The difficult journey to treatment for women suffering from heavy menstrual bleeding: a multi-national survey.
Up to 30% of women of reproductive age experience HMB, which has a substantial impact on their quality of life. A clinical care pathway for women with HMB is an unmet need, but its development requires better understanding of the factors that characterise current diagnosis and management of the condition. This observational, survey-based study assessed the burden, personal experiences, and path through clinical management of women with HMB in Canada, the USA, Brazil, France and Russia using a detailed, semi-structured online questionnaire. After excluding those reporting relevant organic pathology, responses to the questionnaire from 200 women per country were analysed. Around 75% of women with HMB had actively sought information about heavy periods, mostly through internet research. The mean time from first symptoms until seeking help was 2.9 (Standard deviation, 3.1) years. However, 40% of women had not seen a health care professional about the condition. Furthermore, 54% had never been diagnosed or treated. Only 20% had been diagnosed and received appropriate treatment. Treatment was successful in 69% of those patients currently receiving treatment. Oral contraceptives were the treatment most commonly prescribed for HMB, although the highly effective levonorgestrel-intrauterine system was used by only a small proportion of women. This study provides insight into the typical journey of a woman with HMB which may help patients and health care professionals improve the path to diagnosis and treatment, although further research with long-term outcomes is needed.


The adenosine triphosphate-pyrophosphate isotopic exchange reaction: a tool for determination of tryptophan.
Quantitative determination of tryptophan at the picomole level is described, using the ATP-[32P]PPi isotopic exchange reaction catalyzed by tryptophanyl-tRNA synthetase. Sensitivity limits of 500 fmol were obtained. The presence of other amino acids at a 1000-fold excess over tryptophan did not interfere significantly with the quantitative determination of tryptophan. The specificity of the reaction was checked using five tryptophan analogs. These analogs did not prevent the determination of tryptophan when present in the same concentration range as tryptophan. When sensitive determination of a single amino acid is needed, the ATP-[32P]PPi exchange reaction catalyzed by aminoacyl-tRNA synthetases is suggested as a general method and as an alternative to HPLC procedures.


Hemoglobin conversion to hemichrome under the influence of fatty acids.
The effect of free fatty acids on the process of hemoglobin conversion and lipid peroxidation has been studied in model systems and erythrocytes. It has been found that methemoglobin and oxyhemoglobin are converted to the low spin oxidized form, namely, reversible hemichrome under the action of fatty acids. In the case of oxyhemoglobin, an increase in the level of active oxygen forms is observed in the system which initiates the formation of primary and secondary lipid peroxidation products. Incubation of erythrocytes with free fatty acids causes the formation of Heinz bodies and is accompanied by an increase of the lipid peroxidation level.


Mammography Diagnostic Reference Levels (DRLs) in Ghana.
Diagnostic Reference Levels (DRLs) are essential for optimisation in mammography. A local DRL for screen-film mammography has been established in Ghana but none exists for the digital mammography systems. Furthermore, technological advancement is phasing out the use of screen-film mammography and replacing it with digital mammography systems. This study aims to establish the local DRLs used in digital mammography across three institutions in Ghana to guide mammography practice. Average glandular dose (AGD), compressed breast thickness (CBT), age of patients, entrance surface exposure (ESE), kVp, and mAs were retrospectively extracted from three digital mammography systems. The 75th and 95th percentile values were obtained for the AGD of each mammography projection and at CBT of 60 ± 5 mm. The correlation between the AGD and CBT, kVp, mAs, and ESE were investigated. The 75th percentile for the AGD at CBT of 60 ± 5 mm for Centres 1, 2, 3, and all centres were 2.3, 1.8, 2.1, and 2.0 mGy respectively. The DRLs obtained were comparably higher than international studies except those of the United Kingdom. The AGD showed a strong positive correlation with the CBT, kVp, mAs, and ESE. There was variability in the AGD applied across the three centres for the craniocaudal (CC) and mediolateral oblique (MLO) projections. The mean AGD, mAs, and ESE for all the three centres and per centre recorded were higher than previous studies, but the mean kVp and CBT were lower than previous studies. The higher DRLs estimated in this preliminary study indicates that there is a need for dose optimisation in digital mammography practice in Ghana to improve radiation protection. The findings will guide the process of optimisation and limit the variations in the radiation dose during mammography practice.


Finely Tuned Molecular Packing Realized by a New Rhodanine-Based Acceptor Enabling Excellent Additive-Free Small- and Large-Area Organic Photovoltaic Devices Approaching 19 and 12.20% Efficiencies.
A new nonfullerene acceptor (NFA), BTA-ERh, was synthesized and integrated into a PM6:Y7:PC71BM ternary system to regulate the blend film morphology for enhanced device performance. Due to BTA-ERh's good miscibility with host active blend films, an optimized film morphology was obtained with appropriate phase separation and fine-tuning of film crystallinity, which ultimately resulted in efficient exciton dissociation, charge transport, lower recombination loss, and decreased trap-state density. The resulting additive-free quaternary devices achieved a remarkable efficiency of 18.90%, with a high voltage, fill factor, and current density of 0.87 V, 76.32%, and 28.60 mA cm-2, respectively. By adding less of a new small molecule with high crystallinity, the favorable nanomorphology shape of blend films containing NFAs might be adjusted. Consequently, this strategy can enhance photovoltaic device performance for cutting-edge NFA-based organic solar cells (OSCs). In contrast, the additive-free OSCs exhibited good operational stability. More importantly, large-area modules with the quaternary device showed a remarkable efficiency of 12.20%, with an area as high as 55 cm2 (substrate size, 100 cm2) in an air atmosphere via D-bar coating. These results highlight the enormous research potential for a multicomponent strategy for future additive-free OSC applications.


A multicenter analysis of treatment patterns and clinical outcomes of subsequent therapies after progression on palbociclib in HR+/HER2- metastatic breast cancer.
Endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) are standard treatment options for hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). However, the efficacy of standard subsequent therapies after CDK4/6i-based treatment is unclear. This study aimed to examine physician practice patterns and treatment outcomes of subsequent therapies administered after progression on palbociclib therapy in clinical practice. The study included 200 patients with HR+/HER2- MBC who underwent subsequent treatments after progressing on palbociclib-based regimens in five Chinese institutions between August 2017 and April 2020. The treatment pattern, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were reported. A total of 200 patients were included, of whom 147 (73.5%) and 53 (26.5%) received subsequent chemotherapy and endocrine therapy, respectively. The frequently used monochemotherapy regimens were taxane (n = 29), capecitabine (n = 21), and vinorelbine (n = 17), while the endocrine therapy regimens were chidamide plus exemestane (n = 16) and everolimus plus exemestane (n = 9). The overall median PFS (mPFS) was 5.5 months, with no significant difference in mPFS between the chemotherapy and endocrine therapy groups (p = 0.669). However, among patients not sensitive to prior palbociclib treatment, those administered chemotherapy had significantly longer PFS than those administered endocrine therapy (p = 0.006). The mPFS with endocrine therapy after first-, second-, and subsequent-line palbociclib was 13.4, 3.1, and 4.1 months, respectively (p = 0.233); in contrast, the mPFS with chemotherapy was 7.2, 6.5, and 4.9 months after first-, second-, and subsequent-line palbociclib, respectively (p = 0.364). The median OS was not achieved. The ORR was 10.6% among the 198 patients included in the analysis. Physicians prefer chemotherapy over endocrine therapy for the treatment of patients with HR+/HER2- MBC who develop progression on palbociclib. Sensitivity to previous palbociclib treatment might be one of the indicators for predicting response to subsequent treatment.ClinicalTrials.gov identifier: NCT04517318.


The Influence of Face Gaze by Physicians on Patient Trust: an Observational Study.
Physicians' gaze towards their patients may affect patients' trust in them. This is especially relevant considering recent developments, including the increasing use of Electronic Health Records, which affect physicians' gaze behavior. Moreover, socially anxious patients' trust in particular may be affected by the gaze of the physician. We aimed to evaluate if physicians' gaze towards the face of their patient influenced patient trust and to assess if this relation was stronger for socially anxious patients. We furthermore explored the relation between physicians' gaze and patients' perception of physician empathy and patients' distress. This was an observational study using eye-tracking glasses and questionnaires. One hundred patients and 16 residents, who had not met before, participated at an internal medicine out-patient clinic. Physicians wore eye-tracking glasses during medical consultations to assess their gaze towards patients' faces. Questionnaires were used to assess patient outcomes. Multilevel analyses were conducted to assess the relation between physicians' relative face gaze time and trust, while correcting for patient background characteristics, and including social anxiety as a moderator. Analyses were then repeated with perceived empathy and distress as outcomes. More face gaze towards patients was associated with lower trust, after correction for gender, age, education level, presence of caregivers, and social anxiety (β=-0.17, P=0.048). There was no moderation effect of social anxiety nor a relation between face gaze and perceived empathy or distress. These results challenge the notion that more physician gaze is by definition beneficial for the physician-patient relationship. For example, the extent of conversation about emotional issues might explain our findings, where more emotional talk could be associated with more intense gazing and feelings of discomfort in the patient. To better understand the relation between physician gaze and patient outcomes, future studies should assess bidirectional face gaze during consultations.


Genetic analysis of litchi (Litchi chinensis Sonn.) in southern China by improved random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR).
Litchi (Litchi chinensis Sonn., L. chinensis), a type of tree growing in most areas of southern China, produces an edible fruit that is also a source of traditional medicine. Genetic identification of litchi species or cultivars using molecular markers is very important. In this study, a total of six litchi samples from Fujian, Hainan, Guangdong, Guangxi and Sichuan province, as well as one wild Dimocarpus confinis (D. confinis) sample from Guangxi province were collected for genetic analysis. The cluster dendrograms were constructed for genetic analysis on the basis of DNA amplification results by RAPD and ISSR. The improved RAPD amplified DNA with consistent and clear banding patterns. A total of 176 bands were found, indicating a 72.7 % polymorphism in L. chinensis DNA samples. Significant genetic distances were found among the different species or cultivars, with an index of similarity coefficient ranging from 0.59 to 0.87. Similar to RAPD results, ISSR analysis of the L. chinensis DNA samples showed a range of 0.70-0.93 similarity coefficients. The genetic distance between Hainan sample and Sichuan samples was the farthest, which is consistent with their geographic distance. Furthermore, the index of similarity coefficient between D. confinis and L. chinensis was 0.35-0.41 by RAPD and 0.38-0.48 by ISSR, indicating that these two species have significant genetic difference. This study reveals the high level of genetic differences between different litchi species or cultivars, and confirms the significance of the improved RAPD method in genetic characterization of organisms. Taken together, the improved RAPD combined with ISSR analysis can be used frequently for the genetic diversity, germplasm resources preservation, molecular-assisted breeding, and genetic characterization of various organisms.


