Low-Temperature Assembling Strategy of a Nacre-Inspired Lamellar Configuration to Upcycling Biaxially Oriented Polypropylene Film Waste.
The efficient recycling and utilization of plastic waste have become a hot topic of global concern, but conventional mechanical recycling not only deteriorates the performance of recycled plastic but also loses the intrinsic structure and properties of the original product. Herein, an upcycling strategy of a biaxially oriented polypropylene (BOPP) film was proposed by duplicating the lamellar configuration established in nature nacre. Especially the suspension of PP wax was deposited on the surface of the BOPP film by spray-coating, followed by layer-by-layer assembling and hot-pressing at 160 °C above the melting temperature of PP wax but below the initial melting temperature of the BOPP film. In this case, PP wax not only functioned as a binder to enable strong interfacial adhesion between the BOPP films via interfacial diffusion but also acted as a soft phase to insert between the rigid BOPP films, constructing a soft-hard alternatively aligned configuration similar to brick-and-mortar architecture in nature nacre. As a result, the mechanical properties of the lamellar sample markedly outperformed those of the conventional mechanically recycling sample, evidenced by 113 and 1141% increases in tensile strength and impact strength, respectively. This simple and effective method provides a new strategy for efficient upcycling of oriented packaging films, which is important to realize the sustainable recycling of plastic waste.


Two cases of paralitic ileus in onco-hematologic patients.
Paralytic ileus is a severe complication resulting from a variety of disorders. It occurs most commonly in patients with serious underlying medical or surgical conditions. Prompt diagnosis and appropriate management may improve the outcome. We describe 2 cases of onco-hematologic patients who presented this complication after intensive chemotherapy.


[A method for induction of mouse CD8α(+);CD11b(+);jagged2(high);regulatory dendritic cells with mesenchymal stem cells in vitro].
To develop a method for induction of the mouse bone marrow-derived CD8α(+);CD11b(+);jagged2(high);regulatory dendritic cells (DCregs) using mesenchymal stem cells (MSCs) in vitro. BALB/c(H-2(d);)mouse bone marrow cells (BMCs) were isolated and induced to CD8α(+);CD11c(+);CD11b(+);DCs (DCs) by 4 cytokines in vitro for 3 d. The DCs were selected by flow cytometry (FCM), and co-cultured with MSCs for 10 d to get DCregs. Immunophenotypes, cell cycle, Jagged1 and Jagged2 ligands of the Notch pathway of DCs were analyzed by FCM before and after co-culture. The novel DCs were transformed into DCregs successfully. The expressions of CD86, CD80, CD40, and MHC-II significantly decreased (P<0.05), while those of CD205, Jagged1 and Jagged2 obviously increased on DCregs (P<0.05). Meanwhile, the percentage of treated MSCs cells went up in G2 and S phases. MSCs co-cultured with DCs can induce the development of DCregs, which have immune tolerance-associated phenotypes and higher proliferation ability. This mechanism might be related to the up-regulated Jagged1 and Jagged2 expressions and the T-cell Notch pathway activation.


ERK inhibition represses gefitinib resistance in non-small cell lung cancer cells.
Gefitinib, an EGFR tyrosine kinase inhibitor, is used to treat non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, the resistance to gefitinib eventually emerges in most of the patients. To understand its mechanism, we generated two acquired gefitinib-resistant NSCLC cell lines. The resistant cells have slower growth rates, but are more resistant to apoptosis in the presence of gefitinib, compared with their sensitive counterparts. In addition, our genome-wide transcriptome analysis reveals unexpected pathways, particularly autophagy, are dysregulated in the gefitinib-resistant cells. Autophagy is significantly enhanced in resistant cells. Importantly, inhibition of autophagy reduces gefitinib resistance. Furthermore, the phosphorylation of ERK, the extracellular signal-regulated kinase, is activated in resistant cells. Inhibition of ERK phosphorylation abrogates gefitinib resistance by suppressing autophagy both in vitro and in vivo. These findings establish a link between ERK and autophagy in gefitinib resistance, and suggest that the ERK signaling may serve as the potentially therapeutic target for treating gefitinib resistance in NSCLC patients.


The effect of dietary selenium level on lead toxicity in the Japanese quail.
Previous studies (Parizek et al., 1969) have shown significant interactions between selenium and certain heavy metals, particularly mercury and cadmium. Since these elements have an affinity for sulfhydryl groups, it was proposed that a similar interaction might exist with lead. In an initial experiment, adult quail hens were given diets supplemented with 0 and 1 p.p.m. selenium and 0, 500 and 1000 p.p.m. lead in a 2 X 3 factorial arrangement. After 32 days of feeding, body weight, liver weight and egg production decreased in birds fed lead while kidney weights increased. Highly significant decreases in red blood cell delta-aminolevulinic acid dehydratase (RBC-ALAD) activity occurred when lead was added to the diet. Control RBC-ALAD activity was 1337 versus 105, 91, 156 and 110 nmol. porphobilogen produced per ml. of erythrocyte per hour (nmol. PBG/ml. RBC/hr.) for the 500, 1000, 500 plus selenium and 1000 plus groups, respectively. After 85 days of feeding lead to male birds in a second study, selenium appeared to have variable effects on the concentration of lead in liver, kidney and tibia. Selenium supplementation to lead diets resulted in significantly increased levels of lead in kidney tissue while little or no effects were observed on liver or tibia lead levels. RBC-ALAD activity was significantly reduced with lead supplementation and no effect of selenium addition was observed. Electrophoretic gels of serum from birds fed lead containing diets showed increased protein bands in the transferrin and globulin regions regardless of the presence of 1 p.p.m. selenium. A third study was conducted to determine the effects of supplementing an isolated soy protein diet with 0 and 1 p.p.m. selenium and 0 and 3000 p.p.m. lead. Selenium supplementation improved body weights over controls while lead additions caused reduced egg production and ALAD activity. Lead feeding increased tibia/body weight ratios and lead concentrations in liver, kidney and tibia. No significant interaction between lead and selenium was observed.


