Acrosome staining and motility characteristics of sterlet spermatozoa after cryopreservation with use of methanol and DMSO.
In this study we describe acrosome staining and motility characteristics of fresh and cryopreserved sterlet (Acipenser ruthenus L.) spermatozoa using soybean trypsin inhibitor-Alexa conjugate fluorescent staining and computer-aided sperm analysis (CASA), respectively. Methanol or dimethylsulfoxide (DMSO) were used as cryoprotectants. After cryopreservation a decline in sperm motility characteristics occurred, but no differential effect between cryoprotectant was observed. Cryopreservation caused a significant increase in the percentage of spermatozoa with acrosome stained by SBTI-Alexa for samples cryopreserved using DMSO compared to methanol. These data suggest that the low usefulness of DMSO for cryopreservation of sturgeon spermatozoa is related to its harmful specific effect towards the acrosome, probably by causing its precocious triggering, much before any egg contact.


Detection of fetal DNA in maternal plasma by microarray coupled with emulsions PCR.
The presence of fetal DNA in maternal plasma made non-invasive prenatal diagnosis possible. Although fetal DNA has been used in several genetic disease diagnoses, many challenges remained in the detection methods. We attempted to develop a sensitive and reliable microarray coupled with emulsions PCR method to detect the fetal DNA in the plasma of pregnant women. Fetal DNAs extracted from the plasma of pregnant women were amplified in emulsions, and fluorescence was labeled at the same time. The labeled target DNAs were hybridized and detected by the capturing DNA probes on a modified slide. Six Y chromosome special sequences in gene of SRY, DYS and DYZ as the marker of fetal DNAs were detected simultaneously in this study, and the beta-globin gene was detected as marker of total DNA from maternal plasma. An unrelated sequence was also detected as negative control in this study. 76 pregnant women in the first trimester of gestation joined in this study. Conventional PCR and real time PCR were also carried out for comparison. We could detect the fetal DNAs reliably with this method in early stage of gestation. The 6Y chromosome sequences were detected in 40 of the 42 male fetus carrier samples, and no Y special sequence was detected in the female fetus carrier samples. The earliest plasma sample which we could detect in this study was collected on the 31st day after pregnancy. The results suggest that the microarray coupled with emulsions PCR method could be used for fetal DNA detections, and emulsions were useful in DNA amplification as reaction media to overcome the primer incompatibility which frequently encounters in multiplex PCR amplification. Our methods have the potential in high-throughput assays and could be widely used in clinical researches and diagnosis.


Repair and recovery in the epithelial and vascular connective tissues of pig skin after irradiation.
Using split-dose experiments, with varying time intervals between two equal fractions, the total repair capacity and the time of onset of additional recovery was determined for both early and late responses in pig skin. The early epidermal response was studied after beta-irradiation and 250 kV X-rays were used to investigate dermal changes. Based on the results of seven separate single dose studies the ED50 value ( +/- SE) for early moist desquamation was 27.76 +/- 0.91 Gy. With intervals of one and 14 days between two equal fractions similar ED50 values of 35 Gy were obtained. This suggested a recovered dose of approximately 7 Gy for epithelial desquamation, a repair capacity for sublethal injury of 20-25%. Additional recovery possibly due to repopulation, was observed with intervals of greater than or equal to 21 days between fractions. The rate of additional recovery was linearly related to the time interval between doses and was equivalent to 74 cGy/day. Recovery from the first dose was complete within 6 weeks. Evidence for radiation-induced tissue hypoxia was obtained when longer time intervals between doses were used. The more subjective early erythema reaction was also assessed. This reaction produced a similar estimate for the repair capacity and for the time of onset of recovery to that obtained using moist desquamation. This agreement was not maintained with intervals of greater than or equal to 28 days between doses due to an artefact associated with the way erythema reactions were assessed. After irradiation with single doses of X-rays ED50 values of 18.59 +/- 0.49 and 20.53 +/- 0.35 Gy were obtained for the dermal reactions of dusky/mauve erythema and necrosis, respectively. The recovered doses for the dermal responses, with intervals of 1 and 28 days between fractions, were similar, approximately 4.2 Gy, indicating a total repair capacity of 20-25%. Additional dermal recovery was seen only with intervals of greater than 28 days between doses. There was no evidence for "slow repair". Surprisingly complete recovery from the first dose was suggested with an interval of 16 weeks between doses. This finding might be influenced by radiation-induced hypoxia. The time of onset of additional repopulation/recovery and the latency for tissue impairment in epidermal and dermal tissues in pig skin were compared with those for other early and late responding tissues.


Development and validation of machine learning models for the prediction of SH-2 containing protein tyrosine phosphatase 2 inhibitors.
Discovery and development of a new drug to the market is a highly challenging and resource consuming process. Although, modern drug discovery technologies have enabled the rapid identification of lead compounds, translation of the lead compounds into successful clinical candidates remains a big challenge. In recent years, the availability of massive structural and biological data of diverse small molecules and macromolecules has helped the researchers to deep mine the multidimensional data with the help of artificial intelligence-based predictive tools to draw useful insights on the structural features of biological or therapeutic significance. The aim of this study was to utilize the available data on small molecule (SH2)-containing protein tyrosine phosphatase 2 (SHP2) inhibitors to build and develop machine learning (ML) models that can predict the SHP2 inhibitory potential of new compounds. The dataset contained 2739 unique small molecule SHP2 inhibitors obtained from the BindingDB, ChEMBL and recent literature. After curation of the data, the predictive models such as XGBoost, K nearest neighbours, neural networks were developed and validated through a tenfold cross-validation testing procedure. Out of the seven models developed, the XGBoost model showed an excellent performance with ROC AUC score of 0.96 and accuracy of 0.97 on the test data. Moreover, the Shapley Additive Explanations method was applied to assess a more in-depth understanding of the influence of variables on the model's predictions. In summary, the XGBoost model developed in this study can be useful in the identification of novel SHP2 inhibitors and therefore, can accelerate the discovery of novel therapeutics for cancer therapy.


Neuronal injury following permanent middle cerebral artery occlusion in cats.
The border of a chronic infarct is sharply demarcated. We found in our investigation, however, that this is merely a macroscopic diagnosis and does not say anything about the structure of the tissue and the content of morphologically preserved neurons in the marginal zones. In six cats the left cerebral artery was permanently occluded. Eight weeks later the animals were killed and autoradiographic investigations were conducted on cryostat sections to determine rCBF. Adjacent to every 20-microns section, a 10-microns HE section was prepared. Preserved nerve cells were counted in several areas of the cortex in a symmetric fashion in both the infarcted and the contralateral side in the identical regions where rCBF had been measured in the preceding section. Two additional non-ischemic cat brains served as controls, which were investigated in the same manner as described above. A marked loss of neurons was observed in the border zone of the infarct. Only occasionally preserved ganglion cells were seen in each cortical layer. Even in areas one gyrus distant to the margin of the infarct the number of neurons was still reduced by one third as compared to the contralateral side. Starting only with the lateral gyrus the number of ganglionic cells was found to be equal on both sides.


Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision.
The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59-74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51, 789-808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.


Robotic-assisted Roux-en-Y gastric bypass: update from 2 high-volume centers.
Laparoscopic Roux-en-Y gastric bypass (RYGB) is a challenging operation in the most experienced hands. Robotic surgery allows the capabilities of the minimally invasive surgeon to be extended. An increasing number of robotic gastric bypasses are being performed each year with the assumption that the complication rates are decreased. The objectives of the present study were to review the results of robotic-assisted RYGB (RARYGB) from 2 high-volume centers, including 1 university and 1 private practice. We report the most recently compiled, largest series of RARYGB in the world to show the effectiveness, morbidity, and mortality of this method. Databases were searched for patients undergoing RARYGB from 2002 to 2010, and the endpoints were recorded. A total of 1100 RARYGBs matched our search. The patients had a mean preoperative age of 46.9 years, mean weight of 131.9 kg, and mean body mass index of 47.9 kg/m(2). The mean operative time was 155 minutes. There were no conversions. The mean body mass index was 39.8 kg/m(2) at 3 months postoperatively (79% follow-up). Complications were few, and included 2 cases of pulmonary embolism (.19%), 3 cases of deep venous thrombosis (.27%), 1 case of gastrojejunal anastomotic leak (.09%), and 9 cases of staple line bleeding (.82%). No patients died. RARYGB is safe and effective. Although the operative time might be increased, the complication rates, most notably of anastomotic leak, are extremely low.


Effect of anti-nerve growth factor on early and late airway responses in allergic rats.
The increased production of nerve growth factor (NGF) has been associated with allergen-induced airway hyperresponsiveness and enhanced airway inflammation in experimental models of asthma. The aim of this study was to investigate whether a local application of anti-NGF to the lungs may affect the allergen-specific early (EAR) and late (LAR) airway responses to ovalbumin (Ova) of Ova-sensitized brown Norway rats. Rats were sensitized systemically with Ova and were boosted twice intratracheally with Ova aerosol using a microsprayer. Two hours before every boost, the animals were pretreated either with aerosolized anti-NGF or with a control antibody. On day 21, all animals were challenged with inhalational Ova aerosol and pulmonary resistance was recorded in anesthetized, orotracheally intubated animals during the early and late asthmatic responses. In addition, differential cell counts from bronchoalveolar lavage and serum immunoglobulin E (IgE) levels were determined 48 h post-Ova challenge. Pretreatment with anti-NGF significantly attenuated the EAR but had no significant effect on the LAR. Serum IgE levels and inflammatory cell influx into the lungs were not affected by anti-NGF pretreatment. The data from this study suggest that NGF is directly involved in the development of the EAR without affecting the inflammatory airway response or LAR.


