Ranking of non-coding pathogenic variants and putative essential regions of the human genome.
A gene is considered essential if loss of function results in loss of viability, fitness or in disease. This concept is well established for coding genes; however, non-coding regions are thought less likely to be determinants of critical functions. Here we train a machine learning model using functional, mutational and structural features, including new genome essentiality metrics, 3D genome organization and enhancer reporter data to identify deleterious variants in non-coding regions. We assess the model for functional correlates by using data from tiling-deletion-based and CRISPR interference screens of activity of cis-regulatory elements in over 3 Mb of genome sequence. Finally, we explore two user cases that involve indels and the disruption of enhancers associated with a developmental disease. We rank variants in the non-coding genome according to their predicted deleteriousness. The model prioritizes non-coding regions associated with regulation of important genes and with cell viability, an in vitro surrogate of essentiality.


Consensus procedures and their role in pediatric rheumatology.
The Delphi Technique and Nominal Group Technique are two well-recognized consensus-formation methodologies specifically designed to combine judgments from a group of experts. The Delphi Technique utilizes a series of well-defined questionnaire-based surveys, whereas Nominal Group Technique is a structured face-to-face meeting designed to facilitate consensus. Consensus-formation techniques require that each step build on the results of the previous steps. In this review, we describe these techniques, how they work, and their practical application in pediatric rheumatology, where they have been widely used to develop the outcome measures of several chronic rheumatic diseases, including juvenile idiopathic arthritis, rheumatoid arthritis, systemic lupus erythematosus, and idiopathic inflammatory myopathies, as well as the classification criteria for juvenile systemic sclerosis and juvenile vasculitides.


Thyroid cancer surgery in Germany: an analysis of the nationwide DRG statistics 2005-2006.
In 2004, a Diagnosis Related Groups (DRG)-based hospital reimbursement system became mandatory in Germany. The aim of this study was to provide nationwide data on the surgery of thyroid cancer by analyzing DRG statistics of the years 2005 and 2006. The unit of analysis was hospital admission with a diagnosis of thyroid cancer. We assessed the influence of age, sex and region on the relative frequency of thyroid cancer-related hospitalisations with surgery of the thyroid and we measured the association between hospitalisation rates and incidence rates of thyroid cancer among the Federal States of Germany. Over the period 2005 to 2006, 11,107 thyroid cancer-associated hospitalisations included surgical treatment of the thyroid. The age-standardised DRG-based hospitalisation rates and the corresponding cancer registry-based incidences of thyroid cancer were positively associated. Overall, 68% of the hospitalisations with thyroid surgery included a total thyroidectomy. The percentage of surgery of the thyroid with a total thyroidectomy was nearly identical among men and women, decreased among men aged over 60 and varied considerably by region (minimum, 48% in Saarland; maximum, 78% in Saxony-Anhalt). Our analyses of DRG statistics provide for the first time representative population-based data of the surgical management of thyroid cancer patients in Germany. Despite an identical health care system all over Germany and existing guidelines for surgical treatment of thyroid cancer, we observed a considerable regional variation in the proportion of total thyroidectomies performed in Germany.


Optimal targets of chronic kidney disease-mineral and bone disorder markers for Chinese patients with maintenance peritoneal dialysis: a single-center retrospective cohort study.
The chronic kidney disease-mineral and bone disorder(CKD-MBD) is known to be associated with increased mortality in dialysis patients, but whether current global guidelines for CKD-MBD, which were primarily developed from hemodialysis, are suitable for peritoneal dialysis (PD) patients practice require further investigation. This is a single-center retrospective cohort study. In total 491 prevalent PD patients (median follow-ups: 34 months) from Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017 were included and followed until 30 June 2018. In the first dialysis year, the average levels of serum calcium, albumin-corrected calcium (CorCa), phosphorus, and parathyroid hormone (PTH) levels were the interested predictors in Cox proportional regression model. Of these PD patients (age 58 ± 17 years), 52% were male and 36% had diabetic nephropathy. In Cox regression over first-year mean parameters, PTH <100 pg/mL (HR = 1.97, 95% CI 1.32 to 2.94, p < 0.001) and ≥300 pg/mL (HR = 2.24, 95% CI 1.32 to 3.81, p = 0.003) were associated with increased all-cause mortality than that of PTH 100-200 pg/mL. Patients with albumin-corrected serum calcium level < 2.13 mmol/L also had higher risk of death than patients with level of 2.13 to 2.38 mmol/L (HR = 2.06, 95% CI 1.06 to 4.01, p = 0.02). Serum phosphorus ≥1.45 mmol/L were associated with increased all-cause mortality. However, lacking of data on 25-hydroxy vitamin D, alkaline phosphatase, and activated vitamin-D are limitations of our analysis. As one of the largest PD cohort study focusing on CKD-MBD, we demonstrated that the level of CKD-MBD markers in the first PD year are independent predictors of all-cause mortality. PTH 100-300 pg/mL might be the best target for Chinese PD patients.


Prenatal stress, development, health and disease risk: A psychobiological perspective-2015 Curt Richter Award Paper.
The long-term consequences of exposure to excess stress, particularly during sensitive developmental windows, on the initiation and progression of many complex, common physical and mental disorders that confer a major global burden of disease are well established. The period of intrauterine life represents among the most sensitive of these windows, at which time the effects of stress may be transmitted inter-generationally from a mother to her as-yet-unborn child. As explicated by the concept of fetal or developmental programming of health and disease susceptibility, a growing body of evidence supports the notion that health and disease susceptibility is determined by the dynamic interplay between genetic makeup and environment, particularly during intrauterine and early postnatal life. Except in extreme cases, an adverse intrauterine exposure may not, per se, 'cause' disease, but, instead, may determine propensity for disease(s) in later life (by shaping phenotypic responsivity to endogenous and exogenous disease-related risk conditions). Accumulating evidence suggests that maternal psychological and social stress during pregnancy represents one such condition that may adversely affect the developing child, with important implications for a diverse range of physical and mental health outcomes. In this paper we review primarily our own contributions to the field of maternal stress during pregnancy and child mental and physical health-related outcomes. We present findings on stress-related maternal-placental-fetal endocrine and immune/inflammatory processes that may mediate the effects of various adverse conditions during pregnancy on the developing human embryo and fetus. We enunciate conceptual and methodological issues related to the assessment of stress during pregnancy and discuss potential mechanisms of intergenerational transmission of the effects of stress. Lastly, we describe on-going research and some future directions of our program.


The influence of left ventricular geometry on coronary vasomotion in patients with essential hypertension.
The objective of this study was to assess the influence of left ventricular (LV) geometric pattern on coronary vasomotion in patients with essential hypertension. We studied 34 hypertensive patients, who had never been treated, with angiographically normal coronary arteries. Patients were classified into four LV geometric patterns by echocardiography: normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. The responses of coronary vasomotion in left anterior descending artery to vasoactive agents (acetylcholine, isosorbide dinitrate, adenosine triphosphate) were examined using a Doppler guidewire and quantitative coronary angiography. The percent increase in coronary blood flow evoked with acetylcholine (endothelium-dependent vasomotion) showed lowest in concentric hypertrophy, followed by eccentric hypertrophy, concentric remodeling, and normal geometry. The significant linear relationship between acetylcholine-induced coronary blood flow and LV mass was noted. There was no difference in the percent increase in coronary blood flow evoked with isosorbide dinitrate (endothelium-independent vasomotion of conduit vessel) among the four groups. The percent increase in coronary blood flow evoked with adenosine triphosphate (endothelium-independent vasomotion of resistant vessel) was significantly lower in patients with concentric hypertrophy than in the other three groups. The results in this study suggest that coronary vasomotion may be associated with LV geometry in patients with hypertension. The endothelium-dependent vasodilation is impaired progressively as LV hypertrophy advances. The endothelium-independent vasodilation of microvessels is impaired only in concentric hypertrophy. This advanced abnormality of coronary vasomotion may contribute to the high cardiovascular morbidity and mortality in patients with concentric hypertrophy.


Endocytosis in yeast: several of the yeast secretory mutants are defective in endocytosis.
Yeast cells have been shown to internalize lucifer yellow CH by endocytosis. Internalization of the fluorescent dye is time-, temperature-, and energy-dependent, it is not saturable, and the dye is accumulated in the vacuole. Some of the yeast secretory mutants that accumulate endoplasmic reticulum or Golgi bodies are defective for endocytosis at restrictive temperature, while others are not. All of the mutants that accumulate secretory vesicles are defective for endocytosis. These results suggest that efficient transport of proteins from the endoplasmic reticulum to the Golgi apparatus and from the Golgi to secretory vesicles is not necessary for endocytosis. In contrast, endocytosis may be obligatorily coupled with the latest steps of secretion.


Function of aberrant EGFR in malignant gliomas.
The most common alteration of the epidermal growth factor receptor (EGFR) gene in human malignant gliomas is an in-frame deletion of exon 2-7 from the extra-cellular domain. To study the relationship between the expression of this aberrant EGFR and cell proliferation, as well as apoptosis in malignant gliomas, we have developed U-87MG cell transfectants that express the aberrant (mutant-type) or normal (wild-type) EGFR. We analyzed cell number, tumor volume, and MIB-1 positive rate as proliferation markers, and found that in tissue culture, tumors derived from U-87 MG cells (mutant-type) have the same proliferative activity as those derived from U-87 MG cells (wild-type). However, when cells expressing mutant EGFR were implanted into nude mice subcutaneously, the tumorigenic capacity was much enhanced. We also found that the apototic index of tumors derived from U-87 MG cells (mutant-type) was less than 0.1%, whereas that of wild-type tumor was 1%. These results suggest that aberrant EGFR affects the malignancy of glioma by stimulating proliferation and inhibiting apoptosis.


Mechanisms underlying the manipulation of host apoptotic pathways by Toxoplasma gondii.
The establishment of a productive infection by an obligate intracellular pathogen is dependent on subversion of cellular defences. Apoptosis, or programmed cell death, is a property of metazoan cells that plays a critical role in inhibiting the proliferation of invasive organisms and viruses thereby protecting uninfected cells and limiting damage to the host organism. Not surprisingly, manipulation of the machinery of apoptosis plays a critical role in the pathogenesis of several intracellular pathogens. Toxoplasma gondii, arguably one of the most successful protozoan pathogens, has evolved several strategies to inhibit both the initiation and propagation of the apoptotic cascade. Recent work from several groups indicates an exquisite level of sophistication in the mechanisms to inhibit apoptosis along its diverse pathways. Much of this ability appears to centre around the manipulation of host transcription, specifically of genes involved in the pro-survival/anti-apoptotic response effectively manipulating the infected cell into a highly anti-apoptotic state. The implications of these observations extend beyond Toxoplasma biology to the broader area of microbial pathogenesis and cell signalling in mammalian cells.