Alterations in prednisolone disposition as a result of oral contraceptive use and dose.
The disposition of total and free prednisolone has been studied in eight female subjects who used combined oestrogen-progestogen oral contraceptives and in eight female subjects who did not, each of whom received separate intravenous doses of 0.1 mg/kg (low) and 1.0 mg/kg (high) of prednisolone. Mean free prednisolone clearance was reduced congruent to 30% in oral contraceptive users compared to control subjects (P less than 0.001), the difference being greater for the low dose (39%) than for the high dose (24%). Pre-dose plasma cortisol concentrations were elevated two-fold (P less than 0.001) in oral contraceptive users compared to control subjects. These effects are consistent with a mechanism in which the competitive inhibition of free prednisolone clearance by cortisol contributes to the reduction of free prednisolone clearance by oral contraceptive use. Mean total prednisolone clearance and steady state distribution volume showed an approximate two-fold dose dependent increase consistent with a similar increase in plasma prednisolone free fraction (P less than 0.001). Free prednisolone clearance showed an 18% dose dependent decrease (P less than 0.001) but free steady-state distribution volume did not change with dose. At plasma prednisolone concentrations less than 400 ng/ml, prednisolone free fractions at any prednisolone concentration were greater after the low, than after the high dose. This effect is consistent with the displacement of prednisolone by cortisol from transcortin but not from albumin.


Using Living Labs to Explore Needs and Solutions for Older Adults With Dementia: Scoping Review.
Numerous living labs have established a new approach for studying the health, independent living, and well-being of older adults with dementia. Living labs interact with a broad set of stakeholders, including students, academic institutions, private companies, health care organizations, and patient representative bodies and even with other living labs. Hence, it is crucial to identify the types of cocreations that should be attempted and how they can be facilitated through living labs. This study aims to scope publications that examine all types of living lab activities, exploring the needs and expectations of older adults with dementia and seeking solutions, whether they live in the community or long-term health care facilities (LTHFs). This scoping review was reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations for the extension of scoping reviews. We searched six bibliographic databases for publications up to March 2020, and a forward-backward citation chasing was performed. Additional searches were conducted using Google Scholar. The quality of the selected papers was assessed. Of the 5609 articles identified, we read 58 (1.03%) articles and retained 12 (0.21%) articles for inclusion and final analysis. All 12 articles presented an innovative product, developed in 4 main living labs, to assist older adults with cognitive disorders or dementia living in the community or LTHFs. The objectives of these studies were to optimize health, quality of life, independent living, home care, and safety of older adults with cognitive disorders or dementia, as well as to support professional and family caregivers or reduce their burdens. The overall methodological quality of the studies ranged from poor to moderate. This scoping review identified several living labs playing a pivotal role in research aimed at older adults with dementia living in the community or LTHFs. However, it also revealed that living labs should conduct more better-quality interventional research to prove the effectiveness of their technological products or service solutions. RR2-10.2147/SHTT.S233130.


Can staff training reduce behavioural problems in residential care for the elderly mentally ill?
The effect of a brief in-service training programme on the psychosocial management of behavioural disturbance in residential care is described. Although the incidence of problematic behaviour did not change 3 months after training, staff in the experimental homes reported a significant improvement in their management of problematic behaviour, as compared to the control home. However, these effects were not maintained a year later. The importance of post-training supervision and the sociocultural context of the home in the maintenance of psychosocial intervention in residential settings is discussed.


RRM2‑mediated Wnt/β‑catenin signaling pathway activation in lung adenocarcinoma: A potential prognostic biomarker.
The present study aimed to investigate the role and mechanism of action of ribonucleotide reductase M2 (RRM2) in lung adenocarcinoma and its potential as a therapeutic target. Data of patients with lung adenocarcinoma from The Cancer Genome Atlas database were collected and analyzed to evaluate the potential of RRM2 as a biomarker. The expression of RRM2 was evaluated in the A549 cell line and its cisplatin-resistant A549/DDP cell line derivative by western blot and reverse transcription-quantitative PCR. The study also investigated cell proliferation and the mechanism by which RRM2 controls cellular cisplatin resistance using CCK-8 and colony-formation assays. In addition, cell migration was assessed using Transwell assays, and the cell cycle and apoptosis were examined using flow cytometry. RRM2 was highly expressed in lung adenocarcinoma and was associated with the clinical TMN stage. Functional enrichment analysis showed that RRM2 was enriched in the cell cycle. Immune cell infiltration analysis identified 12 types of immune cell that exhibited differences between patients expressing different levels of RRM2. Cellular assays revealed higher levels of RRM2 expression in A549/DDP cells than A549 cells, and its expression was induced by cisplatin. RRM2 knockdown decreased cell proliferation and migration, accelerated apoptosis and caused cell cycle arrest in the S-phase, increasing the sensitivity of A549 and A549/DDP cells to cisplatin through the Wnt/β-catenin signaling pathway. Overexpression of β-catenin reduced the effects of RRM2 knockdown on A549 cells. Lung adenocarcinoma growth may be influenced by RRM2 through the Wnt/β-catenin signaling pathway, suggesting a potential pathway for cancer progression.