Visual pollution real images benchmark dataset on the public roads.
The term quality of life (QoL) refers to a wide range of multifaceted concepts that often involve subjective assessments of both positive and negative aspects of life. It is difficult to quantify QoL as the word has varied meanings in different academic areas and may have different connotations in different circumstances. The five sectors most commonly associated with QoL, however, are Health, Education, Environmental Quality, Personal Security, Civic Engagement, and Work-Life Balance. An emerging issue that falls under environmental quality is visual pollution (VP) which, as detailed in this study, refers to disruptive presences that limit visual ability in public roads with an emphasis on excavation barriers, potholes, and dilapidated sidewalks. Quantifying VP has always been difficult due to its subjective nature and lack of a consistent set of rules for systematic assessment of visual pollution. This emphasizes the need for research and module development that will allow government agencies to automatically predict and detect VP. Our dataset was collected from different regions in the Kingdom of Saudi Arabia (KSA) via the Ministry of Municipal and Rural Affairs and Housing (MOMRAH) as a part of a VP campaign to improve Saudi Arabia's urban landscape. It consists of 34,460 RGB images separated into three distinct classes: excavation barriers, potholes, and dilapidated sidewalks. To annotate all images for detection (i.e., bounding box) and classification (i.e., classification label) tasks, the deep active learning strategy (DAL) is used where an initial 1,200 VP images (i.e., 400 images per class) are manually annotated by four experts. Images with more than one object increase the number of training object ROIs which are recorded to be 8,417 for excavation barriers, 25,975 for potholes, and 7,412 for dilapidated sidewalks. The MOMRAH dataset is publicly published to enrich the research domain with the new VP image dataset.


The acute and chronic effects of MDMA ("ecstasy") on cortical 5-HT2A receptors in rat and human brain.
While the pre-synaptic effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons have been studied extensively, little is known about its effects on post-synaptic 5-HT(2) receptors. Therefore, cortical 5-HT(2A) receptor densities and 5-HT concentration were studied in MDMA treated rats (10 mg/kg s.c.). Furthermore, 5-HT(2A) post-synaptic receptor densities in the cerebral cortex of recent as well as ex-MDMA users were studied using [123I]R91150 SPECT. In rats we observed a decrease followed by a time-dependent recovery of cortical 5-HT(2A) receptor densities, which was strongly and positively associated with the degree of 5-HT depletion. In recent MDMA users, post-synaptic 5-HT(2A) receptor densities were significantly lower in all cortical areas studied, while 5-HT(2A) receptor densities were significantly higher in the occipital cortex of ex-MDMA users. The combined results of this study suggest a compensatory upregulation of post-synaptic 5-HT(2A) receptors in the occipital cortex of ex-MDMA users due to low synaptic 5-HT levels.


Pulmonary arterial pulse pressure and mortality in pulmonary arterial hypertension.
In the Framingham studies, systemic arterial pulse pressure correlated linearly with morbidity and mortality. Right ventricular (RV) systolic dysfunction and pulmonary circulation stiffening result in abnormalities of pulmonary arterial (PA) pulse pressure in PA hypertension (PAH). We investigated the prognostic potential of PA pulse pressure in 67 patients with PAH diagnosed between January 1996 and March 2004 (33 idiopathic PAH, 34 PAH-connective tissue disease). The population was arbitrarily divided into tertiles of PA pulse pressure (= systolic-diastolic PA pressure) and 5-year mortality was assessed using the Kaplan-Meier method. The extent of RV systolic dysfunction and pulmonary circulation stiffening within each tertile was assessed by comparing the mean cardiac index and alpha (a recently described measure of pulmonary circulation distensibility) in each. Independent predictors of mortality were identified by Cox regression. Five-year mortality rates in patients with low, intermediate and high pulse pressures were 40%, 91% and 54%, respectively. Pulse pressure did not independently predict mortality, but cardiac index, 6-min walk test distance and mixed venous oxygen saturation did. Pulse pressure correlated with circulation stiffening (alpha) but did not correlate with cardiac index which tended to be lower in patients with intermediate pulse pressure and high mortality. PA pulse pressure correlated with pulmonary circulation stiffening but did not predict mortality in this study. RV dysfunction provided better prognostic information and probably explains the higher mortality seen in patients with intermediate pulse pressure.


Breast cancer staging by subtype in the Lower Mississippi Delta region States.
To evaluate disparities in breast cancer stage by subtype (categorizations of breast cancer based upon molecular characteristics) in the Delta Regional Authority (Delta), an impoverished region across eight Lower Mississippi Delta Region (LMDR) states with a high proportion of Black residents and high breast cancer mortality rates. We used population-based cancer registry data from seven of the eight LMDR states to explore breast cancer staging (early and late) differences by subtype between the Delta and non-Delta in the LMDR and between White and Black women within the Delta. Age-adjusted incidence rates and rate ratios were calculated to examine regional and racial differences. Multilevel negative binomial regression models were constructed to evaluate how individual-level and area-level factors affect rates of early- and late-stage breast cancers by subtype. For all subtypes combined, there were no Delta/non-Delta differences in early and late stage breast cancers. Delta women had lower rates of hormone-receptor (HR+)/human epidermal growth factor 2 (HER2-) and higher rates of HR-/HER2- (the most aggressive subtype) early and late stage cancers, respectively, but these elevated rates were attenuated in multilevel models. Within the Delta, Black women had higher rates of late-stage breast cancer than White women for most subtypes; elevated late-stage rates of all subtypes combined remained in Black women in multilevel analysis (RR = 1.10; 95% CI = 1.04-1.15). Black women in the Delta had higher rates of late-stage cancers across subtypes. Culturally competent interventions targeting risk-appropriate screening modalities should be scaled up in the Delta to improve early detection.


Cloning and characterization of the rpoH gene of Rhodobacter capsulatus.
By using an oligonucleotide mixture corresponding to a region highly conserved among alternative sigma factors we identified a new sigma factor gene (rpoH) from Rhodobacter capsulatus. This gene encodes a protein of 34 kDa with strong similarity to the RpoH (sigma32) factors from other bacterial species. It was not possible to inactivate the R. capsulatus rpoH gene by introducing a resistance cassette, implying that it is essential for growth. The 5' ends of the mRNAs were mapped to two sequences with similarity to an rpoH- and an rpoD-dependent promoter, respectively. The amounts of both these mRNAs increased after heat shock, but were unaffected by a decrease in oxygen tension. Western analysis using a sigma factor-specific antibody revealed the accumulation of a protein of about 34 kDa after heat shock, and an increase in the amounts of a protein with the same size after reduction of oxygen tension in R. capsulatus cultures.


Zernike expansion of pupil filters: optimization of the signal concentration factor.
Amplitude pupil filters for optimizing the signal concentration factor for a point spread function of given transverse and/or axial widths are derived. The pupil is expanded in a basis of Zernike polynomials. It is shown that the pupil that maximizes the signal concentration factor for a given transverse gain has a quadratically varying amplitude profile, as was shown in a previous paper, while the pupil that maximizes the signal concentration factor for a given axial gain has a quartic amplitude profile.


Simultaneous biopsy and radiofrequency ablation of T1a renal cell carcinoma.
The goal of this study was to retrospectively evaluate the outcome, including feasibility, safety, diagnostic yield, and factors affecting the success of computed tomography fluoroscopy-guided biopsy when performed during the same procedure than radiofrequency ablation (RFA) in renal tumors strongly suspected of being T1a renal cell carcinoma (RCC). Nineteen patients (13 men, 6 women; mean age, 66.7 years) with a total of 19 suspected renal tumors (mean diameter, 1.8cm) underwent computed tomography fluoroscopy-guided biopsy during (n=6) or immediately after (n=13) RFA. All patients were strongly suspected of having RCC on the basis of patient's medical histories and/or the results of imaging investigations. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the 2 groups using univariate analysis. In all tumors, biopsy procedures were technically feasible. No major complications were observed, except for 8 minor post-procedural bleedings. All but one tumor was completely ablated. Local recurrence in the ablation zone as well as tumor seeding in retroperitoneal fat occurred in 1 patient 8.5months after the procedure and were successfully treated with further percutaneous cryoablation. Thirteen tumors were diagnosed as RCC, whereas 6 were ultimately found to contain normal renal tissue (n=5) or connective tissue (n=1). Univariate analysis revealed that none of the variables were significantly different between the diagnostic and non-diagnostic biopsies. The performance of renal tumor biopsy and RFA in the same session is feasible and safe. Although pre-treatment pathological diagnosis would be generally desirable, simultaneous biopsy with RFA can be an option for the patients who are not amenable to pre-treatment biopsy.


Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO.
Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We show here that DO protein levels are modulated during B cell differentiation. Remarkably, germinal center (GC) B cells, which have low levels of DO relative to naive and memory B cells, are shown to have enhanced antigen presentation capabilities. DM protein levels also were somewhat reduced in GC B cells; however, the ratio of DM to DO in GC B cells was substantially increased, resulting in more free DM in GC B cells. We conclude that modulation of DM and DO in distinct stages of B cell differentiation represents a mechanism by which B cells regulate their capacity to function as antigen-presenting cells. Efficient antigen presentation in GC B cells would promote GC B cell-T cell interactions that are essential for B cells to survive positive selection in the GC.


Absorbed dose evaluation of a blood irradiator with alanine, TLD-100 and ionization chamber.
Irradiation of blood bags using X-ray irradiators and dosimetry services are required to ensure uniform dose levels in the range 25-50 Gy to prevent Transfusion Associated Graft versus Host Disease (TA-GvHD). An absorbed dose characterization of a Raycell MK2 X-Irradiator was performed using three different dosimetric systems. Results showed a dosimetric accuracy of the ionization chamber together with the Alanine dosimeter. TLDs measurements exhibited a small overestimation by 4% of the absorbed dose. The Dose Uniformity Ratio (DUR), between maximum and minimum dose levels in the canister, was in good agreement with the manufacturer specifications (≤1.5).


[Osteopetrosis: a case report and review of literature].
A case of type II autosomal dominant osteopetrosis is presented. The boy was admitted to the hospital at the age of 7 years and 6 months due to bilateral leg pain. Apart from radiography no pathology has been found.


Use of computed tomography in evaluation of acute respiratory distress in a 4.5-month-old with bronchogenic cyst.
A 4.5-month-old female presented with stridor and acute respiratory distress. Chest radiographs showed hyperinflation of the left lung. Computed tomography of the chest demonstrated a small bronchogenic cyst not clearly identified by other methods.