A real-time system using deep learning to detect and track ureteral orifices during urinary endoscopy.
To automatically identify and locate various types and states of the ureteral orifice (UO) in real endoscopy scenarios, we developed and verified a real-time computer-aided UO detection and tracking system using an improved real-time deep convolutional neural network and a robust tracking algorithm. The single-shot multibox detector (SSD) was refined to perform the detection task. We trained both the SSD and Refined-SSD using 447 resectoscopy images with UO and tested them on 818 ureteroscopy images. We also evaluated the detection performance on endoscopy video frames, which comprised 892 resectoscopy frames and 1366 ureteroscopy frames. UOs could not be identified with certainty because sometimes they appeared on the screen in a closed state of peristaltic contraction. To mitigate this problem and mimic the inspection behavior of urologists, we integrated the SSD and Refined-SSD with five different tracking algorithms. When tested on 818 ureteroscopy images, our proposed UO detection network, Refined-SSD, achieved an accuracy of 0.902. In the video sequence analysis, our detection model yielded test sensitivities of 0.840 and 0.922 on resectoscopy and ureteroscopy video frames, respectively. In addition, by testing Refined-SSD on 1366 ureteroscopy video frames, the sensitivity achieved a value of 0.922, and a lowest false positive per image of 0.049 was obtained. For UO tracking performance, our proposed UO detection and tracking system (Refined-SSD integrated with CSRT) performed the best overall. At an overlap threshold of 0.5, the success rate of our proposed UO detection and tracking system was greater than 0.95 on 17 resectoscopy video clips and achieved nearly 0.95 on 40 ureteroscopy video clips. We developed a deep learning system that could be used for detecting and tracking UOs in endoscopy scenarios in real time. This system can simultaneously maintain high accuracy. This approach has great potential to serve as an excellent learning and feedback system for trainees and new urologists in clinical settings.


Prevalence of respiratory symptoms and diseases in schoolchildren living in a polluted and in a low polluted area in Israel.
Second and fifth grade schoolchildren living in two communities with different levels of air pollution were studied. The parents of these children filled out ATS-NHLI health questionnaires. The prevalence of reported respiratory symptoms and pulmonary diseases was found to be significantly higher among children growing up in the polluted community (Ashdod) as compared with the low-pollution area (Hadera). Logistic models fitted for the respiratory conditions which differed significantly between both areas of residence also included background variables that could be responsible for these differences. Relative risk values, which were calculated from the logistic models, were in the range of 1.47 for cough without cold to 2.66 for asthma for children from Ashdod, as compared with 1.00 for children from Hadera.


Enhanced absorption of calcium after oral administration of maltitol in the rat intestine.
The enhancing effects of maltitol (alpha-D-glucopyranosyl-1,4-sorbitol) on absorption of calcium by the rat intestine have been studied by use of [45Ca]CaCl2 in-vivo. After intragastric administration of [45Ca]CaCl2 solution with maltitol, plasma 45Ca concentration remained at the maximum level for more than 80 min, whereas for animals given [45Ca]CaCl2 solution without maltitol, plasma 45Ca concentration declined sharply after the peak. Determination of 45Ca radioactivity remaining in the various segments of the gastrointestinal tract revealed that administration of maltitol elicited slower gastric emptying and slower intestinal transit, resulting in extensive 45Ca distribution along the small intestine throughout the experimental period. The luminal contents of the small intestine were significantly higher in rats given maltitol than in the control group. These results suggest that the enhancing action of maltitol on intestinal calcium absorption could be attributed to reduced gastrointestinal calcium transit and increased luminal fluid content, presumably because of the osmotic activity of maltitol; this would not only accelerate the dissolution of calcium into the increased luminal contents, but also enable a larger area of the small intestine to absorb calcium for a longer period of time.


Corrigendum: Beyond effectiveness evaluation: Contributing to the discussion on complexity of digital health interventions with examples from cancer care.
[This corrects the article DOI: 10.3389/fpubh.2022.883315.].


Relationship of the serotonin transporter with prolactin response to meta-chlorophenylpiperazine in cocaine dependence.
Preclinical evidence indicates that exposure to cocaine influences the activity of the serotonin transporter (5-HTT) as well as several 5-HT receptor subtypes. However, little is known about the relationship between the 5-HTT and 5-HT receptors following cocaine exposure in humans. We examined the relationship between platelet 5-HTT, a presynaptic 5-HT measure, and prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a postsynaptic 5-HT receptor agonist in cocaine dependent individuals. Platelet [3H] paroxetine binding sites were assayed and the m-CPP challenge test was performed in 35 African American cocaine dependent individuals and 33 controls. Clinical measures included assessments of drug use severity and depression. Cocaine subjects showed reduced Bmax of [3H] paroxetine (t=4.67, p<0.01) and blunted PRL response to m-CPP (F=21.86, p<0.01) compared to controls. There was a positive correlation between Bmax and delta PRL [peak-baseline PRL] in cocaine subjects (r=0.50, p<0.01) but not in controls (r=0.19). ANCOVA analyses showed that the cocaine subgroup with moderate and severe reduction in Bmax showed a greater blunting in PRL response compared to the subgroup with mild Bmax reductions (F=9.44, p<.005). Multivariate regression models showed that the main effects as well as the interaction of Bmax and severity of cocaine use significantly contributed to impaired PRL response (F=17.90, p<.001). Disturbances in serotonin transporter binding and post-synaptic 5-HT receptor function seem to be associated in cocaine-dependent subjects. Severity of cocaine use appears to mediate this relationship. Whether there is a causal association between the two measures, or cocaine has separate and independent pre- and post-synaptic effects needs to be clarified.


Single fibre motor evoked potentials to brain, spinal roots and nerve stimulation. Comparisons of the 'central' and 'peripheral' response jitter to magnetic and electric stimuli.
Single fibre motor evoked potentials to magnetic and electric non-invasive stimulation of brain, spinal cord and peripheral nerve were recorded in 8 healthy volunteers. The 'central motor jitter' and the 'peripheral motor jitter' were respectively calculated and a comparison between the magnetic and electric modalities was made. The highest degree of latency variability was observed for both magnetic and electric central motor jitter, whilst the peripheral motor jitter to nerve stimulation was as low as the neuromuscular one (range 16-60 microsecond). The magnetic 'central motor jitter' (range 94-1024 microsecond) was much larger than the electric one (range 55-280 microsecond), which was in the order of jitter calculated on H-reflex studies; moreover, the former was organized in a bi- or trimodal distribution. On the contrary, no significant differences were observed between the two modalities when the jitter to nerve stimulation was taken into account. Possible contributions of corticocortical circuitries containing several synaptic interruptions during magnetic as opposed to electric transcranial stimulation, is discussed.


Normative values for exhaled breath condensate pH and its relationship to exhaled nitric oxide in healthy African Americans.
Exhaled breath condensate (EBC) pH and exhaled nitric oxide (FeNO) have been proposed as markers of asthma severity. EBC pH values below 6.5 have been associated with asthma exacerbations. Protonation of airway nitrite occurs at low pH and may contribute to FeNO. To establish normative EBC pH values and to determine the contribution of EBC pH to FeNO in healthy African Americans. Two hundred seventy healthy African American subjects without asthma between 18 and 40 years old were evaluated. Subjects had simultaneous measurement of EBC pH, EBC nitrite, nitrate, and FeNO. The median EBC pH was 8.14 (interquartile range, 7.83-8.28). Of subjects, 11.9% had an EBC pH < or = 6.5. In subjects with EBC pH values below 6.5, there was an inverse correlation between EBC pH and FeNO (r(2) = 0.158; P = .0245; n = 32). In the entire cohort, there was a direct correlation between EBC pH and EBC nitrite (r(2) = 0.163; P < .0001), but there was no correlation between EBC nitrite and FeNO. In multivariate analyses, EBC pH and nitrite did not contribute significantly to FeNO variation while controlling for other confounders of FeNO. There was an increased prevalence (11.9%) of low EBC pH (less than 6.5) in healthy African American subjects compared with white subjects (<5%). EBC pH and nitrite were directly correlated, but there was no correlation between EBC nitrite and FeNO. FeNO correlated with EBC pH at pH values less than 6.5 in univariate but not multivariate analyses. This suggests that EBC pH and nitrite are not significant determinants of FeNO in healthy subjects.


The bridge stenting-based internal drainage in pancreatic trauma patients with main pancreatic duct injury.
Pancreatic trauma is associated with high mortality and morbidity, especially in main pancreatic duct (MPD) injuries. Here, we introduce a novel technique via the placement of bridge stenting-based internal drainage (BSID) along the injured MPD to restore pancreatic tissue integrity. Twelve patients with MPD injury underwent unobstructed BSID as physical support for healing. Six patients with peripheral organ injuries underwent operative end-to-end anastomosis of the MPD by using a polyurethane central venous catheter for the BSID, and the other six patients with isolated proximal MPD rupture received BSID via endoscopic pancreatic stent placement. The BSID technique was successfully performed in all pancreatic trauma patients without the need for a second open surgery. With this simplified BSID-based operation, a short procedure duration (242.7 ± 38.71 min in the surgical group and 100.2 ± 16.24 min in the endoscopic group) and a short hospital stay (13.0 ± 7.05 days) were achieved. However, a few complications (41.67%) still occurred, including pancreatitis, fistula, abscess, pseudocyst, cholangitis, and haemorrhage. Except for the deceased case, all postoperative courses were marked by decreases in the peripancreatic fluid collection, blood amylase recovery, and normal endocrine function. The BSID approach is a feasible surgical approach for the treatment of MPD injury and can be used endoscopically in isolated MPD injuries for its safety and convenience.


