a randomised controlled trial.
There has been immense interest and debate regarding the effectiveness of antibiotic treatment for chronic low back pain. Two randomised controlled trials have examined the efficacy of antibiotics for chronic low back pain with disc herniation and Modic changes, but have reported conflicting results. The aim of this double-blind, randomised, placebo-controlled trial is to determine the efficacy of antibiotic treatment in a broader patient subgroup of chronic low back pain with disc herniation and investigate whether the presence of Modic changes predicts response to antibiotic therapy. One hundred and seventy individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics; advertising in national, community and social media; and posting of flyers in community locations. They will be randomly allocated to receive either amoxicillin-clavulanate (500 mg/125 mg) twice per day for 90 days or placebo. The primary outcome measure of pain intensity will be assessed using the Low Back Pain Rating scale and a 100-mm visual analogue scale at 12 months. Secondary measures of self-reported low back disability and work absence and hindrance will also be examined, and an economic analysis will be conducted. Intention-to-treat analyses will be performed. There is uncertainty about whether antibiotic treatment is effective for chronic low back pain and, if effective, which patient subgroup is most likely to respond. We will conduct a clinical trial to investigate the efficacy of antibiotics compared with placebo in individuals with chronic low back pain and a disc herniation. Our findings will provide high-quality evidence to assist in answering these questions. Australian New Zealand Clinical Trials Registry ACTRN12615000958583 . Registered on 11 September 2015.


Lymphocyte infiltration into normal rat brain following hyperosmotic blood-brain barrier opening.
An investigation was conducted to determine whether lymphocytes were able to infiltrate into the brain parenchyma of normal rats in which hyperosmotic opening of the blood-brain barrier (BBB) had been created by internal carotid infusion of filtered 20% mannitol. Various numbers (1 x 10(6) to 3 x 10(8] of autologous lymphocytes were injected into the internal carotid artery, or via a tail vein, after BBB opening. Lymphocytes were detectable in the brain of rats subjected to high-grade BBB opening and injected with a high number of lymphocytes. Subsets of lymphocytes were examined by immunohistochemical staining using OX19, W3/25 and OX8 monoclonal antibodies. There was no remarkable difference in number between W3/25- and OX8-positive cells. From these results it was suggested that the intensity of BBB opening and the number of lymphocytes flowing in brain vessels are related to the passage of lymphocytes through the BBB.


Perceptrons from memristors.
Memristors, resistors with memory whose outputs depend on the history of their inputs, have been used with success in neuromorphic architectures, particularly as synapses and non-volatile memories. However, to the best of our knowledge, no model for a network in which both the synapses and the neurons are implemented using memristors has been proposed so far. In the present work we introduce models for single and multilayer perceptrons based exclusively on memristors. We adapt the delta rule to the memristor-based single-layer perceptron and the backpropagation algorithm to the memristor-based multilayer perceptron. Our results show that both perform as expected for perceptrons, including satisfying Minsky-Papert's theorem. As a consequence of the Universal Approximation Theorem, they also show that memristors are universal function approximators. By using memristors for both the neurons and the synapses, our models pave the way for novel memristor-based neural network architectures and algorithms. A neural network based on memristors could show advantages in terms of energy conservation and open up possibilities for other learning systems to be adapted to a memristor-based paradigm, both in the classical and quantum learning realms.


Surgery in Malawi - a national survey of activity in rural and urban hospitals.
Malawi is a poor country with few doctors. It has 21 district hospitals all of which have operating theatres but none of which has a permanent surgeon. It also has 4 central hospitals, each with one or more surgeons. Most district hospitals are manned by a single doctor and two or more paramedical clinical officers. All district and central hospitals were visited, and theatre logbooks analysed. All cases performed in 2003 were recorded. In 2003, a total of 48,696 surgical operations were recorded, of which 25,053 were performed in 21 district hospitals and 23,643 in 4 central hospitals. Caesarean section is the commonest major surgical procedure in district hospitals and is performed in approximately 2.8% of all births, compared to 22% in the UK. Very few major general surgical or orthopaedic procedures are carried out in district hospitals. This study underlines Malawi's need for more surgeons to be trained and retained.