Emotional-Behavioral Regulation, Temperament and Parent-Child Interactions Are Associated with Dopamine Transporter Allelic Polymorphism in Early Childhood: A Pilot Study.
International research has highlighted the role played by individual genetic polymorphism, children's emotional-behavioral functioning, and quality of parent-child feeding interaction in shaping children's development. Few studies have focused on the dopamine transporter (DAT1) gene in these processes. In a community sample of 81 families with young children aged between 19 and 28 months (37 males and 44 females), this pilot study aimed to explore possible relationships between children's DAT1 genotype (9/x: 9/9, 9/19 contrasted to 10/10), their own psychological profiles, parental psychopathological risk, and the quality of mother-child and father-child feeding interactions. Children's DAT1 genotype was assessed collecting DNA through buccal; children's temperament and emotional-behavioral regulation, and parental psychopathological risk were assessed, respectively, through report-form and self-report instruments; then, dyadic exchanges were videotaped during a mealtime, and coded based on the Scala di Valutazione dell'Interazione Alimentare (SVIA). Results showed significant differences in the variables under study based on children's DAT1 genotype, with a higher risk associated with the 10/10. Our findings have provided preliminary new evidence on the relationship between a different child's polymorphisms, their own emotional-behavioral functioning, and the quality of the family environment, with important implications for the planning of more targeted prevention programs.


Size-dependent pollination efficiency in Anchusa officinalis (Boraginaceae): causes and consequences.
Bumblebees foraging on the self-incompatible Anchusa officinalis fly between near neighbour plants and between near neighbour inflorescences within plants. Although many-flowered plants attracted most bumblebees these plants received fewer visits on a per flower basis than smaller plants, and each bumblebee visited a smaller proportion of the flowers. The calculated effective visitation rate per flower was highest on plants of an intermediate size. If pollen-carryover was assumed to be limited the most efficient plant was predicted to be smaller since the proportion of fertilized flowers per bumblebee visit is expected to decrease further on the largest plants in relation to the total flower number. These predictions were tested by measuring fruit-set in the field. The percentage fruit-set decreased with plant size at all sizes that were investigated. That the most efficient plant was small indicates that pollen-carryover was indeed limited. However, the low percentage fruit-set associated with large size did not present a serious problem since the total estimated seed production per plant still increased with size. Selection favoring smaller plants may be low or absent in Anchusa.


Functional brain asymmetry for emotions: psychological stress-induced reversed hemispheric asymmetry in emotional face perception.
Empirical evidence has demonstrated functional (mostly right-biased) brain asymmetry for emotion perception, whereas recent studies indicate that acute stress may modulate left and/or right hemisphere activation. However, it is still unknown whether emotion perception can be influenced by stress-induced hemispheric activation since behavioral studies report inconsistent or even contradictory results. We sought to reevaluate this gap. Eighty-eight healthy Caucasian university students participated in the study. In half of the randomly selected participants, acute psychological stress was induced by displaying a brief stressful movie clip (the stress condition), whereas the other half were shown a neutral movie clip (the non-stress condition). Prior to (the baseline) and following the movie clip display an emotion perception task was applied by presenting an emotional (happy, surprised, fearful, sad, angry, or disgusted) or neutral face to the left or right visual field. We found a more accurate perception of emotional and neutral faces presented to the LVF (the right hemisphere) in the baseline. However, we revealed that after watching a neutral movie clip, behavioral performance in emotional and neutral face perception accuracy became relatively equalized for both visual fields, whereas after watching a stressful movie clip, the RVF (the left hemisphere) even became dominant in emotional face perception. We propose a novel hemispheric functional-equivalence model: the brain is initially right-biased in emotional and neutral face perception by default; however, psychophysiological activation of a distributed brain-network due to watching neutral movie clips redistributes hemispheric performance toward relative equivalence. Moreover, even reversed hemispheric asymmetry may occur.


Intramedullary nailing and functional bracing of tibial shaft fractures: 167 cases followed for minimum 2 years.
We treated 167 diaphyseal tibial fractures without reaming and with intramedullary fixation, using an unlocked Küntscher nail. The patients were followed for a minimum of 2 years. The mean time to union was 16 weeks. There were no serious complications, but 1 case of nonunion, 1 case of deep infection and 2 cases of clinically relevant malalignment. Migration of the nail was observed in 11 cases. We conclude that this treatment is simple and gives satisfactory results in diaphyseal fractures after low- or mid-energy trauma.


A blood biomarker test for brain amyloid impacts the clinical evaluation of cognitive impairment.
The objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline. The Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single-arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result on an amyloid positron emission tomography (PET) scan. The primary study outcomes were appropriateness of patient selection as well as result interpretation associated with PrecivityAD blood testing. A 95% (347/366) concordance rate was noted between clinicians' patient selection and the test's intended use criteria. In the final analysis including these 347 patients (median age 75 years, 56% women), prespecified test result categories incorporated 133 (38%) low APS, 162 (47%) high APS, and 52 (15%) intermediate APS patients. Clinicians' pretest and posttest AD diagnosis probability changed from 58% to 23% in low APS patients and 71% to 89% in high APS patients (p < 0.0001). Anti-AD drug therapy decreased by 46% in low APS patients (p < 0.0001) and increased by 57% in high APS patients (p < 0.0001). These findings demonstrate the clinical utility of the PrecivityAD blood test in clinical care and may have added relevance as new AD therapies are introduced.


On Self-Love and Outgroup Hate: Opposite Effects of Narcissism on Prejudice via Social Dominance Orientation and Right-Wing Authoritarianism.
Previous research has obtained mixed findings as to whether feelings of self-worth are positively or negatively related to right-wing ideological beliefs and prejudice. We propose to clarify the link between self-worth and ideology by distinguishing between narcissistic and non-narcissistic self-evaluations as well as between different dimensions of ideological attitudes. Four studies, conducted in three different socio-political contexts: the UK (Study 1, N = 422), the US (Studies 2 and 3, Ns = 471 and 289, respectively), and Poland (Study 4, N = 775), investigated the associations between narcissistic and non-narcissistic self-evaluations, social dominance orientation (SDO), right-wing authoritarianism (RWA), and ethnic prejudice. Confirming our hypotheses, the results consistently showed that after controlling for self-esteem, narcissistic self-evaluation was positively associated with SDO (accounting for RWA), yet negatively associated with RWA (accounting for SDO). These associations were similar after controlling for psychopathy and Machiavellianism (Study 3) as well as collective narcissism and Big Five personality characteristics (Study 4). Studies 2-4 additionally demonstrated that narcissistic self-evaluation was indirectly positively associated with prejudice through higher SDO (free of RWA) but indirectly negatively associated with prejudice through lower RWA (free of SDO). Implications for understanding the role of self-evaluation in right-wing ideological attitudes and prejudice are discussed. Copyright © 2017 The Authors. European Journal of Personality published by John Wiley & Sons Ltd on behalf of European Association of Personality Psychology.


Mini-HoLEP (MILEP) vs HoLEP: a propensity score-matched analysis.
Minimal invasiveness improves outcome in many surgical fields including urology. We aimed to assess intraoperative performance and clinical outcome of miniaturized holmium laser enucleation of prostate (MiLEP) (22FR). We ran a propensity score-matched analysis among all consecutive laser enucleations of prostate performed between 9/2022 and 2/2023. It resulted in two matched comparison groups: MiLEP 22 FR (n = 40) and holmium laser enucleation of prostate (HoLEP 26 Fr) (n = 40). Statistical analysis was performed. MiLEP was associated with significantly less intraoperative irrigation (20.5 L vs 15 L, p = 0.002E-3), less decrease in body core temperature (0.6°C vs 0.1°C, p = 0.003E-5), and less need for meatal dilation (25% vs 78%, p = 0.01E-3). These parameters were identified as being independent in the multivariate analysis. There was a trend toward less and a shorter period of postoperative stress incontinence (SI) for the MiLEP group compared to the HoLEP group: 15% and 42% (p = 0.01) at 1 month, 8% and 14% (p = 0.07) at 2 months, and 0 and 0.3% (p = 1) at 3 months, respectively. There were no differences in prostatic enucleation effectiveness, operative time, hospital stay, complications, and improvement in the international prostate symptom score and quality of life score. MiLEP is feasible and provides better maintenance of body core temperature, reduction in amount of fluid irrigation, and decrease in need for meatal dilation without affecting effectiveness in comparison with HoLEP. MiLEP may reduce early postoperative stress incontinence, thereby shortening the recovery period.


Downregulation of ACE2 is associated with advanced pathological features and poor prognosis in clear cell renal cell carcinoma.
Aims: The aim of this study was to explore the alteration in ACE2 expression and correlation between ACE2 expression and immune infiltration in clear cell renal cell carcinoma (ccRCC). Methods: The authors first analyzed the expression profiles and prognostic value of ACE2 in ccRCC patients using The Cancer Genome Atlas public database. The authors used ESTIMATE and CIBERSORT algorithms to analyze the correlation between ACE2 expression and tumor microenvironment in ccRCC samples. Results: ACE2 was correlated with sex, distant metastasis, clinical stage, tumor T stage and histological grade. Moreover, downregulation of ACE2 was correlated with unfavorable prognosis. In addition, ACE2 expression was associated with different immune cell subtypes. Conclusion: The authors' analyses suggest that ACE2 plays an important role in the development and progression of ccRCC and may serve as a potential prognostic biomarker in ccRCC patients.


Sequential analysis of donor-specific antibodies and pathological findings in acute antibody-mediated rejection in a rat renal transplantation model.
Alloantibodies contribute significantly to renal transplant rejection by activation of complement and various cytokines with a variety of effector cells, and are a major cause of allograft loss. Although there is clinical evidence of antibody- and complement-mediated injury in renal transplantation, the mechanism of antibody-mediated rejection remains largely unknown. In order to understand the sequential production of antibodies and complement components, we presensitized recipient rats by skin transplantation. Anti-donor-specific IgG levels reached a maximum 2 weeks following presensitization after which the rats underwent renal transplantation from the same donor strain. We then evaluated sequential pathological findings based on the Banff classification and several factors related to graft rejection. In this presensitized model, peritubular capillaries were already dilated and stained for C4d. Neutrophil and mononuclear cell infiltration in these capillaries was detected beginning 2 h after transplantation. Donor-specific antibody IgG levels decreased rapidly and anti-IgG antibody stained glomerular and peritubular capillaries in the grafts beginning 2 h after transplantation. Additionally, several cytokines and complement components showed marked changes in the presensitized group. Thus, in the donor-specific presensitized recipient, alloantibodies and complement were activated immediately after transplant. C4d deposition in peritubular capillaries appears to be a key factor for the diagnosis of antibody-associated rejection.


