Bloch theorem dictated wave chaos in microcavity crystals.
Universality class of wave chaos emerges in many areas of science, such as molecular dynamics, optics, and network theory. In this work, we generalize the wave chaos theory to cavity lattice systems by discovering the intrinsic coupling of the crystal momentum to the internal cavity dynamics. The cavity-momentum locking substitutes the role of the deformed boundary shape in the ordinary single microcavity problem, providing a new platform for the in situ study of microcavity light dynamics. The transmutation of wave chaos in periodic lattices leads to a phase space reconfiguration that induces a dynamical localization transition. The degenerate scar-mode spinors hybridize and non-trivially localize around regular islands in phase space. In addition, we find that the momentum coupling becomes maximal at the Brillouin zone boundary, so the intercavity chaotic modes coupling and wave confinement are significantly altered. Our work pioneers the study of intertwining wave chaos in periodic systems and provide useful applications in light dynamics control.


How a faculty group's peer mentoring of each other's scholarship can enhance retention and recruitment.
At a time when schools of nursing seek to retain and recruit faculty ready to meet promotion and tenure requirements, many faculty are less than able to fulfill scholarly expectations. As senior scholars begin to retire, today's faculty groups are a mix of master's-prepared clinicians and recent graduates with professional (doctor of nursing practice) or research doctorates. This means that novice and midcareer faculty often lack the educational preparation for and/or a proper introduction into the scholarly role. A transition that can take 5 years or more, internalizing a scholarly identity is a process that unfolds over time in the course of presenting, publishing, and conducting research with the support of scholarly colleagues. With an eye toward easing this developmental/relational transition, chairs and deans search for professional development approaches to meet the diverse scholarly learning needs of a mixed faculty group. Given a dearth of scholar-mentors, professional development approaches that engage faculty groups in making scholarship a cooperative venture and a collective responsibility are appealing. This article explores whether a project that systematically prepared a faculty group to peer-mentor each other's scholarly success from hire to retire holds promise for fostering academic workplaces productive and pleasurable enough to attract and retain the best and the brightest.


Carcinogenic effects in the Syrian golden hamster of N-methyl-N-formylhydrazine of the false morel mushroom Gyromitra esculenta.
N-Methyl-N-formylhydrazine (MFH) was administered in drinking water as a 0.0078% solution to randomly bred Syrian golden hamsters for life beginning at 6 weeks of age. The treatment gave rise to benign and malignant liver cell tumors, malignant histiocytomas and tumors of the gall bladder and bile ducts. The tumor incidence in these four treated tissues was 43, 34, 11,8%, while in untreated controls it was 0, 0, 0, 0%, respectively. Histopathologically, tumors were classified as benign hepatomas, liver cell carcinomas, malignant histiocytomas, adenomas and adenocarcinomas of the gall bladder, cholangiomas, and cholangiocarcinomas.


Sequential enzyme-catalyzed metabolism of 4-nitrotoluene to S-(4-nitrobenzyl)glutathione.
[14C]-4-Nitrotoluene was metabolized by rat liver postmitochondrial supernatant containing NADPH, reduced glutathione and a sulfate activating system to 4-nitrobenzyl alcohol, 4-nitrobenzyl sulfate, and S-(4-nitrobenzyl) glutathione. Formation of both sulfur-containing metabolites was dependent on the presence of a sulfate activating system. These results suggest that the glutathione conjugate was derived from 4-nitrobenzyl sulfate. Reaction of 4-nitrobenzyl sulfate with glutathione was not detected in pH 7.4 buffer, but rat liver cytosol catalyzed the formation of the glutathione conjugate from 4-nitrobenzyl sulfate. These results show that 4-nitrotoluene is metabolized in rat liver by sequential side chain oxidation, sulfation, and glutathione conjugation. Furthermore, they indicate that, unlike certain other arylmethyl sulfates, 4-nitrobenzyl sulfate is not highly reactive.


Evidence for lactate utilization for fetal lung glycogen synthesis.
Fetal rabbit lungs from 23 day gestation animals were used to investigate the potential role of lactate as a substrate for fetal lung glycogen synthesis. Fetal lactate dehydrogenase activity was approximately twice that found in the adult lung, while the activity of phosphoenolpyruvate carboxykinase was elevated fourfold over the adult value. Pyruvate carboxylase activities were similar in both fetal and adult lungs. Studies employing fetal lung explants in organ culture indicated that the presence of both glucose and lactate may be necessary for glycogen accumulation in the developing fetal lung. These data support the hypothesis that lactate is an important precursor for fetal lung glycogen.


Role of aberrant Sonic hedgehog signaling pathway in cancers and developmental anomalies.
Development is a sophisticated process maintained by various signal transduction pathways, including the Hedgehog (Hh) pathway. Several important functions are executed by the Hh signaling cascade such as organogenesis, tissue regeneration, and tissue homeostasis, among various others. Considering the multiple functions carried out by this pathway, any mutation causing aberrant Hh signaling may lead to myriad developmental abnormalities besides cancers. In the present review article, we explored a wide range of diseases caused by aberrant Hh signaling, including developmental defects and cancers. Finally, we concluded this mini-review with various treatment strategies for Hh-induced diseases.


Endoscopic bipolar electrocoagulation in massive upper gastrointestinal bleeding.
We have reviewed 50 cases of upper gastrointestinal bleeding treated by endoscopic bipolar electrocoagulation (BPEC) and assessed its value in the management of massive bleeding. Initial hemostasis was achieved in 94% of cases with an overall rebleeding rate of 19.1%. The rebleeding rate was high among patients requiring blood transfusions more than 2,000 ml (47.3%) and those with acute gastric mucosal lesion (AGML) (35.3%). In AGML one or two primary sites of bleeding can be effectively controlled initially, but rebleeding tends to occur from other sites. Mortality from the direct effects of bleeding was also high in massive bleeders (33.3%) and those with AGML (22.2%); the overall mortality, including deaths from ongoing underlying diseases, was 38%. Although BPEC failed to alter the fatal outcome of patients with massive acute mucosal bleeding, permanent or temporary hemostasis contributed to reducing the amount of blood transfusions, avoiding emergency operation, preventing rapid deterioration and prolonging the survival time. Endoscopic BPEC has proven to be an effective emergency hemostatic method in massive bleeding of the upper gastrointestinal tract as an alternative to surgical intervention.


Volume regulation and basolateral co-transport of sodium, potassium, and chloride ions in frog skin epithelium.
Frog skin epithelium, which is normally almost tight to chloride, acquires a basolateral leakiness to chloride during osmotic swelling. By measuring the epithelial thickness (volume) after equilibration first with half thiocyanate Ringer, and then full thiocyanate Ringer, one obtains the chloride-free volume. Partial or full recovery of the volume and cellular chloride concentration occurs only when the inside of the skin is exposed to solutions containing K as well as Na and Cl. This recovery process is totally inhibited by low concentrations of bumetanide. The data suggest a basolateral NaKCl2 co-transport.


N6-Methyladenosine dynamic changes and differential methylation in wheat grain development.
More methylation changes occur in late interval than in early interval of wheat seed development with protein and the starch synthesis-related pathway enriched in the later stages. Wheat seed development is a critical process to determining wheat yield and quality, which is controlled by genetics, epigenetics and environments. The N6-methyladenosine (m6A) modification is a reversible and dynamic process and plays regulatory role in plant development and stress responses. To better understand the role of m6A in wheat grain development, we characterized the m6A modification at 10 day post-anthesis (DPA), 20 DPA and 30 DPA in wheat grain development. m6A-seq identified 30,615, 30,326, 27,676 high confidence m6A peaks from the 10DPA, 20DPA, and 30DPA, respectively, and enriched at 3'UTR. There were 29,964, 29,542 and 26,834 unique peaks identified in AN0942_10d, AN0942_20d and AN0942_30d. One hundred and forty-two genes were methylated by m6A throughout seed development, 940 genes methylated in early grain development (AN0942_20d vs AN0942_10d), 1542 genes in late grain development (AN0942_30d vs AN0942_20d), and 1190 genes between early and late development stage (AN0942_30d vs AN0942_10d). KEGG enrichment analysis found that protein-related pathways and the starch synthesis-related pathway were significantly enriched in the later stages of seed development. Our results provide novel knowledge on m6A dynamic changes and its roles in wheat grain development.


Uraemic Encephalopathy in a Persian Cat with Chronic Kidney Disease.
Uraemic encephalopathy (UE) is rarely associated with acute kidney injury or chronic kidney disease in domestic animals, and we now report the first case in a cat. The animal presented with hypothermia, apathy, lethargy, depression, severe dehydration, uraemic breath, elevated serum urea nitrogen and creatine concentrations, and eventual seizures and coma prior to death. Gross necropsy findings included severe bilateral renal scarring, ulcerative stomatitis and glossitis, and uraemic gastropathy. Microscopic lesions of diffuse interstitial fibrosis, multifocal mineralization and lymphoplasmacytic interstitial nephritis were seen in the kidneys. There was symmetrical, bilateral spongy vacuolation of the white matter of the basal nuclei and cerebellum and Alzheimer type II astrocytes in the cerebral cortex and hippocampus. Glial fibrillary acid protein immunolabelling was absent or faint in astrocytes of the cerebral grey matter. UE should be included in the differential diagnosis in animals with chronic kidney disease and neurological signs.


Device for respiration activity measurement enables the determination of oxygen transfer rates of microbial cultures in shaken 96-deepwell microtiter plates.
Mini-bioreactors with integrated online monitoring capabilities are well established in the early stages of process development. Mini-bioreactors fulfil the demand for high-throughput-applications and a simultaneous reduction of material costs and total experimental time. One of the most essential online monitored parameters is the oxygen transfer rate (OTR). OTR-monitoring allows fast characterization of bioprocesses and process transfer to larger scales. Currently, OTR-monitoring on a small-scale is limited to shake flasks and 48-well microtiter plates (MTP). Especially, 96-deepwell MTP are used for high-throughput-experiments during early-stage bioprocess development. However, a device for OTR monitoring in 96-deepwell MTP is still not available. To determine OTR values, the measurement of the gas composition in each well of a MTP is necessary. Therefore, a new micro(µ)-scale Transfer rate Online Measurement device (µTOM) was developed. The µTOM includes 96 parallel oxygen-sensitive sensors and a single robust sealing mechanism. Different organisms (Escherichia coli, Hansenula polymorpha, and Ustilago maydis) were cultivated in the µTOM. The measurement precision for 96 parallel cultivations was 0.21 mmol·L-1 ·h-1 (pooled standard deviation). In total, a more than 15-fold increase in throughput and an up to a 50-fold decrease in media consumption, compared with the shake flask RAMOS-technology, was achieved using the µTOM for OTR-monitoring.