Effects of fatigue on teams and their role in 24/7 operations.
In 24/7 operations, fatigue from extended work hours and shift work is ubiquitous. Fatigue is a significant threat to performance, productivity, safety, and well-being, and strategies for managing fatigue are an important area of research. At the level of individuals, the effects of fatigue on performance are relatively well understood, and countermeasures are widely available. At the level of organizations, the effects of fatigue are also relatively well understood, and organizational approaches to fatigue risk management are increasingly well documented. However, in most organizational settings, individuals work in teams, and teams are the building blocks of the organizational enterprise. Yet, little is known about the effects of fatigue on team functioning. Here we discuss the effects of fatigue at the levels of individuals, teams, and organizations, and how the consequences of fatigue cross these levels to impact overall productivity and safety. Furthermore, we describe the pivotal role of teams in understanding the adverse organizational effects of fatigue in 24/7 operations and argue that teams may be leveraged to mitigate these effects. Systematic investigation of the effects of fatigue on teams is a promising avenue toward advances in fatigue risk management and provide some ideas for how this may be approached.


Smooth pursuit eye movements and schizophrenia: literature review.
To review the scientific literature about the relationship between impairment on smooth pursuit eye movements and schizophrenia. Narrative review that includes historical articles, reports about basic and clinical investigation, systematic reviews, and meta-analysis on the topic. Up to 80% of schizophrenic patients have impairment of smooth pursuit eye movements. Despite the diversity of test protocols, 65% of patients and controls are correctly classified by their overall performance during this pursuit. The smooth pursuit eye movements depend on the ability to anticipate the target's velocity and the visual feedback, as well as on learning and attention. The neuroanatomy implicated in smooth pursuit overlaps to some extent with certain frontal cortex zones associated with some clinical and neuropsychological characteristics of the schizophrenia, therefore some specific components of smooth pursuit anomalies could serve as biomarkers of the disease. Due to their sedative effect, antipsychotics have a deleterious effect on smooth pursuit eye movements, thus these movements cannot be used to evaluate the efficacy of the currently available treatments. Standardized evaluation of smooth pursuit eye movements on schizophrenia will allow to use specific aspects of that pursuit as biomarkers for the study of its genetics, psychopathology, or neuropsychology.


Gut microbiota in Immunoglobulin A Nephropathy: a Malaysian Perspective.
The alteration of the gut microbiome in the gut-kidney axis has been associated with a pro-inflammatory state and chronic kidney disease (CKD). A small-scaled Italian study has shown an association between the gut microbiome and Immunoglobulin A Nephropathy (IgAN). However, there is no data on gut microbiota in IgAN in the Asian population. This study compares the gut microbial abundance and diversity between healthy volunteers and Malaysian IgAN cohort. A comparative cross-sectional study was conducted involving biopsy-proven IgAN patients in clinical remission with matched controls in a Malaysian tertiary centre. Demographic data, routine blood and urine results were recorded. Stool samples were collected and their DNA was extracted by 16S rRNA gene sequencing to profile their gut microbiota. Thirty-six IgAN patients (13 male; 23 female) with the mean age of 45.5 ± 13.4 years and median estimated glomerular filtration rate (eGFR) of 79.0 (62.1-92.2) mls/min/1.73m2 with median remission of 7 years were analysed and compared with 12 healthy controls (4 male; 8 female) with the mean age of 46.5 ± 13.5 years and eGFR of 86.5 (74.2-93.7) mls/min/1.73m2. Other demographic and laboratory parameters such as gender, ethnicity, body mass index (BMI), haemoglobin, serum urea and serum albumin were comparable between the two groups. There were no significant differences seen in the Operational Taxonomic Unit (OTU) and alpha diversity (Shannon index) between IgAN and healthy controls. Alpha diversity increased with increasing CKD stage (p = 0.025). Firmicutes/Bacteroidetes (F/B) ratio was low in both IgAN and healthy cohort. Fusobacteria phylum was significantly increased (p = 0.005) whereas Euryarchaoeota phylum was reduced (p = 0.016) in the IgAN group as compared to the control cohort. Although we found no differences in OTU and alpha diversity between IgAN in remission and control cohort, there were some differences between the two groups at phylum level.


A randomized controlled trial of a soft double lumen embryo transfer catheter versus a firm single lumen catheter: significant improvements in pregnancy rates.
Embryo transfer has changed little since originally described in 1978. Clinicians rate the type of catheter used as the third most important variable in embryo transfer, but there are no adequately powered randomized trials. We compared the clinical pregnancy rates with the single lumen catheter (TCC) and the double lumen catheter (CC) in a randomized single blind trial. A total of 650 cycles of women from the Adelaide University reproductive medicine units in Australia were included in this trial. Patients were <40 years of age undertaking IVF and embryo transfer. Exclusion criteria were: known uterine abnormality, day 3 FSH >10 IU/l, previous difficult embryo transfer and pre-implantation genetic diagnosis. Cycles were randomized from numbered sealed envelopes immediately prior to embryo transfer with stratification for fresh or frozen cycles. There was a significantly higher pregnancy rate in the group treated with the CC compared with the TCC catheter [29.6 versus 20.5% per embryo transfer, odds ratio (OR) = 1.63 (95% confidence interval: 1.14-2.30), P = 0.0076]. The point estimate for the OR was similar for fresh and frozen cycles. The pregnancy rate was increased by 50% and this justifies the increased cost of the soft double lumen catheter and the training of clinical staff required.


Integrative and replicative transformation of Penicillium canescens with a heterologous nitrate-reductase gene.
A wild isolate of Penicillium canescens was subjected to mutagenesis, and 150 chlorate-resistant mutants were isolated and classified in respect of their ability to utilize various nitrogen sources. Strains supposedly deficient in nitrate reductase have been transformed with the nitrate-reductase gene from Aspergillus niger. Transformation probably occurred by non-homologous integration of the transforming vector into the chromosome. Co-transformation with the AMA 1 replicating element from A. nidulans enhanced transformation frequency up to 2000-fold, and was shown to result in autonomous maintenance of replicating concatenates, one of which was re-isolated by transformation of E. coli.


Proliferating cell nuclear antigen (PCNA) immunoreactivity and development of the pineal complex and habenula of the sea lamprey.
The development of the pineal complex and the habenula of the sea lamprey was studied with proliferating cell nuclear antigen (PCNA) immunocytochemistry. The pineal organ and the habenula primordia appeared in late embryos, and neuron differentiation began in prolarvae, as indicated by the presence of PCNA-negative cells. The parapineal primordium could not be distinguished until early prolarval stages, and cell differentiation was delayed to the larval period. Although the number of cycling (PCNA-immunoreactive) cells gradually decreased during the larval period in the three organs studied, their patterns of differentiation were different. We conclude that the unusual developmental pattern observed is related with the complex life cycle of lampreys.


The combined effect of Raspberry Ketone with Resveratrol against oxidative stress and steatohepatitis in rats: Pharmacokinetic and pharmacodynamic studies.
Raspberry Ketone (RK) and Resveratrol (RSV) are natural phenolic antioxidants and anti-inflammatory agents. However, its combined pharmacokinetic and pharmacodynamics potentials are not reported. The study aims to assess the combined effect of RK with RSV to protect rats from carbon-tetrachloride (CCl4) induced oxidative stress and NASH. The toxicant CCl4 was employed at a concentration of 1 mL/kg as a 1:1 (v/v) mixture with olive oil twice weekly for 6 weeks to induce liver toxicity. Animal treatment was followed for 2 weeks. Silymarin was used as a standard control drug to compare the hepatoprotective effect of RK and RSV. Hepatic histology, oxidative stress, MMP, reduced glutathione (GSH), plasma levels of SGOT, SGPT, and lipid profile (total cholesterol and triglycerides) were measured. Anti-inflammation genes (IL-10), and fibrotic genes (TGF-β) were also examined in liver tissue. Oral administration of combined RK with RSV (50 + 50 mg/kg for 2 weeks) showed significantly more hepatoprotection by significantly decreasing elevated plasma markers and lipid profile than alone RK and RSV (100 mg/kg daily for 2 weeks). It also significantly alleviated the hepatic lipid peroxidation, restoring the activities of GSH levels in the liver. RT-PCR and Immunoblotting studies confirmed that significantly upregulation of anti-inflammation genes and protein expression (MMP-9) ameliorated the disease. Pharmacokinetic studies confirmed more synergistic stability in simulated gastric-intestinal fluids (FaSSGF, FaSSIF) and rat liver microsomes (CYP-450, NADPH oxidation & glucuronidation. Moreover, coadministration of drugs augmented the relative bioavailability, Vd/ F (L/Kg), and MRT0-∞( h), which leads to more efficacy. This pharmacokinetic and pharmacodynamic reveals a new adjuvant therapy for the treatment of steatohepatitis.


A novel three base-pair LGI1 deletion leading to loss of function in a family with autosomal dominant lateral temporal epilepsy and migraine-like episodes.
Mutations in LGI1 have been reported in several families with autosomal dominant lateral temporal epilepsy. In a family in which three patients also experienced migraine-like episodes we found a novel three base-pair deletion (c.377_379delACA), resulting in the deletion of an asparagine residue in the second leucine-rich repeat. Functional studies showed that the mutated protein was not secreted when transfected in COS cells, consistent with a causative role in the disease.


The effect of induced metabolic acidosis on vitamin D3 metabolism in rachitic chicks.
The metabolism of vitamin D3 was studied in 3-week-old, vitamin D deficient chicks, fed since hatching with a diet containing 3% ammonium chloride, 1% calcium, and 0.7% phosphorus. When kidney homogenates were incubated in vitro with [3H]25-(OH)D3, the production of 1,25-(OH)2D3 was reduced by 40% in acidotic birds. During in vivo experiments, after injection of [3H]D3 (1220 pM/bird), the level of 1,25-(OH)2D3 was also reduced in blood plasma, intestine, and tibiae in acidotic chicks as compared with the controls. As a large increase in plasma phosphate was found during acidosis, these results are discussed in relation to the possible role of phosphorus in the control of 1,25-(OH)2D3 synthesis.