Drug treatment of type 2 diabetes: Its cost is significantly associated with HbA1c levels.
To examine the relationship between costs of hyperglycaemia drug treatment and glycemic control amongst people with type 2 diabetes (T2D). This observational study utilised data from the QUALIDIAB database on 3,452 T2D patients seen in Diabetes Centers in Argentina. Patients were classified according to their HbA1c value into two groups: on target (OT; HbA1c ≤ 7%), and not on target (NOT; HbA1c > 7%); within each category we considered clinical and metabolic indicators, as well as type of hyperglycaemia treatment. Monthly expenditure on drugs was estimated by micro-costing. Multivariable regression analysis was used to evaluate the association between cost of hyperglycaemia treatment and HbA1c values. In total, 48.9% of the participants have HbA1c OT values. Overall monthly per capita costs of this treatment increased significantly (134%) in the NOT group. Multivariable regression analysis showed that expenditure for hyperglycaemia drugs treatment was significant associated with glycemic control (OR: 0.705), diabetes duration (OR: 1.017), systolic blood pressure (OR: 1.006) and treatment of T2D (OR: 2.622). HbA1c NOT significantly increases drugs monthly cost of hyperglycaemia treatment in people with T2D in a country with an emerging market economy.


Distribution of immunoreactive sites for several components of pro-opiocortin in the pituitary and brain of adult lampreys, Petromyzon marinus and Entosphenus tridentatus.
The occurrence and localization of molecular components of pro-opiocortin in the pituitary and brain of two species of adult lamprey, Petromyzon marinus and Entosphenus tridentatus, were studied immunocytochemically using antisera generated against human pro-gamma-MSH (N-terminal fragment 1Trp to 71Gly of pro-opiocortin), porcine ACTH, alpha-MSH, human beta-endorphin, gamma-endorphin, and methionine enkephalin. (1) In both species of lamprey most cells of the rostral pars distalis and some cells of the caudal pars distalis contained Met-enkephalin-like immunoreactivity. Some of these cells also contained gamma-endorphin-like immunoreactivity. After preabsorbing the antisera with their corresponding antigens or related peptides, the Met-enkephalin/gamma-endorphin-like material was found to be related to Met-enkephalin, but not identical with either Met-enkephalin or gamma-endorphin. However, results of anti-pro-gamma-MSH, anti-ACTH, anti-alpha-MSH, or anti-beta-endorphin were consistently negative in the pars distalis of both lamprey species. (2) Immunoreaction to anti-Met-enkephalin was found in some cells of the pars intermedia in both species of lamprey. Although the positive reaction had been eliminated by preabsorption with synthetic Met-enkephalin, the diffuseness of the positive stain in the pars intermedia cells resembled an artifactual cross-reaction rather than a specific reaction. In P. marinus, but not in E. tridentatus, similar inconsistent and questionable immunoreactions corresponding to ACTH and alpha-MSH also occurred in some pars intermedia cells. Results of other antisera (anti-pro-gamma-MSH, anti-beta-endorphin, or anti-gamma-endorphin) were consistently negative in the pars intermedia of both lamprey species. (3) In both species of lamprey beta-endorphin-like material was found in the hypothalamus. In E. tridentatus only Met-enkephalin-like material was observed in the hypothalamus, and these two substances were distributed in different neuronal elements. After application of anti-pro-gamma-MSH, anti-ACTH, anti-alpha-MSH, or anti-gamma-endorphin, no positive reaction was found in the brain of either species of lamprey. These findings suggest that if a pro-opiocortin-related prohormone exists in the lamprey, it may be chemically different from those of more advanced vertebrates, and it clearly differs in distribution between the brain and parts of the pituitary gland.


Prevalence and hospital resource utilization in tympanoplasty and revision tympanoplasty: a population-based comparative study.
To compare trends, risk factors, prevalence rates, and hospital resource utilization between tympanoplasty and revision tympanoplasty. Retrospective review. All hospitals. This study analyzed 58,038 tympanoplasty procedures and 953 revision tympanoplasty procedures performed in Taiwan from 1996 to 2007. Administrative claims data from the Bureau of National Health Insurance of Taiwan. Odds ratio and 95% confidence intervals were calculated to assess the relative change rate. Regression models were used to predict length of stay (LOS) and hospital treatment costs. The number of tympanoplasties performed per 100,000 patients was 22.97 in 1996. It gradually increased to 26.7 in 2001 and then gradually decreased to 16.61 in 2007. The number of revision tympanoplasties per 100,000 patients during the same period, however, was 0.29 to 0.48. During the study period, the LOS associated with both tympanoplasty and revision tympanoplasty decreased, whereas hospital treatment costs associated with the 2 procedures increased. Considerably decreased LOS and increased hospital treatment costs were associated with age, sex, number of comorbidities, hospital level, hospital volume, surgeon volume, and LOS. High-volume hospitals and surgeons obtained the largest improvements in tympanoplasty outcomes, particularly in LOS and hospital treatment costs. Health care providers and patients should recognize that hospital resource utilization may depend on hospital attributes as well as patient attributes.


Updates and Advances in Cardiovascular Nursing: Peripheral Arterial Disease.
This article focuses on peripheral arterial disease (PAD) of the lower extremities. There is a higher incidence of myocardial infarction, stroke, and cardiovascular death, resulting in higher rates of all-cause mortality compared with patients without PAD. Thus, the presence of PAD is a marker for systemic atherosclerotic disease and can lead to the early detection and treatment of coronary artery disease or cerebrovascular disease. This article reviews the latest information about the prevalence, symptoms, classification, diagnosis, and treatment of PAD. Monitoring and detection of PAD are also discussed, including implications for nursing care.


In high-risk persons, lung cancer screening with CT vs. no or CXR screening reduces lung cancer mortality.
Passiglia F, Cinquini M, Bertolaccini L, et al. Benefits and harms of lung cancer screening by chest computed tomography: a systematic review and meta-analysis. J Clin Oncol. 2021;39:2574-85. 34236916.


Axonal transport of noradrenaline, protein and glycoprotein in cat hypogastric nerves in vitro under conditions of high extracellular glucose.
Inferior mesenteric ganglia with attached hypogastric nerves were removed from anaesthetised cats and maintained in Eagle's Minimal Essential Medium in specially designed organ culture chambers for 48 h at 37 degrees C. The chambers had removable barriers so that the fluid bathing the ganglia was separated from that bathing the nerve trunks by inert silicone grease seals. (3H)-fucose (1.25 muCi/ml) and (14C)-leucine (0.5 muCi/ml) were added to the fluid bathing the ganglia at the start of the experiment. At this time, tight ligatures were applied to the hypogastric nerves so that the incorporated isotopes accumulated proximal to the constrictions due to interrupted axonal transport. The nerve trunks were bathed in medium containing glucose at either 5.5 or 25 mmol/l. At the end of the incubation period, the accumulations, proximal to the constrictions, of incorporated leucine and fucose and of noradrenaline were measured. The high glucose medium caused a 27.5% (p less than 0.001) reduction in the accumulation of fucose and a 19.2% (p less than 0.01) reduction in the accumulation of leucine. The incorporation of these tracers in the ganglia was unaffected by exposure of the nerve trunks to high glucose. The accumulation of noradrenaline proximal to the constrictions was also unaffected. Further experiments were performed to show that the reduced accumulations of fucose and leucine under conditions of high glucose were not due to loss of isotope from macromolecules in the axons nor to the small increase in osmotic pressure effected by addition of extra glucose to the culture medium. It is therefore suggested that elevation of extracellular glucose caused an impairment of axonal transport of incorporated leucine and fucose.


Factors affecting temporal and spatial variations of microcystins in Gonghu Bay of Lake Taihu, with potential risk of microcystin contamination to human health.
A field survey of the seasonal variation of microcystin (MC) concentration was performed in Gonghu Bay (a total of 15 sampling sites) of Lake Taihu from January to December 2008. Microcystis spp. biomass and intra-/extracellular MCs were significantly correlated with water temperature, suggesting the importance of temperature in cyanobacterial blooming in the lake. Higher MC concentration was found in summer and autumn, and peaks of Microcystis biomass and intra-/extracellular MC concentrations were all present in October. Spatially, risk of MCs was higher in littoral zones than in the pelagic area. There were significant correlations between N or P concentrations, and Microcystis biomass or MC content, suggesting that N and P levels affected MC production through influencing Microcystis biomass. Intra-/extracellular MCs and Microcystis biomass had negative exponential relationships with TN:TP, and the maximum values all occurred when TN:TP was <25. Multivariate analyses by PCCA indicated that intra- and extracellular MC concentrations had better correlations with biological factors (such as Microcystis biomass and chl-a) than with physicochemical factors. The maximum MC concentration reached up to 17 micrograms/L MC-LReq, considerably higher than the drinking water safety standard (1 micrograms/L) recommended by the WHO. So it is necessary to take measures to reduce the exposure risk of cyanobacterial toxins to human beings.


Non-covalent crosslinkers for electrospun chitosan fibers.
Electrospun chitosan fibers have numerous potential in biomedical, food, and pharmaceutical applications. However, the mats formed are often not chemically stable in a wide range of pHs unless crosslinked. Here, we report on the use of glycerol phosphate (GP), tripolyphosphate (TPP) and tannic acid (TA) as a new set of non-covalent crosslinkers for electrospun chitosan fibers. Crosslinking with or without heat or base activation were performed either prior to (one-step or activated one-step) or after (two-step or activated two-step) electrospinning with either GP or TA. TPP crosslinking was performed in two-step and activated two-step. FESEM, FTIR and UV-vis transmittance at 600 nm were used to determine fiber surface morphology, chemical interactions and solubility in 1M AA (pH 3), water (~pH 6) and 1 M NaOH (pH 13), respectively. Crosslinking of chitosan with GP and TA yields fibers with a mean diameter range of 145-334 nm and 143-5554 nm, respectively. TPP crosslinking produced branched fibers with mean diameters of 117-462 nm range. Two-step chitosan-TA did not dissolve in 1M AA even after 72 h while all chitosan-TPP, activated two-step chitosan-TA and two-step heat activated chitosan-GP fibers survived in water after 72 h.