Age, gender, and body mass index are associated with renal function after kidney donation.
Renal function is thoroughly evaluated before live kidney donation. However, some donors experience impaired recovery of renal function after donation. Our aim was to assess estimated glomerular filtration rate (eGFR) and mean relative (%) increase in creatinine one yr after donor nephrectomy. The study was based on retrospective data from kidney donors during the period 1997-2009. Pre-operative and one-yr follow-up data were available for 721 of 1067 donors. Mean relative increase in creatinine and eGFR were stratified by gender, body mass index (BMI), and age at donation. At one yr post-donation, overweight (BMI > 5 kg/m(2) ) women 50 yr or older experienced the lowest eGFR of 49.6 ± 8.8 mL/min/1.73 m(2) . Men younger than 50 yr with normal weight (BMI < 25 kg/m(2) ) had the highest eGFR of 66.6 ± 10.4 mL/min/1.73 m(2) . Overweight men 50 yr or older had the highest relative increase in creatinine of 49.4% compared to pre-donation. Men under 50 yr with normal weight had the smallest increase in creatinine of 35.2%. In multivariate analysis, older age (p < 0.001), male gender (p < 0.001), and overweight (p = 0.01) were associated with relative increase in creatinine after donation. Potential donors should be offered counseling regarding overweight, as this is a modifiable risk factor.


Diagnostic accuracy of urinary creatinine concentration in the estimation of differential renal function in patients with obstructive uropathy.
To determine the diagnostic accuracy of spot urine creatinine concentration (UCC) as a new test for the evaluation of differential renal function in obstructed kidneys (DRF(ok)) drained by percutaneous nephrostomy tube (PCNT). In patients with obstructed kidneys drained by PCNT, DRF(ok) was derived from UCC by comparing the value of UCC in the obstructed kidney to the value in the contralateral kidney, and was derived from dimercaptosuccinic acid (DMSA) renal scans and creatinine clearance (CCr) using standard methods. Subsequently, the results of UCC were compared to the results of DMSA and CCr. 61 patients were enrolled. Bland-Altman plots to compare DMSA and UCC showed that the upper limit of agreement was 14.8% (95% CI 10.7-18.5) and the lower limit was -19.9% (95% CI -23.8 to -16.1). The sensitivity and specificity of detecting DMSA DRF(ok) < or = 35% using UCC was 85.2 and 91.2%, respectively. When UCC was compared to CCr, Bland-Altman tests gave an upper limit of agreement of 10.4% (95% CI 7.9-12.8) and a lower limit of agreement of -11.3% (95% CI -13.8 to -8.9). UCC is accurate in the estimation of DRF(ok) drained by PCNT.


An interactive system for computer-aided diagnosis of breast masses.
Although mammography is the only clinically accepted imaging modality for screening the general population to detect breast cancer, interpreting mammograms is difficult with lower sensitivity and specificity. To provide radiologists "a visual aid" in interpreting mammograms, we developed and tested an interactive system for computer-aided detection and diagnosis (CAD) of mass-like cancers. Using this system, an observer can view CAD-cued mass regions depicted on one image and then query any suspicious regions (either cued or not cued by CAD). CAD scheme automatically segments the suspicious region or accepts manually defined region and computes a set of image features. Using content-based image retrieval (CBIR) algorithm, CAD searches for a set of reference images depicting "abnormalities" similar to the queried region. Based on image retrieval results and a decision algorithm, a classification score is assigned to the queried region. In this study, a reference database with 1,800 malignant mass regions and 1,800 benign and CAD-generated false-positive regions was used. A modified CBIR algorithm with a new function of stretching the attributes in the multi-dimensional space and decision scheme was optimized using a genetic algorithm. Using a leave-one-out testing method to classify suspicious mass regions, we compared the classification performance using two CBIR algorithms with either equally weighted or optimally stretched attributes. Using the modified CBIR algorithm, the area under receiver operating characteristic curve was significantly increased from 0.865 ± 0.006 to 0.897 ± 0.005 (p < 0.001). This study demonstrated the feasibility of developing an interactive CAD system with a large reference database and achieving improved performance.