High-Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry Method for the Identification and Quantification of Lipids in Liposomes.
Liposomes are spherical, closed vesicles consisting of at least one lipid bilayer with a water chamber and are widely used to encapsulate bioactive molecules. Lipid membranes, composed of different types of lipids or lipophilic components, determine whether liposomes can achieve the desired purpose and determine the overall quality of liposomes. Thus, the quantification of lipid components and encapsulated molecules is essential to characterize and control the quality of liposomes. Moreover, multicomponent simultaneous determination is the preferred method for lipid component analysis in liposomes. Therefore, the present work describes an analytical methodology for the simultaneous determination of commonly used lipids in liposome formulations, using h igh-performance liquid chromatography coupled with a tandem mass spectrometry (MS) detector (HPLC-MS/MS). HPLC-MS/MS consists of a rapid and highly efficient chromatographic separation of the liposomal components with a C18 column and the subsequent detection of the ingredients through an MS detector, along with an accurate mass fragmentation pattern. The analytical process mainly includes lipid extraction, solution preparation, the optimization of chromatographic conditions, and method validation. We hope this analytical methodology is valuable and efficient and can be applied to the analysis of multiple types of lipids in liposomes, such as raw material quality analysis, formulation study, overall quality control, etc.


Droplet-Based Microfluidic High-Throughput Screening of Enzyme Mutant Libraries Secreted by Yarrowia lipolytica.
Yarrowia lipolytica has emerged as an attractive solution for screening enzyme activities thanks to the numerous tools available for heterologous protein production and its strong secretory ability. Nowadays, activity screening for improved enzymes mostly relies on the evaluation of independent clones in microtiter plates. However, even with highly robotized screening facilities, the relatively low throughput and high cost of the technology do not enable the screening of large diversities, which significantly reduce the probability of isolating improved variants. Droplet-based microfluidics is an emerging technology that allows the high-throughput and individual picoliter droplets manipulation and sorting based on enzymatic substrate fluorescence. This technology is an attractive alternative to microtiter plate screenings with higher throughputs and drastic reduction of working volume and cost.Here, we present a droplet-based microfluidic platform for the screening of libraries expressed in the yeast Y. lipolytica, from the generation of a random mutagenesis library of a heterologous enzyme and its expression in Y. lipolytica to the droplet-based microfluidic procedures composed of cell encapsulation and growth and activity screening or sorting of improved clones.


microRNA-129 overexpression in endothelial cell-derived extracellular vesicle influences inflammatory response caused by myocardial ischemia/reperfusion injury.
Extracellular vesicles (EVs) have the potency to function as modulators in the process of myocardial ischemia/reperfusion (I/R) injury. This investigation was performed to decipher the mechanism of human umbilical vascular endothelial cells (HUVECs)-derived EVs in myocardial I/R injury with the involvement of microRNA-129 (miR-129). HUVECs-secreted EVs were collected and identified. An I/R mouse model was developed, and cardiomyocytes were used for vitro oxygen-glucose deprivation/reperfusion model establishment. Differentially expressed miRNAs in myocardial tissues after EV treatment were assessed using microarray analysis. The target relationship between miR-129 and toll-like receptor 4 (TLR4) was identified using a dual-luciferase assay. Gain- and loss-function studies regarding miR-129 were implemented to figure out its roles in myocardial I/R injury. Meanwhile, the activation of the nuclear factor-kappa-binding (NF-κB) p65 signaling and NOD-like receptor 3 (NLRP3) inflammasome was evaluated. EVs diminished the apoptosis of cardiomyocytes and the secretion of inflammatory factors, and all these trends were reversed by miR-129 reduction. miR-129 bound to the 3'-untranslated region of TLR4 directly. The NF-κB p65 signaling and NLRP3 inflammasome were abnormally activated after I/R injury, whose impairment after EVs was partially restored by miR-129 downregulation. This study illustrated that EVs could carry miR-129 to mitigate myocardial I/R injury via downregulating TLR4 and disrupting the NF-κB signaling and NLRP3 inflammasome.


Why chaotic mixing of particles is inevitable in the deep lung.
Fine/ultrafine particles can easily reach the pulmonary acinus, where gas is exchanged, but they need to mix with alveolar residual air to land on the septal surface. Classical fluid mechanics theory excludes flow-induced mixing mechanisms because of the low Reynolds number nature of the acinar flow. For more than a decade, we have been challenging this classical view, proposing the idea that chaotic mixing is a potent mechanism in determining the transport of inhaled particles in the pulmonary acinus. We have demonstrated this in numerical simulations, experimental studies in both physical models and in animals, and mathematical modeling. However, the mathematical theory that describes chaotic mixing in small airways and alveoli is highly complex; it not readily accessible by non-mathematicians. The purpose of this paper is to make the basic mechanisms that operate in acinar chaotic mixing more accessible, by translating the key mathematical ideas into physics-oriented language. The key to understanding chaotic mixing is to identify two types of frequency in the system, each of which is induced by a different mechanism. The way in which their interplay creates chaos is explained with instructive illustrations but without any equations. We also explain why self-similarity occurs in the alveolar system and was indeed observed as a fractal pattern deep in rat lungs (Proc. Natl. Acad. Sci. USA. 99:10173-10178, 2002).


A computer-assisted emergency department chart audit.
We present a method for a microcomputer-assisted emergency department daily chart audit using a spreadsheet format. Computer technology allows the extraction of a large amount of information from audit data with a minimum of clerical time. The software automatically tabulates, sorts, and updates audit data, and depicts physician performance in a quantitative manner. The software is able to generate a variety of graphics that visually depict physician and departmental performance. The spreadsheet model is flexible, and can be adapted to the needs of various emergency departments or quality assurance activities. The audit has a rapid turnaround time, with charts audited and returned to physicians for feedback within 24 hours of the patient being discharged. Individual physician confidentiality is maintained throughout.


Diagnosis and treatment of pediatric vallecular cysts and pseudocysts.
To review the experience at a children's hospital diagnosing and treating vallecular cysts. To determine if cyst type, operative mode, or ages are risk factor(s) for recurrence. Chart review of eleven children with vallecular cysts and pseudocysts from 1997 to 2009. The most common presenting symptoms were stridor (8/12, 67%), respiratory distress (7/12, 58%), and feeding difficulties (4/12, 33%). Symptoms of gastroesophageal reflux disease were present in 67% of patients and 17% carried a concurrent diagnosis of laryngomalacia. Eleven of twelve patients required operative intervention, the majority of which were transoral endoscopic procedures. Three patients (3/11, 27%) had recurrences. Two of these patients required only a second procedure, but one patient required multiple procedures. Fifty percent (2/4) of the patients 2 years or older experienced a recurrence, whereas only 14% (1/7) of the patients less than 2 years old had a recurrence, a difference which was not statistically significant (p=0.49). Pseudocysts tended to recur more frequently than vallecular cysts. (p=0.13). Surgical approach (marsupialization versus total excision) did not affect recurrence rate. One patient with a small, asymptomatic cyst was observed and continues to be symptom-free. There were no surgical complications. Vallecular cysts and pseudocysts are rare congenital lesions of the upper aerodigestive tract. Vallecular pseudocysts tended to recur more than vallecular cysts in our series. Surgery is the treatment of choice for symptomatic patients; smaller cysts may be followed closely.


Effect of ursodeoxycholic acid on biochemical parameters, hepatocyte proliferation and liver histology in galactosamine hepatitis in the rat.
The effect of oral administration of ursodeoxycholic acid (UDCA) on biochemical parameters, liver histology and liver cell proliferation was investigated in rats with galactosamine hepatitis. Treatment with UDCA led to a decrease of aminotransferases, but did not show any significant changes in liver histology or liver cell proliferation. The improvement of liver enzymes without change of histology in this animal model of hepatitis following treatment with UDCA is in agreement with results obtained from clinical trials with UDCA in patients with chronic viral hepatitis.


Fetal cardiac and extracardiac flows preceding intrauterine death.
Extracardiac and cardiac flow velocity waveforms were recorded in a severely growth-retarded fetus 1 day and a few hours before fetal death. At the first scan, the typical Doppler patterns of a growth-retarded fetus were found, but the brain-sparing effect was lost at the last examination and a huge tricuspid insufficiency was demonstrated.


Covalent linkage of lipoprotein to peptidoglycan is not essential for outer membrane stability in Proteus mirabilis.
Isolated rigis layers from Proteus mirabilis harvested at different growth phases were degraded by endo-N-acetylmuramidase from Chalaropsis B, and the degradation products were investigated. The results show the complete absence of covalently linked lipoprotein in exponential-phase cultures. Stationary cells, however, possess covalently linked lipoprotein in amounts similar to those found in Escherichia coli or Salmonella typhimurium during all growth phases. The overall peptidoglycan structure did not change during transition from logarithmic to stationary growth. Implications of these findings for the organization of the outer membrane are discussed.


Finite element analysis of a ram brain during impact under wet and dry horn conditions.
In this study, ram impacts at 5.5 m/s are simulated through finite element analysis in order to study the mechanical response of the brain. A calibrated internal state variable inelastic constitutive model was implemented into the finite element code to capture the brain behavior. Also, constitutive models for the horns were calibrated to experimental data from dry and wet horn keratin at low and high strain rates. By investigating responses in the different keratin material states that occur in nature, the bounds of the ram brain response are quantified. An acceleration as high as 607 g's was observed, which is an order of magnitude higher than predicted brain injury threshold values. In the most extreme case, the maximum tensile pressure and maximum shear strains in the ram brain were 245 kPa and 0.28, respectively. Because the rams do not appear to sustain injury, these impacts could give insight to the threshold limits of mechanical loading that can be applied to the brain. Following this motivation, the brain injury metric values found in this research could serve as true injury metrics for human head impacts.


Federal and state cooperation necessary but not sufficient for effective regional mental health systems: insights from systems modelling and simulation.
For more than a decade, suicide rates in Australia have shown no improvement despite significant investment in reforms to support regionally driven initiatives. Further recommended reforms by the Productivity Commission call for Federal and State and Territory Government funding for mental health to be pooled and new Regional Commissioning Authorities established to take responsibility for efficient and effective allocation of 'taxpayer money.' This study explores the sufficiency of this recommendation in preventing ongoing policy resistance. A system dynamics model of pathways between psychological distress, the mental health care system, suicidal behaviour and their drivers was developed, tested, and validated for a large, geographically diverse region of New South Wales; the Hunter New England and Central Coast Primary Health Network (PHN). Multi-objective optimisation was used to explore potential discordance in the best-performing programs and initiatives (simulated from 2021 to 2031) across mental health outcomes between the two state-governed Local Health Districts (LHDs) and the federally governed PHN. Impacts on suicide deaths, mental health-related emergency department presentations, and service disengagement were explored. A combination of family psychoeducation, post-attempt aftercare, and safety planning, and social connectedness programs minimises the number of suicides across the PHN and in the Hunter New England LHD (13.5% reduction; 95% interval, 12.3-14.9%), and performs well in the Central Coast LHD (14.8% reduction, 13.5-16.3%), suggesting that aligned strategic decision making between the PHN and LHDs would deliver substantial impacts on suicide. Results also highlighted a marked trade-off between minimising suicide deaths versus minimising service disengagement. This is explained in part by the additional demand placed on services of intensive suicide prevention programs leading to increases in service disengagement as wait times for specialist community based mental health services and dissatisfaction with quality of care increases. Competing priorities between the PHN and LHDs (each seeking to optimise the different outcomes they are responsible for) can undermine the optimal impact of investments for suicide prevention. Systems modelling provides essential regional decision analysis infrastructure to facilitate coordinated federal and state investments for optimal impacts.