Proposal of a grading system for squamous cell carcinoma of the lung - the prognostic importance of tumour budding, single cell invasion, and nuclear diameter.
The prognostic markers of lung squamous cell carcinoma (LSCC) are less investigated. The aim of our study was to evaluate tumour budding (TB), minimal cell nest size, nuclear diameter (ND), and spread through air spaces (STAS) among patients with resected LSCC, semi-quantitatively. Furthermore, we aimed to identify a grading system for the best prognostic stratification of LSCC. Patients who underwent surgical resection at the Department of Surgery, University of Szeged between 2010 and 2016 were included. Follow-up data were collected from medical charts. Morphological characteristics were recorded from histologic revision of slides. Kaplan-Meier analysis, log rank test and Cox proportional-hazards model, ROC curve analysis, and intraclass correlation were utilised. Altogether 220 patients were included. In univariate analysis, higher degree of TB, infiltrative tumour border, larger ND, the presence of single cell invasion (SCI) and STAS were associated with adverse prognosis. Based on our results, we proposed an easily applicable grading scheme focusing on TB, ND, and SCI. In multivariate analysis, the proposed grading system (pOS < 0.001, pRFS < 0.001) and STAS (pOS = 0.008, pRFS < 0.001) were independent prognosticators. Compared to the previously introduced grading systems, ROC curve analysis revealed that the proposed grade had the highest AUC values (AUCOS: 0.83, AUCRFS: 0.78). Each category of the proposed grading system has good (ICC: 0.79-0.88) reproducibility. We validated the prognostic impact of TB, SCI, ND, and STAS in LSCC. We recommend a reproducible grading system combining TB, SCI, and ND for proper prognostic stratification of LSCC patients. Further research is required for validation of this grading scheme.


Planning and use of therapeutic mammoplasty--Nottingham approach.
Therapeutic mammaplasty, the use of reduction mammaplasty and radiotherapy to surgically treat breast cancer, is an established technique for selected breast cancers and can extend the role of breast conserving surgery. Most frequently described is the use of a wise pattern reduction for tumours that lie within the expected mammaplasty excision. However, mammaplasty techniques can be safely adapted to treat patients with cancers in all areas of the breast. An approach to selection and planning surgery is presented which has evolved from the experience of other units and our first 50 clinical cases over a 3-year period. The outcomes of these 50 cases are found in the accompanying article. Technique will vary depending upon the tumour position. Breast cancers may lie within the normal excision site of a recognised mammaplasty method (scenario A) or outside of the expected excision sites (scenario B). In scenario A, a range of recognised techniques can be performed without adaptation to widely excise the tumour and re-shape the breasts. In scenario B the techniques need to be adapted. Three decisions are needed for planning in scenario B; the skin incision, the nipple-aereola complex (NAC) pedicle orientation and finally the method of filling the cancer defect. The latter can be achieved by either extending the nipple pedicle or by creating a secondary pedicle within the breast dissection. Either method will move tissue that is normally excised into the cancer defect. For central tumours an inferior pedicle is usually used to both fill the defect and re-create the nipple.


Genomic DNA with transformation-related activity and melanoma antigen expression.
We have analyzed the mouse melanoma antigen with monoclonal antibodies established by syngeneic immunization. To further understand the structure of this antigen at a molecular level, we have cloned the genomic DNA controlling the expression of melanoma antigen by cosmid library transfection and a monoclonal antibody. In the process of analyzing this DNA fragment we found that it contained a gene related with transformation, which was proved by tumor formation in nude mice inoculated with NIH/3T3 transfectants of this DNA fragment. We discuss the structure of the gene product based on the deduced amino acid sequence of cDNA, which maps the genome bearing transformation-related activity.


Up-regulation of PCSK6 by lipid oxidation products: A possible role in atherosclerosis.
Atherosclerosis is a degenerative disease characterized by lesions that develop in the wall of large- and medium-sized arteries due to the accumulation of low-density lipoproteins (LDLs) in the intima. A growing bulk of evidence suggests that cholesterol oxidation products, known as oxysterols, and the aldehyde 4-hydroxy-2-nonenal (HNE), the major pro-atherogenic components of oxidized LDLs, significantly contribute to atherosclerotic plaque progression and destabilization, with eventual plaque rupture. The involvement of certain members of the protein convertase subtilisin/kexin proteases (PCSKs) in atherosclerosis has been recently hypothesized. Among them, PCSK6 has been associated with plaque instability, mainly thanks to its ability to stimulate the activity of matrix metalloproteinases (MMPs) involved in extracellular matrix remodeling and to enhance inflammation. In U937 promonocytic cells and in human umbilical vein endothelial cells, an oxysterol mixture and HNE were able to up-regulate the level and activity of PCSK6, resulting in MMP-9 activation as demonstrated by PCSK6 silencing. Inflammation, enhanced by these lipid oxidation products, plays a key role in the up-regulation of PCSK6 activity as demonstrated by cell pretreatment with NS-398, with epigallocatechin gallate or with acetylsalicylic acid, all with anti-inflammatory effects. For the first time, we demonstrated that both oxysterols and HNE, which substantially accumulate in the atherosclerotic plaque, up-regulate the activity of PCSK6. Of note, we also suggest a potential association between PCSK6 activity and MMP-9 activation, pointing out that PCSK6 could contribute to atherosclerotic plaque development.


Ontogenetic instars of Hermannia longisetosa Subas amp; Shtanchaeva, 2013, with remarks on juveniles of Hermanniidae (Acari: Oribatida).
Information on the morphological ontogeny of the majority species of the family Hermanniidae is still lacking. In this work, the ontogenetic instars of the Mediterranean species, Hermannia longisetosa Subas Shtanchaeva, 2013 are studied, based on material from northwestern Spain. Comparative characteristics of juveniles of species belonging to different genera of Hermanniidae are given based on our own data and available literature sources, and the major characteristics of larvae and nymphs are presented. An updated family and generic diagnoses based on juveniles of Hermanniidae are proposed. At the moment, the juveniles of two genera, Hermannia and Phyllhermannia are known, which differ from one another in the pattern of cuticle plications of the gastronotum; number of solenidia on leg tarsi I and II; number of setae on palp femur; setal formula of leg IV in protonymph; and the arrangement of gastronotic setae of c- and d-series.


Client buy-in: An essential consideration for graded motor imagery in hand therapy.
This is a cross-sectional survey research. Current evidence provides efficacy of graded motor imagery (GMI) in chronic pain conditions but also reveals barriers to its implementation. The purpose of this study was to describe current utilization of GMI in hand therapy practice. Survey tool, informed by literature and Revised Neurophysiology of Pain Questionnaire (NPQ) was electronically distributed to members of the American Society of Hand Therapists. 132 therapists completed the survey. 65.2% reported they would always or very likely use GMI in clients with central sensitization, but no relationship between the likelihood of therapists using GMI to score achieved on the NPQ was found. Lack of patient buy-in, was the main barrier cited. "Sell it well" with pain neuroscience education the most cited strategy. GMI is frequently used in clients with central sensitization but requires client buy-in. Understanding and explaining pain mechanism is essential for implementing GMI.


Transcriptional control of glutamatergic differentiation during adult neurogenesis.
Neurogenesis, the production of new neurons, occurs in two specialized niches in the adult brain, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. In the SGZ, neural stem cells (NSCs) give rise to glutamatergic granule neurons that integrate into the granule cell layer. In the SVZ, NSCs generate a more diverse cohort of new neurons, including GABAergic, dopaminergic, and glutamatergic neurons, all of which migrate to the olfactory bulb through the rostral migratory stream. In both adult neurogenic niches, specific transcription factors have been shown to direct fate specification and lineage commitment. This review summarizes current progress on the transcriptional control of glutamatergic neurogenesis in the SGZ and SVZ, highlighting commonalities as well as differences in their transcriptional programs. In particular, we focus on work from our laboratory and others indicating that precise, sequential expression of transcription factors regulates the progression from NSC to lineage-committed progenitor, and ultimately regulates the production and differentiation of adult-born glutamatergic neurons.


Contrast-Enhanced Ultrasound for Monitoring Treatment Response in Different Stages of Hepatocellular Carcinoma.
The capacity of contrast-enhanced ultrasound (CEUS) to detect microvessel perfusion has received much attention in cancer imaging since it can be used to evaluate the enhancement patterns of the lesions during all vascular phases in real time, with higher temporal resolution as compared other imaging modalities. A rich body of literature has demonstrated the potential usefulness of CEUS in the assessment of HCC in response to both locoregional and systemic therapies. It is useful to evaluate the efficacy of ablation immediately after treatment to provide guidance for the retreatment of residual unablated tumors. In patients treated with transarterial chemoembolization (TACE), CEUS showed a high degree of concordance with computed tomography and magnetic resonance for the differentiation of responders from non-responders. Dynamic CEUS (D-CEUS) has emerged as a promising tool for the depicting changes in tumor perfusion during anti-angiogenetic treatment that can be associated with tumor response and clinical outcome. This article provides a general review of the current literature regarding the usefulness of CEUS in monitoring HCC response to therapy, highlighting the role of the procedure in different stages of the disease.


Integrative analysis identifies CXCL11 as an immune-related prognostic biomarker correlated with cell proliferation and immune infiltration in multiple myeloma microenvironment.
The interaction between tumor cells and tumor microenvironment (TME) has an important impact on progression and prognosis of multiple myeloma (MM), and has been proven to be promising therapeutic targets. This study intended to explore the relationship between TME and prognosis and identify valuable biomarkers of MM. The transcriptomic and clinical information of MM retrieved from the Gene Expression Omnibus (GEO) were used to establish the model. The curve of Kaplan-Meier survival and the time-dependent receiver operating characteristic (ROC) were used to appraise the predictive ability. A nomogram was established for clinical application. Furthermore, the CIBERSORT algorithm was used to investigate the relation between IRGPI with the infiltration of immune cells. We also used histology, as well as in vitro and in vivo experiments to validate these findings. The results demonstrated an immune-related gene-based prognostic index (IRGPI) combined with clinical information. Patients were separated into high- and low-risk groups based on risk score, which had significantly difference in survival status and immune infiltrations. Furthermore, we identified CXCL11 as a key factor, which positively promotes the progression of MM and correlate with macrophage M2-like polarization and tumor immune cells infiltration. Our findings suggest the IRGPI significantly demonstrate the differential prognosis and prediction of immune cells infiltration. It provides some insights into the complex interaction between myeloma tumor cells and the TME, as well as in the development of a novel biomarker target for anti-MM therapy.