The need for substance abuse after-care: longitudinal analysis of Oxford House.
There is a need to explore the processes of social support and self-efficacy change over time among individuals in recovery homes, and to assess the extent to which residents remain abstinent, obtain and maintain employment, refrain from criminal activity, and utilize health care systems both while within the and after leaving such settings. Residents were recruited and interviewed at an initial baseline phase and then re-interviewed at three subsequent 4-month intervals. Oxford Houses are recovery home residences for individuals with substance abuse and dependence problems who seek a supportive, democratic, mutual-help setting. A national US sample of Oxford House residents (n=897: 604 men, 293 women). Information was gathered on abstinence, social support, self-efficacy, employment, criminal history, and medical care utilization. Change in cumulative abstinence was predicted by support for alcohol use, abstinence self-efficacy, and length of residency in OH (i.e., less than versus >or=6 months), even after controlling for initial time spent in OH. Results suggest that receiving abstinence support, guidance, and information from recovery home members committed to the goal of long-term sobriety may enhance residents' abstinence self-efficacy and enable persons recovering from alcohol and other drug addiction to reduce the probability of a relapse.


Altered inhibitory input to Purkinje cells of dystrophin-deficient mice.
We investigated evoked EPSPs and spontaneous IPSPs in cerebellar slices from dystrophin-deficient mdx mice. In the presence of the GABA(A) antagonist bicuculline the increase in EPSP amplitude was less in mdx Purkinje cells compared to control, and the amplitude of miniature IPSCs in mdx cells was also significantly less than in controls. This reduced inhibitory input is most likely due to the reported reduction in the size of GABA(A) channel clusters.


Plasticity of vagal afferents at the site of an incision in the wall of the stomach.
Our objectives were to determine whether the vagal afferent innervation of the stomach reorganizes after surgery and to observe how different wound closure techniques might influence such a process. The smooth muscle wall of the stomach served as a model because it is densely innervated by vagal axons and is frequently compromised by gastric surgery. Male Sprague-Dawley rats were assigned to one of six groups: three groups served as controls in which the stomach was exposed surgically and a) subjected to no further manipulation, b) traumatized with suture needle punctures of the muscle wall, or c) insulted by the placement of knotted suture thread in the stomach muscle; three surgical groups received a 1.0 cm incision through the ventral muscle wall of the stomach that was closed using either a) absorbable sutures, b) fibrin glue, or c) n-butyl cyanoacrylate. Rats were killed 4 to 7 months post-surgery. Prior to euthanasia, Micro-Ruby was injected into the left nodose ganglion of each rat to label vagal afferent axons and terminals. Twelve days post-injection, the stomachs were processed for microscopy. All groups recovered quickly from surgery, without differences in body weight. The presence of suture material in the muscle wall of the stomach was sufficient to produce reorganization of nearby vagal afferents. In addition, we observed that an incision of the smooth muscle wall of the stomach and the associated damage to vagal afferents provoked reorganization and regeneration of vagal afferents. Vagal remodeling at the incision was characteristic of axonal patterns found in neuromas (unlike the organized regeneration and differentiation that can occur after axotomy central to the target organ). Vagal afferent terminals located at the site of the incision were free nerve endings and growth cone profiles, and not the characteristically complex end organs normally found in the smooth muscle. Finally, the pattern of vagal plasticity was influenced by the wound closure technique used. Overall, the remodeling of afferents was aberrant in nature, and such neural pathology could contribute to the neuropathic symptoms and hyperalgesias associated with gastrointestinal trauma and bariatric surgery.


Effectiveness of transbronchial needle aspiration in the diagnosis of exophytic endobronchial lesions and submucosal/peribronchial diseases of the lung.
The role of transbronchial needle aspiration (TBNA) in diagnosing endobronchial lung cancers has not been elucidated. The definitive combination of procedures that offers the best diagnostic yield following fiberoptic bronchoscopy remains controversial. This study was designed to investigate the diagnostic yield of transbronchial needle aspiration and other cytologic and histologic diagnostic procedures (i.e., forceps biopsy, brushing, and washing) and to assess the optimal combination for diagnosing endobronchial lung cancers. This prospective study included 95 patients presenting with visible tumors detected during bronchoscopic procedure as either an exophytic endobronchial lesion (EEL) or submucosal-peribronchial disease (SPD). Transbronchial needle aspiration, forceps biopsy, brushing, and washing were performed in all patients, and 91 patients were diagnosed. Rates of positive results were 75.8% for needle aspiration, 71.6% for forceps biopsy, 61.1% for brushing, and 32.6% for washing. Needle aspiration was used as the sole diagnostic method in 11, forceps biopsy was the sole diagnostic method in 5, and brushing was the sole diagnostic method in 4 patients. Washing was not used as the sole diagnostic method in any case. Forceps biopsy yielded the highest diagnostic rate for an EEL (86.4%); however, when compared with needle aspiration (77.9%), no significant difference was observed between these two procedures (P = 0.302). In patients with a diagnosis of SPD, needle aspiration was determined to be the sole diagnostic method in eight patients. In this group of patients, the highest rate of diagnosis was achieved with needle aspiration (72.2%), and when compared with forceps biopsy (47.2%), a significant difference between the two procedures (forceps biopsy versus needle aspiration) was observed (P = 0.049). By adding transbronchial needle aspiration to the conventional diagnostic methods (forceps biopsy, brushing, and washing), the rate of diagnosis increased from 82.1% to 95.8% (P = 0.001), and in patients with a diagnosis of SPD, this rate increased from 69.4% to 94.4% (P = 0.008). In patients with a diagnosis of an EEL, addition of needle aspiration led to an increase in diagnostic yield but this difference was not statistically significant (89.8% versus 96.6%, P = 0.250). In endobronchial lung cancers, transbronchial needle aspiration is a safe method that can be used together with conventional diagnostic procedures to increase the diagnostic yield and should be considered a valuable diagnostic tool, particularly in cases of SPD. The highest rate of diagnostic yield in this study was obtained using a combination of forceps biopsy, transbronchial needle aspiration, and brushing; washing did not contribute to this high rate.


Monocytes differentiated into macrophages and dendritic cells in the presence of human IFN-λ3 or IFN-λ4 show distinct phenotypes.
Human IFN-λ4 is expressed by only a subset of individuals who possess the ΔG variant allele at the dinucleotide polymorphism rs368234815. Recent genetic studies have shown an association between rs368234815 and different infectious and inflammatory disorders. It is not known if IFN-λ4 has immunomodulatory activity. The expression of another type III IFN, IFN-λ3, is also controlled by genetic polymorphisms that are strongly linked to rs368234815. Therefore, it is of interest to compare these two IFNs for their effects on immune cells. Herein, using THP-1 cells, it was confirmed that IFN-λ4 could affect the differentiation status of macrophage-like cells and dendritic cells (DCs). The global gene expression changes induced by IFN-λ4 were also characterized in in vitro generated primary macrophages. Next, human PBMC-derived CD14+ monocytes were used to obtain M1 and M2 macrophages and DCs in the presence of IFN-λ3 or IFN-λ4. These DCs were cocultured with CD4+ Th cells derived from allogenic donors and their in vitro cytokine responses were measured. The specific activity of recombinant IFN-λ4 was much lower than that of IFN-λ3, as shown by induction of IFN-stimulated genes. M1 macrophages differentiated in the presence of IFN-λ4 showed higher IL-10 secretion than those differentiated in IFN-λ3. Coculture experiments suggested that IFN-λ4 could confer a Th2-biased phenotype to allogenic Th cells, wherein IFN-λ3, under similar circumstances, did not induce a significant bias toward either a Th1 or Th2 phenotype. This study shows for the first time that IFN-λ4 may influence immune responses by immunomodulation.


Multimodal mechanisms and enhanced efficiency of atrial fibrillation cardioversion by pulmonary delivery of a novel flecainide formulation.
Inhaled flecainide significantly alters atrial electrical properties with the potential to terminate atrial fibrillation (AF) efficiently by optimizing dose and drug formulation. Seventeen Yorkshire pigs were studied. Intrapericardial acetylcholine and burst pacing were used to induce AF. Effects of a novel cyclodextrin formulation (hydroxypropyl-ß-cyclodextrin [HPßCD]) of flecainide (75 mg/mL, 0.5 or 1.0 mg/kg, bolus) instilled intratracheally at 2 minutes after AF initiation were studied. Concentration time-area analyses of flecainide HPßCD were compared to the traditional acetate formulation. Intratracheal instillation of flecainide HPßCD accelerated the conversion of AF to sinus rhythm in a dose-proportional manner, shortening AF duration by 47% (P = .014) and 79% (P = .002) at the lower and higher doses, respectively, compared to intratracheal sterile water placebo. AF dominant frequency was reduced by 11% (P = .04) and 29% (P = .004) respective to dose. At 2 minutes after intratracheal flecainide HPßCD, atrial depolarization (Pa ) duration increased by 12% (P = .02) and 17% (P = .009) at the lower and higher doses, respectively. At this time, the PR interval was prolonged by 9% (P = .04 for the higher dose) and AV node conduction was slowed, decreasing the ventricular rate during AF by 16% (P = .002) and 28% (P = .007) for the lower and higher doses. Flecainide HPßCD achieved the more efficient conversion of AF than the acetate formulation, reflected in a markedly reduced area under the curve (P = .04). Intratracheal instillation of the new flecainide HPßCD formulation effectively terminates AF through efficient multimodal actions including slowing of atrial conduction velocity and decreasing AF dominant frequency, allowing reduced net drug delivery and inhalation time.


Data on the evolutionary history of the V(D)J recombination-activating protein 1 - RAG1 coupled with sequence and variant analyses.
RAG1 protein is one of the key component of RAG complex regulating the V(D)J recombination. There are only few studies for RAG1 concerning evolutionary history, detailed sequence and mutational hotspots. Herein, we present out datasets used for the recent comprehensive study of RAG1 based on sequence, phylogenetic and genetic variant analyses (Kumar et al., 2015) [1]. Protein sequence alignment helped in characterizing the conserved domains and regions of RAG1. It also aided in unraveling ancestral RAG1 in the sea urchin. Human genetic variant analyses revealed 751 mutational hotspots, located both in the coding and the non-coding regions. For further analysis and discussion, see (Kumar et al., 2015) [1].


Endoscopic removal of a massive trichobezoar in a pediatric patient by using a variceal ligator cap: A case report and literature review.
A trichobezoar is commonly formed in the gastrointestinal tract by ingestion of an individual's own hair. A trichobezoar formed by hair and artificial materials constitutes a rare etiology scarcely reported in the current literature. A mixture with hair-like synthetic fibers not only increases the risk for trichobezoar formation but also makes it more difficult for endoscopic removal. Herein, we report on a case in which a trichobezoar, caused by the consumption of human hair and synthetic yarn, was successfully removed endoscopically with a variceal ligator cap without further complications for the patient. This case report aims to raise awareness among endoscopists that using a variceal ligator cap may be a suitable option in the management of large trichobezoars containing synthetic fibers.