Transcatheter arterial chemoembolization (TACE) or embolization (TAE) for symptomatic bone metastases as a palliative treatment.
This study was designed to evaluate the effect of transcatheter arterial chemoembolization (TACE)/embolization (TAE) for symptomatic bone metastases especially in palliation. Between April 2006 and December 2009, 24 bone metastatic lesions of 18 patients (8 women and 10 men; mean age, 64 years) underwent palliative TACE or TAE. A total of 40 sessions were performed, with 1-4 sessions per lesion. The primary lesions included hepatocellular carcinoma, colorectal cancer, renal cell cancer, ovarian cancer, thyroid cancer, uterine cervical cancer, and esophageal cancer. Symptomatic lesions involved thoracic spine, lumbar spine, pelvis, rib, and femur. The procedures were performed with a coaxial catheter technique to catheterize selectively target arteries. If not possible due to small branches, blood flow alteration by coil was achieved. Gelatin sponge was the initial embolic materials. As anti-cancer agents, epirubicin, fluorouracil, and mitomycin were mainly used in consideration for primary lesion and past treatment. Sufficient devascularization of targeted lesions was obtained in 18 of 24 (75%) lesions without any serious complication. Pain relief was obtained in 20 lesions (83%), with significantly decrease in the visual analogue scale score (P < 0.001). A relationship was found between the devascularization grade and pain relief (r = 0.49, P < 0.05). Follow-up CT images at 1 month of nine lesions (50%) revealed necrotic change in the tumors. Palliative TACE/TAE for symptomatic bone metastases could be a suitable treatment method because it is minimally invasive, repeatable, effective, and rapid-acting.


Antibacterial Collagen Composite Membranes Containing Minocycline.
Collagen membranes have been used as bioresorbable barrier membranes in guided tissue/bone regeneration. However, the collagen membranes currently used in clinics lack an active antibacterial function, although infection at surgical sites presents a realistic challenge for guided tissue/bone regeneration. In this study, we successfully prepared novel and advanced collagen composite membranes from collagen and complexes of heparin and chelates of minocycline and Ca2+ ions. These membranes were characterized for chemical structures, morphology, elemental compositions and tensile strength. In vitro release studies were conducted to evaluate the release kinetics of minocycline from these membranes. Agar disk diffusion assays were used to assess their sustained antibacterial capability against model pathogenic bacteria Staphylococcus aureus. The chemical and physical characterization confirmed the successful synthesis of minocycline-loaded collagen composite membranes, namely NCCM-1 and NCCM-2. Both membranes had weaker tensile strength as compared with commercial collagen membranes. They achieved sustained release of minocycline for at least 4 weeks in simulated body fluid (pH 7.4) at 37°C. Moreover, both membranes demonstrated potent sustained antibacterial effects against Staphylococcus aureus. These results suggested that the advanced collagen composite membranes containing minocycline can be exploited as novel guided tissue regeneration membranes or wound dressing by providing additional antibacterial functions.


Temporary changes of visual outcomes and anterior chamber parameters after phacoemulsification and low-add-power segmented intraocular lens implantation for primary angle closure disease.
To evaluate the temporary changes in visual outcomes and anterior segment parameters after cataract surgery plus low-add bifocal intraocular lens (IOL) implantation for primary angle closure disease (PACD). This retrospective comparative case-control study included two groups: low-add-power segmented IOL and monofocal IOL. Postoperative examination involved evaluation of uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), uncorrected intermediate visual acuity (UIVA), and spherical equivalent (SE). Anterior segment examination was performed using anterior segment optical coherence tomography. This study included 19 eyes of 11 consecutive patients who underwent cataract surgery. The low-add group had better UDVA than the monofocal group at 3 months postoperatively, better UIVA at 1 month postoperatively, better UNVA at 1 week postoperatively. In the low-add group, SE increased at 1 and 3 months postoperatively compared with 1 week postoperatively. In the monofocal group, objective SE decreased at 1 and 3 months postoperatively compared with 1 week postoperatively. In the low-add group, the anterior chamber depth (ACD) became significantly deep gradually at 1 and 3 months compared with at 1 week postoperatively. In the monofocal group, the ACD became significantly shallow gradually at 1 and 3 months than at 1 week postoperatively. The low-add-power segmented IOL achieved better far and intermediate distance visual acuity after cataract surgery in PACD patients than did the monofocal IOL. The ACD became deeper and SE showed a hyperopic shift with the low-add-power segmented IOL at 1 and 3 months after cataract surgery compared with at 1 week after cataract surgery.


Cryoextraction of orbital capillary hemangioma diagnosed by technetium-99m-labeled red blood cell scintigraphy.
The authors report a case of an infant in whom orbital capillary hemangioma was diagnosed using technetium-99m-labeled red blood cell scintigraphy. The tumor was subsequently removed by transconjunctival cryoextraction.


First appearance of type II neurons during ontogenesis in the spiral ganglion of the rat. An immunocytochemical study.
Ontogenesis of spiral ganglion in the rat was studied using antibodies to three subunits of neurofilaments (NFs): NF 68 KDa, NF 160 KDa and NF 200 KDa. The expression of immunoreactivity was examined with 3 immunocytochemical methods: indirect immunofluorescence, peroxidase-antiperoxidase and avidin-biotin complex. Aim of the study was to detect the time of differentiation of the spiral ganglion type II neurons. At 16 and 18 days of gestation, most neuron cell bodies express immunoreactivity to only two NF subunits: NF 68 and NF 160, but at birth they react with the antibodies to all 3 subunits albeit weakly. Nevertheless, a small population (about 7%) of nerve cells that strongly reacts against all 3 NF subunits emerges in the basal turn, already at 20 days of gestation. Two to 3 days after birth, the strongly stained cells are dispersed throughout the entire ganglion. The intensity of their reaction to the NF antibodies is similar to that seen in the adult animal. The strong immunoreactivity of this selective neuronal population suggest, that they correspond to the type II spiral ganglion neurons. Our results imply that the differentiation between the type I and the type II of spiral neurons in the rat occurs perinatally.


Severe Coronavirus Disease 2019 That Recovered from Respiratory Failure by Treatment That Included High-dose Intravenous Immunoglobulin.
We herein report a case of severe coronavirus disease 2019 (COVID-19) in which high-dose intravenous immunoglobulin (IVIg) treatment achieved significant clinical improvement of deterioration of pulmonary inflammation after temporary clinical improvement. In the present case, clinical and radiological deterioration occurred despite a decrease in viral load, suggesting that deterioration was caused by reactivation of proinflammatory factors, such as tumor necrosis factor-α and interleukin-6, rather than direct viral effects. IVIg treatment may provide not only immunosuppressive effects but also inhibition of proinflammatory cytokines, indicating that treatment including IVIg may be effective by inhibiting cytokine storm in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.


Enzyme immobilization by covalent bonding.
Enzyme immobilization by covalent bonding to an insoluble polymer has the supposed advantage of irreversible binding of the enzyme to the support matrix. Many of the bonds commonly employed are not 100% stable in use, however. Unless some care is taken to ensure that the enzyme can withstand the reaction conditions, substantial loss of enzyme activity will occur. Even under favorable conditions, 60% loss of activity is not uncommon.


Intuitive theories inform children's beliefs about intergroup obligation.
In addition to emerging from children's direct experiences with collaborative partners and groups, children's beliefs about obligation also arise from a process of intuitive theory-building in early childhood. On this account, it is possible for at least some of children's beliefs to emerge in the absence of specific experiences where obligations are held among fellow members of a group "we."


Newly identified thin membranous tissue in the deep infratemporal region.
Recently, the importance of deglutition has attracted attention due to its role in the prevention of aspiration pneumonia. We therefore observed the anatomy of the pharynx of 57 hemi-sections of adult Japanese cadavers (male 32 sides, female 25 sides). A previously unidentified tissue was observed in the infratemporal fossa. This unidentified tissue was a thin membranous tissue that existed between the medial pterygoid and the superior constrictor in all of the cadavers examined. The previously unknown membranous tissue consisted of collagenous and muscular fibers and was innervated mainly by a branch of the mandibular nerve.


Post-COVID seizure: A new feature of "long-COVID".
Novel coronavirus SARS-CoV-2 has created unprecedented healthcare challenges. Neurologic deficits are often an important presenting symptom. To date, the only reported post-infectious COVID-19 manifestations of neurologic disease include cognitive deficits and dysfunction of the peripheral nervous system. Here we report that seizure can also be a post-COVID-19 or "long-COVID" complication. We present a 71-year-old man with hypertension, diabetes mellitus, and COVID-19 diagnosed by RT-PCR who initially presented with posterior circulation stroke-like symptoms, which completely resolved after emergent thrombolysis. Six days later, the patient returned with seizure activity, supported by radiographic and electroencephalographic studies. Notably, he was negative for SARS-CoV-2, and no other provoking factor was uncovered after a comprehensive work-up. To our knowledge, this is the first report of post-infectious seizures after a case of COVID-19, highlighting the potential importance of monitoring for neurologic symptoms in COVID-19 patients, even after convalescence.


Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans.
The rs738409 C→G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance. The I148M mutation impedes triglyceride hydrolysis in vitro, and its carriers have an increased risk of developing severe liver disease. We explored whether the rs738409 PNPLA3 G allele influences the ability of weight loss to decrease liver fat or change insulin sensitivity. We recruited 8 subjects who were homozygous for the rs738409 PNPLA3 G allele (PNPLA3-148MM) and 10 who were homozygous for the rs738409 PNPLA3 C allele (PNPLA3-148II). To allow comparison of changes in liver fat, the groups were matched with respect to baseline age, sex, body mass index, and liver fat. The subjects were placed on a hypocaloric low-carbohydrate diet for 6 d. Liver fat content (proton magnetic resonance spectroscopy), whole-body insulin sensitivity of glucose metabolism (euglycemic clamp technique), and lipolysis ([(2)H(5)]glycerol infusion) were measured before and after the diet. At baseline, fasting serum insulin and C-peptide concentrations were significantly lower in the PNPLA3-148MM group than in the PNPLA3-148II group, as predicted by study design. Weight loss was not significantly different between groups (PNPLA3-148MM: -3.1 ± 0.5 kg; PNPLA3-148II: -3.1 ± 0.4 kg). Liver fat decreased by 45% in the PNPLA3-148MM group (P < 0.001) and by 18% in the PNPLA3-148II group (P < 0.01). Weight loss is effective in decreasing liver fat in subjects who are homozygous for the rs738409 PNPLA3 G or C allele. This trial was registered at www.hus.fi as 233775.