Inhaled IgG1 antibodies: The buffering system is an important driver of stability during mesh-nebulization.
In the past decade, oral inhalation has been a thriving focus of research to administer antibody directly to the lungs as an aerosol, for local treatment of respiratory diseases. Formulation of inhaled antibodies is central for the stability of antibody, lung safety and to ensure inhaler performances. Surfactants have already been shown to prevent antibody degradation during aerosolization, but little is known about the impact of other components of liquid formulations on the structural stability of antibodies. Here, we report for the first time to the best of our knowledge, a significant effect of the buffering system on monoclonal antibodies stability, during mesh-nebulization. While the monoclonal antibody extensively aggregated in citrate buffer after nebulization and required high concentration of polysorbate 80 (PS80) to maintain protein integrity, acetate and histidine buffers resulted in a slight to moderate aggregation without PS80 and low concentration of PS80 was sufficient to stabilize antibody during mesh-nebulization.


Validation of self-reported proximity to agricultural crops in a case-control study of neural tube defects.
Self-reported perinatal exposures to chemicals or pollutant sources in case-control studies of birth defects may be inaccurate due to misreporting among mothers. In a case-control study of neural tube defects delivered in California in 1987-1988, mothers of case and control infants were asked whether they lived within 0.25 mile (400 m) of agricultural crops. Responses were compared against a gold standard derived from historical agricultural land-use survey maps. The odds ratio for self-reported proximity to any crops (1.62, 95% confidence interval: 1.08, 2.43) appeared to be positively biased compared with the estimate for map-based proximity (1.17, 95% confidence interval: 0.79, 1.71). This pattern was also observed for proximity to specific crops such as nonpermanent and orchard crops. For vineyards, however, we observed an increased risk associated with map-based proximity (odds ratio=2.45, 95% confidence interval: 1.08, 5.58) but not with self-reported proximity (1.09, 95% confidence interval: 0.51, 2.34). The sensitivity of self-reported proximity to any crops was greater for case (65.7%) than control mothers (50.0%) while specificity was about the same for case and control mothers (87.5 vs. 89.3%), suggesting that control mothers under-reported proximity to crops. Differential reporting was also observed between geographic regions, urban and rural residents, and across levels of maternal employment and education. These results suggest differential reporting between case and control mothers as well as an influence from maternal demographic characteristics on reporting accuracy.


Estimation of the "normal" growth of Swedish infants at term. Preliminary report.
Using the Swedish Medical Birth Registry for 1983 the birthweights were studied from the 38th to the 42nd week of gestation. Several criteria were used in order to retain a "normal" population of infants without signs of pathology. The mothers all negated smoking. Of about 93 000 livebirths roughly 10% fulfilled the criteria. Both in the infants who were the first-born child (n = 5.640) and in those who were the second-born child (n = 3.599) there was a successively higher mean birthweight for each completed week until 41 weeks. After that a graph connecting the mean values showed a significant flattening.


[Some important issues regarding the combination of treatments in bipolar patients].
Combined therapy, that is psychotherapy plus pharmacological treatment in the management of bipolar disorder proved higher efficacy than each individual treatment. This article reviews situations that may interfere with such treatment.


Numbers of Brain Deaths and Deceased Donors in Hospitals in Istanbul Region That Have Transplantation Units: A Retrospective Analysis Between the Years 2005 and 2015.
Turkey is one of the countries facing a serious organ shortage problem, with thousands of patients with end-stage organ failure. The Social Security Institution started to increase the reimbursement for transplantation operations in 2007 to solve this problem, and this policy has continued since then. Although the number of transplantation centers and operations in Turkey increased in this term, according to organ donation and transplantation statistics from the Ministry of Health, the rate of organ retrieval from deceased organ donors has decreased. This study was performed with the purpose of retrospectively analyzing (between the years 2005 and 2015) the number of brain deaths and donors after brain death in hospitals that are affiliated with the Istanbul Regional Coordination Office and have transplantation units. Data were collected via the website of the Ministry of Health. Hospitals were categorized as those directly affiliated with the Ministry of Health, university hospitals, and private hospitals. This study found that the number of transplantation centers has increased >3 times since 2005, and the number of private transplantation centers has increased 9 times for the same period. We also found that the number of brain deaths, donors after brain death in hospitals, and number of brain deaths and donors after brain death per hospital had varied throughout the study years. Although the number of transplantation centers has increased since 2005, the number of brain deaths and donors after brain death has not increased to the same extent for this period in these hospitals that have transplantation units.


Odorous urine following asparagus ingestion in man.
The production of odorous urine after the ingestion of asparagus has been shown to occur in 43% of 800 volunteers investigated. This characteristic is reproducible over a 12-month-period and has been shown to remain with individuals for virtually a lifetime. Family studies suggest that the ability to produce the odorous urine is inherited as an autosomal dominant trait.


Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function.
Asynchronous patterns of contraction and relaxation may contribute to hemodynamic and functional impairment in heart failure. In 1993, we introduced biventricular pacing as a novel method to treat heart failure by synchronous stimulation of the right and left ventricles after an appropriate atrioventricular delay. The objectives of this study were to assess the early and long-term effects of this therapy on functional capacity and left ventricular function in patients with severe heart failure and left bundle branch block. Twelve patients with end-stage congestive heart failure, sinus rhythm and complete left bundle branch block were treated with biventricular stimulation at optimized atrioventricular delay. The NYHA functional class and maximal bicycle exercise capacity were assessed. Systolic and diastolic left ventricular function were studied with echocardiography and radionuclide angiography. Data was collected at various intervals during 1-year follow-up. Cumulative survival [95% CI] was 66.7% [40.0,93.4] at 1 year and 50 % [21.8, 78.2] at 2 and 3 years. Median NYHA class improved from class IV to class II at 1 year (p=0.008). After 6 weeks an increase in exercise capacity occurred, which was sustained. A less restrictive left ventricular filling pattern, an increase in dP/dt and left ventricular ejection fraction, and a decrease in mitral regurgitation were observed early and long-term. Biventricular pacing at optimized atrioventricular delay results in improvement in functional capacity, which is associated with improved systolic and diastolic left ventricular function, and a decrease in mitral regurgitation during short- and long-term follow-up.


Isotopic evidence for dramatic climatic changes in East Africa during the Pleistocene.
Rainfall decreased dramatically in the Lake Turkana region 1.8-2.0 Myr ago and in the Olduvai Gorge region 0.5-0.6 Myr ago. This is documented by a major increase in the delta18O values of pedogenic and groundwater carbonates at these times. The data suggest that meteoric water of the earlier, more humid climate was 2-4 per mil lower in 18O content than modern waters of these regions.


Transcription in human fibroblasts permissively infected by human cytomegalovirus strain AD169.
We used cloned subgenomic DNA fragments of human cytomegalovirus strain AD169 as hybridization reagents to analyze the sites of transcription and abundance of viral RNA in permissively infected human embryonic lung cells. RNA extracted from immediate early, early, middle, and late times in the infection was attached to filters and hybridized with excess cloned subgenomic fragments. Each hybridization was performed with an internal standard to allow quantitation of the RNA concentration and standardization for the variation in probe complexity and specific activity. We found immediate early transcription in the AD169 strain occurring primarily from three regions in the long unique segment at 0.061-0.110, 0.117-0.142, and 0.588-0.616 map units. A low level of transcription was also detected from the long unique segment at 0.230-0.372, 0.419-0.437 and 0.703-0.707 map units and the short unique segment and terminal repeats at 0.00-0.046, 0.776-0.854, and 0.892-1.00 map units. At 8 hr after infection in the presence of de novo protein synthesis, the transcription pattern was changed. Two of the major immediate early sites at 0.061-0.110 and 0.117-0.142 map units were represented less abundantly in the absence of cycloheximide while the site at 0.588-0.616 map units was represented at the same level. The most abundant early RNA was synthesized from the terminal repeat sequences and part of the short unique segment at 0.00-0.046, 0.776-0.822, and 0.892-1.00 map units. Steady-state RNA from the midpoint of the infection hybridized with most regions of the genome. Abundantly transcribed regions included the abundant early sites mentioned above (0.00-0.046, 0.588-0.616, 0.776-0.822, and 0.892-1.00 map units), several new sites in the long unique segment at 0.104-0.110, 0.576-0.588, 0.653-0.664, 0.703-0.707, and 0.766-0.776 map units and the L-S junction fragment at 0.804-0.854 map unit. RNA from late in the infection hybridized to all subgenomic fragments. The sites of de novo RNA synthesis along the genome were determined by hybridizing pulse-labeled RNA to individual cloned subgenomic fragments attached to filters. Transcription from the terminal repeat sequences and the long unique segment at 0.576-0.588 map unit accounted for 40% of the total viral RNA synthesized from 22 to 28 hr after infection. Of the total de novo RNA synthesis from 71 to 77 hr after infection, 4.3% was virus specific and 47% of the total de novo synthesized viral RNA hybridized to the terminal repeat sequences.


Factors affecting calf mortality in Iranian Holstein dairy herds.
The objective of this study was to document mortality reasons and risk factors for mortality in dairy calves in the northeast of Iran. This was a prospective cohort study of calves born on ten commercial dairy herds from 21 March 2009 to 20 March 2010. A total of 4097 live calves were followed for 90 days after birth. For each calf details of sex, parity of the dam, type of parturition and season of birth were recorded. The interval (in days) from the date of birth to the date of death and the reason for death was recorded for those calves that died before 90 days of age. A Cox proportional hazards model, including a frailty term to account for unmeasured herd-level effects was developed to quantify the effect of factors associated with time to death. Two hundred and sixty-six (6.5%, 95% CI: 5.8-7.3%) of the 4097 live-born calves died or were euthanised before 90 days of age. The most important reasons for death were digestive tract disorders (58% of all deaths, 95% CI: 52-64%) followed by respiratory diseases (13% of all deaths, 95% CI: 9-17%). Calves exposed to dystocia at birth had 2.09 (95% CI: 1.49-2.92) times the daily hazard of death compared with calves born from a normal calving. The daily hazard of death for calves born in the summer was 1.93 (95% CI: 1.41-2.64) times greater than the hazard for those calves born in the autumn. Inclusion of the herd-level frailty term had a significant effect on hazard estimates indicating that the study herds were heterogeneous in the distribution of unmeasured herd-level factors influencing calf survival. Our results show that diarrhoea is the most important cause of calf mortality in dairy herds in this area of Iran and that environmental and management factors affect calf mortality rate.