Production of 2,3-butylene glycol from whey by Klebsiella pneumoniae and Enterobacter aerogenes.
Production of 2,3-butylene glycol from whey with Klebsiella pneumoniae and Enterobacter aerogenes was studied. Sterilization of the whey was unnecessary. Acid whey required neutralization, but sweet whey did not. Butylene glycol production was most efficient at 33 degrees C for Klebsiella pneumoniae and at 37 degrees C for Enterobacter aerogenes. Aeration significantly improved yields. Klebsiella pneumoniae produced more butylene glycol than did Enterobacter aerogenes in unsupplemented whey. The addition of 50 mM sodium acetate to whey increased the production of butylene glycol and acetoin by Enterobacter aerogenes; it also increased the production of glycol by Klebsiella pneumoniae, but the increase in this case was offset by a decrease of production of acetoin. Maximal yields of the glycol plus acetoin in whey were obtained in 48 to 64 h, but Enterobacter aerogenes required about 160 h for complete utilization of the lactose. Highest yields were about .3 M butylene glycol plus acetoin, which corresponds to the production of about 10 kg of glycol from 380 liters of whey.


Exercise and COPD: therapeutic responses, disease-related outcomes, and activity-promotion strategies.
Chronic obstructive pulmonary disease (COPD) reduces patients' exercise capacities and their abilities to perform daily physical activities, thereby increasing morbidity and mortality rates. The cycle of dyspnea, deconditioning, and declining physical activity not only accelerates the progression of COPD but also increases the risk for developing or aggravating metabolic and cardiovascular diseases. Cardiovascular and metabolic comorbidities also limit physical function, and their disabling effects in combination with COPD may be greater than the effects of each disease alone. The impact of COPD and its treatment on the ability to exercise, and the degree of physical activity in daily life, can be measured by field-based tests (eg, the 6-minute walk test or incremental and endurance shuttle-walk test), laboratory-based tests (eg, incremental or constant work-rate treadmill and cycle-ergometer tests), and physical activity assessments (eg, questionnaires and accelerometers). Walking tests increase oxygen consumption and desaturation in patients with COPD more than cycling tests with similar work-rate profiles and may more closely resemble patients' normal activities. Despite the questionable relevance of exercise testing to patients' daily functionality, exercise parameters remain important predictors of survival in patients with COPD. Treatment of COPD (pharmacotherapy, pulmonary rehabilitation, or both) can increase exercise capacity and physical activity in daily life, which potentially slows the decline of lung function, reduces the frequencies of exacerbations and hospitalizations, decreases mortality, slows the progression of comorbidities, improves health-related quality of life, and increases the activity reserve for routine function. This article examines the interactions of reduced physical activity and decreased exercise capacity with the progression of COPD, comorbidities, and mortality. The article also describes the available exercise tests for patients with COPD and reviews the evidence indicating that treating COPD improves exercise capacity. Notably, it appears that even mild COPD reduces exercise capacity and daily physical activity, indicating the need for early intervention.


Mitochondria-Targeted Molecules as Potential Drugs to Treat Patients With Alzheimer's Disease.
Alzheimer's disease (AD) is the most common multifactorial mental illness affecting the elderly population in the world. Its prevalence increases as person ages. There is no known drug or agent that can delay or prevent the AD and its progression. Extensive research has revealed that multiple cellular pathways involved, including amyloid beta production, mitochondrial structural and functional changes, hyperphosphorylation of Tau and NFT formation, inflammatory responses, and neuronal loss in AD pathogenesis. Amyloid beta-induced synaptic damage, mitochondrial abnormalities, and phosphorylated Tau are major areas of present research investigations. Synaptic pathology and mitochondrial oxidative damage are early events in disease process. In this chapter, a systematic literature survey has been conducted and presented a summary of antioxidants used in (1) AD mouse models, (2) elderly populations, and (3) randomized clinical trials in AD patients. This chapter highlights the recent progress in developing and testing mitochondria-targeted molecules using AD cell cultures and AD mouse models. This chapter also discusses recent research on AD pathogenesis and therapeutics, focusing on mitochondria-targeted molecules as potential therapeutic targets to delay or prevent AD progression.