Recuperative thickening for sludge retention time and throughput management in anaerobic digestion with thermal hydrolysis pretreatment.
This study evaluated the application of recuperative thickening (RT) to enhance anaerobic digestion (AD) performance for AD systems with thermal hydrolysis pretreatment (THP). RT was applied for two different reasons: (a) for increasing the sludge retention time (SRT) to degrade slowly hydrolyzable materials more efficiently and (b) for maintaining SRT at decreased hydraulic retention time (HRT) thus showing potential for increased AD throughput rates. A SRT increase from 15 to 30 days by RT application did not improve AD performance or hydrolysis rates significantly as 15-day SRT was already a factor 2 higher than the estimated washout SRT. When applying RT to increase throughput rates (HRT of 7 days) while maintaining 15-day SRT, no negative impact on biogas production or hydrolysis kinetics was observed. It was estimated that RT application on THP digesters can increase digester throughput by 100% and thus show clear potential for further AD intensification. PRACTITIONER POINTS: Increased SRT from 15 to 30 days through recuperative thickening application did not improve biogas production. A lower required minimum SRT (6-7 days) was estimated in THP-AD systems compared to conventional AD. Operation at decreased HRT by RT application resulted in similar AD performance under constant organic loading rates. A 100% increase in throughput rates can be applied using RT without decreasing AD performance.


Management of stored grain pest with special reference to Callosobruchus maculatus, a major pest of cowpea: A review.
Bruchids are most pernicious pest of stored grain pulses, especially in the tropical and subtropical areas. They penetrate into the fully grown matured pods, grains in fields and also during post-harvest storage. Among bruchids, Callosobruchus maculatus is the prominent pest having ubiquitous distribution. Chemical/synthetic insecticides provides adequate control against the C. maculatus on the pulses. However, the use of synthetic insecticides induces adverse health outcomes in agricultural workers and many causes various diseases such as cancers, genomic damage, oxidative stress, neurological disorders and respiratory, metabolic and thyroid effects. Therefore, alternative effective, safe and sustainable pest control, integration of different compatible methods should be taken into considerations. One of the possible managements might be use of traditional as well modern pest management practices. Traditional techniques include sealed containers, inert materials, harvesting time, alternate host, intercropping, storing un-threshed pulses, cleanliness, vegetable oil etc. Modern techniques such as temperature, freezing and heating, radiation treatments, resistance varieties, natural control, botanical extracts, chemical and microbial, transgenic approach, cold plasma treatments etc. thus integrated pest management might be alternative approach to combat the effect of pest. Therefore, present review aims to considers various measures for the handling of bruchids with special reference to Callosobruchus maculatus and integrated molecular inventions to decrease bruchids populations and enhance pulse productivity in pulses.


A novel support vector machine ensemble model for estimation of free lime content in cement clinkers.
Free lime (f-CaO) content is a crucial quality parameter for cement clinkers in rotary cement kiln. Due to lack of hardware sensors, f-CaO content in cement clinker is mostly obtained by offline laboratory measurement, making timely control rather difficult and even impossible. In this work, a soft sensor approach named as support vector machine ensemble (ESVM) model is proposed to estimate f-CaO content. The process data employed to train and test the model were collected from a cement plant in China, covering a time span of about 30 days. The raw data were preprocessed by filters and time-series matching. The processed data were then clustered by fuzzy c-means clustering algorithm to capture process features at different operating conditions. For each individual cluster, a base SVM regressor was trained to estimate f-CaO content. Finally, an ensemble model consisting of four base SVM regressors was established to estimate f-CaO content at multifarious process conditions. The effectiveness of the proposed ESVM model was investigated by comparing it with manual measurements and other models available in literature. The results demonstrate that the proposed ESVM model achieves improvements in model accuracy as well as generalization capability. The proposed ESVM model has a broad application space in cement production process for automatic monitoring of f-CaO content.


Survival outcomes in sinonasal carcinoma with neuroendocrine differentiation: A NCDB analysis.
Sinonasal carcinoma with neuroendocrine differentiation (SCND) is a rare group of tumors with poor prognosis. Treatment and sequence of therapies are still unclear. The goal of this study is to analyze treatment outcomes in SCND using a national database. The National Cancer Database was queried for SCND from 2004 to 2014. Patient demographics, tumor characteristics and treatment paradigms were tabulated. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on overall survival (OS). A total of 415 patients were identified. Most patients were male (61.2%), with a median age of 58 years and the most common primary site was the nasal cavity (52.5%). T4 tumors were observed in 67.7% of cases. Unimodality (41.9%) and bimodality (43.9%) therapies were the most common treatment modalities. Radiation therapy was the only treatment administered in 30% of the patients, while 27.2% received definitive chemoradiation (CRT) and 11.6% had surgery with adjuvant CRT. In our Cox-PH model, age (HR = 1.04, p < 0.001), T4 (HR = 2.6, p = 0.004) and N2/N3 (HR = 2.18, p = 0.001) were associated with worse survival. Trimodality (HR = 0.49, p = 0.005) and bimodality (HR = 0.65, p = 0.009) therapies had a better OS compared to unimodality. Patients treated with definitive CRT or surgery with adjuvant CRT had a significant increase in OS (p = 0.01 and 0.002 respectively). SCND appears to be best treated using a multimodality approach with definitive CRT or surgery followed by CRT. Neoadjuvant chemotherapy could be helpful in selecting the best treatment strategy.


Conservative management of COVID-19 associated hypoxaemia.
This correspondence argues that happy hypoxaemic patients should not be intubated as long as they remain happy https://bit.ly/3csrpWO.


Ion-exchange voltammetry of dopamine at Nafion-coated glassy carbon electrodes: quantitative features of ion-exchange partition and reassessment on the oxidation mechanism of dopamine in the presence of excess ascorbic acid.
The incorporation/exclusion features of dopamine (DA), ascorbic acid (AA) and uric acid (UA) are evaluated for Nafion (NA)-coated glassy carbon electrodes (GCE) of different thicknesses. The ion-exchange partition of DA(+) between the NA film and the sodium phosphate electrolyte is evaluated by determining the partition coefficient (k(D)) and the apparent diffusion coefficient (D(app)) in thick NA films which were 401 and 1.5 x 10(-9) cm(2) s(-1), respectively. The solution diffusion coefficient was found to be 6.0 x 10(-6) cm(2) s(-1). Also, the effect of NA loading and of the voltammetric timescale on DA voltammetry in the presence of excess AA is assessed, at physiologic like conditions. It is demonstrated that, although AA is excluded at the NA coating, a catalytic regeneration of DA, induced by AA, occurs at the interface NA film/electrolyte resulting from the diffusion of the o-quinone product of DA oxidation from the electrode surface to that interface. The interference of AA in the voltammetric signal of DA is eliminated using 18 microg mm(-2) NA films and v> or =0.5 V s(-1). Therefore, fast, selective and sensitive voltammetric analysis of DA at concentrations<100 microM in the presence of excess AA, e.g., 1 mM is achieved.


Low-intensity optical bistability in an active Fabry-Perot mirror induced by input-phase-insensitive parametric downconversion.
A Fabry-Perot resonator filled with second-order nonlinear optical material is investigated. Attention is devoted to making the resonator act as a nonlinear mirror for ultralow-intensity light signals that can be switched by a control beam at the second-harmonic frequency. The interaction process is an input-phase-independent parametric downconversion. The theoretical problem is solved through implementation of a dummy variable method optimized for a parametric process. Efficient amplification and bistability of low-intensity signals have been found.


Phospholipase C epsilon scaffolds to muscle-specific A kinase anchoring protein (mAKAPbeta) and integrates multiple hypertrophic stimuli in cardiac myocytes.
To define a role for phospholipase Cε (PLCε) signaling in cardiac myocyte hypertrophic growth, PLCε protein was depleted from neonatal rat ventricular myocytes (NRVMs) using siRNA. NRVMs with PLCε depletion were stimulated with endothelin (ET-1), norepinephrine, insulin-like growth factor-1 (IGF-1), or isoproterenol and assessed for development of hypertrophy. PLCε depletion dramatically reduced hypertrophic growth and gene expression induced by all agonists tested. PLCε catalytic activity was required for hypertrophy development, yet PLCε depletion did not reduce global agonist-stimulated inositol phosphate production, suggesting a requirement for localized PLC activity. PLCε was found to be scaffolded to a muscle-specific A kinase anchoring protein (mAKAPβ) in heart and NRVMs, and mAKAPβ localizes to the nuclear envelope in NRVMs. PLCε-mAKAP interaction domains were defined and overexpressed to disrupt endogenous mAKAPβ-PLCε complexes in NRVMs, resulting in significantly reduced ET-1-dependent NRVM hypertrophy. We propose that PLCε integrates multiple upstream signaling pathways to generate local signals at the nucleus that regulate hypertrophy.


Increased visual bias in children with developmental coordination disorder: Evidence from a visual-tactile temporal order judgment task.
Previous studies have suggested that children with developmental coordination disorder (DCD) rely heavily on vision to perform movements, which may contribute to their clumsy movements. However, few studies have objectively and quantitatively investigated the perceptual biases of children with DCD. A visual-tactile temporal order judgment (TOJ) task was used to measure and compare the perceptual biases of 19 children with DCD and 19 age- and sex-matched typically developing children. The point of subjective equality, which demonstrates when "visual first" and "tactile first" judgment probabilities are equal (50%), obtained by analyzing the results of the visual-tactile TOJ task, was used as an indicator of perceptual biases. Further, variables (age and manual dexterity in all participants; motor function, autism spectrum disorder and attention-deficit hyperactivity disorder traits, and depressive symptoms in children with DCD) associated with perceptual biases were examined with correlation analysis. Children with DCD had significantly stronger visual bias than typically developing children. Overall correlation analysis showed that increased visual bias was significantly correlated with poor manual dexterity. Children with DCD had a strong visual bias, which was associated with poor manual dexterity.