Salt and temperature-dependent conformation changes in spectrin from human erythrocyte membranes.
ORD and CD measurements of spectrin, in both the dimer and tetramer association state, indicate a high proportion of alpha-helix in this protein. At temperatures below 27 degrees C and in 0.1 M NaCl, the tetramer has an apparent helix content of 73% and the dimer, 68%. The conformation of both states is dependent on salt concentration and temperature. Low ionic strength solutions of spectrin display lowered sedimentation coefficients and a decreased apparent helix content, indicating perhaps a slight refolding and expansion of the molecule. In addition, spectrin in low ionic strength solutions undergoes a broad temperature-dependent transition spread from 20 to 50 degrees C, while in the presence of salt the transition is sharp and centered on 49 degrees C. The temperature-dependent changes in low ionic strength solutions appear to parallel the dissociation of tetramer to dimer.


Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis.
Tumor-derived immune suppression is considered to be a major mechanism of tumor evasion from the immune system destruction, however, little is known regarding the induction of T-cell functional suppression by tumor-derived exosomes. Herein, we investigate tumor-derived exosomes involved in normal immunological communications as means of inhibiting an antitumor T-cell response. Exosomes derived from LNCaP, a human prostate cancer cell line, were visualized by FACS and identified based on size (80-200 nm) in comparison to marker beads. Exosomes from tumor cell line inhibited T-cell proliferation. Dose-dependent apoptosis of T cells was induced by co-culture with tumor exosomes. Addition of anti-FasL antibody blocked the apoptosis induction by tumor exosomes. This study suggests that induction of T-cell apoptosis by tumor-derived exosomes appears to be a novel mechanism of tumor immune evasion.


Contrast-enhanced ultrasound evaluation of splenic embolization in patients with definite left-sided infective endocarditis.
The purpose of the study described here was to prospectively evaluate the significance of embolization of the spleen in patients with definite left-sided infective endocarditis (IE) using contrast-enhanced ultrasound (CEUS). From March through October 2012, 6 consecutive patients (4 females and 2 males, aged 27 to 83 years) with definite left-sided IE according to the revised Duke criteria were enrolled. All patients gave informed written consent, and the study was performed in conformity with the ethical guidelines of the Declaration of Helsinki. All patients underwent CEUS of the spleen within 1 week of the definite diagnosis of IE. A blood pool second-generation contrast agent and an ultrasound machine with contrast harmonic imaging technology were used for CEUS. Fifteen consecutive patients (7 females and 8 males, aged 39 to 88 years) who underwent CEUS from October through November 2012 for the study of focal liver lesions constituted the control group. The number of patients did not permit statistical analysis. Splenic CEUS revealed infarctions in 5 patients and an infarcted area in the only patient with negative echocardiography. All splenic CEUS procedures in the control group were negative. In this study, CEUS of the spleen, a repeatable and low-cost imaging technique, easily allowed bedside detection of asymptomatic and even tiny infarctions, and revealed a high rate of embolization in patients with definite left-sided IE. Indeed, splenic CEUS, if applied to the workup of patients with suspect IE, has the potential to accelerate or upgrade the diagnosis itself.


Mutagenic Distinction between the Receptor-Binding and Fusion Subunits of the SARS-CoV-2 Spike Glycoprotein and Its Upshot.
We observe that a residue R of the spike glycoprotein of SARS-CoV-2 that has mutated in one or more of the current variants of concern or interest, or under monitoring, rarely participates in a backbone hydrogen bond if R lies in the S1 subunit and usually participates in one if R lies in the S2 subunit. A partial explanation for this based upon free energy is explored as a potentially general principle in the mutagenesis of viral glycoproteins. This observation could help target future vaccine cargos for the evolving coronavirus as well as more generally. A related study of the Delta and Omicron variants suggests that Delta was an energetically necessary intermediary in the evolution from Wuhan-Hu-1 to Omicron.


The inferior laryngeal nerve: surgical and anatomic considerations. Report of 251 thyroidectomies.
This surgical anatomic study aimed to determine (1) the anatomic relation of the laryngeal inferior nerve with the inferior thyroid artery, (2) the existence of extralaryngeal branches of division of the nerve and (3) the size of the nerve seen macroscopically. Two hundred and fifty-one patients underwent thyroid surgery during a period of 30 months. There were 50 males and 201 females. The male population underwent 28 total thyroidectomies, 13 left lobectomies and 9 right lobectomies. The female population underwent 124 total thyroidectomies, 33 left lobectomies and 44 right lobectomies. On the right side: the nerve was found superficial to the artery in 70.24% of females and 51.35% of males, the nerve was divided in 23.81% of females and 21.62% of males and seemed unusually thin in 14.29% of females and 5.41% of males. On the left side: the nerve was found superficial to the artery in 87.26% of females and 95.12% of males, the nerve was divided in 15.29% of females and 14.63% of males and seemed unusually thin in 10.83% of females and 2.44% of males. In conclusion, the inferior laryngeal nerve is characterized by its important anatomic variations, especially on the right side. These variations might be different even between males and females. Knowledge of these variations is very important in order to best identify and preserve the inferior laryngeal nerve during thyroid surgery.


Fomivirsen: clinical pharmacology and potential drug interactions.
Fomivirsen sodium is a 21-base phosphorothioate oligodeoxynucleotide complementary to the messenger RNA of the major immediate-early region proteins of human cytomegalovirus, and is a potent and selective antiviral agent for cytomegalovirus retinitis. Following intravitreal administration, fomivirsen is slowly cleared from vitreous with a half-life of approximately 55 hours in humans. Preclinical studies show that fomivirsen distributes to retina and is slowly metabolised by exonuclease digestion. Clearance from retina was shown to be similarly slow following loading from the vitreous. The estimated half-life for clearance of fomivirsen from retina was 78 hours in monkeys following a 115-microg dose. Because of the low doses coupled with slow disposition from the eye, measurable concentrations of drug are not detected in the systemic circulation following intravitreal administration. Systemically administered phosphorothioate oligodeoxynucleotides are highly bound to albumin and alpha2-macroglobulin in blood plasma. Because fomivirsen does not compete for oxidative metabolic processes involved in clearance of many xenobiotics, the most likely mechanism for drug interactions may be altered protein binding of a coadministered drug. The extremely low systemic exposure to this oligodeoxynucleotide following intravitreal administration largely negates its potential ability to interact with systemically administered drugs. Even if fomivirsen were able to access the blood, protein binding assays indicate that drugs that are site I and site II binders of albumin (warfarin, ibuprofen, salicylic acid) are not displaced in the presence of phosphorothioate oligodeoxynucleotides of various sequences at concentrations orders of magnitude higher than that seen for fomivirsen. Administration of fomivirsen with numerous systemically administered antiretrovirals (for example zidovudine and zalcitabine) as well as systemically administered anticytomegalovirus agents such as foscarnet and ganciclovir has been reported to be well tolerated. The only reported warning is a recommendation against administration within 2 to 4 weeks of cidofovir treatment due to an increased risk of ocular inflammation.


Informing Intervention Strategies to Reduce Energy Drink Consumption in Young People: Findings From Qualitative Research.
To determine young people's knowledge of energy drinks (EDs), factors influencing ED consumption, and intervention strategies to decrease ED consumption in young people. Eight group interviews with young people (aged 12-25 years). Community groups and secondary schools in Perth, Western Australia. Forty-one young people, 41% of whom were male and 73% of whom consumed EDs. Factors influencing ED consumption and intervention strategies informed by young people to reduce ED consumption. Two researchers conducted a qualitative content analysis on the data using NVivo software. Facilitators of ED consumption included enhanced energy, pleasant taste, low cost, peer pressure, easy availability, and ED promotions. Barriers included negative health effects, unpleasant taste, high cost, and parents' disapproval. Strategies to reduce ED consumption included ED restrictions, changing ED packaging, increasing ED prices, reducing visibility in retail outlets, and research and education. Because many countries allow the sale of EDs to people aged <18 years, identifying ways to minimize potential harm from EDs is critical. This study provided unique insights into intervention strategies suggested by young people to reduce ED consumption. In addition to more research and education, these strategies included policy changes targeting ED sales, packaging, price, and visibility. Future research might examine the feasibility of implementing such interventions.


Comprehensive analysis of differentially expressed mRNA and circRNA in Ankylosing spondylitis patients' platelets.
Ankylosing spondylitis (AS) is a chronic inflammatory disease significantly decreasing the quality of life. Platelets play an important and active role in the development of AS. Accumulating evidence demonstrated platelets contain diverse RNA repository inherited from megakaryocytes or microvesicles. Platelet RNAs are dynamically affected by pathological conditions and could be used as diagnostic or prognostic biomarkers. However, the role of the platelet RNAs in AS is elusive. In this study, we compared mRNA and circRNA profiles in platelets between AS patients and healthy controls using RNA sequencing and bioinformatic analysis, and found 4996 mRNAs and 2942 circRNAs were differently expressed. The significantly over-expressed mRNAs in AS patients are involved in platelet activity, gap junction, focal adhesion, rap1 and toll and Imd signaling pathway. The previous identified platelet-derived immune mediators such as P2Y1, P2Y12, PF4, GPIbα, CD40L, ICAM2, CCL5 (RANTES), TGF-β (TGF-β1 and TGF-β2) and PDGF (PDGFB and PDGFA) are also included in these over expressed mRNAs, implying these factors may trigger inflammatory cascades and promote the development of AS. Additionally, we found two down-regulated circRNA (circPTPN22 and circFCHSD2) from the intersection analyses of platelets and spinal ligament tissues of AS patients. The circRNA-miRNA-mRNA regulatory network of these two circRNAs was constructed, and the target mRNAs were enriched in Th17 cell differentiation, inflammatory bowel disease, cell adhesion molecules, cytokine-cytokine receptor interaction, Jak-STAT and Wnt signaling pathway, all these pathways participate in the bone remodeling and pro/anti-inflammatory immune regulation in AS. Then, qRT-PCR was performed to validate the expression of selected key mRNAs and circRNAs and the results demonstrated that the expression levels of P2Y12, GPIbα, circPTPN22 and circFCHSD2 were consistent with the sequencing analysis. In addition, the high expression of five predicted miRNAs interacting with circPTPN22 and circFCHSD2 were also detected in AS by qRT-PCR. Taken together, our study presents a comprehensive overview of mRNAs and circRNAs in platelets in AS patients and offers new insight into the mechanisms of platelet involving in the pathogenesis of AS. The mRNAs and circRNAs identified in this study may serve as candidates for diagnosis and targeted treatment of AS.