An Electrochemical Cholesterol Biosensor Based on A CdTe/CdSe/ZnSe Quantum Dots-Poly (Propylene Imine) Dendrimer Nanocomposite Immobilisation Layer.
We report the preparation of poly (propylene imine) dendrimer (PPI) and CdTe/CdSe/ZnSe quantum dots (QDs) as a suitable platform for the development of an enzyme-based electrochemical cholesterol biosensor with enhanced analytical performance. The mercaptopropionic acid (MPA)-capped CdTe/CdSe/ZnSe QDs was synthesized in an aqueous phase and characterized using photoluminescence (PL) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, transmission electron microscopy (TEM), X-ray power diffraction (XRD), energy dispersive X-ray (EDX) spectroscopy. The absorption and emission maxima of the QDs red shifted as the reaction time and shell growth increased, indicating the formation of CdTe/CdSe/ZnSe QDs. PPI was electrodeposited on a glassy carbon electrode followed by the deposition (by deep coating) attachment of the QDs onto the PPI dendrimer modified electrode using 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC), and N-hydroxysuccinimide (NHS) as a coupling agent. The biosensor was prepared by incubating the PPI/QDs modified electrode into a solution of cholesterol oxidase (ChOx) for 6 h. The modified electrodes were characterized by voltammetry and impedance spectroscopy. Since efficient electron transfer process between the enzyme cholesterol oxidase (ChOx) and the PPI/QDs-modified electrode was achieved, the cholesterol biosensor (GCE/PPI/QDs/ChOx) was able to detect cholesterol in the range 0.1⁻10 mM with a detection limit (LOD) of 0.075 mM and sensitivity of 111.16 μA mM-1 cm-2. The biosensor was stable for over a month and had greater selectivity towards the cholesterol molecule.


Synchronous adrenocortical neoplasms, paragangliomas, and pheochromocytomas: syndromic considerations regarding an unusual constellation of endocrine tumors.
The most common clinical syndromes presenting with paragangliomas and/or pheochromocytomas as their endocrine components are multiple endocrine neoplasia type 2, neurofibromatosis, Von Hippel-Lindau syndrome, Carney-Stratakis syndrome, Carney triad, and the recently described hereditary paraganglioma syndrome. Only Carney triad is known to also present with adrenocortical adenomas, currently representing the only described syndrome in which all 3 of the aforementioned tumors are found together. In most cases, prototypical lesions of the triad such as gastrointestinal stromal tumor and pulmonary chondromas are also seen. We present a case of a young woman with synchronous paragangliomas, adrenal/extra-adrenal cortical neoplasms, and pheochromocytoma without genetic mutations for multiple endocrine neoplasia 2, Von Hippel-Lindau syndrome, neurofibromatosis, and succinate dehydrogenase. We speculate that this represents a previously undescribed presentation of Carney triad and, at the very least, indicates the need for monitoring for the development of other tumors of the triad.


[Mortality and morbidity among municipal waste workers in Rome: a cohort study].
The adverse health effects associated with waste treatment processes are of great concern as large population groups and workers may be exposed to refuse-derived toxic substances. The main effects are respiratory and gastrointestinal infections, reduced lung function, irritations, allergic reactions, and injuries. To evaluate morbidity and mortality among a cohort of municipal waste workers in Rome. All 6839 workers (18.6% women) involved in waste collection, transportation and landfill disposal employed since 01/01/1994, with a minimum period of employment of five years were enrolled and with follow-up until 31/12/2009. The assessment of vital status was carried out through linkages with information systems (municipality records, mortality and hospital information systems), and through contacts with municipalities of residence. Gender specific standardized mortality (SMR) and hospitalization (SHR) ratios were calculated, using regional population mortality (and hospitalization) rates. Overall, in this cohort workers had the same mortality as the population of the Region. Hospitalizations for natural causes were significantly higher than expected among workers involved in transportation (SHR = 1.25, 95% CI = 1.13-1.38) and in waste collection (SHR(men) = 1.14, 95% CI = 1.07-1.22; SHR(women) = 1.65, 95% CI = 1.47-1.84). Among women there was an excess of hospitalizations for respiratory diseases (SHR = 1.95, 95% CI = 1.33-2.77), for digestive system disorders (SHR = 1.37, 95% CI = 1.03-1.79) and for injuries and intoxications (SHR = 2.28, 95% CI = 1.69-2. 99). The study did not find any increased mortality among the workers of either sexes. Female workers deserve further surveillance mainly due to an increased risk of trauma and respiratory and gastrointestinal disorders.


Antibodies to collagen in scleroderma.
Using the enzyme-linked immunosorbent assay (ELISA), we detected antibodies to interstitial (type I) and basement membrane (type IV) collagens in the sera of patients with scleroderma (systemic sclerosis). Antibodies against type IV collagen were found in significant levels in these patients and correlated with the presence of abnormal pulmonary diffusion capacity. Levels of antibodies to type I collagens also correlated significantly with pulmonary diffusion capacity. Absorption of sera with type I or type IV collagens before analysis in the ELISA eliminated reactivity in an antigen-specific pattern, indicating that these antibodies reacted with determinants specific for either type I or type IV collagens. The removal of immune complexes by ultracentrifugation had no effect on serum antibody levels. Autoantibodies to basement membrane and interstitial collagens may participate in the pathogenesis of scleroderma.