Arthroscopic lift, drill, fill and fix (LDFF) is an effective treatment option for primary talar osteochondral defects.
The purpose of this study was to describe the mid-term clinical and radiological results of a novel arthroscopic fixation technique for primary osteochondral defects (OCD) of the talus, named the lift, drill, fill and fix (LDFF) technique. Twenty-seven ankles (25 patients) underwent an arthroscopic LDFF procedure for primary fixable talar OCDs. The mean follow-up was 27 months (SD 5). Pre- and post-operative clinical assessments were prospectively performed by measuring the Numeric Rating Scale (NRS) of pain in/at rest, walking and when running. Additionally, the Foot and Ankle Outcome Score (FAOS) and the Short Form-36 (SF-36) were used to assess clinical outcome. The patients were radiologically assessed by means of computed tomography (CT) scans pre-operatively and 1 year post-operatively. The mean NRS during running significantly improved from 7.8 pre-operatively to 2.9 post-operatively (p = 0.006), the NRS during walking from 5.7 to 2.0 (p < 0.001) and the NRS in rest from 2.3 to 1.2 (p = 0.015). The median FAOS at final follow-up was 86 for pain, 63 for other symptoms, 95 for activities of daily living, 70 for sport and 53 for quality of life. A pre- and post-operative score comparison was available for 16 patients, and improved significantly in most subscores. The SF-36 physical component scale significantly improved from 42.9 to 50.1. Of the CT scans at 1 year after surgery, 81% showed a flush subchondral bone plate and 92% of OCDs showed union. Arthroscopic LDFF of a fixable primary talar OCD results in excellent improvement of clinical outcomes. The radiological follow-up confirms that fusion of the fragment is feasible in 92%. This technique could be regarded as the new gold standard for the orthopedic surgeon comfortable with arthroscopic procedures. Prospective case series, therapeutic level IV.


Split-hand/feet malformation in three tamilian families and review of the reports from India.
Split-hand/foot malformation (SHFM) is a rare condition which can be either syndromic or nonsyndromic. We report three unrelated pedigrees, one with autosomal dominant (AD) inheritance and the other two with autosomal recessive (AR) pattern. We also briefly review the published reports from India.


The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis.
Autoreactive T cells are a regular component of the healthy immune system. It has been proposed that some of these autoreactive T cells even might have a protective function. Recent studies support this notion by demonstrating that: a) myelin-autoreactive T cells show neuroprotective effects in vivo, and b) activated antigen-specific human T cells and other immune cells produce bioactive brain-derived neurotrophic factor (BDNF) and other neurotrophic factors in vitro. Furthermore, BDNF is expressed in different types of inflammatory cells in brain lesions of patients with acute disseminated leukoencephalopathy or multiple sclerosis. It seems plausible that the immune cell-mediated import of BDNF and other neurotrophic factors into the central nervous system has functional consequences and implications for the therapy of multiple sclerosis and other neuroimmunological diseases.


Precursors of mitochondrial proteins are degraded in the cytosol at different rates.
The stability of rat liver mitochondrial protein precursors in the cytosol was investigated. The precursors were synthesized in a post-mitochondrial supernatant from rat liver, and mitochondria were then added at different times. The amount and pattern of proteins incorporated were determined. The precursors have different rates of transport into mitochondria. Some precursors are stable in the cytosol while most are degraded rapidly, with a half-life of about 30 min at 30 degrees C.


Modelling relative motion to facilitate intra-limb coordination.
The importance of relative motion information when modelling a novel motor skill was examined. Participants were assigned to one of four groups. Groups 1 and 2 viewed demonstrations of a skilled cricket bowler presented in either 'video' or 'point light' format. Group 3 observed a single point of light pertaining to the 'wrist' of the skilled bowler only. Participants in Group 4 did not receive a demonstration and acted as controls. During 60 acquisition trials, participants in the demonstration groups viewed a model five times before each 10-trial block. Retention was examined the following day. Intra-limb coordination was assessed for the right elbow relative to the wrist in comparison to the model. The demonstration groups showed greater concordance with the model than the control group. However, the 'wrist' group performed less like the model than the 'point light' and 'video' groups, who did not differ from each other. These effects were maintained in retention. Relative motion information aided the acquisition of intra-limb coordination, while making this information more salient (through point lights) provided no additional benefit. The motion of the model's bowling arm was replicated more closely than the non-bowling arm, suggesting that information from the end-effector is prioritized during observation for later reproduction.


Successful termination of ventricular tachycardia with intrinsic anti-tachycardia pacing.
Intrinsic anti-tachycardia pacing (iATP) is a novel automated ATP algorithm that employs post-pacing interval (PPI) to design the next ATP sequence based on an analysis of the prior failed ATP sequence. A patient with hypertrophic cardiomyopathy received an implantable cardioverter-defibrillator (ICD) (Cobalt™ XT DR, Medtronic, Minneapolis, MN, USA) following an episode of syncope due to macro-reentrant ventricular tachycardia (VT) (right bundle branch block configuration, cycle length [CL] 280 ms). The VF zone was set to VTCL <300 ms and iATP therapy was prescribed before and during capacitor charging. The iATP was initiated when VT recurred 3 months later. The first attempt with an assumption of 150 ms propagation time from the pacing site to the VT circuit (9 pulses) could not reset the VT, leaving a PPI of 650 ms. A subsequent attempt involving 20 pulses with an assumption of 250 ms propagation time terminated the VT. Failure to reach the circuit is a major cause of unsuccessful ATP. In this regard, iATP is expected to have theoretical advantages over empirical and traditional ATP therapies. To the best of our knowledge, this is the first intracardiac electrogram illustrating how automated precision ATP terminates VT in a clinical setting.


Adenotonsillectomy outcomes in obese adolescents with obstructive sleep apnea.
(1) To assess adenotonsillectomy (AT) outcomes in adolescents with obesity and with obstructive sleep apnea (OSA); (2) To identify clinical factors predicting OSA in adolescents following AT. Adolescents 12 to 18 years old with obesity who underwent AT for OSA were included. Subjects had pre-AT and post-AT polysomnogram. Nonobese adolescents with OSA that underwent AT were included as a comparison. Seventy adolescents with obesity with a mean age of 14.2 years and a mean body mass index of 38.0 kg/m2 were included. Patients in the nonobese group (n = 32) were similar demographically to the obese group, with the exception of body mass index. The majority of adolescents with obesity (74%) had severe OSA (apnea-hypopnea index [AHI] ≥ 10 events/h) with a mean baseline AHI of 33.9 events/h (standard deviation 28.5). The obese and control groups experienced clinically meaningful improvements in AHI following AT, with median change scores of 18.3 (95% confidence interval -29.2, -11.2, P < .001) and 14.6 (95% confidence interval -25.5, -8.5, P < .001), respectively. In the adolescents with obesity, 48% had an AHI < 5 events/h on postoperative PSG. However, adolescents with obesity were 7 times more likely (odds ratio = 7.1, 95% confidence interval [2.24, 22.48], P = .001) to have moderate or severe persistent OSA (AHI > 5 events/h) after AT compared with patients who were not obese. The need for post-AT positive airway pressure therapy was significantly higher in adolescents with obesity, with 37.1% of participants requiring this therapy (odds ratio = 8.3, 95% confidence interval 1.8, 37.6, P < .001). AT results in improvement in polysomnogram parameters in adolescents with obesity and OSA. However, patients with obesity are at high risk for persistent OSA. Future research should include prospective trials to compare outcomes between AT and positive airway pressure therapy for adolescents with obesity. Kearney TC, Vazifedan T, Baldassari CM. Adenotonsillectomy outcomes in obese adolescents with obstructive sleep apnea. J Clin Sleep Med. 2022;18(12):2855-2860.


Functional analysis of metal tolerance proteins isolated from Zn/Cd hyperaccumulating ecotype and non-hyperaccumulating ecotype of Sedum alfredii Hance.
The Zn/Cd hyperaccumulating ecotype (HE) of Sedum alfredii Hance can accumulate 24- and 28-fold higher leaf and stem Zn concentrations when compared with the non-hyperaccumulating ecotype (NHE) of Sedum. Heterologous expression of a metal tolerance protein (MTP1) encoding gene from HE plants (SaMTP1) or the homologous gene from NHE plants (SnMTP1) suppressed Zn(2+) hypersensitivity in the Δzrc1 yeast mutant. In plants, SaMTP1 localized to the tonoplast. Furthermore, MTP1 transcript level in the shoot of HE plants was more than 80-fold higher than that of NHE plants. The transcript level of SaMTP1 in shoot was up-regulated 1-fold by Zn(2+) while the expression of SnMTP1 was slightly inhibited. These data suggest that SaMTP1 can play an important role in Zn accumulation in HE plants.


Sleep characteristics in Brazilian children and adolescents: a population-based study.
To evaluate sleep characteristics in Brazilian children and adolescents aged 0-19 years and determine the prevalence of sleep disturbances (SDs) and their association with regional differences and socioeconomic status (SES). The target population was divided into three age groups: 0-3 years, 4-12 years, and 13-19 years. An online questionnaire based on Brazilian versions of instruments for sleep assessment was made available to participants from 2014 to 2017. Sleep habits were characterized following the recommendations of the instruments and of the National Sleep Foundation. Data were evaluated by bivariate analyses and logistic regression analyses (p ≤ 0.05). A total of 1180 respondents were included, representative of all Brazilian regions and SES levels. Inadequate bedtime habits and total sleep time below the recommended levels were observed in all age groups. Overall SD prevalence was 25.5%. Increased risk of SDs was associated with a current health problem in children aged 0-3 years, with hospitalization after birth and sleeping in parents' bed in children aged 4-12 years, and with medication use and playing video games/using the cell phone before sleep in adolescents. There was no significant difference in SD rates between the regions. There was an increased risk of SDs in children with low SES (0-3 years), lower middle SES (4-12 years), and high SES (13-19 years). Brazilian children and adolescents overall present inadequate sleep habits and sleep duration lower than recommended. SDs increased with age, reaching a peak in adolescence, with an influence of SES on these disturbances.