Lysophospholipids prevent binding of a cytolytic protein ostreolysin to cholesterol-enriched membrane domains.
Ostreolysin, a 15kDa pore-forming protein from the oyster mushroom (Pleurotus ostreatus), binds specifically to cholesterol-enriched membrane domains existing in the liquid-ordered phase, and lyses cells and lipid vesicles made of cholesterol and sphingomyelin. We have monitored binding of sub-lytic concentrations of ostreolysin to membranes of Chinese Hamster Ovary cells and rat somatotrophs, using primary anti-ostreolysin and fluorescence-labeled secondary antibodies detected by confocal microscopy. Depletion of more than 40% membrane cholesterol content by methyl-beta-cyclodextrin dramatically decreased ostreolysin binding. Immunostaining showed that ostreolysin is not co-localized with raft-binding proteins, cholera toxin B-subunit or caveolin, suggesting that natural membranes display heterogeneity of cholesterol-enriched raft-like microdomains. Impaired ostreolysin binding was also observed after treating the cells with lysophosphatidylinositol. Effects of lysophosphatidylinositol on binding of ostreolysin to immobilized large sphingomyelin/cholesterol (1/1, mol/mol) unilamellar vesicles were studied by a surface plasmon resonance technique. Injection of ostreolysin during the lysophosphatidylinositol dissociation phase showed an inverse relationship between ostreolysin binding and the quantity of lysophosphatidylinositol in the membranes of lipid vesicles. It was concluded that lysophospholipids prevent binding of ostreolysin to cell and to artificial lipid membranes resembling lipid rafts, by partitioning into the lipid bilayer and altering the properties of cholesterol-rich microdomains.


The Kärger vs bi-exponential model: Theoretical insights and experimental validations.
We revise three common models accounting for water exchange in pulsed-gradient spin-echo measurements: a bi-exponential model with time-dependent water fractions, the Kärger model, and a modified Kärger model designed for restricted diffusion, e.g. inside cells. The three models are compared and applied to experimental data from yeast cell suspensions. The Kärger model and the modified Kärger model yield very close results and accurately fit the data. The bi-exponential model, although less rigorous, has a natural physical interpretation and suggests a new experimental modality to estimate the water exchange time.


Placental miRNAs in feto-maternal communication mediated by extracellular vesicles.
A complex network composed of at least 1900 microRNA (miRNA) species orchestrates the development and function of the human placenta. These molecules regulate genes and pathways operating major functional processes in trophoblast cells such as proliferation, invasion, differentiation, and metabolism. Nevertheless, the cellular localization and role of most placental miRNAs remain to be determined. The existence of eutherian- (C14MC) and primate-specific miRNA clusters (C19MC), together with human placenta-specific miRNAs, indicate the relevance of these molecules in evolution and diversification of the placenta, including the acquisition of its unique features in humans. They may be related also to diseases that are exclusively present in primates, such as preeclampsia. Changes in the miRNA expression profile have been reported in several placental pathologies. Which miRNAs are involved in the pathomechanism of these diseases or act to maintain placental homeostasis is uncertain. Placenta-derived miRNAs are packed into extracellular vesicles (EVs) and distributed through the maternal circulation to distant organs, where they contribute to adaptations required during pregnancy. Similarly, the placenta also receives molecular information from other tissues to adapt fetoplacental metabolic demands to the maternal energetic supply. These processes can be impaired in pathologic conditions. Therefore, the collection of circulating placental miRNAs constitutes potentially a minimally-invasive approach to assess the fetoplacental status and to diagnose pregnancy diseases. Future therapies may include manipulation of miRNA levels for prevention and treatment of placental complications to protect maternal health and fetal development.


Comparing Indirect and Combined Effects of Mindfulness and Compassion Practice Among Schoolchildren on Inter- and Intra-personal Abilities.
During the last decade, mindfulness-based interventions have been implemented in the educational system. Such programs could follow several approaches, including an indirect approach, in which interventions are delivered only to teachers and a combination in which interventions are delivered to both teachers and students. Because of the importance of teacher's involvement in programs designed to help children, we compared students' impact of indirect, combined, and control groups over time. The indirect program delivered was the "Call to Care - Israel for Teachers," and the direct program was the "Call to Care Israel" for students. Both programs employ mindfulness, compassion, and training of social-emotional skills, with a unique emphasis on care. Two hundred 4th and 5th grade students were divided into indirect (2 classrooms), combined (3 classrooms), or control groups (3 classrooms). Each condition was implemented in a different school; schools were randomly divided into groups. The interventions were delivered by trained facilitators and included 20 weekly meetings. Outcomes for students were measured before the intervention, after it ended, and 6 months later. Hierarchical linear models revealed that both the indirect and the combined approaches were effective in improving well-being, anxiety, attention, and teacher's availability and acceptance, while only the combined approach was effective in improving mindfulness, somatization, classroom atmosphere, and pro-social behavior. Our results suggest that the combined approach is more beneficial than the indirect approach. However, given the scalability and cost of the indirect approach, it should also be considered an effective alternative. The online version contains supplementary material available at 10.1007/s12671-022-01955-y.


Nodes of Ranvier in acrylamide neuropathy: voltage clamp and electron microscopic analysis of rat sciatic nerve fibres at proximal levels.
Adult male rats were injected with acrylamide monomer (50 mg/kg i.p., 3 times/week). The animals developed hind limb paresis and distal motor nerve conduction velocity decreased. Three of 14 examined isolated myelinated sciatic nerve fibres showed a reduced excitability. In the remaining fibres the action potentials were normal. Potential clamp analysis of nodes of Ranvier in the single fibres revealed large delayed nodal K currents in 6 cases. Four of these 6 fibres exhibited a markedly increased membrane capacitance and in 2 fibres an increased Na permeability was found. Electron microscopic examination of sciatic nerves revealed comparatively subtle internodal and nodal-paranodal alterations in large myelinated fibres. Internodally, focal aggregates of tubulovesicular profiles could be found and some Schwann cells were hypertrophic. Paranodally, axonal evaginations penetrated in between the terminating myelin lamellae. Some paranodes had a very thin myelin covering and/or exhibited varying degrees of myelin sheath retraction. In the nodal axon domains lacking an axolemmal undercoating and partly non-undercoated axolemmal protrusions could be found. Similar physiological and morphological alterations occur in the rat sciatic nerve above a neuroma. Therefore, the presently observed proximal changes may, to some extent, represent non-specific alterations, secondary to a target deprivation caused by the distal axon degeneration typical for acrylamide neuropathy.


Miscoding-induced stalling of substrate translocation on the bacterial ribosome.
Directional transit of the ribosome along the messenger RNA (mRNA) template is a key determinant of the rate and processivity of protein synthesis. Imaging of the multistep translocation mechanism using single-molecule FRET has led to the hypothesis that substrate movements relative to the ribosome resolve through relatively long-lived late intermediates wherein peptidyl-tRNA enters the P site of the small ribosomal subunit via reversible, swivel-like motions of the small subunit head domain within the elongation factor G (GDP)-bound ribosome complex. Consistent with translocation being rate-limited by recognition and productive engagement of peptidyl-tRNA within the P site, we now show that base-pairing mismatches between the peptidyl-tRNA anticodon and the mRNA codon dramatically delay this rate-limiting, intramolecular process. This unexpected relationship between aminoacyl-tRNA decoding and translocation suggests that miscoding antibiotics may impact protein synthesis by impairing the recognition of peptidyl-tRNA in the small subunit P site during EF-G-catalyzed translocation. Strikingly, we show that elongation factor P (EF-P), traditionally known to alleviate ribosome stalling at polyproline motifs, can efficiently rescue translocation defects arising from miscoding. These findings help reveal the nature and origin of the rate-limiting steps in substrate translocation on the bacterial ribosome and indicate that EF-P can aid in resuming translation elongation stalled by miscoding errors.


Using extracellular matrix for regenerative medicine in the spinal cord.
Regeneration within the mammalian central nervous system (CNS) is limited, and traumatic injury often leads to permanent functional motor and sensory loss. The lack of regeneration following spinal cord injury (SCI) is mainly caused by the presence of glial scarring, cystic cavitation and a hostile environment to axonal growth at the lesion site. The more prominent experimental treatment strategies focus mainly on drug and cell therapies, however recent interest in biomaterial-based strategies are increasing in number and breadth. Outside the spinal cord, approaches that utilize the extracellular matrix (ECM) to promote tissue repair show tremendous potential for various application including vascular, skin, bone, cartilage, liver, lung, heart and peripheral nerve tissue engineering (TE). Experimentally, it is unknown if these approaches can be successfully translated to the CNS, either alone or in combination with synthetic biomaterial scaffolds. In this review we outline the first attempts to apply the potential of ECM-based biomaterials and combining cell-derived ECM with synthetic scaffolds.


Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis.
The essential roles of overexpression of eukaryotic translation initiation factor 4E (eIF4E) and aberrant activation of β-catenin in lung cancer development have been recently identified. However, whether there is a direct connection between eIF4E overexpression and β-catenin activation in lung cancer cells is unknown. In this study, we show that antibiotic drug rifabutin targets human lung cancer cells via inhibition of eIF4E-β-catenin axis. Rifabutin is effectively against lung cancer cells in in vitro cultured cells and in vivo xenograft mouse model through inhibiting proliferation and inducing apoptosis. Mechanistically, eIF4E regulates β-catenin activity in lung cancer cells as shown by the increased β-catenin phosphorylation and activity in cells overexpressing eIF4E, and furthermore that the regulation is dependent on phosphorylation at S209. Rifabutin suppresses eIF4E phosphorylation, leads to decreased β-catenin phosphorylation and its subsequent transcriptional activities. Depletion of eIF4E abolishes the inhibitory effects of rifabutin on β-catenin activities and overexpression of β-catenin reverses the inhibitory effects of rifabutin on cell growth and survival, further confirming that rifabutin acts on lung cancer cells via targeting eIF4E- β-catenin axis. Our findings identify the eIF4E- β-catenin axis as a critical regulator of lung cancer cell growth and survival, and suggest that its pharmacological inhibition may be therapeutically useful in lung cancer.


Distinct VH repertoires in primary and secondary B cell lymphocyte subsets in the preimmune repertoire of A/J mice: the CRI-A idiotype is preferentially associated with the HSA(low) B cell subset.
The anti-arsonate immune response of A/J mice is characterized by the occurrence of several recurrent idiotypes with a different temporal pattern of expression. The CRI-A idiotype is typically a memory idiotype since it appears late in the primary and dominates the secondary as well as subsequent immune responses. The CRI-C idiotype is present throughout the responses, including the primary one. Naive adult A/J mice treated repeatedly with anti-mu or anti-delta monoclonal antibodies exhibit a completely different balance of HSA(low) and HSA(high) B cell subsets and an opposite idiotype profile after immunization with p-azophenylarsonate coupled to hemocyanin. Anti-mu treatment leads to a striking enhancement of the HSA(low) cell subset associated with an earlier important synthesis of CRI-A(+) antibodies, while anti-delta treatment enhances significantly the HSA(high) compartment with a strong decrease of CRI-A and persistence of CRI-C1 antibodies. Semiquantitative PCR analysis reveals that the presence of CRI-A transcripts is associated with the HSA(low) compartment, while CRI-C transcripts are mainly associated with HSA(high) B cell subsets. This has been demonstrated with spleen cells of adult A/J mice treated with anti-mu or anti-delta antibodies and also with purified B cell subsets of unimmunized adult A/J mice and on neonatal spleen cells. It appears that the memory (CRI-A) idiotype is selected into the HSA(low) B cell subset before antigen arrival.