Pre-menarcheal physical activity predicts post-menarcheal lean mass and core strength, but not fat mass.
Youth exercise is associated with improved body composition, but details regarding timing and persistence are limited. We examined pre- and circum-menarcheal organized physical activity exposure (PA) as a factor in development of early post-menarcheal lean mass, fat mass and muscle strength. Participants in a longitudinal study of musculoskeletal growth using dual energy X-ray absorptiometry (DXA) were included based on: 1) Whole body DXA scans: 0.5-1.5 years pre-menarche, 0.5-1.5 years post-menarche; 2) PA records for ⋝6 months preceding the first DXA (prePA) and for the inter-DXA interval (circumPA). Dominant arm grip strength and sit-ups tests coincided with DXA scans; PA, height and maturity were recorded semi-annually. Regressions correlated PA with lean mass/fat mass/strength, accounting for maturity, body size, and baseline values. Seventy girls [baseline: 11.8 yrs (sd 1.0), follow-up: 13.9 years (sd 1.0)] demonstrated circum-menarcheal gains of 25-29% for lean and fat mass and 33% for grip strength. PREPA correlated with pre- and post-menarcheal lean mass, sit-ups and pre-menarcheal fat mass (p<0.05), but not grip strength. CIRCUMPA correlated with only post-menarcheal sub-head lean mass (p=0.03). Lean mass and core strength at 1-year post-menarche were more strongly predicted by pre-menarcheal organized PA than by recent circum-menarcheal PA.


Chemical characterization of decomposition products of pyrazolidinedione-3,5 derivatives. Part 1: Identification of decomposition products and mechanism of degradation of 4-prenyl-1,2-diphenyl-3,5-pyrazolidine-dione in an aqueous solution.
From an aqueous solution of 4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione sodium salt (Prenazone) subjected to accelerated ageing at 80 degrees C in anaerobic and in aerobic conditions the following decomposition products were isolated: N,N'-diphenylhydrazide-5-methyl-4-hexenoic acid,N,N'-diphenylhydrazide-2-carboxy-5-methyl-4-hexenoic acid, N,N'-diphenylhydrazide-2-carboxy-2-hydroxy-5-methyl-4-hexenoic acid, trans- and cis-azobenzene. The isolated compounds were identified by means of thin-layer chromatography, elemental analyses, UV, IR spectrophotometry and taking into consideration their chemical transformations. A decomposition mechanism of Prenazone Sodium in aqueous solutions maintained at 80 degrees C is proposed.


Fighting for Equal Spiritual Voice: The Case of the "Women of the Wall".
Our study contributes to the ongoing debate about women's rights and religious feminism. The context for analysis of women's experiences is the "Women of the Wall" who have been struggling for the past 30 years for their right to practice their spiritual rituals (praying at the Western Wall) in a hegemonic and masculine arena. We suggest that the "Women of the Wall" and their battle for spiritual equality threaten the hegemonic masculinity. Moreover, this feminist battle expands the feminist revolution and the fights for women's equality to the religious arena which is dominated by hegemonic masculinity. The implementation of the Listening Guide, a feminist methodology, assists us in uncovering various voices, representing different aspects of the experiences of the "Women of the Wall" in a conflict zone. These narratives reveal juxtapositions of feelings of competence, determination and vulnerability and shed light on the women's struggle for gender equality in a hegemonic masculine domain.


Scoliosis circa 2000: radiologic imaging perspective. I. Diagnosis and pretreatment evaluation.
Plain film imaging remains important for the diagnosis and surveillance of scoliosis, as well as for the detection of complications after surgery. Advances in CT and MR imaging have greatly improved the ability to detect or confirming non-idiopathic causes of scoliosis, including abnormalities within the spinal canal. Three-dimensional thinking has become more important in evaluating and understanding scoliosis.


Disulfide bridges in extracellular domains of angiotensin II receptor type IA.
Angiotensin II receptor type IA (AT1A) has a cysteine (Cys) residue in each of four extracellular domains, and these Cys residues are believed to form two disulfide bridges. However, the question as to which pairs of Cys residues form disulfide bridges have not been experimentally determined. We constructed four mutants of rat AT1A, in which extracellular Cys residues were individually replaced by glycine (mutant C-1, C-2, C-3 and C-4). Further, we constructed two double mutants, in which two extracellular Cys residues were simultaneously substituted for by glycine. The binding affinity for angiotensin II in a double mutant C-1 + 4 (Cys18,274Gly) was similar to that in individually substituted mutants (C-1, C-2, C-3 and C-4) whereas the ligand binding of a double mutant C-2 + 4 (Cys101,274Gly) was completely abolished. The bindings of the non-peptide AT1A antagonist [125I]EXP-985 to mutants C-1, C-4 and C-1 + 4 were only slightly reduced whereas in mutant C-2, C-3 and C-2 + 4 the specific binding for [125I]EXP-985 was completely abolished. These results suggest that disulfide bridges in AT1A are formed between Cys18 and Cys274, and between Cys101 and Cys180, and the latter disulfide bond is essential for the binding of the non-peptidic antagonists [125I]EXP-985 or losartan.


MicroRNA-199a-3p suppresses the invasion and metastasis of nasopharyngeal carcinoma through SCD1/PTEN/AKT signaling pathway.
MicroRNAs (miRs) are 18-25 nucleotides non-coding RNAs, which contribute to tumorigenesis. Previous studies have demonstrated that miR-199a-3p is dysregulated in human nasopharyngeal carcinoma (NPC), but its role in NPC progression still largely unknown. The current study aimed to determine the potential role of miR-199a-3p in NPC progression and the underlying mechanisms. In this study, miR-199a-3p was found to be prominently down-regulated in NPC tissues and cells. The cellular assay showed that transfection of miR-199a-3p markedly repressed the migration, invasion and induced epithelial-mesenchymal transition (EMT) in both 5-8F and CNE-2 cell lines. By dual-luciferase reporter, western blotting and gas chromatography assays, we found that SCD1 is not only highly expressed in NPC tissues and negatively associated with the prognosis of NPC patients but also can be apparently downregulated by miR-199a-3p in NPC cells, suggesting that SCD1 is a direct target gene of miR-199a-3p. Moreover, inhibition of miR-199a-3p expression activated PI3K/Akt signaling and up-regulated the expression of MMP-2. With tumor xenograft models in nude mice, we also showed that miR-199a-3p repressed tumor growth in vivo. Our study demonstrated that miR-199a-3p inhibited migration and invasion of NPC cells through downregulating SCD1 expression, thus providing a potential target for the treatment of NPC.


Cognitive and visual task effects on gaze behaviour and gait of younger and older adults.
Cognitive dual tasks alter gait of younger and older adults and recent research has demonstrated that they also influence gaze behaviour and standing postural control. These findings suggest that age-related changes in cognitive and gaze function might increase fall risk in older adults. The purpose of this study was to determine the effect cognitive and visual dual tasks on the gait and gaze behaviour of younger and older adults. Ten older and ten younger adults walked for 3 min on a treadmill at preferred walking speed under three conditions, single task, cognitive and visual dual task conditions. Gait dynamics were measured using accelerometry and gaze behaviour was measured using wearable eye-trackers. Stride time variability and centre of mass (COM) motion complexity increased in dual-task conditions in older adults but had no difference for younger adults. Dual tasks had limited effect on gaze behaviour; however, visual input duration was greater, and visual input frequency and saccade frequency were lower in older than younger adults. The gaze adaptations in older adults may be the result of slower visual processing or represent a compensatory strategy to suppress postural movement. The increase in gait COM motion complexity in older adults suggests the dual tasks led to more automatic gait control resulting from both cognitive and visual tasks.


Evolving Our Understanding: Housing Instability as an ACE for Young Children.
We investigated the conceptualization and impact of adverse childhood experiences (ACEs) in a sample of 231 children ages 3-5 living in poverty and experiencing homelessness, focusing specifically on caregiver well-being and housing instability. Data was collected using the Neurodevelopmental Ecological Screening Tool (NEST), which screens for developmental risk and resilience across three domains (neurodevelopmental, caregiver, and environment). We used structural equation modelling (SEM) to test the association between domains and ACE scores and assessed the impact on neurodevelopmental constructs. Fifty-five percent of the sample had high ACE scores (> 3), which were associated with lower attention, social skills, and emotional regulation. ACEs were strongly associated with 0.17 standard deviation units of higher levels of caregiver distress (p < .001), which was also associated with 0.26 standard deviation units of lower levels of child neurodevelopmental functioning (p = .001). For each unit increase in housing instability, there was a three-fourths increase in ACE (0.78 ACE at p = .004); four or more moves were associated with the worst neurodevelopmental outcomes (53% of the sample). We must use an ecological, developmental lens to understand how early adversity impacts children, at what age, and in what context. Housing stability plays a critical role in developmental well-being and should be accounted for in conceptualizations of child ACE scales. Caregiver and child relationships are reciprocal, and so the impacts of ACEs are also bidirectional. Our policies and practices at individual, community, and systemic levels should account for these dynamics to improve child well-being.


Factors that influence efficiency in performing ENT cases: a qualitative and quantitative analysis.
The aim of this study was to assess procedures with high turnover time to procedure time ratios, estimate the effect of productivity changes on case efficiency, and determine causative factors. We specifically focused on suspension direct microlaryngoscopy (SML) (CPT 31526) cases because significantly greater productivity was possible for these cases in terms of ratios. After determining process times, we developed economic scenarios that employed time-reductions, and then assessed involved staff opinions using brainstorming and cause--effect methods. Improving all process times by 30% achieved up to a 50% improvement in revenue and the return on investment in additional scope equipment occurred within 2 months.


Dual signal amplification for highly sensitive electrochemical detection of uropathogens via enzyme-based catalytic target recycling.
We report an ultrasensitive electrochemical approach for the detection of uropathogen sequence-specific DNA target. The sensing strategy involves a dual signal amplification process, which combines the signal enhancement by the enzymatic target recycling technique with the sensitivity improvement by the quantum dot (QD) layer-by-layer (LBL) assembled labels. The enzyme-based catalytic target DNA recycling process results in the use of each target DNA sequence for multiple times and leads to direct amplification of the analytical signal. Moreover, the LBL assembled QD labels can further enhance the sensitivity of the sensing system. The coupling of these two effective signal amplification strategies thus leads to low femtomolar (5fM) detection of the target DNA sequences. The proposed strategy also shows excellent discrimination between the target DNA and the single-base mismatch sequences. The advantageous intrinsic sequence-independent property of exonuclease III over other sequence-dependent enzymes makes our new dual signal amplification system a general sensing platform for monitoring ultralow level of various types of target DNA sequences.