Transport of a fluorescent phosphatidylcholine analog from the plasma membrane to the Golgi apparatus.
We have examined the internalization and degradation of a fluorescent analog of phosphatidylcholine after its insertion into the plasma membrane of cultured Chinese hamster fibroblasts. 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)-aminocaproyl phosphatidylcholine (C6-NBD-PC) was incorporated into the cell surface by liposome-cell lipid transfer at 2 degrees C. The fluorescent lipid remained localized at the plasma membrane as long as the cells were kept at 2 degrees C; however, when the cells were warmed to 37 degrees C, internalization of some of the fluorescent lipid occurred. Most of the internalized C6-NBD-PC accumulated in the Golgi apparatus although a small amount was found randomly distributed throughout the cytoplasm in punctate fluorescent structures. Internalization of the fluorescent lipid at 37 degrees C was blocked by the presence of inhibitors of endocytosis. Incubation of cells containing C6-NBD-PC at 37 degrees C resulted in a rapid degradation of the fluorescent lipid. This degradation occurred predominantly at the plasma membrane. The degradation of C6-NBD-PC resulted in the release of NBD-fatty acid into the medium. We have compared the internalization of the fluorescent lipid with that of a fluorescent protein bound to the cell surface. Both fluorescent lipid and protein remained at the plasma membrane at 2 degrees C and neither were internalized at 37 degrees C in the presence of inhibitors of endocytosis. However, when incubated at 37 degrees C under conditions that permit endocytosis, the two fluorescent species appeared at different intracellular sites. Our data suggest that there is no transmembrane movement of C6-NBD-PC and that the fluorescent probe reflects the internalization of the outer leaflet of the plasma membrane lipid bilayer. The results are consistent with the Golgi apparatus as being the primary delivery site of phospholipid by bulk membrane movement from the plasma membrane.


Deletions in the polyAlanine-containing transcription factor FOXL2 lead to intranuclear aggregation.
Mutations of FOXL2, a gene encoding a forkhead transcription factor, have been shown to cause the blepharophimosis-ptosis-epicanthus inversus syndrome. This genetic disorder is characterized by eyelid and craniofacial abnormalities associated or not with premature ovarian failure. We have previously shown that mutant FOXL2 with an expanded polyAlanine (polyAla) tract forms large aggregates both in the nucleus and in the cytoplasm of transfected cells, whereas the wild-type protein localizes in the nucleus in a rather diffuse manner. Premature stop codons in FOXL2 have been considered so far as null alleles. However, we demonstrate here that such nonsense mutations may lead to the production of N-terminally truncated proteins by re-initiation of translation downstream of the stop codon. Surprisingly, the truncated proteins strongly aggregate in the nucleus, partially localize in the cytoplasm and retain a fraction of the wild-type protein. We also show that a complete deletion of the polyAla tract of FOXL2 induces a significant intranuclear aggregation. Our results enlarge the spectrum of mutations inducing FOXL2 aggregation.


Sensory disturbances associated with serotonin reuptake inhibitors: brief review.
Serotonin reuptake inhibitors (SRIs) are occasionally associated with sensory symptoms, which are one of the less recognized adverse effects. A PUBMED search supplemented with manual search was made to review the relevant literature. Anesthesia, paresthesia, and mastalgia have been reported to occur with this group of medications. The possible pathophysiology and management strategies are discussed.


PD-L1-Expressing Extracellular Vesicles for the Treatment of Pneumonia.
Acute respiratory distress syndrome (ARDS) is a severe lung condition with a high mortality rate and a lack of effective drug therapy. In this work, we developed mesenchymal stem cell (MSC)-derived extracellular vesicles with high PD-L1 expression (MSC-EVs-PD-L1) for treating lipopolysaccharide (LPS)-induced pneumonia by intratracheal administration. We found an upregulation of PD-1 expression in the inflammatory region of murine lungs; hence, MSC-EVs-PD-L1 exerted immunosuppressive effects via the PD-1/PD-L1 signaling pathway. Furthermore, we treated LPS-induced pneumonia mice by intratracheal administration, which enabled heavy drug accumulation in the lungs of mice and better therapeutic efficacy compared to systemic administration. Our results suggest that MSC-EVs-PD-L1 has the potential to provide a universal platform technology for the immunotherapy of pneumonia.


Impact of novel agents on patient-relevant outcomes in patients with previously untreated chronic lymphocytic leukemia who are not eligible for fludarabine-based therapy.
Chronic lymphocytic leukemia (CLL) is an orphan disease that primarily affects the elderly. The majority of symptomatic patients eligible for frontline treatment are unfit for fludarabine based chemoimmunotherapy. Historical treatment includes chlorambucil (Chl), bendamustine/rituximab (BR), and chlorambucil/rituximab/ChlR combination. Clinical guidelines now recommend the use of novel agents, such as ibrutinib (Ibr), in both frontline and relapse settings and other novel agents, such as idelalisib (with rituximab), in relapse settings. Despite compelling clinical results for novel agents, follow-up in clinical trials is relatively short and, thus, the comparative long-term benefits are still unknown. The authors developed a simulation model to generate treatment specific lifetime estimates of Overall Survival (OS) and Quality Adjusted Life Years (QALYs) for treatment with BR, Chl, ChlR, and Ibr. Two potential clinical scenarios were modelled: with and without novel agents for treating CLL. The model was based on health states relating to first- and second-line progression-free survival (PFS), post-progression survival, and death. Where novel agents were assumed unavailable, mean OS ranged from 5.4-8.5 years and QALYs from 3.5-6.1. Where novel agents were available, the mean OS increased to 10.0 years, with a corresponding increase in QALYs to 7.6. Frontline Ibr use followed by Physician's Choice, including novel agents at relapse, resulted in projected increase in OS of between 18% (1.5 years) and 85% (4.6 years), corresponding to a 25-117% increase in QALYs, compared with currently available traditional therapies. The limitations of this analysis include immature OS data and the assumption of equivalent efficacy across all novel agents in terms of their impact on PFS and OS. The use of novel agents is predicted to yield substantive gains in predicted lifetime OS and QALY improvements compared to traditional therapies in CLL patients who are ineligible for fludarabine-based chemoimmunotherapy.