High Entropy Pr-Doped Hollow NiFeP Nanoflowers Inlaid on N-rGO for Efficient and Durable Electrodes for Lithium-Ion Batteries and Direct Borohydride Fuel Cells.
The selection and design of new electrode materials for energy conversion and storage are critical for improved performance, cost reduction, and mass manufacturing. A bifunctional anode with high catalytic activity and extended cycle stability is crucial for rechargeable lithium-ion batteries and direct borohydride fuel cells. Herein, a high entropy novel three-dimensional structured electrode with Pr-doped hollow NiFeP nanoflowers inlaid on N-rGO was prepared via a simple hydrothermal and self-assembly process. For optimization of Pr content, three (0.1, 0.5, and 0.8) different doping ratios were investigated. A lithium-ion battery assembled with NiPr0.5 FeP/N-rGO electrode achieved an outstanding specific capacity of 1.61 Ah g-1 at 0.2 A g-1 after 100 cycles with 99.3 % Coulombic efficiencies. A prolonged cycling stability of 1.02 Ah g-1 was maintained even after 1000 cycles at 0.5 A g-1 . In addition, a full cell battery with NiPr0.5 FeP/N-rGO∥LCO (Lithium cobalt oxide) delivered a promising cycling performance of 0.52 Ah g-1 after 200 cycles at 0.15 A g-1 . Subsequently, the NiPr0.5 FeP/N-rGO electrode in a direct borohydride fuel cell showed the highest peak power density of 93.70 mW cm-2 at 60 °C. Therefore, this work can be extended to develop advanced electrode for next-generation energy storage and conversion systems.


Properties of normal and glycated human hemoglobin in presence and absence of antioxidant.
We present a novel approach to study properties of normal (HbA) and nonenzymatically glycated (HbA(Ic), HbA(Ia+b)) human hemoglobin using absorption spectroscopy and differential scanning calorimetry. The effect of the presence of the antioxidant fisetin on glycation of HbA is studied. Here, absorption spectroscopy has been fruitfully exploited to observe the formation of the glycated hemoglobin. With the differential scanning calorimetry, we studied the thermal unfolding of the protein hemoglobin at various conditions. The thermogram of the pure HbA showed two transition regions, with the occurrence of a partially unfolded intermediate state (the formation of which is mainly reversible) prior to complete denaturation (irreversible process). The denaturation temperature of HbA was found to be strongly dependent on the heating rate. Furthermore, there is a significant cooperativity between the two transition regions in pure HbA. The overall denaturation for the glycated hemoglobin takes place at a lower temperature, suggesting a decrease in the stability of the protein when it is glycated. In presence of fisetin, glycation is inhibited to a certain extent and the thermograms match well with that of normal HbA. Implications of the results are discussed.


Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts.
Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is a rare multisystem disorder characterized by extensive intracranial calcifications and cysts, leukoencephalopathy, and retinal vascular abnormalities. Additional features include poor growth, skeletal and hematological abnormalities, and recurrent gastrointestinal bleedings. Autosomal-recessive inheritance has been postulated. The pathogenesis of CRMCC is unknown, but its phenotype has key similarities with Revesz syndrome, which is caused by mutations in TINF2, a gene encoding a member of the telomere protecting shelterin complex. After a whole-exome sequencing approach in four unrelated individuals with CRMCC, we observed four recessively inherited compound heterozygous mutations in CTC1, which encodes the CTS telomere maintenance complex component 1. Sanger sequencing revealed seven more compound heterozygous mutations in eight more unrelated affected individuals. Two individuals who displayed late-onset cerebral findings, a normal fundus appearance, and no systemic findings did not have CTC1 mutations, implying that systemic findings are an important indication for CTC1 sequencing. Of the 11 mutations identified, four were missense, one was nonsense, two resulted in in-frame amino acid deletions, and four were short frameshift-creating deletions. All but two affected individuals were compound heterozygous for a missense mutation and a frameshift or nonsense mutation. No individuals with two frameshift or nonsense mutations were identified, which implies that severe disturbance of CTC1 function from both alleles might not be compatible with survival. Our preliminary functional experiments did not show evidence of severely affected telomere integrity in the affected individuals. Therefore, determining the underlying pathomechanisms associated with deficient CTC1 function will require further studies.