Availability of glutamine from peptides and acetylglutamine for human tumor-cell cultures.
In a recent study we showed that the growth behavior of a hematopoietic cell line (K 562) in culture was the same when using glutamine-containing dipeptides or glutamine as substrate. In this article we study the growth behavior of different tumor cells, originating from the hematopoietic system (K 562), stomach (Kato III), pancreas (Panc 1), and breast (T 47 D), to test the biological activity as preclinical in vitro screening system. We compared L-glutamine (GLN), N-acetyl-L-glutamine (ACE-GLN), L-alanyl-L-glutamine (ALA-GLN), and glycyl-L-glutamine (GLY-GLN). Cell proliferation was measured with the incorporation of [3H] thymidine or the MTT assay (cleavage of 3-(4,5-dimethyldiazol-2-yl)-2-5-diphenyl tetrazolium bromide by mitochondria). In all investigated cell types cell growth was stimulated when using glutamine-containing dipeptides or ACE-GLN instead of a glutamine-free media (not significant for T 47 D). However, GLN or ALA-GLN was advantageous to GLY-GLN or ACE-GLN when measuring cell proliferation with the MTT-assay up to 72 hours. However, alanylglutamine does not enhance proliferation, compared with free glutamine.


More than one way to skin a thyroid. Managing pediatric hypothyroidism with weekly intramuscular levothyroxine.
Oral levothyroxine (L-T4) supplementation is usually an effective therapy in pediatric hypothyroidism, except in patients with malabsorption or pseudomalabsorption. In these cases, parenteral L-T4 may be required, but there is a paucity of information about this delivery method in the pediatric population. We present three cases of pediatric patients with primary hypothryoidism unresponsive to oral L-T4 that were successfully treated with intramuscular (IM) L-T4. This is the first pediatric case series of successful IM L-T4 therapy in refractory primary hypothyroidism. Our case series demonstrates that once weekly IM L-T4 dosing may be a safe and well tolerated treatment regimen for pediatric patients.


Enhanced purinergic contractile responses and P2X1 receptor expression in detrusor muscle during cycles of hypoxia-glucopenia and reoxygenation.
Bladders from patients with detrusor overactivity have an increased atropine-resistant contractile response to nerve stimulation. The bladder has also been shown to be very susceptible to hypoxia-glucopenia and reperfusion injury, leading to the hypothesis that episodes of hypoxia-glucopenia and reoxygenation result in increased atropine-resistant responses to nerve stimulation in the detrusor muscle. Detrusor muscle strips were suspended in a Perspex organ bath chamber of volume 0.2 ml perfused with Krebs solution at 37°C aerated with 21% O2, 5% CO2 and the balance nitrogen. Hypoxia-glucopenia was induced by switching perfusion to Krebs solution without glucose, gassed with 95% nitrogen and 5% CO2. Atropine-resistant contractile responses increased by 40.5 ± 7.3% after four cycles of hypoxia-glucopenia (10 min) and reoxygenation (1 h), whereas α,β-methylene ATP-resistant responses did not increase. Expression of P2X1 receptors in the bladder was increased after hypoxia-glucopenia and reoxygenation cycling, and ATP release from stimulated bladder strips during cycling was also increased. Other P2X receptor-mediated mechanisms may also be involved in the augmentation of bladder contraction during hypoxia-glucopenia and reoxygenation cycling, because a non-specific P2X antagonist blocked most of the augmented response, whereas a P2X1-specific antagonist prevented only part of the augmentation of contractile response induced by hypoxia-glucopenia and reoxygenation. In conclusion, four cycles of hypoxia-glucopenia and reoxygenation increased the purinergic, but not the cholinergic, contractile responses to nerve stimulation. Increased P2X1 receptor expression and ATP release may have contributed to the augmentation of contractile response induced by hypoxia-glucopenia and reoxygenation. Purinergic antagonists may, therefore, be a useful therapeutic option for the treatment of overactive bladder with increased purinergic-mediated contractions.


Aerosol containment device for airway management of patients with COVID-19: a narrative review.
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is highly contagious. To protect healthcare workers from infection during airway management, some expert recommendations and guidelines recommended wearing P2/N95 masks, goggles or glasses, glove, face-shields, and gowns as standard personal protective equipment (PPE). Nevertheless, several simulation studies have suggested that the standard PPE may not fully protect healthcare workers. Dr. Hsien Yung Lai introduced an acrylic box ("aerosol box") as a part of PPE during airway management. Since then, several companies and healthcare workers have made their own modified devices ("aerosol containment device"), and the use of such a device has spread worldwide, without being formally assessed for its effectiveness, efficacy and safety. Several simulation studies have indicated that "aerosol containment device" would make tracheal intubation more difficult. In addition, the device would prevent the spread of droplets from a patient, but may increase the risk of healthcare workers being exposed to a higher concentration of viral aerosols. Therefore, the current state of knowledge indicates that an "aerosol containment device" without vacuum mechanism has only limited efficacy in protecting healthcare workers from viral transmission.


Heavy metal distribution, fractionation, and biotoxicity in sediments around villages in Baiyangdian Lake in North China.
The effects of human activities on heavy metal distributions and fractionation in sediments from villages around Baiyangdian Lake (BYDL), North China, were assessed. The concentrations of Cd, Cr, Cu, Ni, Pb, and Zn in sediments from five villages were determined, and the potential ecological risk index, risk assessment code, and Chironomus sp. larvae toxicity assay were used to assess the bioavailabilities and toxicities of the metals. The contribution of Cd to the potential ecological risk was 45.13-89.53%, the highest among the heavy metals investigated. The contributions of Cd, Pb, and Zn in the non-residual fractions to the total concentrations were 66.23-90.57%, 18.31-96.28%, and 8.89-76.84%, respectively, which indicated that these metals had important anthropogenic sources and were very bioavailable. The mean risk assessment codes decreased in the order of Cd (49.82%) > Zn (20.95%) > Cu (9.35%) > Pb (6.88%) > Ni (4.85%) > Cr (0.30%), and the toxicity of Cd and Zn to biota around BYDL is of concern. The mean survival rate of Chironomus sp. larvae in sediments from Dizhuang village was 44.02%, which indicated that there was a high degree of heavy metal toxicity, particularly in waterways around the village. Carboxylesterase and superoxide dismutase analysis results indicated that heavy metals could markedly increase or decrease enzyme activities in Chironomus sp. larvae. Overall, the results indicated that heavy metal pollution in villages around BYDL should be taken into consideration for its ecological management.


Comparing the efficacy of salvage regimens for relapsed/refractory B-cell acute lymphoblastic leukaemia: a systematic review and network meta-analysis.
The complete remission (CR) rate and overall survival (OS) of relapsed/refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL) are not satisfactory. The available salvage regimens include standard chemotherapy, inotuzumab ozogamicin, blinatumomab and cluster of differentiation (CD)19 chimeric antigen receptor T cells (CAR T), and the NCCN guidelines recommend all of these therapies with no preference. Dual CD19/CD22 CAR T-cells have emerged as new treatments and have shown some efficacy, with high CR rates and preventing CD19-negative relapse. However, direct comparisons of the CR rate and long-term survival among the different salvage therapies are lacking. Databases including PubMed, Embase, Web of Science and Cochrane were searched from inception to January 31, 2022, for relevant studies. The outcomes of interest were complete remission/complete remission with incomplete haematologic recovery (CR/CRi) rates and 1-year overall survival (OS) rates. Odds ratios (ORs) were generated for binary outcomes, and the mean difference (MD) was generated for consecutive outcomes by network meta-analysis. CD19 CAR T-cells demonstrated a significantly better effect in improving the CR/CRi rate than blinatumomab (OR = 8.32, 95% CI: 1.18 to 58.44) and chemotherapy (OR = 16.4, 95% CI: 2.76 to 97.45). In terms of OS, CD19 CAR T-cells and dual CD19/CD22 CAR T-cells both had a higher 1-year OS rate than blinatumomab, inotuzumab ozogamicin and chemotherapy. There was no significant difference between CD19 CAR T-cells and dual CD19/CD22 CAR T-cells in terms of 1-year OS and CR/CRi rates. CD19 CAR T-cells are effective in inducing CR, and CD19 CAR T-cells and dual CD19/CD22 CAR T-cells show benefits for overall survival. More high-quality randomized controlled trials and longer follow-ups are needed to confirm and update the results of this analysis in the future.


The effects of different endocrine disruptors defining compound-specific alterations of gene expression profiles in the developing testis.
Environmental contaminants considered endocrine disruptors have been shown to affect testis development and function but the mechanisms of action are not clear. We now have analyzed the effects on the transcriptome in testes of mice exposed to mono-(2-ethylhexyl)-phthalate (9.2; 46.3 or 92.7 mg/kg/d), zearalenone (1.3; 3.9 or 6.6 mg/kg/d), lindane (16.6; 32.2 or 64.4 mg/kg/d), bisphenol-A (0.16; 16 or 64 mg/kg/d) or 17β-estradiol (0.006; 0.012 or 0.048 mg/kg/d). The compounds were orally administered in the drinking water during distinct developmental periods: (A) mothers were exposed only during the two weeks before mating; (B) the exposure was continued during pregnancy until birth or (C) exposure was continued for a further four weeks after birth. Testes were studied at four weeks of age. Mono-(2-ethylhexyl)-phthalate and zearalenone, both produced specific alterations of gene signatures. Interestingly, this was irrespective of the concentration of the toxicant or the developmental period during which exposure occurred.


Laser Ablation for Cerebral Metastases.
Laser interstitial thermal therapy is a minimally invasive surgical alternative to craniotomy that uses laser light through a fiber optic probe placed within a target lesion to create thermal tissue damage, resulting in cellular death. It is used in neuro-oncology to treat inaccessible lesions and obviate morbidity in high-risk patients. Overall complication rates and outcome measures are comparable with those seen in radiation and/or craniotomy. Laser interstitial thermal therapy can be an effective option for recurrent brain metastases. Prospective, randomized trials must be performed to evaluate the efficacy of laser interstitial thermal therapy as a primary treatment for brain metastases.