Relative contribution of motor impairments to limitations in activity and restrictions in participation in adults with hemiplegic cerebral palsy.
To determine which motor impairments make a significant relative contribution to upper limb activity limitations, and whether activity limitations are related to participation restrictions in people with hemiplegic cerebral palsy. An observational study. Neurological Rehabilitation Research Group at Faculty of Health Sciences, The University of Sydney. Twenty-three people with hemiplegic cerebral palsy participated. Four motor impairments (strength, coordination, spasticity and contracture), upper limb activity and participation were measured. Multiple regression was used to determine the relative contribution of motor impairments to activity limitations. Linear regression was used to determine the correlation between activity and participation. The four motor impairments accounted for 63% of the variance in upper limb activity with coordination independently accounting for 21% (P<0.01). Upper limb activity accounted for 13% of the variance in participation (P=0.10). The findings imply that coordination of four motor impairments makes the largest independent relative contribution to activity limitations, whereas upper limb activity makes less contribution to participation in people with mild and moderate hemiplegic cerebral palsy.


A three-dimensional fractional solution for air contaminants dispersal in the planetary boundary layer.
In this study, we investigated some closed-form solutions for solving atmospheric dispersion issues under variable atmospherical hypothesis, in a vertically positioned non-homogeneous planetary boundary-layer. In our context, a nonidentical expansion for the solution of the fractional advection-diffusion equation in a non-integer dimensional-space was examined. In a nutshell, a Sturm-Liouville eigenvalue problem with more reliable information concerning the initial value problem is discussed. The performance of the model was estimated by presenting numerical simulations against experimental data. Under these meteorological conditions, fractional-order models performed far better than those of the classical integer-order ones.


An Electrochemical DNA Sensing System Using Modified Nanoparticle Probes for Detecting Methicillin-Resistant Staphylococcus aureus.
We have developed a novel, highly sensitive, biosensing system for detecting methicillin-resistant Staphylococcus aureus (MRSA). The system employs gold nanoparticles (AuNPs), magnetic nanoparticles (mNPs), and an electrochemical detection method. We have designed and synthesized ferrocene- and single-stranded DNA-conjugated nanoparticles that hybridize to MRSA DNA. Hybridized complexes are easily separated by taking advantage of mNPs. A current response could be obtained through the oxidation of ferrocene on the AuNP surface when a constant potential of +250 mV vs. Ag/AgCl is applied. The enzymatic reaction of L-proline dehydrogenase provides high signal amplification. This sensing system, using a nanoparticle-modified probe, has the ability to detect 10 pM of genomic DNA from MRSA without amplification by the polymerase chain reaction. Current responses are linearly related to the amount of genomic DNA in the range of 10-166 pM. Selectivity is confirmed by demonstrating that this sensing system could distinguish MRSA from Staphylococcus aureus (SA) DNA.


Case report: treatment of superior sagittal sinus thrombosis with urokinase.
Sagittal sinus thrombosis (SSST) is a rare disease with high mortality. Definitive therapy is not known, but anticoagulation or addressing the underlying etiology have been the most often utilized approaches. We here report the second case of postpartum sagittal sinus thrombosis successfully treated with urokinase. Though there are no studies to support this therapy it may be safe and efficacious in refractory cases.


Keratitis caused by Absidia corymbifera in an immunocompetent male with no corneal injuries.
Case Report A healthy 55-years-old male went to emergency due to a white infiltrate in the left eye without corneal trauma which partially responds to antibiotic treatment. The infiltrate worsened by the use of topical steroids. Direct microscopic evaluation and Gram stain are a valuable diagnostic tool for the detection of Absidia filaments. There is a successful treatment with anphotericin and posaconazole. Discussion Keratitis caused by Zygomicetes are unusual. This is a rare condition in healthy patients with no corneal trauma. The treatment with amphotericin and posaconazole are synergistic against filamentous fungi.


Identification of occupational cancer risks in British Columbia: a population-based case-control study of 1129 cases of bladder cancer.
We collected information on lifetime occupational histories, smoking, and alcohol consumption from 15,463 incident cancer cases. Occupational risk factors for bladder cancer are presented in this report. A matched case-control design was used. All cases were diagnosed with bladder cancers, with controls being internal controls consisting of all other cancer sites, excluding lung and unknown primary. Data were analyzed using conditional logistic regression for matched sets data and the likelihood ratio test. Excess bladder cancer risks was observed in a number of occupation and industries, particularly those involving exposure to metals, including aluminum, paint and solvents, polycyclic aromatic hydrocarbons, diesel engine emissions, and textiles. The results of our study are in line with those from the literature and further suggest that exposure to silica and to electromagnetic fields may carry an increased risk of bladder cancer.


Differential protein expression in Streptococcus uberis under planktonic and biofilm growth conditions.
The bovine pathogen Streptococcus uberis was assessed for biofilm growth. The transition from planktonic to biofilm growth in strain 0140J correlated with an upregulation of several gene products that have been shown to be important for pathogenesis, including a glutamine ABC transporter (SUB1152) and a lactoferrin binding protein (gene lbp; protein SUB0145).


Synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing a cleavable moiety with anti-platelet activity.
A novel series of prodrugs consisting of dabigatran and 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) were synthesized. The pharmacological results show that all of them possess the effect of anti-platelet aggregation induced by thrombin in vitro. Moreover, one of those compounds, Y-2 (ED(50) = 2.1 ± 1.3 mg/kg) shows more potent activity for inhibiting thrombosis in vivo than that of dabigatran etexilate (ED(50) = 4.4 ± 2.2 mg/kg).


21-Gene Assay and Breast Cancer Mortality in Ductal Carcinoma In Situ.
The inability to identify individuals with ductal carcinoma in situ (DCIS) who are at risk of breast cancer (BC) mortality have hampered efforts to reduce the overtreatment of DCIS. The 21-gene recurrence score (RS) predicts distant metastases for individuals with invasive BC, but its prognostic utility in DCIS is unknown. We performed a population-based analysis of 1362 individuals of DCIS aged 75 years or younger at diagnosis treated with breast-conserving therapy. We examined the association between a high RS (defined a priori as >25) and the risk of BC mortality by using a propensity score-adjusted model accounting for the competing risk of death from other causes, testing for interactions. All statistical tests were 2-sided. With 16 years median follow-up, 36 (2.6%) died of BC, and 200 (14.7%) died of other causes. The median value of the RS was 15 (range = 0-84); 29.6% of individuals had a high RS. A high RS was associated with an 11-fold increased risk of BC mortality (hazard ratio = 11.27, 95% confidence interval [CI] = 3.00 to 42.33; P < .001) in women aged 50 years or younger at diagnosis treated with breast-conserving surgery alone, culminating in a 9.4% (95% CI = 2.3% to 22.5%) 20-year risk of BC death. For women with a high RS, treatment with radiotherapy was associated with a 71% (hazard ratio = 0.29, 95% CI = 0.10 to 0.89; P = .03) relative and a 5% absolute reduction in the 20-year cumulative risk of death from BC. The 21-gene RS predicts BC mortality in DCIS and combined with age (50 years or younger) at diagnosis can identify individuals for whom radiotherapy reduces the risk of death from BC.


[Robots in the operating room-(co)operation during surgery].
Medical robotics has the potential to improve surgical and endoluminal procedures by enabling high-precision movements and superhuman perception. To present historical, existing and future robotic assistants for surgery and to highlight their characteristics and advantages for keyhole surgery and endoscopy. In particular, historical medical robots and conventional telemanipulators are presented and compared with minimally invasive continuum robots and novel robotic concepts from practice and research. In addition, a perspective for future generations of surgical and endoluminal robots is offered. Robot-assisted medicine offers great added value for quality of intervention as well as safety for surgeons and patients. In the future, more surgical steps will be performed (semi-)autonomously and in cooperation with the experts.


Glycogen storage disease type III with hypoketosis.
A rare case of glycogen storage disease type III with unusually absent ketone body production during hypoglycemia is presented. A 10-month-old boy presented with asymptomatic hepatomegaly. GOT/GPT 2555/1160 IU/L, CK 302 IU/L, triglycerides 1223 mg/dL, cholesterol 702 mg/dL and uric acid 7.9 mg/dL. After a 9-hour fast, glucose was 27 mg/dL and adequate lipolysis without ketogenesis was observed (total/free carnitine 34.5/20 micromol/L, free fatty acids 1620 micromol/L and beta-hydroxybutyrate 172 micromol/L). Result of MCT (medium-chain triglycerides) load test: basal hydroxybutyrate 29 micromol/L rose to 5748 micromol/L. Treatment with a fat-restricted diet supplemented with formula containing MCT was initiated and the patient presented a satisfactory initial evolution. Three months later, CK were 3000 IU/L. Muscle biopsy was diagnostic of glycogenosis. Enzymatic activity in skin fibroblasts was 0% for amylo-1,6-glucosidase. The diagnosis of glycogenosis type III was established. Echocardiography performed at that time showed non-obstructive ventricular hypertrophy. Until now hypoketosis during hypoglycemia has only been described in glycogenosis type I.


Splenic and portal vein thrombosis in pancreatic metastasis from renal cell carcinoma.
Pancreatic metastases from previously treated renal cell carcinoma are uncommon. Surgical resection of pancreatic metastasis remains the only worthwhile modality of treatment. A case where pancreatic metastasis from previously resected right sided renal cell carcinoma was resected with a subtotal left pancreatectomy is described. An unusual feature was the presence of a large splenic vein tumor thrombus extending into the portal vein with associated portal hypertension. The patient underwent an uneventful portal vein resection with primary anastomosis. This is possibly the first documented case of portal vein renal tumor thrombosis in a case of isolated pancreatic metastasis from previously operated renal cell carcinoma in published world surgical literature.


Breaking the cycle--control of breathlessness in chronic lung disease.
The attacks of breathlessness experienced by patients with chronic lung disease set up a frightening cycle of lack of exercise and worsening lung function unless patients take control of their condition. Nurses can help them.


Correlation of oocyte morphometry parameters with woman's age.
Aim of this study was to evaluate morphometric parameters of metaphase II oocytes, including cytoplasm diameter (CD), zona pellucida thickness (ZPT) and width of the perivitelline space (PS), in relation with zona pellucida birefringence, spindle presence and age of the woman. Oocytes were classified into groups according to zona birefringence (low or high zona birefringence, LZB and HZB, respectively) and presence or absence of a visible spindle (SP and aSP, respectively). HZB oocytes showed a thicker zona (17.7 ± 0.3 μm) than LZB oocytes (16.7 ± 0.3 μm, p < 0.01). Moreover, PS was narrower in HZB and SP oocytes than in LZB (p < 0,001) and aSP (p < 0,05) oocytes. Finally, we found that CD and ZPT linearly decrease with age of the woman (CD r = 0.028: p < 0.01; ZPT r = 0.050: p < 0.0001). Our results evidence an association in human oocytes between zona pellucida and spindle birefringence and defined morphometric parameters and a decrease of oocyte size and ZPT as a function of women's age.