Dermatomycoses in Indonesia.
A review of mycologic surveys and case reports indicates the unique occurrence of deep and superficial fungus infections of the skin as encountered in Indonesia, confirming that each country has its own pathogenic mycologic flora. Such diseases as phycomycosis, histoplasmosis, mycetoma, chromomycosis, cryptococcosis, and dermatophytosis are common.


Health coaching for undergraduate nursing students: a pilot study for an action research.
The Nursing undergraduate degree educational program represents an intensive and complex course, and includes a number of professionalizing practical internships, and for these reasons it requires an action to support and improve. Coaching is based on the premise that people have personal strengths and abilities which, through a interview, can be directed to solving their problems. Several studies demonstrate the efficacy of Health Coaching in different University, but never have been measured benefits regard skills improving. The objective of the study is to assess the impact of a health coaching program on the nursing students. A pre-post quasi-experimental study was conducted, involving the activation of a Health Coaching Program for 25 nursing students selected through convenience sampling, based on their fulfillment of the inclusion criteria. The Health Coaching Program was administered by the Health Coaching Academy. This study also evaluated parameters such as: level of concentration in study, motivation, problem solving and reorganization skills, study organization skills, psycho-physical-emotional state comprehension, decision-making skills and self-esteem, noting a statistically significant increase post-HC program. A statistically significant improvement was also found in the students' perception of their own stress management skills after the course. This study strengthens the hypothesis that HC programs contribute to improving performance of nursing students. Those conclusions need to be corroborated by future studies on the topic to further support the hypothesis that programs of HC within the learning nursing contexts can lead to a tangible benefit for students of the health professions.


[Sport activity in children and adolescents: temperament and emotional traits].
Aim of this study is to evaluate anxiety and temperament characteristics in developmental age subjects who practised agonistic sport (individual or team sports) in comparison with a sample group of subjects who practice no agonistic sports. Sixty subjects aged from 10 to 16 years were enrolled in the study and divided into 3 groups: 20 subjects practised individual agonistic sport (Group A), 20 subjects practised team agonistic sports (Group B) and 20 subjects who practised non agonistic sport as control group, (Group C). The following tests were used: multidimensional anxiety scale for children (MASC) to evaluate anxiety, EAS scale (Buss e Plomin) to evaluate temperament (emotionability, activity, sociability and shyness for younger children). MASC scale scores underline generalized anxiety with higher significantly score in subjects who practised agonistic sports (Group A and B) compared with Group C. Anxiety symptoms were more evident in subjects who practised individual discipline compared with those who practised team sports. EAS scale indicated that temperament of subjects who practised agonistic sport was characterised by a considerable aptitude for sociability with low emotionability/activity levels in comparison to control group. None of the 3 groups showed a psychopathologic profile.


[Side Effects of Continuous Fentanyl Infusion for Postoperative Pain Relief in Children].
There have been many reports on the use of morphine for postoperative pain relief in children, but the use of fentanyl for this purpose has not frequently been described. We clarified the details of side effects exhibited in children who had received continuous fentanyl infusion for postoperative pain relief The subjects are 1,166 children aged between 0 and 14 years who underwent continuous fentanyl infusion for postoperative pain relief within the previous 4 years. Fentanyl was administered at a dose of 0.5 or 1.0 μg x kg(-1) x hr(-1), and with continuous use of pulse oximeter, the pulse rate, SpO2, respiratory rate, BP, sedation score, and presence/absence of nausea/vomiting were recorded every 2 hours. The frequencies of side effects were retrospectively examined. Severe side effects, including respiratory depression, for which mask ventilation or tracheal intubation was required were observed in 0.77% of cases. No subjects died or developed permanent sequelae. Nausea/vomiting occurred in 25.4% of cases. Using monitoring systems that facilitate the early detection of and intervention in respiratory depression, we can safely administer continuous fentanyl infusion for postoperative pain relief in children. It is necessary to adopt countermeasures against nausea/vomiting.


A novel lung recruitment technique in pediatric patients with congenital heart diseases: A case series.
Lung recruitment techniques are employed to help in improvement of pulmonary mechanics, facilitate early weaning, and shorten the duration of mechanical ventilation. We are reporting a novel lung recruitment technique employed in four children with left lung atelectasis, who underwent corrective surgery for congenital heart disease. From January 2020 to March 2021, four pediatric cardiac patients having left lung atelectasis, undergoing corrective surgery were subjected to lung recruitment technique and had elective endobronchial intubation and suctioning with chest physiotherapy in the form of vibration and percussion. This was done along with intermittent ventilation with 100% oxygen. Successful recruitment of lung segments and clearance of atelectasis were confirmed by auscultation and chest X-ray in all four patients. All the cases were successfully weaned off the ventilator within 24-48 h. One patient had an opposite lung collapse after extubation, which was managed conservatively with chest physiotherapy. Another patient had bradycardia and desaturation during the procedure, which was improved after withdrawing the tube and instituting two lung ventilation with 100% oxygen. This novel lung recruitment technique helps in recruitment of collapsed lung segments and thus helps in early weaning and shortens the duration of mechanical ventilation.