The prevalence, odds and predictors of lifespan comorbid eating disorder among people with a primary diagnosis of bipolar disorders, and vice-versa: Systematic review and meta-analysis.
There are scarce and discrepant data about the prevalence and correlates of co-occurring eating disorders (EDs) among people with a primary diagnosis of bipolar disorder (BD), and vice-versa, compelling a systematic review and meta-analysis on the matter. MEDLINE/PsycINFO databases were systematically searched for original studies documenting BD⇌ED comorbidity across the lifespan, from inception up until April 20th, 2020. Random-effects meta-analysis and meta-regression analyses were conducted, accounting for multiple moderators. Thirty-six studies involved 15,084 primary BD patients. Eleven studies encompassed 15,146 people with primary EDs. Binge eating disorder (BED) occurred in 12.5% (95%C.I.=9.4-16.6%, I2=93.48%) of BDs, while 9.1% (95%C.I.=3.3-22.6%) of BEDs endorsed BD. Bulimia Nervosa (BN) occurred in 7.4% (95%C.I.=6-10%) of people with BD, whereas 6.7% (95%C.I.=12-29.2%) of subjects with BN had a diagnosis of BD. Anorexia Nervosa (AN) occurred in 3.8% (95%C.I.=2-6%) of people with BDs; 2% (95%C.I.=1-2%) of BD patients had a diagnosis of AN. Overall, BD patients with EDs had higher odds of being female vs. non-ED controls. Several moderators yielded statistically significant differences both within- and between different types of BDs and EDs. Scant longitudinal studies, especially across different EDs and pediatric samples. High heterogeneity despite subgroup comparisons. Limited discrimination of the quality of the evidence. The rates of BD⇌ED comorbidity vary across different diagnostic groups, more than they do according to the "direction" of BD⇌ED. Further primary studies should focus on the risks, chronology, clinical impact, and management of the onset of intertwined BD⇌ED across different ages, promoting a continuum approach.


Serum alkaline phosphatase is a prognostic marker in bone metastatic disease of the extremity.
The purpose of this study was to determine the prognostic value of serum alkaline phosphatase for treatment decision making in metastatic bone disease. 1090 patients who underwent surgery for extremity metastatic disease were retrospectively identified at two tertiary care centers. The association between alkaline phosphatase and mortality was assessed by bivariate and multivariate analyses. Three-month and one-year mortality rates were 305 (29%) and 639 (62%), respectively. Alkaline phosphatase was associated with mortality at both three months and one year. Serum alkaline phosphatase may be a useful marker in prognostic algorithms for patients with extremity metastatic disease.


In vivo effects of human dialyzable leukocyte lysate. III. Modulation of the spleen cell proliferative response to antigen by components of leukocyte dialysates and an initial characterization of an ampliative nucleoside.
The augmentative effects of isolated components of human dialyzable leukocyte lysates upon the proliferative response to antigen were investigated. Sequential Sephadex G-25 and Bio-Gel P-4 chromatography separated five distinct fractions which, 24 hr after injection into Keyhole limpet hemacyanin (KLH)-sensitive mice, either augmented or suppressed the in vitro spleen cell proliferative response to KLH. An amplifier molecule was isolated from one of the augmentative fractions by high-pressure, reverse-phase liquid chromatography. Preliminary structural analysis of the amplifier component indicated a nucleoside structure, similar to--but possibly distinct from--thymidine.


Comparison of Epidural Bupivacaine and Buprenorphine to Bupivacaine and Butorphanol for Postoperative Analgesia in Lower Limb Orthopedic Surgery.
Postoperative analgesia is of utmost importance in the treatment of patients undergoing surgery. Good postoperative pain management reduces hospital stay and improves early ambulation. This study compared the efficacy of epidural bupivacaine with buprenorphine to butorphanol in lower limb orthopedic surgery. This study was carried out to investigate the onset of analgesia, the extent of analgesia, sedation score, and side effects of butorphanol with bupivacaine versus buprenorphine with bupivacaine. In a clinical trial study, 100 patients who underwent elective orthopedic lower limb surgery were randomly allocated to two groups. A total of 100 patients with American Society of anesthesiologists grades I and II posted for lower limb orthopedic surgery were enrolled in this randomized, double-blind study. The patients were divided into groups A and B. Subarachnoid block was achieved with 3.4 mL of 0.5% bupivacaine. The pain was monitored by the visual analog scale postoperatively. The patients in group A received bupivacaine with buprenorphine, and group B received bupivacaine with butorphanol when they complained of pain in the postoperative period. The onset of analgesia, duration of analgesia, sedation score, and side effects were compared between the two groups. The onset of analgesia was observed earlier in group A than in group B (7.7 ± 1.6 vs. 12.6 ± 1.7 minutes, P < 0.001). The duration of analgesia was longer in group A than in group B (590 ± 40 vs. 480 ± 54 minutes, P < 0.001). Pulse rates and mean arterial pressures were significantly different (P < 0.001). Side effects were common in both groups. Buprenorphine added to bupivacaine provides earlier onset and longer postoperative epidural analgesia than epidural butorphanol with bupivacaine.


Grading operative findings at laparoscopic cholecystectomy following the new scoring system in Duhok governorate: Cross sectional study.
Numerous preoperative scoring systems predict difficult laparoscopic cholecystectomy. Recently, the intraoperative difficulties which are facing surgeons are studied. A new scoring system categorize patients according to many intraoperative findings with a final outcome whether converting to open cholecystectomy or continuing laparoscopically. This prospective study included 120 patients admitted for laparoscopic cholecystectomy for symptomatic gallstones from October 2019 to August 2020. Intraoperative difficulties were evaluated and patients were categorized according to intraoperative scoring for cholecystitis severity and compared depending to the rate of conversion to the open technique. Most patient were middle aged females having multiple gallstones, the mean operation time was 35 min and 7.8% of patients were converted to open cholecystectomy because of intraoperative difficulty.There was a significant correlation between the conversion rate and each of distended and/or contracted gall bladder, inability to grasp the gall bladder with traumatic forceps, stone ≥1 cm impacted in Hartman's pouch, and bile or pus outside gallbladder (P values: 0.002, 0.000, 0.008 and 0.015) respectively, and no significant correlation with gallbladder adhesions, adhesions from previous upper abdominal surgery, BMI>30, and Time to identify cystic artery and duct >90 min (P values: 0.123, 1, 1, 0.078) respectively. New intraoperative scoring systems are valuable in predicting difficulties and preventing increase operation time and possible injuries. The main points of difficulties are distended or contracted gallbladder, large stone impaction, difficult grasping the wall of the gall bladder and the presence of bile or pus outside the gall bladder.


A support vector machine approach to classify human cytochrome P450 3A4 inhibitors.
The cytochrome P450 (CYP) enzyme superfamily plays a major role in the metabolism of commercially available drugs. Inhibition of these enzymes by a drug may result in a plasma level increase of another drug, thus leading to unwanted drug-drug interactions when two or more drugs are coadministered. Therefore, fast and reliable in silico methods predicting CYP inhibition from calculated molecular properties are an important tool which can be applied to assess both already synthesized as well as virtual compounds. We have studied the performance of support vector machines (SVMs) to classify compounds according to their potency to inhibit CYP3A4. The data set for model generation consists of more than 1300 structural diverse drug-like research molecules which were divided into training and test sets. The predictive power of SVMs crucially depends on a careful selection of parameters specifying the kernel function and the penalty for misclassifications. In this study we have investigated a procedure to identify a valid set of SVM parameters which is based on a sampling of the parameter space on a regular grid. From this set of parameters, either single SVMs or SVM committees were trained to distinguish between strong and weak inhibitors or to achieve a more realistic three-class assignment, with one class representing medium inhibitors. This workflow was studied for several kernel functions and descriptor sets. All SVM models performed significantly better than PLS-DA models which were generated from the corresponding descriptor sets. As a very promising result, simple two-dimensional (2D) descriptors yield a three-class model which correctly classifies more than 70% of the test set. Our work illustrates that SVMs used in combination with simple 2D descriptors provide a very effective and reliable tool which allows a fast assessment of CYP3A4 inhibition potency in an early in silico filtering process.


Modulation by horizontal eye position of the vestibulo-collic reflex induced by tilting in the frontal plane in the alert cat.
In alert cats, during sinusoidal rotations of head and trunk en bloc around a longitudinal axis, in darkness or in light, the vestibulo-collic reflex induces neck muscle contractions. The phase and gain diagrams are consistent, in the frequency range 0.2 to 1.2 Hz, with previous results from anesthetized or decerebrate cats. In addition, neck muscle contractions are modulated by horizontal eye position, as is the case for rotations in the horizontal plane, around the vertical (Z) axis. Neck muscle contraction is consequently under control of both eye position and head tilt angle. This synergy of eye and head could suppress the effects of vestibulo-collic reflex during orienting reactions.


Sternocleidomastoid Flap in Parotid Surgery: A Case Series.
Superficial and deep parotidectomies are known treatments for benign and malignant neoplasms of parotid glands. Due to the gland's proximity to facial nerve and other vital structures, this surgery carries the highest risk of facial nerve palsy. Another frequently overlooked complication, which can be detrimental to patient's life style is Frey's syndrome, or gustatory sweating. Other complications include flap necrosis and various contour deformities. We conducted this study on a group of 40 patients of parotid swellings to assess usage of sternocleidomastoid flap in prevention of Frey's syndrome, contour deformities, flap necrosis, salivary fistula and drain related injuries. We divided the patients in two groups based on the usage of sternomastoid flap. In Group A, the patients underwent superficial or total parotidectomies with a partial thickness, superiorly based sternomastoid flap. In Group B, no sternomastoid flap was placed. The incidence of Frey's syndrome was seen to be 3 times in Group B, while a visible contour deformity was seen in a third of patients in Group B, with Group A reporting no incidence. Also Group A, did not see any cases of flap necrosis or salivary fistula, while Group B saw 3 and 2 cases respectively. Also, among the two revision cases done in Group A, the one with previously placed sternomastoid flap (done by us 3 years back) had an excellent plane preserved, while another revision case without sternomastoid flap saw a complete adherence of facial nerve to overlying skin, resulting in Grade II permanent facial palsy. Parotidectomy is a technically challenging surgery in regards to important structures in the vicinity. Even with ostensibly perfect technique, facial nerve injury can occur for unknown reasons. All in all, sternomastoid flap is an acceptable modality to fill the parotidectomy defect, improve the facial contour and reduce the incidences of Frey's syndrome and skin necrosis.


Identification of motoneurons supplying the tensor veli palatini muscle in the guinea pig and cat: an horseradish peroxidase study.
Identification of motoneurons supplying the tensor veli palatini muscle was attempted by the horseradish peroxidase (HRP) method in the guinea pig and cat. After HRP injection into the tensor veli palatini muscle, HRP-labeled neurons were seen in the regions closely medial to the cluster of the lateral pterygoid motoneurons in the dorsolateral division of the trigeminal motor nucleus. In the guinea pig the tensor veli palatini motoneurons were observed at the level of the whole rostrocaudal extent of the trigeminal motor nucleus, while in the cat they were seen at the level of the rostral two-thirds of the nucleus.


Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors.
Most T lymphocytes, including regulatory T cells (Treg cells), differentiate in the thymus. The age-dependent involution of this organ leads to decreasing production of T cells. Here we found that the output of new Treg cells from the thymus decreased substantially more than that of conventional T cells. Peripheral mouse and human Treg cells recirculated back to the thymus, where they constituted a large proportion of the pool of Treg cells and displayed an activated and differentiated phenotype. In the thymus, the recirculating cells exerted their regulatory function by inhibiting interleukin 2 (IL-2)-dependent de novo differentiation of Treg cells. Thus, Treg cell development is controlled by a negative feedback loop in which mature progeny cells return to the thymus and restrain development of precursors of Treg cells.


'She gave it her best shot right away': patient experiences of biomedical and patient-centered communication.
Medical educators and researchers recommend a patient-centered interviewing style, but little empirical data exists regarding what aspects of physician communication patients like and why. We investigated patient responses to videotaped doctor-patient vignettes to ascertain what they liked about patient-centered and biomedical communication. We conducted semi-structured interviews with 230 adult medicine patients who viewed videotapes depicting both patient-centered and biomedical physician communication styles. We used a mixed methods approach to derive a "ground-up" framework of patient communication preferences. Respondents who preferred different communication styles articulated different sets of values, important physician behaviors, and physician-patient role expectations. Participants who preferred the patient-centered physician (69%) liked that she worked with and respected patients and explored what the patient wanted. Participants who preferred the biomedical physician (31%) liked that she prevented harm, demonstrated medical authority, and delivered information clearly. Patients like (and dislike) patient-centered communication for thoughtful, considered reasons that appear grounded in their values and expectations about physicians, patients, and the clinical encounter. Better understanding the diversity of patient communication preferences may lead to more effective and individualized care.


Reactions of the tumour bed to lethally irradiated tumour cells, and the Révész effect.
Subdermal inoculation of the foot of the rat with lethally irradiated (LI) Walker tumour (W256) cells, mixed with viable (V) W256 cells, decreased the latent period for initiation of allogeneic tumour growth without significantly affecting its rate. This Révész effect decreased with increase in the number of inoculated V cells, and with decrease in age of recipient. LI cells of a different (Y-P388) rat tumour exerted a Révész effect, even in recipients which had been immunized with LI (Y-P388) tumour cells. Local pre-irradiation of the site of inoculation of V cells decreased both the latent period and rate of tumour growth. It acted independently of a Révész effect, and the decrease in tumour growth rate was partly due to emigration of V cells from the inoculum, producing metastases. LI, but not heat-killed cells, induced prolonged swelling of the tumour bed in unimmunized and tumour-immunized rats, which, unlike inflammatory swelling, was inhibited by pre-irradiation of the foot. It is postulated that the Révész effect is due to enhancement of survival of V cells by trophic substances which are principally elaborated by LI (AND V) cells, but also by the tumour bed, due to innate growth and trophic reactions of its tissues to the presence of tumour cells.


Cerebrovascular response to maternal hyperoxygenation in fetuses with hypoplastic left heart syndrome depends on gestational age and baseline cerebrovascular resistance.
Compared with normal fetuses, fetuses with hypoplastic left heart syndrome (HLHS) have smaller brain volumes and are at higher risk of brain injury, possibly due to diminished cerebral blood flow and oxygen content. By increasing cerebral oxygen delivery, maternal hyperoxygenation (MH) might improve brain development and reduce the risk of brain injury in these fetuses. This study investigated whether gestational age and baseline cerebrovascular resistance affect the response to MH in fetuses with HLHS. The study population comprised 43 fetuses with HLHS or HLHS variant referred for fetal echocardiography between January 2004 and September 2008. Middle cerebral artery (MCA) pulsatility index (PI), a surrogate measure of cerebrovascular resistance, was assessed between 20 and 41 weeks' gestation at baseline in room air (RA) and after 10 min of MH. Z-scores of MCA-PI were generated. A mixed-effects model was used to determine whether change in MCA-PI depends upon gestational age and baseline MCA-PI. In RA and following MH, MCA-PI demonstrated a curvilinear relationship with gestational age in fetuses with HLHS, peaking at around 28 weeks and then falling more steeply near term. MCA-PI Z-score declined in a linear manner, such that it was 1.4 SD below that in normal fetuses at 38 weeks. Increase in MCA-PI Z-score after MH was first seen at ≥ 28 weeks. A baseline MCA-PI Z-score ≤ -0.96 was predictive of an increase in cerebrovascular resistance in response to MH. In fetuses with HLHS, MCA-PI first increases in response to MH at ≥ 28 weeks' gestation. A baseline MCA-PI Z-score ≤ -0.96 predicts an increase in cerebrovascular resistance in response to MH. These results may have implications for clinical trials utilizing MH as a neuroprotective agent. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Repeated Sprint Protocols With Standardized Versus Self-Selected Recovery Periods in Elite Youth Soccer Players: Can They Pace Themselves? A Replication Study.
Replicating the studies of Gibson et al and Brownstein et al to assess performance, and physiological, and perceived variables during a repeated sprint protocol (RSP) with standardized versus self-selected recovery in youth soccer players. Nineteen male soccer players (age 13.1 [1.3] y) completed 2 separate RSPs. RSP1: 10 × 30-m sprints with 30-second recovery and RSP2: 10 × 30-m sprints interspersed with self-selected recovery periods. Mean time of both 10 × 30-m RSPs and self-selected recovery periods of RSP2 were assessed. Heart rate, blood lactate concentration, and rates of perceived exertion were measured following RSPs. RSP2 revealed longer recovery periods (RSP1: 30.0 [0.0] s; RSP2: 39.0 [7.7] s; P < .001; effect size d = 1.648) with shorter repeated sprint time (mean 30-m sprint time: RSP1: 4.965 [0.256] s; RSP2: 4.865 [0.227] s; P = .014; d = 0.414). Blood lactate concentration (P = .002-.005; d = 0.730-0.958), heart rate (P < .001; d = 1.353), and rates of perceived exertion (RSP1: 14.9 [1.9]; RSP2: 12.9 [2.1]; P = .016; d = 1.046) were higher following RSP1. In contrast to the original studies, the present replication study demonstrated that self-selected recovery periods during a RSP leads to better repeated sprint performance compared with standardized recovery periods in youth soccer players. The better repeated sprint performance with individual recovery durations in RSP2 was achieved with less physiological and perceived effort.


Multiplexed ion beam imaging analysis for quantitation of protein expresssion in cancer tissue sections.
This corrects the article DOI: 10.1038/labinvest.2017.50.


The role of the isoniazid therapeutic test in tuberculous uveitis.
Of 38 cases of uveitis examined from 1970 to 1980 in which a tuberculous cause was considered, we classified 18 as presumed tuberculous on the basis of a positive response to isoniazid. We compared these patients to a control group who had a positive skin test but a negative response to the isoniazid therapeutic test. We found a family history of tuberculosis in seven of the 18 (P less than .05) and a more common (18 of 36 eyes) incidence of iridocyclitis (P less than .05) than of other types of uveitis. A uveitis patient who has a positive tuberculin skin test of any size or strength should undergo the isoniazid therapeutic test to ensure that a possible diagnosis of tuberculous uveitis is not missed. Tuberculosis should be suspected in both granulomatous and non granulomatous uveal lesions, especially in cases of chronic iridocyclitis.


Factors that influence how adults select oral over-the-counter analgesics: A systematic review.
Oral over-the-counter (OTC) analgesics such as acetaminophen, aspirin, ibuprofen, and naproxen sodium are widely used to treat pain. Although generally considered safe, inappropriate use can lead to injury. This study aimed to explore patient attitudes, beliefs, and perceptions about the efficacy and potential risks of oral OTC analgesics and to identify factors that adult patients use to make decisions about these medications. We searched MEDLINE, CINAHL, Scopus, and Embase to identify studies published in English between January 2000 and June 2019. We included randomized controlled trials, controlled trials, observational studies, systematic reviews, and meta-analyses that included OTC analgesics. Authors worked independently during study selection, data extraction, and analysis and then compared their findings and discussed discrepancies until consensus was reached. We evaluated study quality using the Study Quality Assessment Tool and Critical Appraisal of a Cross-Sectional Study. We identified 10,898 unique articles, of which 53 were included in this systematic review. A total of 36 studies included acetaminophen, 25 included nonsteroidal anti-inflammatory drugs (NSAIDs), and 19 did not specify a product. Adults had mixed perceptions about the effectiveness of analgesics. Knowledge of the risks of high doses of acetaminophen (liver toxicity) and NSAIDs (gastrointestinal bleeding or nephrotoxicity) was generally low and declined with less formal education. Individuals with severe or recurrent pain were more likely to exceed the maximum recommended dose of the medication. Although participants reported considering a variety of factors when deciding between different OTC analgesics, there was no clear medication that was generally preferred. Our review was comprehensive; however, the quality of the studies was generally good to fair. Adults frequently use oral OTC analgesics and possess a diverse set of beliefs about the efficacy and safety of the products. Pharmacists are well positioned to provide guidance to support the effective and safe use of these products.


"Medicalization" of community services for the elderly.
Research on medical care cost containment has indicated that the community-based service system is undergoing a process of restructuring within the context of an increasingly competitive environment and strong pressures to "medicalize" medical care services.


Extraction of impacted mandibular third molars - the effect of osteotomy at two speeds on peripheral bone: a histopathological analysis.
The aim of this study was to find out the ideal speed for making a precise osteotomy with minimal damage to the surrounding bone. Thirty-six patients were divided into two groups (n=18 in each) depending on the speed of the handpiece used for osteotomy (slow=20000rpm and fast=40000rpm). Samples were taken from the peripheral bone and examined histologically to measure the margins of the osteotomy, the amount of debris produced, and the degree of thermal osteonecrosis. The osteotomy made with the high speed handpiece was better than that made with the low speed one on all counts. The margins in the high speed group were more or less precisely as required, with less debris and no thermal necrosis, which illustrated the efficacy of a high speed osteotomy. These findings can apply to other procedures that involve osteotomies in maxillofacial surgery.