Inhibition of anti-class I cytotoxicity by anti-class II monoclonal antibodies (MoAb). I. Blocking of bulk non-DR and non-DQ-directed cytotoxic T cells by MoAb against DR, DQ, and DP.
We previously demonstrated that although human cytotoxic T lymphocytes (CTL) generated against a lymphoblastoid cell line (LCL) mutant that had lost DR and DQ (formerly known as MB) expression were directed primarily at class I antigens, the lytic activity of such CTL could be inhibited by monoclonal antibodies (MoAb) against monomorphic determinants on DR molecules. Furthermore, the inhibitory effect was found to occur by binding of the MoAb to the target cell, not the effector cell, because lysis of LCL target cells not expressing DR was not inhibited. In this paper we extend this phenomenon to show (i) that MoAbs directed against DQ and DP class II gene products also inhibit the lysis of LCL target cells by CTLs recognizing class I antigens; and (ii) that not all DR-specific MoAbs blocked target cell lysis by non-DR specific CTLs. In addition, when PBLs were used to stimulate the generation of CTLs in mixed leukocyte culture (MLC), inhibition using anti-class II (DR, DQ, and DP) MoAb occurred only when LCLs but not PHA blasts were used as targets. This might be explained by elevated expression of class II molecules on LCLs compared to PHA blasts.


Karyopherin alpha 2 is a novel prognostic marker and a potential therapeutic target for colon cancer.
Karyopherin alpha 2 (KPNA2), a member of the karyopherin family, plays a vital role in carcinogenesis. Yet its role in colon cancer is poorly characterized. We sought to clarify the clinical significance of its dysregulated expression in human colon tumor specimens. We evaluated KPNA2 mRNA and protein expression by real-time polymerase chain reaction and Western blotting in 40 primary colon cancer tissues and paired adjacent normal colon mucosa specimens. KPNA2 protein expression in colon tissue microarray of tumor and normal tissue specimens and lymph node metastasis specimens obtained from 195 colon cancer patients were analyzed immunohistochemically. The effect of KPNA2 knockdown on carcinogenesis potential of human colon cancer cells was determined using Cell Counting Kit-8 (CCK8), colony formation, cell migration, and tumorigenesis in nude mice. KPNA2 was expressed at higher levels in colon tumors and lymph node metastasis specimens than in normal tissues. Patients with KPNA2-positive tumors were significantly correlated with the American Joint Committee on Cancer (AJCC) stage (p = 0.01), T-classification (p = 0.018), regional lymph node metastasis (p = 0.025), distant metastasis (p = 0.014), and differentiated degree (p = 0.001). KPNA2 was shown to be an independent prognostic indicator of disease-free survival (HR 1.681; 95 % CI: 1.170-2.416; p = 0.005) and overall survival (HR 2.770; 95 % CI: 1.314-5.837; p = 0.007) for patients with colon cancer. Knockdown of KPNA2 expression inhibited colon cancer cell proliferation, colony formation, and migration. KPNA2 might play an important role in colorectal carcinogenesis and functions as a novel prognostic indicator and a potential therapeutic target for colorectal cancer.


The effect of co-cultivation of Rhodococcus erythropolis with other bacterial strains on biological activity of synthesized surface-active substances.
Surface-active substances synthesized by Rhodococcus erythropolis ІMВ Ас-5017 during co-cultivation with inducing bacteria either Bacillus subtilis BT-2 or Escherichia coli ІЕM-1 (SASI) had the higher antimicrobial and antiadhesive activities in comparison with surface-active substances synthesized in the medium without cells of inducing bacteria (SAS). Minimum inhibitory concentrations of SASI ranged from 3 to12 μg/mL and were in 4-32 times lower than the same parameter for SAS. Treatment of abiotic surfaces (ceramic, steel, and glass) with SASI decreased adhesion of bacteria Staphylococcus aureus BMC-1 or yeasts Candida albicans D-6 to the level of 10-32 % in comparison with 32-87 % after treatment of surfaces with SAS. Destruction of bacterial and yeast biofilms treated with SASI was in the range from 40 to 94 %, while it was 32-65 % in the case when SAS was used. Increasing of biological activity of surface-active substances synthesized by R. erythropolis in co-culture with inducing bacteria E. coli or B. subtilis was shown for the first time.