High vagal tone and rapid extinction learning as potential transdiagnostic protective factors following childhood violence exposure.
Childhood exposure to violence is strongly associated with psychopathology. High resting respiratory sinus arrhythmia (RSA) is associated with lower levels of psychopathology in children exposed to violence. High RSA may help to protect against psychopathology by facilitating fear extinction learning, allowing more flexible autonomic responses to learned threat and safety cues. In this study, 165 youth (79 female, aged 9-17; 86 exposed to violence) completed assessments of violence exposure, RSA, and psychopathology, and a fear extinction learning task; 134 participants returned and completed psychopathology assessments 2 years later. Resting RSA moderated the longitudinal association of violence exposure with post-traumatic stress disorder (PTSD) symptoms and externalizing psychopathology, such that the association was weaker among youths with higher RSA. Higher skin conductance responses (SCR) during extinction learning to the threat cue (CS+) was associated with higher internalizing symptoms at follow-up and greater SCR to the safety cue (CS-) was associated with higher PTSD, internalizing, and externalizing symptoms, as well as the p-factor, controlling for baseline symptoms. Findings suggest that higher RSA may protect against emergence of psychopathology among children exposed to violence. Moreover, difficulty extinguishing learned threat responses and elevated autonomic responses to safety cues may be associated with risk for future psychopathology.


Investigating the surface dose contribution of intrafractional kV imaging in CyberKnife-based stereotactic radiosurgery.
CyberKnife treatment consists of hundreds of noncoplanar beams and numerous intrafractional images that can be taken during a single treatment fraction; thus, doses because of imaging should be considered in this technique. The aim of this study is to investigate the in-field and out-of-field surface doses induced from kV imaging system during stereotactic radiosurgery (SRS) treatment. The imaging-induced surface doses were measured at the center of the imaging field and within ±15-cm distance from the center in both craniocaudal and lateral directions. TLD100H thermoluminescence dosimeters and EBT2 gafchromic films were used to take the measurements at the locations of 0, ±5, ±10, and ±15 cm in the 2 orthogonal directions on abdominal region of a Rando phantom. The surface dose contributions of imaging system for the 4 most commonly used energy options of 90, 100, 110, and 120 kVp with 3 mAs options of 10, 30, and 90 mAs were measured and compared. Imaging dose values have a positive correlation with both parameters of energy and mAs. The energy options of 100, 110, and 120 kVp, in average, induced 60%, 101%, and 141% more doses per mAs than 90 kVp energy in the imaging field center. A threefold increase in mAs values, i.e., from 10 mAs to 30 mAs and from 30 mAs to 90 mAs, caused higher dose in field center with a factor of 2.53 ± 0.08 when the energy value was kept constant. The in-field dose distributions within ±10 cm in both directions showed a flat pattern with a standard deviation lower than 5%, whereas the out-of-field doses at ±15-cm distance from the field center suddenly dropped to almost half of the central doses. Although a single imaging attempt causes a very low dose compared with the therapeutic dose level, one should be aware of the cumulative surface dose increase with higher imaging number. Proper patient setup, fiducial usage, and reduction of both the mAs values and the imaging numbers should be, therefore, considered to keep the cumulative surface dose in a lower level.


Heritability of hand preference in chimpanzees (Pan).
Heritability in hand preference was examined in 76 chimpanzees by comparing strength and direction of hand preference between offspring and parents and among half-siblings reared in different environments. For two separate measures of handedness, offspring had the same hand preference as their biological parent significantly more often then would be predicted by chance. Half-siblings exhibited patterns of hand preference which significantly deviated from chance. In no instance did rearing environment account for a significant proportion of variance. These results strongly suggest a heritability component to the expression of hand preference in chimpanzees.


An Uncertainty Visual Analytics Framework for fMRI Functional Connectivity.
Analysis and interpretation of functional magnetic resonance imaging (fMRI) has been used to characterise many neuronal diseases, such as schizophrenia, bipolar disorder and Alzheimer's disease. Functional connectivity networks (FCNs) are widely used because they greatly reduce the amount of data that needs to be interpreted and they provide a common network structure that can be directly compared. However, FCNs contain a range of data uncertainties stemming from inherent limitations, e.g. during acquisition, as well as the loss of voxel-level data, and the use of thresholding in data abstraction. Additionally, human uncertainties arise during interpretation due to the complexity in understanding the data. While existing FCN visual analytics tools have begun to mitigate the human ambiguities, reducing the impact of data limitations is an open problem. In this paper, we propose a novel visual analytics framework with three linked, purpose-designed components to evoke deeper interpretation of the fMRI data: (i) an enhanced FCN abstraction; (ii) a temporal signal viewer; and (iii) the anatomical context. Each component has been specifically designed with novel visual cues and interaction to expose the impact of uncertainties on the data. We augment this with two methods designed for comparing subjects, by using a small multiples and a marker approach. We demonstrate the enhancements enabled by our framework on three case studies of common research scenarios, using clinical schizophrenia data, which highlight the value in interpreting fMRI FCN data with an awareness of the uncertainties. Finally, we discuss our framework in the context of fMRI visual analytics and the extensibility of our approach.