[3H]substance P binding in the intermediolateral cell column and striatum of the rat.
[3H]substance P binding was studied in the intermediolateral cell column and striatum in the rat using slide-mounted sections. The intermediolateral cell column had a single high affinity binding component with a dissociation constant, Kd = 1.45 nM and the number of sites, Bmax = 18.1 fmol per mg protein. The striatum had a Kd = 0.77 nM and a Bmax = 23.5 fmol per mg protein. The relative potency of various substance P-like tachykinins in displacing [3H]substance P suggested that both these areas may contain a substance P-P (for physalaemin) receptor subtype. (D-Pro4, D-Trp7,9)substance P(4-11), a substance P antagonist, has a relatively low affinity (micromolar range) in both these areas.


Unveiling the Electrocatalytic Activity of the GdBa0.5Sr0.5Co2-xCuxO5+δ (x ≥ 1) Oxygen Electrodes for Solid Oxide Cells.
The A-site cation-ordered GdBa0.5Sr0.5Co2-xCuxO5+δ (GBSCC) double perovskites are evaluated regarding the development of high-performance oxygen electrodes for reversible solid oxide cells (rSOCs). The aims are to maximally decrease the content of toxic and expensive cobalt by substitution with copper while at the same time improving or maintaining the required thermomechanical and electrocatalytic properties. Studies reveal that compositions with 1 ≤ x ≤ 1.15 are particularly interesting. Their thermal and chemical expansions are decreased, and sufficient transport properties are observed. Complementary density functional theory calculations give deeper insight into oxygen defect formation in the considered materials. Chemical compatibility with La0.8Sr0.2Ga0.8Mg0.2O3-δ (LSGM) and Ce0.9Gd0.1O2-δ (GDC) solid electrolytes is evaluated. It is documented that the GdBa0.5Sr0.5Co0.9Cu1.1O5+δ oxygen electrode enables obtaining very low electrode polarization resistance (Rp) values of 0.017 Ω cm2 at 850 °C as well as 0.111 Ω cm2 at 700 °C, which is lower in comparison to that of GdBa0.5Sr0.5CoCuO5+δ (respectively, 0.026 and 0.204 Ω cm2). Systematic distribution of relaxation times analyses allows studies of the electrocatalytic activity and distinguishing elementary steps of the electrochemical reaction at different temperatures. The rate-limiting process is found to be oxygen atom reduction, while the charge transfer at the electrode/electrolyte interface is significantly better with LSGM. The studies also allow elaborating on the catalytic role of the Ag current collector as compared with Pt. The electrodes manufactured using materials with x = 1 and 1.1 permit reaching high power outputs, exceeding 1240 mW cm-2 at 850 °C and 1060 mW cm-2 at 800 °C, for the LSGM-supported cells, which can also work in the electrolysis mode.


Machine-learning for the prediction of one-year seizure recurrence based on routine electroencephalography.
Predicting seizure recurrence risk is critical to the diagnosis and management of epilepsy. Routine electroencephalography (EEG) is a cornerstone of the estimation of seizure recurrence risk. However, EEG interpretation relies on the visual identification of interictal epileptiform discharges (IEDs) by neurologists, with limited sensitivity. Automated processing of EEG could increase its diagnostic yield and accessibility. The main objective was to develop a prediction model based on automated EEG processing to predict one-year seizure recurrence in patients undergoing routine EEG. We retrospectively selected a consecutive cohort of 517 patients undergoing routine EEG at our institution (training set) and a separate, temporally shifted cohort of 261 patients (testing set). We developed an automated processing pipeline to extract linear and non-linear features from the EEGs. We trained machine learning algorithms on multichannel EEG segments to predict one-year seizure recurrence. We evaluated the impact of IEDs and clinical confounders on performances and validated the performances on the testing set. The receiver operating characteristic area-under-the-curve for seizure recurrence after EEG in the testing set was 0.63 (95% CI 0.55-0.71). Predictions were still significantly above chance in EEGs with no IEDs. Our findings suggest that there are changes other than IEDs in the EEG signal embodying seizure propensity.


Five-year real-world outcomes of anti-vascular endothelial growth factor monotherapy versus combination therapy for polypoidal choroidal vasculopathy in a Chinese population: a retrospective study.
To evaluate 5-year outcomes of anti-vascular endothelial growth factor (VEGF) monotherapy and combination therapy of anti-VEGF agents and photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV) in a real-world Chinese population. Retrospective study. Fifty-three eyes of 46 patients with subtype 1 and 2 PCV followed up for at least 60 months were grouped into three regimens: anti-VEGF monotherapy, PDT combining with anti-VEGF therapy initially, and PDT combining with deferred anti-VEGF therapy. Main outcome measure was best-corrected visual acuity (BCVA) using logarithm of minimal angle of resolution (logMAR). The mean BCVA of eyes with subtype 1 PCV (n = 28) deteriorated from 0.69 logMAR at baseline to 1.25 logMAR at months 60 (P = 0.001), while the mean BCVA of eyes with subtype 2 PCV (n = 25) sustained stable from 0.62 logMAR at baseline to 0.57 at months 60 (P = 0.654). No significant differences of visual outcomes were found between the 3 treatment regimens for subtype 1 PCV. Anti-VEGF monotherapy and initial combination treatment had better visual outcomes in eyes with subtype 2 PCV than deferred combination group during part of follow-up significantly. Initial combination group needed a less number of PDT than deferred combination group (P < 0.001). Compared with subtype 1 PCV, subtype 2 PCV has a more favorable visual outcome in real world. All the regimens presented unfavorable visual outcomes for subtype 1 PCV. Anti-VEGF monotherapy and initial combination therapy should be superior to deferred combination therapy in the long-term management of subtype 2 PCV. Prospective randomized studies of larger size are needed to determine the long-term efficacy and safety of various treatment for PCV in real world.


[Subcutaneous mass as initial manifestation of an osteolytic metastasis].
A 69-year-old woman was admitted for evaluation of a left occipital subcutaneous tumour which had grown during the preceding eight weeks from 2 × 2 cm to 4 × 4 cm. Sonography revealed a pressure-sensitive subcutaneous mass with osteolytic destruction in the occipital bone. Cranial magnetic resonance imaging confirmed the osteolytic lesion. Thoracic computed tomography showed a lesion in the upper left lobe of the lung with metastases in the hilar lymph nodes. Transbronchial biopsy revealed a bronchial carcinoma. After resection of the osteolytic lesion its histology was confirmed to be an osseous metastasis of the carcinoma. Palliative chemotherapy and cranial irradiation were initiated. Solitary osteolytic lesions of the skull occur in the context of osseous metastases. Other possible causes include solitary plasmocytoma and eosinophilic granuloma.


The Mechanisms of lncRNA-Mediated Multidrug Resistance and the Clinical Application Prospects of lncRNAs in Breast Cancer.
Breast cancer (BC) is a highly heterogeneous disease and presents a great threat to female health worldwide. Chemotherapy is one of the predominant strategies for the treatment of BC; however, multidrug resistance (MDR) has seriously affected or hindered the effect of chemotherapy. Recently, a growing number of studies have indicated that lncRNAs play vital and varied roles in BC chemoresistance, including apoptosis, autophagy, DNA repair, cell cycle, drug efflux, epithelial-mesenchymal transition (EMT), epigenetic modification and the tumor microenvironment (TME). Although thousands of lncRNAs have been implicated in the chemoresistance of BC, a systematic review of their regulatory mechanisms remains to be performed. In this review, we systematically summarized the mechanisms of MDR and the functions of lncRNAs mediated in the chemoresistance of BC from the latest literature. These findings significantly enhance the current understanding of lncRNAs and suggest that they may be promising prognostic biomarkers for BC patients receiving chemotherapy, as well as therapeutic targets to prevent or reverse chemoresistance.


Determinants of exaggerated difference in morning and evening blood pressure measured by self-measured blood pressure monitoring in medicated hypertensive patients: Jichi Morning Hypertension Research (J-MORE) Study.
Morning blood pressure (BP) surge in ambulatory BP monitoring was a risk factor for stroke in our previous study. We studied the determinants of the morning minus evening systolic BP difference (ME difference) in self-measured BP monitoring, as a possible risk factor for stroke in medicated hypertensive patients. Nine hundred sixty-nine hypertensive outpatients receiving stable antihypertensive drug treatment were studied using self-measured BP monitoring in the morning and evening. The ME difference ranged from -37.3 to 53.3 mm Hg (mean 7.9 mm Hg). The highest quartile (Q4) of the ME difference group (>15.0 mm Hg) had older age (68.0+/-9.8 years v 66.2+/-10.3 years, P=.01) and higher prevalence of men (48.3% v 39.9%, P=.02), regular alcohol drinkers (34.7% v 26.0%, P=.01) and beta-blocker use (26.9% v 19.9%, P=.03) than the other quartile groups (Q1 to Q3), whereas there was no significant difference in the average of morning and evening (ME average) BP. In logistic regression analysis controlling for ME average and other confounding factors, independent risks for Q4 of ME difference were older age (10 years older: odds ratio [OR] 1.21, P=.01, 95% confidence interval (CI) 1.04-1.42), regular alcohol drinker (OR 1.51, P=.04, 95% CI 1.01-2.26), and beta-blocker use (OR 1.50, P=.02, 95% CI 1.06-2.12). Older age, beta-blocker use, and regular alcohol drinking were significant determinants of the exaggerated ME difference in medicated hypertensive patients.