Ecological and morphological attributes of parthenogenetic Japanese Schwiebea species (Acari: Acaridae).
We examined life history traits and spermathecal morphology of both sexual and thelytokous Schwiebea mite species to determine ecological and morphological attributes during the evolution of parthenogenesis in this lineage. We reconstructed a molecular phylogeny of eight Japanese species using the internal transcribed spacer 1 (ITS1) of the ribosomal DNA (rDNA) and compared the sex ratio, developmental period, and egg number (fecundity) of each species within a species group by rearing them in the laboratory. Habitat preference was also analyzed from both collection and literature data. The reconstructed molecular phylogeny suggested that parthenogenesis evolved independently multiple times in this lineage. There were three clusters in the tree, in each of which the idiosoma, leg, setae, and spermathecal morphology of females was similar or identical; this suggested that mites in the same cluster were sister species. There was no relationship between sexual mode and life history traits or habitat preference. These results suggest that sexual and asexual species use different microhabitats. Because S. similis (sexual), S. elongata (thelytokous), and S. estradai (thelytokous) were in the same cluster and spermathecae of the first two were similar while that of the last was distinctively reduced, we hypothesized that speciation occurred in this order and that spermathecae are reduced and eventually lost during the course of parthenogenetic evolution.


Modeling the population-level impact of opioid agonist treatment on mortality among people accessing treatment between 2001 and 2020 in New South Wales, Australia.
The individual-level effectiveness of opioid agonist treatment (OAT) in reducing mortality is well established, but there is less evidence on population-level benefits. We use modeling informed with linked data from the OAT program in New South Wales (NSW), Australia, to estimate the impact of OAT provision in the community and prisons on mortality and the impact of eliminating excess mortality during OAT initiation/discontinuation. Dynamic modeling. A cohort of 49 359 individuals who ever received OAT in NSW from 2001 to 2018. Receipt of OAT was represented through five stages: (i) first month on OAT, (ii) short (1-9 months) and (iii) longer (9+ months) duration on OAT, (iv) first month following OAT discontinuation and (v) rest of time following OAT discontinuation. Incarceration was represented as four strata: (i) never or not incarcerated in the past year, (ii) currently incarcerated, (iii) released from prison within the past month and (iv) released from prison 1-12 months ago. The model incorporated elevated mortality post-release from prison and OAT impact on reducing mortality and incarceration. Among the cohort, mortality was 0.9 per 100 person-years, OAT coverage and retention remained high (> 50%, 1.74 years/episode). During 2001-20, we estimate that OAT provision reduced overdose and other cause mortality among the cohort by 52.8% [95% credible interval (CrI) = 49.4-56.9%] and 26.6% (95% CrI =22.1-30.5%), respectively. We estimate 1.2 deaths averted and 9.7 life-years gained per 100 person-years on OAT. Prison OAT with post-release OAT-linkage accounted for 12.4% (95% CrI = 11.5-13.5%) of all deaths averted by the OAT program, primarily through preventing deaths in the first month post-release. Preventing elevated mortality during OAT initiation and discontinuation could have averted up to 1.4% (95% CrI = 0.8-2.0%) and 3.0% (95% CrI = 2.1-5.3%) of deaths, respectively. The community and prison opioid agonist treatment program in New South Wales, Australia appears to have substantially reduced population-level overdose and all-cause mortality in the past 20 years, partially due to high retention.


Incorporating virtual reality graphics with brain imaging for assessment of sport-related concussions.
There is a growing concern that traditional neuropsychological (NP) testing tools are not sensitive to detecting residual brain dysfunctions in subjects suffering from mild traumatic brain injuries (MTBI). Moreover, most MTBI patients are asymptomatic based on anatomical brain imaging (CT, MRI), neurological examinations and patients' subjective reports within 10 days post-injury. Our ongoing research has documented that residual balance and visual-kinesthetic dysfunctions along with its underlying alterations of neural substrates may be detected in "asymptomatic subjects" by means of Virtual Reality (VR) graphics incorporated with brain imaging (EEG) techniques.