Magnetic resonance imaging of focal cortical dysplasia: Comparison of 3D and 2D fluid attenuated inversion recovery sequences at 3T.
Focal cortical dysplasia (FCD) is a frequent finding in drug resistant epilepsy. The aim of our study was to evaluate an isotropic high-resolution 3-dimensional Fluid-attenuated inversion recovery sequence (3D FLAIR) at 3T in comparison to standard 2D FLAIR in the diagnosis of FCD. In a prospective study, 19 epilepsy patients with the MR diagnosis of FCD were examined with a sagittal 3D FLAIR sequence with modulated refocusing flip angle (slice thickness 1.10mm) and a 2D FLAIR in the coronal (thk. 3mm) and axial planes (thk. 2mm). Manually placed regions of interest were used for quantitative analysis. Qualitative image analysis was performed by two neuroradiologists in consensus. Contrast between gray and white matter (p ≤ 0.02), the lesion (p ≤ 0.031) or hyperintense extension to the ventricle (p ≤ 0.021) and white matter was significantly higher in 2D than in 3D FLAIR sequences. In the visual analysis there was no difference between 2D and 3D sequences. Conventional 2D FLAIR sequences yield a higher image contrast compared to the employed 3D FLAIR sequence in patients with FCDs. Potential advantages of 3D imaging using surface rendering or automated techniques for lesion detection have to be further elucidated.


Increased accumulation of iodine-123-IMP in the pulmonary inflammatory lesion surrounding a lung cancer.
In a patient with primary lung cancer, increased accumulation of I-123-IMP was observed in a pulmonary inflammatory lesion surrounding a lung cancer which was delineated as a photon deficient area. Ga-67-citrate uptake was observed in both the inflammatory and cancerous areas. These findings suggest that I-123-IMP may have the potential to accumulate differently in a variety of pathological conditions of the lung and thus may be a clinically useful lung imaging agent.


Toxic shock syndrome: a review.
TSS is a recently described acute febrile illness characterized by hypotension, rash, desquamation, and multisystemic involvement. While most common in menstruating women, TSS also occurs in men and non-menstruating women. It is now known that the disease is caused by one or more toxins produced by the S aureus organism. Treatment of TSS consists primarily of fluid resuscitation and supportive care. Anti-staphylococcal antibiotics are indicated primarily to reduce the rate of recurrence in menstrually related cases. In wound-related TSS, antibiotics are necessary to treat the primary wound infection and to prevent recurrent disease. Currently, the case fatality rate is stable at less than 3% and the major long-term complication of survivors is the risk of recurrence.


How do patients perceive the AI-radiologists interaction? Results of a survey on 2119 responders.
In this study we investigate how patients perceive the interaction between artificial intelligence (AI) and radiologists by designing a survey. We created a survey focused on the application of Artificial Intelligence in radiology which consisted of 20 questions distributed in three sections:Only completed questionnaires were considered for analysis. 2119 subjects completed the survey. Among them, 1216 respondents were over 60 years old, showing interest in AI even though they were not digital natives. Although >45% of the respondents reported a high level of education, only 3% said they were AI experts. 87% of respondents favored using AI to support diagnosis but would like to be informed. Only 10% would consult another specialist if their doctor used AI support. Most respondents (76%) said they would not feel comfortable if the diagnosis was made by the AI alone, highlighting the importance of the physician's role in the emotional management of the patient. Finally, 36% of respondents were willing to discuss the topic further in a focus group. Patients' perception of the use of AI in radiology was positive, although still strictly linked to the supervision of the radiologist. Respondents showed interest and willingness to learn more about AI in the medical field, confirming how patients' confidence in AI technology and its acceptance is central to its widespread use in clinical practice.


Protein kinase inhibitors attenuate cardiac swelling-induced amino acid release in the rat.
Rat Langendorff heart preparations have been used to study the efflux of cardiac amino acids into coronary artery perfusates during brief (5-min) periods of exposure to hyposmotic stress (70 mM NaCl). Coronary flow rates, heart rates and intra-aortic pressures were recorded. Amino acid levels were measured by high-performance liquid chromatography. Hyposmotic stress caused marked percentage increases in taurine, glutamate and aspartate levels in the coronary perfusate, with smaller increases in phosphoethanolamine, glycine and alanine and non-significant increases in serine and glutamine. Amino acid levels declined during reperfusion with isosmotic Krebs-Henseleit bicarbonate buffer. Inhibition of protein kinase C with chelerythrine chloride (5 microM) depressed the osmotically-induced release of aspartate, glutamate, taurine and glycine. The protein tyrosine kinase inhibitor, genistein, reduced the anisosmotic efflux of aspartate, glutamate, taurine and phosphoethanolamine. Lavendustin A, another inhibitor of tyrosine kinase, depressed the osmotically evoked release of aspartate, glutamate and taurine. These studies demonstrate the involvement of protein kinase C and tyrosine kinases in the efflux of amino acids from the osmotically challenged rat heart and imply that these enzymes are involved in the mechanisms responsible for volume regulation by cardiac cells.


Citicoline oral solution in glaucoma: is there a role in slowing disease progression?
To assess the effect of citicoline on visual field rates of progression in patients with progressing glaucoma. Forty-one patients with a diagnosis of progressing glaucoma received citicoline in oral solution for 2 years. Included were patients with a disease progression of at least -1 dB/year (at MD, mean deviation) for at least 3 years before entering the study despite controlled intraocular pressure (IOP). Patients were followed with 4 visual field examinations per year for 2 years. At baseline, the mean rate of progression was -1.1 (±0.7) dB/year despite the fact that the IOP had been below 18 mm Hg for at least 3 years. At study inclusion, the mean IOP was 15.5 (±2.6) mm Hg and the mean MD was -9.2 (±6.7) dB in the worst eye. Starting from the first cycle of treatment with citicoline, the mean rate of progression significantly changed to -0.15 (±0.3) dB/year at the end of the study (p = 0.01). This study seems to indicate that supplementation with citicoline might significantly slow down glaucomatous rates of progression.


Construction and direct immunization of eukaryotic expression plasmid encoding human soluble B lymphocyte stimulator.
B lymphocyte stimulator of the tumor-necrosis-factor family (BLyS) enhances B cell survival, a function indispensable to B cell maturation. This factor plays a crucial role in enhancing immune responses. Here, to study the primary immune effect of BLyS gene in animals, we constructed recombinant eukaryotic expression plasmid of the human soluble BLyS by using expression vector pcDNA3.1 (-). The recombinant plasmid pcDNA3.1BLyS was injected subcutaneously into BALb/C mice and this administration induced the sustained expression of human BLyS and specific IgG against the recombinant BLyS protein. This study shows that recombinant eukaryotic expression plasmid, pcDNA3.1BLyS, might be used in human gene therapy.


Association of maternal antiretroviral use with microcephaly in children who are HIV-exposed but uninfected (SMARTT): a prospective cohort study.
Perinatal HIV transmission has substantially decreased with combination antiretroviral regimens, but complications in children who are HIV-exposed but uninfected, such as microcephaly, warrant ongoing surveillance. We aimed to evaluate whether individual in utero antiretroviral exposures were associated with increased risk of microcephaly based on long-term follow-up of infants and children who are HIV-exposed but uninfected. We evaluated children aged younger than 18 years who were HIV-exposed but uninfected with at least one head circumference measurement while enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study at 22 clinical sites in the USA, including Puerto Rico. This prospective cohort study was done by the Pediatric HIV/AIDS Cohort Study network. Microcephaly was defined as having a head circumference Z score <-2 according to the 2000 US Centers for Disease Control and Prevention growth charts for children 6-36 months old and according to Nellhaus standards (head circumference <2nd percentile) after 36 months (SMARTT criteria); an alternate definition for microcephaly was based on applying Nellhaus standards across all ages (Nellhaus criteria). Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero antiretroviral exposure and microcephaly status, adjusted for potential confounders. Neurodevelopmental functioning was compared in children who are HIV-exposed but uninfected with or without microcephaly. Between March 21, 2007, and Aug 1, 2017, 3055 participants enrolled in SMARTT had at least one head circumference measurement. The cumulative incidence of microcephaly over a median of 5·1 years of follow-up (IQR 3·0-7·2) was 159 (5·2%, 95% CI 4·4-6·1) by Nellhaus criteria and 70 (2·3%, 1·8-2·9) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4·7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (adjusted RR 2·02, 95% CI 1·16-3·51) and SMARTT criteria (2·56, 1·22-5·37). These associations were more pronounced in children exposed to combination regimens of efavirenz that included zidovudine plus lamivudine than those including tenofovir plus emtricitabine. Protective associations were observed for darunavir exposure (adjusted RR 0·50, 95% CI 0·24-1·00). Children who are HIV-exposed but uninfected with microcephaly had lower mean scores on neurodevelopmental assessments at age 1 and 5 years and a higher prevalence of neurodevelopmental impairment than those without microcephaly. These findings support consideration of alternatives to efavirenz as part of first-line antiretroviral therapy for pregnant women. Eunice Kennedy Shriver National Institute of Child Health and Human Development.


The interaction energy between two parallel plates with constant surface charge density.
On the basis of Langmuir's suggestion we simplify the Poisson-Boltzmann equation and derive the relation of surface potential, potential midway, and the plate distance. Thus we obtain the interaction force and energy equations between two dissimilar plates in the case of constant surface charge density. Agreement with the exact numerical values of the interaction of dissimilar plates is good. This method may not only apply to the cases of high constant potential but to the case of high constant charge density.