Expression of the thrombin receptor PAR-1 correlates with tumour cell differentiation of pancreatic adenocarcinoma in vitro.
Patients with pancreatic cancer frequently suffer from thrombosis due to excess thrombin generation. Yet, the effects of thrombin on pancreatic cancer are still poorly understood. The thrombin receptor PAR-1 is responsible for cellular effects of thrombin. PAR-1 plays an important role in the progression of different solid tumours in vitro. In breast cancer the level of PAR-1 expression correlates with invasiveness. Our aim was to correlate PAR-1 mRNA and protein expression level with the grade of differentiation of pancreatic tissue and cancer cell lines. PAR-1 protein was not detectable in the epithelium of healthy pancreas. Analysis of PAR-1 protein expression by immunofluorescence staining of pancreatic cancer cell lines revealed a correlation to the grade of differentiation. Quantitative analysis of PAR-1 protein expression by Western Blot analysis confirmed these observations. Analysis of PAR-1 mRNA expression showed low levels in healthy pancreas compared to pancreatic cancer tissue and the pancreatic cancer cell line MIA PaCa-2. The level of PAR-1 mRNA differed up to 25 fold between the respective pancreatic cancer cell lines. The eminent differences in PAR-1 expression, both protein and mRNA, between healthy pancreatic tissue and pancreatic cancer in vivo and in vitro emphasise the putative role of PAR-1 in pancreatic cancer progression.


Pre-induction ripening of the cervix with extra-amniotic prostaglandin E2 in gel.
Pre-induction ripening of the unfavorable cervix was attempted in 104 normal term gravidas by means of a single extra-amniotic instillation of a viscous gel containing 0.5 mg prostaglandin E2. The procedure was highly successful and no adverse effect on mother or fetus was observed.


Efficient Generation of Pretraining Samples for Developing a Deep Learning Brain Injury Model via Transfer Learning.
The large amount of training samples required to develop a deep learning brain injury model demands enormous computational resources. Here, we study how a transformer neural network (TNN) of high accuracy can be used to efficiently generate pretraining samples for a convolutional neural network (CNN) brain injury model to reduce computational cost. The samples use synthetic impacts emulating real-world events or augmented impacts generated from limited measured impacts. First, we verify that the TNN remains highly accurate for the two impact types (N = 100 each; [Formula: see text] of 0.948-0.967 with root mean squared error, RMSE, ~ 0.01, for voxelized peak strains). The TNN-estimated samples (1000-5000 for each data type) are then used to pretrain a CNN, which is further finetuned using directly simulated training samples (250-5000). An independent measured impact dataset considered of complete capture of impact event is used to assess estimation accuracy (N = 191). We find that pretraining can significantly improve CNN accuracy via transfer learning compared to a baseline CNN without pretraining. It is most effective when the finetuning dataset is relatively small (e.g., 2000-4000 pretraining synthetic or augmented samples improves success rate from 0.72 to 0.81 with 500 finetuning samples). When finetuning samples reach 3000 or more, no obvious improvement occurs from pretraining. These results support using the TNN to rapidly generate pretraining samples to facilitate a more efficient training strategy for future deep learning brain models, by limiting the number of costly direct simulations from an alternative baseline model. This study could contribute to a wider adoption of deep learning brain injury models for large-scale predictive modeling and ultimately, enhancing safety protocols and protective equipment.


Drug target prioritization by perturbed gene expression and network information.
Drugs bind to their target proteins, which interact with downstream effectors and ultimately perturb the transcriptome of a cancer cell. These perturbations reveal information about their source, i.e., drugs' targets. Here, we investigate whether these perturbations and protein interaction networks can uncover drug targets and key pathways. We performed the first systematic analysis of over 500 drugs from the Connectivity Map. First, we show that the gene expression of drug targets is usually not significantly affected by the drug perturbation. Hence, expression changes after drug treatment on their own are not sufficient to identify drug targets. However, ranking of candidate drug targets by network topological measures prioritizes the targets. We introduce a novel measure, local radiality, which combines perturbed genes and functional interaction network information. The new measure outperforms other methods in target prioritization and proposes cancer-specific pathways from drugs to affected genes for the first time. Local radiality identifies more diverse targets with fewer neighbors and possibly less side effects.


Decalepis hamiltonii root extract attenuates the age-related decline in the cognitive function in Drosophila melanogaster.
Age-associated accumulation of oxidative damage linked to decline of antioxidant defense mechanism, leads to impairment of cognitive function in many organisms. These damages can pass through generations and affect the cognitive quality of progenies. In Drosophila, classical olfactory conditioning results in the formation of different types of memory. Age-related memory impairment (AMI) causes reduction in middle term memory (MTM) and parental senescence causes decline in short-term memory (STM) of the offspring. We have further examined the neuromodulatory effect of Decalepis hamiltonii (Dh) root extract, which is a cocktail of novel antioxidant molecules, on the biochemical oxidative defenses in relation to cognitive ability of the aged flies and their offspring. There is a strong correlation between the age-related decline in the activity of the antioxidant enzymes and the lower cognitive ability of the aged flies and their offspring. Feeding of aged flies in the diet containing 0.1% Dh, markedly enhances the cognitive ability of both aged flies and their offspring which is associated with enhanced antioxidant defenses as evident for the activity of superoxide dismutase (SOD) and catalase. Our findings, for the first time, show that the antioxidant-rich Dh root extract attenuates the age-related decline in cognitive ability of Drosophila, and also shows ameliorative effect on the memory of the offspring.


Saturated-fat diet induces moderate diabetes and severe glomerulosclerosis in hamsters.
Diets high in saturated fat are thought to be a risk factor for Type 2 diabetes and associated complications. We investigated effects of a medium and high saturated fat diet on the development of diabetes-associated pathologies in Golden Syrian hamsters, an animal that reacts to dietary lipids in a fashion similar to humans. Three diets containing 46.5 kcal %, 267.3 kcal %, and 488.2 kcal % as saturated fat respectively, were studied. Metabolic parameters were measured up to 20 weeks. Electron microscopy was used to examine the structure of the pancreas, aorta and kidney. Increased saturated fat consumption was associated with: (i) gradual imbalance of homeostasis, and severe structural alterations of acinar, beta cells and capillaries in the pancreas, and of the kidney glomeruli; (ii) severe hypertriglyceridaemia and augmented creatinine concentrations related to disturbances of the renal function, progressing to nodular glomerulosclerosis and nephropathy; (iii) reduced early insulin secretion in response to glucose; (iv) switch of the aortic endothelium to a secretory phenotype. The results show that high-caloric saturated fat intake induced diabetes in hamsters, probably linked to delayed insulin secretion. The model was also associated with the development of a range of pathologies characteristic to human diabetes, including nephropathy and defects in vasculature. Thus, high-fat fed hamsters provide a new model that is likely to be useful in understanding the cellular and molecular mechanisms involved in the pathogenesis of diabetes.


A novel antimicrobial peptide isolated from centipede Scolopendra subspinipes mutilans stimulates neutrophil activity through formyl peptide receptor 2.
In this study, we identified scolopendrasin X, a novel antimicrobial peptide (AMP), from centipede Scolopendra subspinipes mutilans. Scolopendrasin X strongly stimulated mouse neutrophils, resulting in intracellular calcium increase, chemotactic migration through pertussis toxin-sensitive G-protein and phospholipase C pathway, and increased superoxide anion production in neutrophils. Target receptor for scolopendrasin X, formyl peptide receptor (FPR)2 mediated scolopendrasin X-induced neutrophil activation. Moreover, scolopendrasin X significantly blocked inflammatory cytokine production induced by lipopolysaccharide in mouse neutrophils. Taken together, our results suggest that the novel AMP scolopendrasin X can be used as a material to regulate neutrophil activity through FPR2.


Purification and characterization of N-acetyl-D-galactosamine-binding lectin from Falcata japonica.
An N-acetyl-D-galactosamine-binding lectin from Falcata japonica seeds was purified by affinity column chromatography of N-acetyl-D-galactosamine coupled to epoxy-activated Sepharose 6B. A 1000-fold purification of lectin was obtained from the crude extracts. The purified lectin agglutinated blood group A red cells, but neither blood group B nor O red cells. Polyacrylamide gel electrophoresis of the lectin showed one diffuse band. Molecular weights of 125,000 and 117,000 were estimated by gel filtration and ultracentrifugal analysis, respectively. SDS-polyacrylamide gel electrophoresis of the lectin also showed a single band which has a molecular weight of 34,000. Therefore, the lectin molecule was estimated to be a tetramer composed of four identical non-covalently bound subunits. F. japonica lectin was a glycoprotein containing 5% total carbohydrate, and the amino acid composition was characterized by a high content of aspartic acid, serine and glycine, a low content of methionine and the absence of cysteine.


Group I metabotropic glutamate receptors modulate late phase long-term potentiation in hippocampal CA1 pyramidal neurons: comparison of apical and basal dendrites.
The hippocampal long-term potentiation (LTP) at Schaffer collateral synapses onto CA1 pyramidal neurons has been widely studied as a cellular model of activity-dependent enhancement of synaptic transmission. The apical (stratum radiatum) and basal dendrites (stratum oriens) of hippocampal CA1 pyramidal neurons differ in LTP induction and maintenance. Here, the role of mGlu receptors in the induction and maintenance of late-LTP was investigated, in comparison of these two compartments. My results show that mGlu1 receptor modulates late-LTP in apical dendrites and basal dendrites, whereas mGlu5 receptor modulates late-LTP only in apical dendrites.


CT scan and gas encephalography in diagnosis of arachnoid cyst and epidermoid cyst of Galen's cistern.
The CAT scan is insufficient to make the differential diagnosis between an arachnoid cyst and an epidermoid cyst in the cistern of Galen. Gas encephalography is necessary. This procedure reveals arachnoid cysts of the commmunicating type, but is insufficient in distinguishing between an epidermoid cyst and a non-communicating arachnoid cyst. In this situation, histograms of the absorption values in each section of the lesion may be helpful for the diagnosis.


Appropriate use of antifungals: impact of an antifungal stewardship program on the clinical outcome of candidaemia in a French University Hospital.
The objective of this study was to compare clinical outcomes of patients with candidaemia before and after implementation of an antifungal stewardship program (AFSP). This study included all consecutive cases of candidaemia identified from January 2012 to December 2015 in a French University Hospital. Data were collected retrospectively for a period of 2 years before implementation of the AFSP, and prospectively for 2 years after. All cases were reviewed by a multidisciplinary panel of experts including infectiologists, a microbiologist and pharmacists to have a complete follow-up of patients. 33 and 37 patients were finally included in the first and second period, respectively. The sites of entry of the candidaemia cases studied were as follows: intraabdominal in 29 cases (41.4%), central venous catheter 21 (30.0%), other or unknown: 20 (28.6%). Infectiologist consultations increased from 36.4 to 86.5% between the two periods with a significative impact on daily blood cultures which were more frequently performed in the second period (p = 0.04), and the use of echinocandins which was more frequent in the second period (97.1% of cases vs 78.8%, p = 0.03). The 3-month mortality rate declined from 36.4% in the first period to 27.0% in the second period (p = 0.4). Despite the insufficient number of candidaemia cases and the presence of other unmodifiable risk factors of mortality which did not allow us to show a significant effect on the 3-month mortality, AFSP had a significant effect on daily blood cultures and echinocandin use as first-line therapy.