Tomographic assessment of nasal septal changes following surgical-orthodontic rapid maxillary expansion.
Nine adult patients with transverse maxillary deficiency were examined for incidence of nasal septal deviation following surgical-orthodontic rapid maxillary expansion. The osteotomies for facilitation of maxillary expansion did not include sectioning of the nasal septum. The procedure did include sectioning of the lateral maxillary walls, the pterygomaxillary suture, and the midpalatal sutures. For each patient, four graduated coronal tomograms through the incisal, molar, tuberosity, and pterygoid areas were taken prior to and not less than 4 months after surgical intervention. Results showed no significant change in the nasal septal position from before to after surgery. Analysis of the nature of maxillary movement in the coronal plane revealed rotational as opposed to bodily expansion, with inferior rotation of the palatal vault. Significant increases in the available nasal airway space were recorded. These increases were attributed primarily to shrinkage of inflamed nasal mucosa. In view of the recorded data, surgical sectioning of the nasal septum to prevent septal deviation by surgical-orthodontic rapid maxillary expansion is not warranted.


Cost and utility of routine admission laboratory testing for psychiatric inpatients.
We retrospectively evaluated the cost and utility of routine laboratory testing for psychiatric patients admitted to an acute inpatient hospital. Medical records were reviewed for 252 patients accounting for 305 sequential admissions over a recent 3-month period. Of the patient population, 49.6% had one or more coexisting medical illnesses. Overall, 6% of the abnormal laboratory findings resulted in changes in medical management: 49.2% of complete blood counts were abnormal, and 11.6% led to changes in medical management. Of the 20-factor blood chemistry analyses, 86.2% were abnormal, and 4.7% led to changes in medical management. Of the urinalyses, 85.3% were abnormal, and 2.2% led to changes in medical management. Of 277 screening syphilis titers, 5 were positive but only 1 was a potential new finding. The average cost to the facility for laboratory testing was $65 per patient admission, and the average cost per change in medical management resulting from the laboratory studies was $1070.


Quantification and interpretation of attributable mortality in core clinical infectious disease journals.
Attributable mortality is an important metric that mirrors the public health effect of a potentially harmful infection by accounting not only for the effect of infection on mortality, but also for its prevalence within the target population. We did a systematic literature review to identify how attributable deaths were quantified and interpreted in core clinical infectious diseases journals between Jan 1, 2013, and April 6, 2020. Of the 1591 abstracts screened, 234 entered the primary analysis. Our summary of the epidemiological measures used in these articles reveals fundamental shortcomings in the conception of attributable mortality. Because of its importance as a basis for decision making on public health matters, it is essential to correctly quantify and report on attributable mortality. Our recommendation for quantification and reporting of attributable deaths aids clinical researchers in the correct statistical assessment of the burden of infections. Fictional as well as real data is used to illustrate these issues.


The influence of diabetes mellitus and hypercorticism on the wound healing of experimental myocardial infarction in rats.
In diabetic and glucocorticoid-treated rats myocardial infarction is produced by coronary artery ligation. After the ligation was performed the animals were given 3H-thymidine or 3H-proline at different times. The following parameters were determined: number of DNA- and tropocollagen-synthesizing connective-tissue cells both at the infarction border and infarction site; mean silver-grain density above the nuclei or cells; number of mitoses. The labelling and mitotic indices as well as the standard deviation (in percent) from the mean values were calculated. The following results were obtained: 1. The retarded formation of collagen fibres in diabetic animals is caused by a reduced number of tropocollagen-synthesizing fibroblasts and by a diminished synthesizing performance of the individual cells. 2. Glucocorticoids have a pronounced inhibitory effect on granulation-tissue formation, The 3H--thymidine indices are strikingly low. The synthesis of collagen precursors in the fibroblasts is reduced. The release of tropocollagen from the connective-tissue cells is slowed down.


Influence of different regions of the H-2 complex on the rate of clearance of Salmonella typhimurium.
The rate of clearance of Salmonella typhimurium from the mouse spleen is under H-2 linked genetic control. The results of the present study, with H-2 recombinant mice on a C57BL/10 background, suggest the involvement of at least two loci, one in the D region and the other in the K-A alpha chromosomal segment.


Almost automorphic solutions for shunting inhibitory cellular neural networks with time-varying delays.
This paper is concerned with the shunting inhibitory cellular neural networks with time-varying delays. Under some suitable conditions, we establish some criteria on the existence and global exponential stability of the almost automorphic solutions of the networks. Numerical simulations are given to support the theoretical findings.