Frame count reserve.
The Doppler wire-derived (relative) coronary flow velocity reserve (CVR) that is used to evaluate functional significance of a coronary stenosis is a method performed only by interventional cardiologists. An angiographic method would be useful in the diagnostic catheterization laboratory. For this purpose, we investigated the relation between TIMI frame count reserve (FCR) and CVR. In 38 patients, (relative) FCR of left anterior descending (LAD) and left circumflex coronary artery (LCx) was calculated by using manual, synchronized contrast agent injections and compared with (relative) CVR. In addition, vessel length was measured with an intracoronary guidewire and frame count flow velocity was calculated and compared with average peak velocity. There was a strong correlation between FCR and CVR (r=0.62, P<0.001) and between relative FCR and relative CVR (r=0.84, P<0.001). The LAD was significantly longer than the LCx (mean, 14.3+/-1.6 cm versus 11.4+/-1.8 cm, P<0.001), and, therefore, TIMI frame count of LAD was significantly higher than of LCx (mean basal 32.5+/-15.1 versus 23.6+/-9.1 and hyperemic 12.1+/-6.6 versus 8.7+/-3.2, both P<0.02). However, all flow velocity measurements and estimations of volume flow were not different for LAD compared with LCx. There were also no differences between mean FCR and CVR of LAD or LCx, of both vessels compared with each other and between mean relative FCR and relative CVR. The (relative) frame count reserve can be used to estimate (relative) coronary flow velocity reserve.


New peptides with immunomodulatory activity identified from rice proteins through peptidomic and in silico analysis.
The new food-derived bio-functional peptides are urgently needed globally, but the separation and purification process for obtaining the immunopeptides from food is low efficiency and highly time-consuming. In the present study, rice proteins were extracted and identified by using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Furthermore, a strategy combining immuno-prediction and in silico simulation was used to screen for peptides showing immunomodulatory activity, including inhibition of the release of nitric oxide, tumor necrosis factor-α, and the interleukins IL-6 and IL-1β in lipopolysaccharide-induced RAW264.7 mouse macrophages. This LC-MS/MS identification and immuno-prediction method may provide insights for the potential identification of more food-derived immunopeptides.


Flow cytometric evaluation of lymphocyte transformation test based on 5-ethynyl-2'deoxyuridine incorporation as a clinical alternative to tritiated thymidine uptake measurement.
In clinical laboratories, the evaluation of lymphocyte proliferative response (lymphocyte transformation test-LTT) is routinely performed by the measurement of [(3)H]-thymidine uptake after stimulation. In this study we evaluated the performances of a recently developed non-radioactive test based on the detection by flow cytometry of 5-ethynyl-2'deoxyuridine (EdU) incorporation for the measurement of LTT in routine lab conditions. After definition of optimal protocol parameters, EdU incorporation test showed good repeatability and reproducibility. Moreover, this assay was flexible enough to fit important clinical laboratory constraints (delayed stimulation, low number of cells and delayed analysis after staining). Importantly, correlations between results obtained with EdU and [(3)H]-thymidine incorporation assays were excellent both in healthy volunteers and pediatric and septic patients. In particular, the two techniques identified patients presenting with altered LTT. Upon confirmation in a larger cohort of patients, EdU incorporation assay may be a relevant non-radioactive candidate for LLT in clinic.


Optic atrophy and macular degeneration as initial presentations of subacute sclerosing panencephalitis.
To report a case of subacute sclerosing panencephalitis in which the initial clinical presentations were optic atrophy and macular degeneration. Observational case report. A 9-year-old boy with visual loss attributable to optic atrophy and macular degeneration had a diagnostic examination. The visual acuity levels of both eyes were light perception at presentation. Fundus examination revealed bilateral optic atrophy and macular degenerative changes including retinal pigment epithelial atrophy, macular scarring, and epiretinal membrane formation. The antimeasles IgG titers were high both in serum and cerebrospinal fluid samples. Neurologic symptoms of myoclonus, ataxia, motor, and mental disabilities occurred 4 months after the onset of first visual disturbances and 2 weeks after the patient applied to our clinic. Children with optic atrophy and macular degenerative lesions should be examined for sclerosing panencephalitis, even if the classical neurologic symptoms of this disease are not present.


Two new agaricoid species of the family Clavariaceae (Agaricales, Basidiomycota) from China, representing two newly recorded genera to the country.
Two new lamellar species, Camarophyllopsis olivaceogrisea and Hodophilus glaberripes, of the family Clavariaceae were discovered in the subtropical zone of China. Camarophyllopsis olivaceogrisea is morphologically characterized by its hygrophanous basidiomata, greenish gray to dull green pileus, shortly decurrent lamellae, broadly elliptic basidiospores 4-5.5 × 3.5-4.5 μm in size, and cutis-like pileipellis composed of cylindrical cells. Hodophilus glaberripes is mainly characterized by its white to brownish pileus, glabrous stipe, slight yam bean smell, broadly elliptic basidiospores 5-6.5 × 4-5 μm in size, and epithelium-like pileipellis composed of inflated cells. Phylogenetic placement of the two species was determined by the combined analyses of a DNA data matrix containing ITS and LSU, and showed that collections of the two species formed two independent lineages in the Camarophyllopsis and Hodophilus clades respectively. The delimitation of C. olivaceogrisea and H. glaberripes were evaluated using molecular, morphological, and ecological methods. This is the first report of the genera Camarophyllopsis and Hodophilus in China.


Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1.
Structurally, the monocyte chemotactic proteins MCP-1, -2, and -3 form a subfamily of the C-C or beta-chemokines. Like other chemokines, MCPs are produced by a variety of cells on stimulation with cytokines (interleukin-1, tumor necrosis factor-alpha, interferon-gamma), bacterial and viral products or mitogens. MCP-1 levels are enhanced during infection and inflammation, which are characterized by leukocyte infiltration. In vitro, MCPs are chemotactic for a distinct spectrum of target cells and show different specific biological activities depending on the cell type and the chemokine tested. MCP-3 has the broadest range in that it activates monocytes, dendritic cells, lymphocytes, natural killer cells, eosinophils, basophils, and neutrophils. The most sensitive cells to all three MCPs are lymphocytes and monocytes. MCP-1 is a potent basophil activator but does not attract eosinophils, whereas, at higher concentrations, MCP-2 also stimulates both eosinophils and basophils. The signal transduction of MCPs on monocytes involves at least two G protein-linked C-C chemokine receptors: C-C CKR-1 binds MCP-3 and C-C CKR-2 binds MCP-1 and MCP-3 but not MCP-2. Receptor binding leads to enhanced [Ca2+]i for all chemokines except for MCP-2.


Enhancement of immunity by a DNA melanoma vaccine against TRP2 with CCL21 as an adjuvant.
Tyrosinase-related protein-2 (TRP2) is a weak antigen expressed in murine and human melanomas. Induction of antibody (Ab) response and T-cell immunity toward TRP2 with DNA plasmid vaccines has not been efficient to date. Recent studies have suggested that a chemokine ligand for the CCR7 (CCL21) present on T-cells and dendritic cells is important in activating and regulating immunity. We investigated the effectiveness of CCL21 as an adjuvant with an HVJ anionic liposomal TRP2 DNA (plasmid) vaccine to enhance anti-TRP2 Ab, cytokines, delayed-type hypersensitivity, T-cell responses, and tumor protection against B16 melanoma cells. Induction of anti-TRP2 immunity depended mainly on cell-mediated immunity, which was regulated by timing and route of CCL21 administration with DNA vaccine. The optimum protocol was to administer CCL21 im 24 h before DNA vaccine at the same vaccination site. Two vaccinations (prime/boost) were essential for induction of strong anti-TRP2 cell-mediated immunity. CCL21 administration 3 days before or 24 h after DNA vaccine, simultaneous with DNA vaccine, or at different sites (iv, opposite leg) was not effective. This study demonstrated that CCL21 was an effective adjuvant to enhance TRP2-specific immunity induced by a plasmid DNA cancer vaccine.


Exercise and Diet Counseling Trends From 2002 to 2015: A Serial Cross-Sectional Study of U.S. Adults With Cardiovascular Disease Risk.
Exercise and dietary behavioral counseling are effective clinical practices recommended by the U.S. Preventive Services Task Force to reduce cardiovascular disease risk among high-risk individuals. Medical Expenditure Panel Survey data from 2002 to 2015 were analyzed in 2018. Prevalence ratios of exercise, dietary, and both types of counseling among individuals with overweight or obesity with additional cardiovascular disease risk factors were calculated and adjusted for demographic covariates (N=116,048). Adjusted prevalence ratios were calculated for sociodemographic and health factors associated with counseling receipt using 2014-2015 data. From 2002 to 2015, adjusted prevalence ratios ranged from 43% to 63%. Compared with 2002, receipt of both types of counseling was 6% higher in 2015 (49%, 95% CI=48%, 51%). In 2015, compared with privately insured people, those without insurance (prevalence ratio=0.91, 95% CI=0.84, 0.99) or on Medicare (prevalence ratio=0.77, 95% CI=0.73, 0.82) were less likely to receive counseling. Individuals with 3 (prevalence ratio=1.46, 95% CI=1.39, 1.54), 4 (prevalence ratio=1.74, 95% CI=1.63, 1.85), or 5 (prevalence ratio=1.89, 95% CI=1.67, 2.15) cardiovascular disease risk factors received counseling more frequently than those with 2 cardiovascular disease risk factors. Female participants (prevalence ratio=1.07, 95% CI=1.03, 1.11) and racial minorities (Hispanics: prevalence ratio=1.31, 95% CI=1.24, 1.38; Blacks: prevalence ratio=1.11, 95% CI=1.05, 1.18; Asians: prevalence ratio=1.12, 95% CI=1.01, 1.24) reported higher rates of counseling. Despite modest improvements since 2002, up to 37% of individuals at high cardiovascular disease risk were not receiving exercise counseling, and 43% were not receiving dietary counseling in 2015. Continued implementation and scale up of effective programs to increase behavioral lifestyle counseling among high-risk populations are needed more than ever to mitigate the U.S. cardiometabolic disease burden.


The parotid gland: a new target organ for vitamin D action.
Radioactively labelled cholecalciferol was administered continuously to rats which were fed a vitamin D-deficient diet. It has been possible to show that all the metabolites of the cholecalciferol which normally occur in known target tissues of vitamin D are present in the parotid gland, and the pattern resembled that obtained for the kidney, a known target tissue for vitamin D action. The accumulation of cholecalciferol metabolites in the parotid gland was shown to be functional, as a calcium-binding protein was found to be present in the gland, possessing similar properties to the renal vitamin D-dependent calcium-binding protein.