The oral management of patients who have received radiotherapy to the head and neck region.
Several thousand patients are diagnosed annually with head and neck cancer (HANC) in the United Kingdom. This represents a significant proportion of all cancers that are diagnosed and a common treatment modality for this is radiotherapy to the head and neck region. Radiotherapy can be highly successful in managing HANC but also has several side-effects in the oral cavity and associated structures. These sequelae present considerable short and long-term problems for dental professionals involved in the care of HANC suffers.


Iliac Fossa Muscle Splitting Incision in Laparoscopic Donor Nephrectomy: A comparison With the Suprapubic Approach.
To compare the outcomes of a transverse suprapubic incision with peritoneal access through the midline (SPM) and an iliac fossa muscle splitting (IFMS) incision for kidney retrieval during laparoscopic donor nephrectomy (LDN). This observational retrospective comparative cohort study was performed using data from a prospectively maintained database to compare the outcomes of 2 different incisions (SPM n = 35 and IFMS n = 35) used for kidney retrieval during LDN. All incisions were infiltrated with local anesthesia at the time of closure. The primary outcome measure was postoperative analgesic requirements. Secondary outcome measures included donor complication rates and recipient outcomes. Selection bias was minimized by the study of 2 consecutive series of donors. Overall, 28 of the 70 (40%) of the total cohort were male. There was no difference between age (IFMS 49 ± 12 vs SPM 49 ± 11 years, P = .317), body mass index (IFMS 26.5 ± 3.9 vs SPM 25.9 ± 3.3 kg/m2, P = .493), and total postoperative opioid analgesic requirements (IFMS 213 ± 168 vs SPM 211 ± 168 mg, P = .807) between the 2 groups. The volume of local anesthetic infiltrated during wound closure was higher in the IFMS 0.470 ± 0.160 vs SPM 0.370 ± 0.234 mL/kg (P = .030) and associated with a reduction in postoperative opioid requirements (r = -0.511, P = .002). There were no major donor or recipient postoperative complications in either group and no difference in renal allograft function at 3-, 6-, 9-, or 12 months post-transplant. An iliac fossa muscle splitting incision is a straightforward and safe approach, providing a reasonable alternative to the more traditional and widely used suprapubic incision for kidney retrieval during LDN.


Management of Buccal Screw Access Hole Positioning for Implant Fixed Complete Dentures: A Report of Two Patients and a Proposed Decision Tree.
The present report demonstrated the use of two methods to correct the positioning of buccal screw access holes in both implant- and abutment-level implant-supported fixed complete dentures in two patients. The report suggests that nonaxially tightened abutments (in this report, dynamic abutments), angled multi-unit abutments, and the use of a milled framework with individual crowns aid in masking buccal screw access holes while maintaining the benefits of a screw-retained design. A decision tree is also proposed to facilitate the workflow when faced with such clinical scenarios.


Investigation of momentary negative symptoms in patients with early psychosis in daily life: An experience sampling study.
Negative symptoms are a key therapeutic target in promoting functional recovery in early psychosis intervention, but momentary negative symptom manifestations remain understudied in the early stage of illness. We employed an experience-sampling methodology (ESM) to evaluate momentary affective experiences, hedonic capacity for an event recalled, current activities and social interactions, and associated appraisals for 6 consecutive days in 33 clinically-stable early psychosis patients (within 3 years of treatment for first-episode psychosis) and 35 demographically-matched healthy controls. Adjusted multilevel linear-mixed models revealed higher intensity and variability of negative affect in patients than controls, but no group difference in affect instability as well as positive affect intensity and variability. Patients demonstrated no significantly greater anhedonia for event, activity or social interactions relative to controls. Higher preference for company (when alone) and to be alone (when in company) was observed in patients than controls. No significant group difference in pleasantness to be alone or proportion of time being alone. Our results indicate no evidence for blunting of affective experiences, anhedonia (social and non-social) and asociality in early psychosis. Future research complementing ESM with multiple digital phenotyping measures will facilitate more refined negative symptom assessment in the daily life of patients with early psychosis.


Compatibility and aerosol characteristics of beclomethasone mixed with N-acetylcysteine.
Mixing different kind inhalation medications for simultaneous inhalation is widely used in the treatment of chronic respiratory diseases, and it can minimize the administration time and improve patient adherence. To our knowledge, it is unclear whether beclomethasone (BDP, Clenil®) can bemixed with acetylcysteine (NAC, Fluimucil®), because the in vitro physico-chemical compatibility and aerosol characteristics of the mixture are unknown. In this study, we investigated physical compatibility, including the appearance, pH, osmotic pressure and chemical stability, as well as aerosol characteristics, including particle size corresponding to 10%/50%/90% of the cumulative percentage of total particle volume (X10/X50/X90), volume median droplet diameter (VMD), mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD) and geometric standard deviation (GSD), delivery rate, and total delivery of the above solutions. After mixing, there were no significant changes in visual appearance, pH, osmolality and drug content of the mixtures at room temperature for 12 h. The FDP of BDP in the mixture decreased by 16.49%, whereas the NAC increased by 10.85%. The delivery rates of BDP and NAC in the mixture decreased by 66.05% and 45.54%, and total delivery increased by 13.20% and 25.29%, respectively. However, the MMAD, FPF, particle size and GSD of the mixture were almost unchanged. We demonstrated that these admixtures are physico-chemically compatible but that coadministration of beclomethasone with acetylcysteine can markedly affect output and aerosol characteristics.


Vocal cord paralysis after transcatheter coil embolization of patent ductus arteriosus.
In patients with patent ductus arteriosus (PDA) after Gianturco coil embolization, vocal cord paralysis (VCP) had not been previously described. This study investigates the risk factors of coil embolization associated with VCP. We reviewed the medical records of all patients who had undergone transcatheter closure of PDA with a Gianturco coil between March 1998 and May 2001, and 75 patients (age range, 6 months to 55 years; mean age, 5.5 years) were identified. The procedure was performed with local anesthesia and with sedation in some young children. No patient required general anesthesia or endotracheal intubation. Three of the 75 patients had hoarseness caused by VCP after coil embolization. Patients with VCP had a longer ductus length (P <.01) and a smaller ductus diameter (P <.01) than patients without VCP. The pathogenesis of VCP may be caused by tense stretching and angulation of the ductus arteriosus induced by the implanted coil, which leads to compression injury of the adjacent left recurrent laryngeal nerve. A long ductus length (> or =12 mm) and a small ductus diameter (<1 mm) are significant risk factors of VCP after coil embolization in children <1 year of age. We recommend that coil embolization be performed very carefully in patients with PDA.


Selective embolization of vascular complications following renal biopsy of the transplant kidney.
The incidence of postbiopsy vascular lesions of the transplanted kidney is unknown. The complications of these lesions should be promptly recognized and treatment initiated when indicated. We have found transplant angiography and selective arterial embolization to be a safe and effective modality.


The functional role of cardiac activity in perception and action.
SKORA, L.I., J.J.A. LIVERMORE and K. Roelofs. The functional role of cardiac activity in perception and action. NEUROSCI BIOBEHAV REV X(X) XXX-XXX, 2022. Patterns of cardiac activity continuously vary with environmental demands, accelerating or decelerating depending on circumstances. Simultaneously, cardiac cycle affects a host of higher-order processes, where systolic baroreceptor activation largely impairs processing. However, a unified functional perspective on the role of cardiac signal in perception and action has been lacking. Here, we combine the existing strands of literature and use threat-, anticipation-, and error-related cardiac deceleration to show that deceleration is an adaptive mechanism dynamically attenuating the baroreceptor signal associated with each heartbeat to minimise its impact on exteroceptive processing. This mechanism allows to enhance attention afforded to external signal and prepare an appropriate course of action. Conversely, acceleration is associated with a reduced need to attend externally, enhanced action tendencies and behavioural readjustment. This novel account demonstrates that dynamic adjustments in heart rate serve the purpose of regulating the level of precision afforded to internal versus external evidence in order to optimise perception and action. This highlights that the importance of cardiac signal in adaptive behaviour lies in its dynamic regulation.


Studies on the human spontaneous electromyelogram (EMycloG). I. Normal subjects.
Using an intrathecal recording technique, the spontaneous electrical activity (EMyeloG) of the spinal cord was recorded in 25 normal human subjects. Very fast, continuous, irregular activity was analysed from the lumbo-sacral or cervical enlargement of the spinal cord after excluding volume-conducted potentials such as ECG and EMG. It was demonstrated that these spontaneous action potentials could be divided into two basic groups: (a) negative-positive diphasic waves, and (b) positive monophasic or positive-negative diphasic waves. Both waves were less than 50 microV and shorter than 10 msec. Their discharge rates were irregular, changing from time to time and from case to case. It is proposed that these spontaneous EMyeloGs recorded from normal human subjects are similar to those of 'background activity' described in the cat. Therefore they may share the same origin.


High nutrient-use efficiency during early seedling growth in diverse Grevillea species (Proteaceae).
Several hypotheses have been proposed to explain the rich floristic diversity in regions characterised by nutrient-impoverished soils; however, none of these hypotheses have been able to explain the rapid diversification over a relatively short evolutionary time period of Grevillea, an Australian plant genus with 452 recognised species/subspecies and only 11 million years of evolutionary history. Here, we hypothesise that the apparent evolutionary success of Grevillea might have been triggered by the highly efficient use of key nutrients. The nutrient content in the seeds and nutrient-use efficiency during early seedling growth of 12 species of Grevillea were compared with those of 24 species of Hakea, a closely related genus. Compared with Hakea, the Grevillea species achieved similar growth rates (root and shoot length) during the early stages of seedling growth but contained only approximately half of the seed nutrient content. We conclude that the high nutrient-use efficiency observed in Grevillea might have provided a selective advantage in nutrient-poor ecosystems during evolution and that this property likely contributed to the evolutionary success in Grevillea.


Correction: Effects of Verapamil SR and Atenolol on 24-Hour Blood Pressure and Heart Rate in Hypertension Patients with Coronary Artery Disease: An International Verapamil SR-Trandolapril Ambulatory Monitoring Substudy.
[This corrects the article DOI: 10.1371/journal.pone.0122726.].