Perceived racial discrimination and polysubstance use among racial/ethnic minority adolescents in the United States.
Polysubstance use among adolescents is a significant public health concern, yet most studies on adolescent substance use focus on a singular substance. This study is one of the first to investigate the association between perceived racial discrimination (PRD) in school and polysubstance use among racial/ethnic minority adolescents using a nationally representative sample. Data was from the 2021 Adolescent Behaviors and Experiences Survey. The sample included 4145 racial/ethnic minority adolescents (52.8% female). Hierarchical binary logistic regression was used to examine the association between PRD in school and polysubstance use among racial/ethnic minority adolescents. About 12% of racial/ethnic minority adolescents engaged in polysubstance use and 23.4% reported experiencing PRD in school sometimes/most of the time/always. Controlling for other factors, experiencing PRD in school sometimes/most of the time/always was associated with 1.52 times higher odds of polysubstance use when compared to adolescents who never experienced PRD in school (OR=1.52, p=.044, 95% CI=1.01-2.30). Cyberbullying victimization, symptoms of depression, and being emotionally abused by a parent during COVID-19 were also associated with polysubstance use. Controlling for demographic characteristics and psychosocial stressors, PRD in school was significantly associated with higher odds of polysubstance use among racial/ethnic minority adolescents. The findings of this study could inform clinicians and policymakers of the association between PRD in school and polysubstance use, which could contribute to early identification of polysubstance use among racial/ethnic minority adolescents.


PTPN13 acts as a tumor suppressor in clear cell renal cell carcinoma by inactivating Akt signaling.
Protein tyrosine phosphatase, nonreceptor type 13 (PTPN13), has emerged as a critical cancer-related gene that is implicated in a wide range of cancer types. However, the role of PTPN13 in clear cell renal cell carcinoma (ccRCC) is poorly understood. In the present study, we aimed to evaluate whether PTPN13 participates in the progression of ccRCC. Decreased expression of PTPN13 was found in ccRCC tissues, which predicted a shorter survival rate in ccRCC patients. PTPN13 expression was also lower in ccRCC cell lines, and the upregulation of PTPN13 repressed the proliferation, colony formation and invasion, but enhanced the apoptosis of ccRCC cells. In contrast, the silencing of PTPN13 produced the opposite effects. Further data showed that PTPN13 overexpression decreased the phosphorylation of Akt, while PTPN13 silencing increased the phosphorylation of Akt. Treatment with Akt inhibitor markedly abrogated the PTPN13 silencing-evoked oncogenic effect in ccRCC cells. Xenograft tumor experiments revealed that overexpression of PTPN13 remarkably restricted the tumor formation and growth of ccRCC cells in vivo associated with inactivation of Akt. In conclusion, our data demonstrated that overexpression of PTPN13 restricts the proliferation and invasion of ccRCC cells through inactivation of Akt. Our study suggests a tumor suppressive function of PTPN13 in ccRCC and highlights the potential role of PTPN13 in the progression of ccRCC.


First snapshot on behavioral characteristics and related factors of patients with chronic kidney disease in South Korea during the COVID-19 pandemic (June to October 2020).
The recent novel coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented changes in behavior. We evaluated the current status of precautionary behavior and physical activity in chronic kidney disease (CKD) patients during the COVID-19 pandemic. A population of CKD patients (n = 306) registered in the Study on Kidney Disease and Environmental Chemicals (SKETCH, Clinical Trial No. NCT04679168) cohort recruited from June 2020 to October 2020 was included in the study. We conducted a questionnaire survey related to risk perception of COVID-19, precautionary behavior, and physical activity. There were 187 patients (61.1%) with estimated glomerular filtration rate of <45 mL/min/1.73 m2 . This population showed a higher degree of risk perception for COVID-19 than the general population. Age was the most significant determinant of risk perception among CKD patients. During the pandemic, social distancing and hygiene-related behavior were significantly increased (p < 0.001). The frequency of exercise was decreased only in those who took regular exercise, without diabetes, or with a lower Charlson comorbidity index (CCI) (p < 0.001), with no change among the other groups. Socioeconomic status and comorbidities significantly affected behavioral characteristics regardless of the category. Education and income were significantly associated with precautionary behaviors such as staying at home and hand sanitizer use. Patients with higher CCI status significantly increased frequency of exercise (adjusted odds ratio, 2.10; 95% confidence interval, 1.01-4.38). CKD patients showed higher risk perception with active precautionary behavioral changes than the general population. Healthcare providers should be aware of the characteristics to comprise precautionary behavior without reducing physical activity.


Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases.
The aim of this study is to evaluate the relationship between maternal single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine (HCY) level and offspring congenital heart diseases (CHDs). 338 mothers with offspring CHDs as case group and 306 mothers of normal children as control group were recruited. Their pregnant histories were interviewed by questionnaire and the MTHFR rsl801133 and rsl801131 were genotyped. The case-control analysis was used to find out the relationship between maternal SNPs of MTHFR gene and offspring CHDs. And the plasma HCY concentration of the mothers of CHDs children was detected. This case-case study was intended to find out the relevance between maternal HCY level and SNPs of MTHFR gene. There were significant differences in the gender of children, occupation of mothers, family history with CHDs, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHDs group and control group (P < 0.05). MTHFR rs1801133 was significantly associated with their offspring CHDs in mothers. The polymorphism of maternal MTHFR rs1801133 increased plasma HCY level, especially the homozygous mutation. Besides the environmental factors, our results suggested that the maternal MTHFR rs1801133 polymorphism might be a risk factor of their offspring CHDs, which may be due to the hyperhomocysteinemia by abnormal metabolism of HCY.


Altered transcriptional activity of c-fos promoter plasmids in v-raf-transformed NIH 3T3 cells.
In cells transformed by v-raf, an oncogenic counterpart of the serine/threonine kinase Raf-1, regulatory elements of the c-fos promoter were active under conditions of cell growth or stimulation for which they were inactive in untransformed control cells. This suggests that v-raf transforms by deregulating transcription of early response genes.


Growth inhibition of high-intensity focused ultrasound on hepatic cancer in vivo.
To investigate the damaging effect of high-intensity focused ultrasound (HIFU) on cancer cells and the inhibitory effect on tumor growth. Murine H22 hepatic cancer cells were treated with HIFU at the same intensity for different lengths of time and at different intensities for the same length of time in vitro, the dead cancer cells were determined by trypan blue staining. Two groups of cancer cells treated with HIFU at the lowest and highest intensity were inoculated into mice. Tumor masses were removed and weighed after 2 wk, tumor growth in each group was confirmed pathologically. The death rate of cancer cells treated with HIFU at 1 000 W/cm2 for 0.5, 1, 2, 4, 8, and 12 s was 3.11+/-1.21%, 13.37+/-2.56%, 38.84+/-3.68%, 47.22+/-5.76%, 87.55+/-7.32%, and 94.33+/-8.11%, respectively. A positive relationship between the death rates of cancer cells and the length of HIFU treatment time was found (r = 0.96, P<0.01). The death rate of cancer cells treated with HIFU at the intensity of 100, 200, 400, 600, 800, and 1 000 W/cm2 for 8 s was 26.31+/-3.26%, 31.00+/-3.87%, 41.97+/-5.86%, 72.23+/-8.12%, 94.90+/-8.67%, and 99.30+/-9.18%, respectively. A positive relationship between the death rates of cancer cells and the intensities of HIFU treatment was confirmed (r = 0.98, P<0.01). The cancer cells treated with HIFU at 1 000 W/cm2 for 8 s were inoculated into mice ex vivo. The tumor inhibitory rate was 90.35% compared to the control (P<0.01). In the experimental group inoculated with the cancer cells treated with HIFU at 1 000 W/cm2 for 0.5 s, the tumor inhibitory rate was 22.9% (P<0.01). By pathological examination, tumor growth was confirmed in 8 out of 14 mice (57.14%, 8/14) inoculated with the cancer cells treated with HIFU at 1 000 W/cm2 for 8 s, which was significantly lower than that in the control (100%, 15/15, P<0.05). HIFU is effective on killing or damage of H22 hepatic cancer cells in vitro and on inhibiting tumor growth in mice ex vivo.


A prognostic significance of nucleolar organizer region (AgNOR) in renal cell carcinoma.
Evaluation of prognostic significance of nucleolar organizer regions (NORs) in renal cell carcinoma (RCC). Nuclear organizer regions were quantified in a series of 59 cases of RCC by the silver colloid method, and the NOR index was obtained from the ratio between mean NOR counts in each neoplastic nucleus and in normal nucleus. The patients were staged pathologically and divided into 2 groups by average NOR index of all cases, which was 0.76. Correlations between the NOR index and other parameters were statistically analyzed, and the prognostic value of the NOR index was also examined. The NOR indices from each group were correlated with the survival curve. In low stage tumors (pT1 or 2 N0M0), the low NOR index group had a survival rate of almost 100 per cent while in those patients with higher NOR indices, there was a significantly increased mortality (p < 0.01). In patients presenting with high stage tumors (excluding pT1 and 2 N0M0), the survival rate was significantly improved in those patients with a low NOR index (p < 0.01). On the other hand, the patients with a low NOR index have a better prognosis than those with a high NOR index within each tumor grade (p < 0.01). Statistical analysis by the log rank test indicated NORs to be a significant predictor of survival over the whole series within low and high pathological stages and within each tumor grade. Analysis of the data with Cox's proportional hazard model showed that NOR index had a stronger hazard ratio than grade or stage of tumor (p = 0.0005). Our study has demonstrated that NOR index is a new prognostic indicator for patients with RCC (p = 0.0005).


A novel method for simultaneous glutamate and extracellular activity measurement in brain slices with high temporal resolution.
Measurement of neurotransmitters during normal or altered function in cerebral slices could be an important tool to better understand the relationship between biochemical changes and electrophysiological activity. Some attempts of this analysis have been made; however, the current techniques do not have the appropriate time resolution to establish this relationship. The use of electrochemical biosensors has allowed for good time resolution, but problems related to the reduction of signal noise and biofouling of the electrode surface could be an important issue. In this work, we propose a new alternative to simultaneously measure glutamate and electrical activity with a high temporal resolution in brain slices. This approach is based on the use of enzymatic reactors that generate a fluorescent derivative from glutamate that can be measured at high temporal resolution. The results presented here show a reliable measurement of this neurotransmitter in brain slices obtained from intact animals under the effect of a glutamate transporter blocker DL-threo-beta-benzyloxyaspartate as well as the potassium channel blocker 4-aminopyridine. Differences in the levels of glutamate and high frequency and amplitude discharges as an effect of drug administration were found in brain slices obtained from epileptic rats (p<0.05). In conclusion, this method could be used to measure neurotransmitter concentration online at a near physiological temporal resolution, which can then be correlated to the electrical activity that is simultaneously recorded.