Association of antenatal corticosteroids with kidney function in adolescents born preterm with very low birth weight.
Investigate if antenatal corticosteroids (ANCS) are associated with worse kidney function in adolescence and if greater adiposity magnifies this association. Prospective cohort of 162 14-year-olds born preterm with very low birth weight (<1500 g). Outcomes were estimated glomerular filtration rate (eGFR) and first-morning urine albumin-to-creatinine ratio (UACR). We used adjusted generalized linear models, stratified by waist-to-height ratio (WHR) ≥ 0.5. Fifty-five percent had ANCS exposure and 31.3% had WHR ≥ 0.5. In adjusted analyses of the entire cohort, ANCS was not significantly associated with eGFR or UACR. However, the ANCS-eGFR association was greater in those with WHR ≥ 0.5 (β -16.8 ml/min/1.73 m2, 95% CL -31.5 to -2.1) vs. WHR < 0.5: (β 13.9 ml/min/1.73 m2, 95% CL -0.4 to 28.1), interaction term p = 0.02. ANCS exposure was not associated with worse kidney function in adolescence, though ANCS may be associated with lower eGFR if children develop obesity by adolescence.


In vivo turnover rate of acetylcholine in rat brain parts at elevated steady-state concentration of plasma choline.
Cortical and striatal turnover rates of acetylcholine TR(ACh) were estimated by applying steady-state tracer kinetics in rats killed by microwave irradiation following a constant i.v. infusion of 3H-Ch. In control rats TR(ACh) was 3.6 nmol . g-1 . min-1 in the cortex and 23.8 nmol . g-1 . min-1 in the striatum. When steady-state plasma concentrations of Ch were increased from 17 to 140 mumol . 1-1 by a 15-min infusion of unlabelled Ch the corresponding TR(ACh) were 3.6 nmol . g-1 . min-1 and 21.4 nmol . g-1 . min-1, respectively. These results indicate that increased plasma levels of Ch are not accompanied by increased synthesis of brain ACh.


MycoNews 2021: President's message, IMA statutes, news, reports, awards, personalia, and book news.
This third annual edition of MycoNews starts with a message from IMA President Wieland Meyer regarding the adoption of new statutes for the IMA, the postponement of IMC12 to 2024, and announcing Marc Stadler as President-elect. The new statutes are included in full. News is provided on the launch of a World Fungus Day, acceptance of the term Funga as an equivalent to Fauna and Flora by the IUCN Species Survival Commission, new arrangements and dates for IMC12 now to be held in Maastricht in July 2024, and revised arrangements for the publication of proposals to change any rules governing the nomenclature of fungi. Reports are provided for IAL9, the symposium of the International Association for Lichenology in Brazil mainly conducted virtually, MycoRise Up! in Poland, and the centenary of the German Mycological Society (DGFM). Birthday greetings from IMA go to David Farr, Marie-Agnés Letrouit-Galinou, Maria Olech, Angela Restrepo, Carol Shearer, James Trappe, and Shun-ichi Udagawa. Tributes are also paid to the passing of the distinguished mycologists Heinz Butin, Karl Esser, Grégoire Hennebert, Jack Rogers, Kálman Vánky, and Bodo Wanke. The contribution concludes with news of seven new mycological books published in 2020-2021, and another forthcoming in 2022.


CRNDE inducing cisplatin resistance through SRSF1/TIA1 signaling pathway in ovarian cancer.
CRNDE is known to be an important predictive factor of prognosis in many tumors; however, its role in cisplatin resistance is still unknown in ovarian cancer. The aim of the current research was to investigate the association between CRNDE and cisplatin resistance. QRT-PCR and in situ hybridization assay were employed to detect the expression of CRNDE in ovarian cancer cells and tissues; CCK8 assay, AnnexinV-FITC apoptosis assay and Trans-well assay, to determine the cell proliferation, apoptosis and invasion; and RNA-pull down assay, mass spectrometry analysis, gene microarray to search the targeted gene of CRNDE and SRSF1. Association of CRNDE with SRSF1 was determined in ovarian cancer cells and nude mice. It was found that CRNDE and SRSF1 expression were higher in the cisplatin resistant ovarian cancer cells than their control cells. High expression of CRNDE and SRSF1 led to cisplatin resistance. While inhibition of CRNDE or SRSF1 sensitized ovarian cancer to cisplatin in vitro and in vivo. Moreover, as indicated in RIP assay, SRSF1 was potentially the targeted gene of CRNDE, and CRNDE promoting SRSF1 expression to induce cisplatin resistance; as indicated in gene microassay, there was significantly positive correlation between SRSF1 and TIA1, and SRSF1 promoting TIA1 expression. In conclusion, CRNDE induced cisplatin resistance in ovarian cancer through SRSF1/TIA1 signaling pathway; thus, CRNDE inhibitor or SRSF1 inhibitor combined with cisplatin might act as a novel promising approach to ovarian cancer.


Two separate regions essential for nuclear import of the hnRNP D nucleocytoplasmic shuttling sequence.
Heterogeneous nuclear ribonucleoprotein (hnRNP) D/AUF1 functions in mRNA genesis in the nucleus and modulates mRNA decay in the cytoplasm. Although it is primarily nuclear, it shuttles between the nucleus and cytoplasm. We studied the nuclear import and export of the last exon-encoding sequence common to all its isoforms by its expression as a green fluorescent protein-fusion protein in HeLa cells and by heterokaryon assay. The C-terminal 19-residue sequence (SGYGKVSRRGGHQNSYKPY) was identified as an hnRNP D nucleocytoplasmic shuttling sequence (DNS). In vitro nuclear transport using permeabilized cells indicated that nuclear import of DNS is mediated by transportin-1 (Trn-1). DNS accumulation in the nucleus was dependent on Trn-1, Ran, and energy in multiple rounds of nuclear transport. Use of DNS with deletions, alanine scanning mutagenesis and point mutations revealed that two separate regions (the N-terminal seven residues and the C-terminal two residues) are crucial for in vivo and in vitro transport as well as for interaction with Trn-1. The N- and C-terminal motifs are conserved in the shuttling sequences of hnRNP A1 and JKTBP.


Achieving coronal plane alignment in total knee arthroplasty through modified preoperative planning based on long-leg radiographs: a prospective study.
This prospective study was undertaken to examine whether the desired coronal plane alignment of limb and prosthetic components in total knee arthroplasty (TKA) could be achieved precisely using conventional jig-based methods by modifying the preoperative planning of bone resection utilizing long-leg radiographs (LLRs). The study included consecutive 245 TKA procedures. Pre- and postoperative radiological variables, i.e., the mechanical axis (hip-knee-ankle [HKA] axis), mechanical lateral distal femoral angle (mLDFA), and medial proximal tibial angle (MPTA), and their outliers were evaluated. Statistical analysis was performed using SPSS version 21.0. The mean postoperative HKA axis, mLDFA and MPTA was 179.80 ± 1.81° (p < 0.01; 95% CI: 8.09-9.67), 90.35 ± 1.54° (p < 0.01; 95% CI: 1.33-2.02), and 90.26 ± 1.25° (p < 0.01; 95% CI: 4.41-5.20), respectively. The postoperative HKA axis on the coronal plane was 180 ± 3° in 235 knees (95.92%, 4.08% outliers). Femoral and tibial components were implanted in an acceptable position, withing 90 ± 3° of the mechanical axis of the femur and tibia on the coronal plane in 238 (97.14%, 2.86% outliers) and 243 (99.18%, 0.8% outliers) knees, respectively. Modified preoperative planning for TKA on LLRs is a reliable and consistent method to achieve the desired limb and component alignment on the coronal plane without adding financial or logistical costs. II.


Prostaglandin production by the oocyte cumulus complex around the time of fertilization and the effect of prostaglandin E on the development of the early bovine embryo.
The oocyte-cumulus complex (25 oocytes per 250 microL medium) produced prostaglandin-F2 alpha (PGF2 alpha) and PGE2 during maturation, immediately following fertilization and for at least 48 h after fertilization. The data suggest that PG production is important in the development of the oocyte; addition of PGE2 (5 ng mL-1) to the fertilization medium increased the rate of cleavage and groups of oocytes with low cleavage rates produced far less PG than groups with high cleavage rates. Measurement of PG in the maturation medium could therefore be a means of assessing the suitability of oocytes for fertilization.


Modelling mitochondrial ROS production by the respiratory chain.
ROS (superoxide and oxygen peroxide in this paper) play a dual role as signalling molecules and strong oxidizing agents leading to oxidative stress. Their production mainly occurs in mitochondria although they may have other locations (such as NADPH oxidase in particular cell types). Mitochondrial ROS production depends in an interweaving way upon many factors such as the membrane potential, the cell type and the respiratory substrates. Moreover, it is experimentally difficult to quantitatively assess the contribution of each potential site in the respiratory chain. To overcome these difficulties, mathematical models have been developed with different degrees of complexity in order to analyse different physiological questions ranging from a simple reproduction/simulation of experimental results to a detailed model of the possible mechanisms leading to ROS production. Here, we analyse experimental results concerning ROS production including results still under discussion. We then critically review the three models of ROS production in the whole respiratory chain available in the literature and propose some direction for future modelling work.


Rip it, stitch it, click it: A Chemist's guide to VLP manipulation.
Viruses are some of nature's most ubiquitous self-assembled molecular containers. Evolutionary pressures have created some incredibly robust, thermally, and enzymatically resistant carriers to transport delicate genetic information safely. Virus-like particles (VLPs) are human-engineered non-infectious systems that inherit the parent virus' ability to self-assemble under controlled conditions while being non-infectious. VLPs and plant-based viral nanoparticles are becoming increasingly popular in medicine as their self-assembly properties are exploitable for applications ranging from diagnostic tools to targeted drug delivery. Understanding the basic structure and principles underlying the assembly of higher-order structures has allowed researchers to disassemble (rip it), reassemble (stitch it), and functionalize (click it) these systems on demand. This review focuses on the current toolbox of strategies developed to manipulate these systems by ripping, stitching, and clicking to create new technologies in the biomedical space.


Supplemental Screening for Patients at Intermediate and High Risk for Breast Cancer.
The sensitivity of mammography is more limited in patients with dense breasts and some patients at higher risk for breast cancer. Patients with intermediate or high risk for breast cancer may begin screening earlier and benefit from supplemental screening techniques beyond standard 2-dimensional mammography. A patient's individual risk factors for developing breast cancer, their breast density, and the evidence supporting specific modalities for a given clinical scenario help to determine the need for supplemental screening and the modality chosen. Additional factors include the availability of supplemental screening techniques at an individual institution, cost, insurance coverage, and state-specific breast density legislation.