Asthma-chronic obstructive pulmonary disease overlap syndrome.
Overlap of asthma and chronic obstructive lung disease (ACO) in patients with obstructive lung disease is growing in recognition, though there is no consistent agreement on the diagnostic criteria for the disease process. Patients with ACO have distinct clinical characteristics and trajectories, which are representative of a heterogenous, multifactorial, and incompletely understood inflammatory pathophysiology. Current treatment strategies are focused on titration of inhaled therapies such as long-acting bronchodilators, with increasing interest in the use of targeted biologic therapies aimed at the underlying inflammatory mechanisms. Future directions for research will focus on elucidating the varied inflammatory signatures leading to ACO, the development of consistent diagnostic criteria and biomarkers of disease, and improving the clinical management with an eye toward targeted therapies.


Hybrid nanoscale inorganic cages.
Cage structures exhibit inherent high symmetry and beauty, and both naturally occurring and synthetic molecular-scale cages have been discovered. Their characteristic high surface area and voids have led to their use as catalysts and catalyst supports, filtration media and gas storage materials. Nanometre-scale cage structures have also been synthesized, notably noble-metal cube-shaped cages prepared by galvanic displacement with promising applications in drug delivery and catalysis. Further functionality for nanostructures in general is provided by the concept of hybrid nanoparticles combining two disparate materials on the same system to achieve synergistic properties stemming from unusual material combinations. We report the integration of the two powerful concepts of cages and hybrid nanoparticles. A previously unknown edge growth mechanism has led to a new type of cage-structured hybrid metal-semiconductor nanoparticle; a ruthenium cage was grown selectively on the edges of a faceted copper(I) sulphide nanocrystal, contrary to the more commonly observed facet and island growth modes of other hybrids. The cage motif was extended by exploiting the open frame to achieve empty cages and cages containing other semiconductors. Such previously unknown nano-inorganic cage structures with variable cores and metal frames manifest new chemical, optical and electronic properties and demonstrate possibilities for uses in electrocatalysis.


Rheumatoid Vasculitis Presenting with Incidental Renal Infarcts: Case Report and Literature Review.
Rheumatoid vasculitis is a rare and late complication of rheumatoid arthritis, affecting small to medium sized vessels. Inflammation in the vessel wall produces an occlusive vasculopathy with downstream infarction. We present the case of a 70-year-old female with long standing stable RA status post recent COVID-19 vaccination admitted with community acquired Legionnaires disease found to have an incidental renal infarct on chest imaging without a clear etiology. She improved from a respiratory standpoint but then had a fever spike with repeat imaging showing a second renal infarct and CT angiography showing extensive beading with aneurysmal dilation in the bilateral hepatic and renal arteries consistent with vasculitis. Given extensive RA history, there was a high index of suspicion for rheumatoid vasculitis and she was treated with pulse steroids followed by Rituximab with tapering of steroids and clinical recovery. Her presentation is unique given the salient features, extensive multi-vessel disease without localizing symptoms and potential role of Legionella infection or COVID-19 vaccine in immune activation.


Technological properties of Lactococcus lactis subsp. lactis bv. diacetylactis obtained from dairy and non-dairy niches.
Lactococcus lactis subsp. lactis bv. diacetylactis strains are often used as starter cultures by the dairy industry due to their production of acetoin and diacetyl, important substances that add buttery flavor notes in dairy products. Twenty-three L. lactis subsp. lactis isolates were obtained from dairy products (milk and cheese) and dairy farms (silage), identified at a biovar level, fingerprinted by rep-PCR and characterized for some technological features. Fifteen isolates presented molecular and phenotypical (diacetyl and citrate) characteristics coherent with L. lactis subsp. lactis bv. diacetylactis and rep-PCR allowed the identification of 12 distinct profiles (minimum similarity of 90%). Based on technological features, only two isolates were not able to coagulate skim milk and 10 were able to produce proteases. All isolates were able to acidify skim milk: two isolates, in special, presented high acidifying ability due to their ability in reducing more than two pH units after 24 h. All isolates were also able to grow at different NaCl concentrations (0 to 10%, w/v), and isolates obtained from peanut and grass silages presented the highest NaCl tolerance (10%, w/v). These results indicate that the L. lactis subsp. lactis bv. diacetylactis isolates presented interesting technological features for potential application in fermented foods production. Despite presenting promising technological features, the isolates must be assessed according to their safety before being considered as starter cultures.


Experiences with telemedicine among family medicine residents at king saud university medical city during the COVID-19 pandemic: a cross-sectional study.
The healthcare system experienced various challenges during the coronavirus disease 2019 (COVID-19) pandemic, and a wide range of safety measures were implemented, including limiting the number of patients allowed to visit primary care clinics and follow-up through telemedicine clinics. These changes have accelerated the growth of telemedicine in medical education and affected the training of family medicine residents throughout Saudi Arabia. Therefore, this study aimed to evaluate the experiences of family medicine residents with telemedicine clinics as a part of their clinical training during the COVID-19 pandemic. A cross-sectional study was conducted with 60 family medicine residents at King Saud University Medical City, Riyadh, Saudi Arabia. An anonymous 20-item survey was administered between March and April 2022. The participants included 30 junior and 30 senior residents, with a 100% response rate. The results revealed that most (71.7%) participants preferred in-person visits during residency training, and only 10% preferred telemedicine. In addition, 76.7% of the residents accepted the inclusion of telemedicine clinics in training if such clinics constituted not more than 25% of the training program. Moreover, most participants reported receiving less clinical experience, less supervision, and less discussion time with the attending supervisor when training in telemedicine clinics compared with in-person visits. However, most (68.3%) participants gained communication skills through telemedicine. Implementing telemedicine in residency training can create various challenges in education and influence clinical training through less experience and less clinical interaction with patients if it is not structured well. With the growth of digital healthcare, further structuring and testing of a paradigm that involves using telemedicine in residents' training programs prior to implementation should be considered for better training and patient care.


Whole Genome Amplification of Labeled Viable Single Cells Suited for Array-Comparative Genomic Hybridization.
Understanding details of a complex biological system makes it necessary to dismantle it down to its components. Immunostaining techniques allow identification of several distinct cell types thereby giving an inside view of intercellular heterogeneity. Often staining reveals that the most remarkable cells are the rarest. To further characterize the target cells on a molecular level, single cell techniques are necessary. Here, we describe the immunostaining, micromanipulation, and whole genome amplification of single cells for the purpose of genomic characterization. First, we exemplify the preparation of cell suspensions from cultured cells as well as the isolation of peripheral mononucleated cells from blood. The target cell population is then subjected to immunostaining. After cytocentrifugation target cells are isolated by micromanipulation and forwarded to whole genome amplification. For whole genome amplification, we use GenomePlex(®) technology allowing downstream genomic analysis such as array-comparative genomic hybridization.


Rat-bite fever complicated by vertebral osteomyelitis: A case report.
Rat-bite fever (RBF) is a challenging diagnosis transmitted by the bite of the rats. We present the first reported case of RBF complicated by vertebral osteomyelitis. It is important to consider performing the MRI to differentiate vertebral osteomyelitis from simple back pain to determine the appropriate duration of antibiotic therapy.


Local perfusion of mCPP into ventromedial hypothalamic nucleus, but not into lateral hypothalamic area and frontal cortex, inhibits food intake in rats.
The serotonergic (5-hydroxytryptamine, 5-HT) system is extensively implicated in feeding behavior. In recent years, 5-HT receptors have been classified into 14 subtypes, and activation of 5-HT1B and 5-HT2C receptors inhibits food intake in rats. However, the precise functions in local brain areas of these receptor subtypes are unclear. Frontal cortex (FC), lateral hypothalamic area (LH), or ventromedial hypothalamic nucleus (VMH) are involved in control of feeding behavior. We investigated the effects of 5-HT1B and 5-HT2C receptor stimulations in the three local brain areas on feeding behavior and on 5-HT metabolism. We perfused mCPP, 5-HT(1B/2C) agonist, at multiple doses via a microdialysis probe into the three local brain areas and observed food intake. Extracellular concentrations of 5-HT and 5-HIAA were measured simultaneously. Perfusion of 1 mM mCPP into VMH, but not into LH nor FC at any dose, induced significant reduction of food intake compared with control. The extracellular concentrations of 5-HT were markedly increased in all three areas, but the concentrations of 5-HIAA were not changed by mCPP perfusions. These results indicate that the effects of 5-HT1B or 5-HT2C receptor activation on feeding behaviors depended on the brain regions, and that 5-HT1B or 5-HT2C receptors in VMH, but not in FC or in LH, play important roles in the regulation of food intake. The results also suggested that mCPP acts not only as a 5-HT(1B/2C) agonist, but also as a 5-HT releaser or as a re-uptake inhibitor. Further studies using antagonists should be conducted.


Nasal molding: a cultural practice causing respiratory distress in a term infant.
A case of respiratory distress secondary to the cultural practice of "nasal molding" is reported. Nasal molding should be included as an entity causing nasal obstruction without choanal atresia. Furthermore, this report underscores the role of interpreters in provision of health care.


Production, Purification, and Titration of First-Generation Adenovirus Vectors.
Vectors based on human adenovirus are highly efficient tools for transient genetic modifications of cells or tissues in vitro and in vivo. They can be utilized for gene addition strategies, knockdown strategies and as transfer vectors for designer nucleases and CRISPR/Cas. They are characterized by high genomic stability and can be produced to high titers. This chapter describes the method how to produce, purify and titrate adenovirus vectors based on human adenovirus type 5.


A method to mitigate spatio-temporally varying task-correlated motion artifacts from overt-speech fMRI paradigms in aphasia.
Quantifying accurate functional magnetic resonance imaging (fMRI) activation maps can be dampened by spatio-temporally varying task-correlated motion (TCM) artifacts in certain task paradigms (e.g., overt speech). Such real-world tasks are relevant to characterize longitudinal brain reorganization poststroke, and removal of TCM artifacts is vital for improved clinical interpretation and translation. In this study, we developed a novel independent component analysis (ICA)-based approach to denoise spatio-temporally varying TCM artifacts in 14 persons with aphasia who participated in an overt language fMRI paradigm. We compared the new methodology with other existing approaches such as "standard" volume registration, nonselective motion correction ICA packages (i.e., AROMA), and combining the novel approach with AROMA. Results show that the proposed methodology outperforms other approaches in removing TCM-related false positive activity (i.e., improved detectability power) with high spatial specificity. The proposed method was also effective in maintaining a balance between removal of TCM-related trial-by-trial variability and signal retention. Finally, we show that the TCM artifact is related to clinical metrics, such as speech fluency and aphasia severity, and the implication of TCM denoising on such relationship is also discussed. Overall, our work suggests that routine bulkhead motion based denoising packages cannot effectively account for spatio-temporally varying TCM. Further, the proposed TCM denoising approach requires a one-time front-end effort to hand label and train the classifiers that can be cost-effectively utilized to denoise large clinical data sets.


Urinary ascites without hydronephrosis in a neonate with urethral atresia.
Urethral atresia is a rare and usually fatal cause of prenatal bladder outlet obstruction. We present a case of urethral atresia with urinary ascites to highlight the difficulties in making the diagnosis in the absence of hydronephrosis. We also discuss possible reasons why this patient maintained normal renal and pulmonary function.


Aneuploidy involving chromosome 1 in failed-fertilized human oocytes is unrelated to maternal age.
To study whether maternal meiotic errors in failed-fertilized oocytes involving chromosome 1 occur at frequencies similar to those involving other autosomes, and whether their frequency is affected by maternal age. Using fluorescence in situ hybridization (FISH), frequencies of aneusomy and chromatid pre-division involving chromosomes 1, 16, 18, and 21 were determined for 273 failed-fertilized oocytes. The aneuploidy rate for chromosome 1 was 15.8%, and was neither age-dependent nor significantly different from that for chromosomes 16, 18 or 21. Only chromosome 16 exhibited an age-dependent increase in aneusomy rates. The frequency of chromatid pre-division was lower for chromosome 1 than for chromosome 18 (11.9% vs. 25.4%; p = 0.01), but not different from that for chromosomes 16 or 21. Aneuploidy involving chromosome 1 in failed-fertilized oocytes is unrelated to maternal age and occurs at a frequency similar to that for chromosomes 16, 18, and 21.


Quantum computing classical physics.
In the past decade, quantum algorithms have been found which outperform the best classical solutions known for certain classical problems as well as the best classical methods known for simulation of certain quantum systems. This suggests that they may also speed up the simulation of some classical systems. I describe one class of discrete quantum algorithms which do so--quantum lattice-gas automata--and show how to implement them efficiently on standard quantum computers.


Persistence of uranium groundwater plumes: contrasting mechanisms at two DOE sites in the groundwater-river interaction zone.
We examine subsurface uranium (U) plumes at two U.S. Department of Energy sites that are located near large river systems and are influenced by groundwater-river hydrologic interaction. Following surface excavation of contaminated materials, both sites were projected to naturally flush remnant uranium contamination to levels below regulatory limits (e.g., 30 μg/L or 0.126 μmol/L; U.S. EPA drinking water standard), with 10 years projected for the Hanford 300 Area (Columbia River) and 12 years for the Rifle site (Colorado River). The rate of observed uranium decrease was much lower than expected at both sites. While uncertainty remains, a comparison of current understanding suggests that the two sites have common, but also different mechanisms controlling plume persistence. At the Hanford 300 A, the persistent source is adsorbed U(VI) in the vadose zone that is released to the aquifer during spring water table excursions. The release of U(VI) from the vadose zone and its transport within the oxic, coarse-textured aquifer sediments is dominated by kinetically-limited surface complexation. Modeling implies that annual plume discharge volumes to the Columbia River are small (<one pore volume). At the Rifle site, slow oxidation of naturally reduced, contaminant U(IV) in the saturated zone and a continuous influx of U(VI) from natural, up-gradient sources influence plume persistence. Rate-limited mass transfer and surface complexation also control U(VI) migration velocity in the sub-oxic Rifle groundwater. Flux of U(VI) from the vadose zone at the Rifle site may be locally important, but it is not the dominant process that sustains the plume. A wide range in microbiologic functional diversity exists at both sites. Strains of Geobacter and other metal reducing bacteria are present at low natural abundance that are capable of enzymatic U(VI) reduction in localized zones of accumulated detrital organic carbon or after organic carbon amendment. Major differences between the sites include the geochemical nature of residual, contaminant U; the rates of current kinetic processes (both biotic and abiotic) influencing U(VI) solid-liquid distribution; the presence of detrital organic matter and the resulting spatial heterogeneity in microbially-driven redox properties; and the magnitude of groundwater hydrologic dynamics controlled by river-stage fluctuations, geologic structures, and aquifer hydraulic properties. The comparative analysis of these sites provides important guidance to the characterization, understanding, modeling, and remediation of groundwater contaminant plumes influenced by surface water interaction that are common world-wide.


Magnetic fields increase cell survival by inhibiting apoptosis via modulation of Ca2+ influx.
Static magnetic fields with intensities starting from 6 gauss (6x10(-4) tesla, T) were found to decrease in an intensity-dependent fashion, reaching a plateau at 6 x 10(-3) T, the extent of cell death by apoptosis induced by several agents in different human cell systems. This is not due to a change in the mode of cell death (i.e., to necrosis) or to a delay of the process itself; rather, the presence of magnetic fields allows the indefinite survival and replication of the cells hit by apoptogenic agents. The protective effect was found to be mediated by the ability of the fields to enhance Ca2+ influx from the extracellular medium; accordingly, it was limited to those cell systems where Ca2+ influx was shown to have an antiapoptotic effect. Magnetic fields thus might interfere with human health by altering/restoring the equilibrium between cell death and proliferation; indeed, the rescue of damaged cells may be the mechanism explaining why magnetic fields that are not mutagenic per se are often able to increase mutation and tumor frequencies.


Safe sex norm questionnaire for female sex workers: development and validation study in Iran.
The aim of the present study was to develop and validate a safe sex norm questionnaire as an appropriate instrument which would be adaptable to the female sex worker (FSW) population. A mixed method study. Appropriate content was prepared through a literature review. Content validation indices were assessed using interviews with content experts and lay experts. A conservative approach was used to assess the inter-rater agreement among the participants about the instrument relevance and clarity. The scale content validity index was computed using the average method. Non-parametric Mokken scale analysis was used for assessing scalability and unidimensionality of the questionnaire in a sample of 170 FSWs in Tehran. To evaluate the reliability and internal consistency of the questionnaire intra-class correlation and Cronbach's alpha were employed. A list of 34 items was finalized, with subscales for actual behavioral norms and for perceived norms. The relevance of the actual and perceived norms subscales in the final questionnaire was higher than 96%; clarity of the subtests was 99% and higher. The comprehensiveness of the actual and perceived norms subscales was 85% for both. Mokken scale analysis showed that the two subscales were distinct constructs, and all items are good indicators for the constructs. Our findings support that the safe sex norm questionnaire is a valid and reliable measure that would be useful to harm reduction programs and help effective HIV prevention among female sex workers.


Secukinumab for the treatment of generalized pustular psoriasis: A case report.
Generalized pustular psoriasis (GPP) is a rare subtype of psoriasis that manifests as a generalized pustular eruption. A 31-year-old female was admitted to the hospital in June 2021 with a widespread erythematous, itchy, and scaly rash for a week. The patient has a 10-year history of psoriasis vulgaris. GPP complicated by a late-stage viral infection and early-stage renal damage. Weekly subcutaneous injections of 300 mg of secukinumab for a month, followed by monthly (every 4 weeks) injections of 300 mg of secukinumab for 20 weeks. The symptoms of pustules and erythema were reduced, and the patient reported pain relief soon after the first injection. The patient had no serious adverse reactions during treatment and follow-up. Secukinumab might be an optional treatment strategy for GPP.


Bis(2-amino-3,5-di-chloro-pyridinium) hexa-chlorido-stannate(IV) dihydrate.
The title hybrid compound, (C5H5N2Cl2)2[SnCl6]·2H2O, was synthesized and its structure was identified by single-crystal X-ray diffraction. The structure is non-polymeric (0D) in terms of containing isolated [SnCl6]2- polyhedra. The special position (0,0,0) of the SnIV atom in the crystal structure gives rise to a stacking structure with alternating cationic and anionic layers parallel to (001). The water mol-ecules are inter-calated between these layers, which are linked by cation-anion hydrogen bonds and dominant non-covalent inter-actions. The stability of the three-dimensional network for this compound is also discussed.


Varicella-zoster virus-specific cell-mediated immunity in subjects with herpes zoster.
Though cell-mediated immunity (CMI) against varicella-zoster virus (VZV) is critical for prevention of the onset of herpes zoster (HZ), clinicians currently lack a simplified procedure to monitor CMI. We have recently developed an assay, called the IFN-γ release assay, and showed that it is a simple and reliable method to determine VZV-specific CMI. In the present study, we applied an IR assay to measure the VZV-specific CMI of patients with HZ. VZV-specific CMI levels were significantly high at the onset of the disease, but were decreased several weeks later. In contrast, CMI VZV-specific antibody titers increased in convalescent phase compared to those in acute phase. Thus, this technology is likely to be very useful in monitoring ongoing VZV-specific immune status.


Fructose-sensitive thermal transition behaviour of boronic ester-bearing telechelic poly(2-isopropyl-2-oxazoline).
Boronic ester-bearing telechelic poly(2-isopropyl-2-oxazoline) (B-PiPrOx-B) exhibited a hydrophilic-hydrophobic phase transition near human-body temperature in aqueous media. The thermal transition temperature of B-PiPrOx-B changed notably upon addition of fructose.


Assessing the relative incidence of mitochondrial DNA A3243G in migraine without aura with maternal inheritance.
To determine whether patients with migraine without aura with maternal "inheritance" are affected by a monosymptomatic form of the MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) or carry the most common mitochondrial DNA (mtDNA) mutation associated with MELAS, namely the A3243G transition in the transfer RNA (tRNA)Leu(UUR) gene. The association between migraine and abnormal mitochondrial function has been suggested on clinical, biochemical, and neuroradiological grounds. Migraine attacks with vomiting and cerebral infarctions, most often in the posterior cerebral regions, which are reminiscent of complicated migraine, are typical features of MELAS. The observation that migrainous patients have affected mothers more often than affected fathers suggests a possible role for maternally transmitted genetic factors. We studied 25 patients with migraine with aura whose mothers were also affected. A sensitive polymerase chain reaction restriction fragment length polymorphism analysis was used to detect mutated genomes. We failed to detect the MELAS mutation, but migraine may still be associated with point mutations of mtDNA other than A3243G or with as-yet-unidentified nuclear DNA factors related to mitochondrial function.