Synthesis of novel taspine diphenyl derivatives as fluorescence probes and inhibitors of breast cancer cell proliferation.
Two novel taspine diphenyl derivatives (Ta-dD) were designed and synthesized by introducing different coumarin fluorescent groups into the basic structure of Ta-dD. The main advantage of these two compounds is that they can be used as fluorescence probes and inhibitors simultaneously. In the present study, the fluorescent properties of the probes were measured and their inhibition of four breast cancer cell lines was tested. Different concentrations of the fluorescence probe were added to MCF-7 breast cancer cells for fluorescence imaging analysis under normal conditions. The results suggested that both of the new compounds have not only fluorescence but also the ability to inhibit effects on different breast cancer cell lines, which indicates their possible further use as dual functional fluorescence probes in tracer analysis.


Searches for Lepton flavor violation in the decays tau{+/-}-->e{+/-}gamma and tau{+/-}-->mu{+/-}gamma.
Searches for lepton-flavor-violating decays of a tau lepton to a lighter mass lepton and a photon have been performed with the entire data set of (963+/-7)x10{6} tau decays collected by the BABAR detector near the Upsilon(4S), Upsilon(3S) and Upsilon(2S) resonances. The searches yield no evidence of signals and we set upper limits on the branching fractions of B(tau{+/-}-->e{+/-}gamma)<3.3x10{-8} and B(tau{+/-}-->mu{+/-}gamma)<4.4x10{-8} at 90% confidence level.


Nanofat in Plastic Reconstructive, Regenerative, and Aesthetic Surgery: A Review of Advancements in Face-Focused Applications.
Nanofat is a relatively novel technique in fat grafting that has gained significant interest in the fields of regenerative medicine, aesthetic and translational research. It involves the extraction of autologous fat from a patient, which is then transformed into "nanofat", consisting of small fat particles with a diameter of less than 0.1 mm and containing high concentrations of stem cells and growth factors. This article focuses on the use of nanofat in facial rejuvenation and its potential for lipomodelling. Fat tissue is a "stem cell depot" and nanofat contains many stem cells that can differentiate into various cell types. The Lipogem technology, developed in 2013, enables the isolation of nanofat with an intact perivascular structure, utilizing the high concentration of mesenchymal stromal cells near the pericytes of the adipose vascular system. Nowadays nanofat is used primarily for cosmetic purposes particularly in rejuvenating and improving the appearance of the skin, especially the face. Indeed, it has wide applicability; it can be used to treat fine lines, wrinkles, acne scars, sun-damaged skin, scar repair, and as an alopecia treatment. However, further studies are needed to assess the long-term efficacy and safety of this technique. In conclusion, nanofat is a safe and minimally invasive option for tissue regeneration with considerable therapeutic potential. This study reviews the application and effects of nanofat in regenerative medicine and facial cosmetic surgery.


Inflammatory myofibroblastic tumor of the uterus with prominent myxoid change.
A surgical case of inflammatory myofibroblastic tumor arising in the uterine corpus and exhibiting prominent myxoid change of the stroma is reported. The patient was a 63-year-old woman with a large tumor mass that filled the uterine cavity and measured 11 cm in maximal dimension. The tumor had a gelatinous appearance and consisted of a loose proliferation of stellate or polygonal cells on a myxomatous background. Fascicular proliferation of spindle cells was also observed focally, and a chronic inflammatory cell infiltration was seen in many areas. Tumor cells had mild atypism and were immunoreactive for vimentin, alpha-smooth muscle actin, and anaplastic lymphoma kinase (ALK). Focal immunoreactivity for high-molecular-weight caldesmon (h-caldesmon) was also noted. The patient has been free from recurrence for 8 months. Inflammatory myofibroblastic tumor of the uterus occasionally shows prominent myxoid change of the stroma, and differentiation from myxoid leiomyosarcoma is problematic in these cases. Based on the immunoreactivity of tumor cells for ALK and h-caldesmon, the present tumor was considered inflammatory myofibroblastic tumor showing a focal phenotypic transition from myofibroblasts to smooth muscle cells.


[A new method of high-dose intraarterial chemotherapy of the pancreas using direct hemoperfusion (DHP) under portal venous isolation (PVI)].
Surgical resection for pancreatic cancer is severely limited by the extent of the disease at the time of diagnosis. Chemotherapy has been the treatment of choice for unresectable cases. We developed a new method of intraarterial chemotherapy for pancreatic body and tail cancers using direct hemoperfusion (DHP) under portal venous isolation (PVI). Adriamycin (ADR, 3 mg/kg) was infused into the splenic arteries of mongrel dogs for 5 min after clamping off blood flow to the stomach and the duodenum. In group A (n = 5), this was simply done, and in group B (n = 5) the portal venous blood was isolated by clamping at the porta hepatis and pumped through the DHP circuit to the jugular vein for 20 min from the start of drug infusion. The peak systemic level (microgram/ml) of group B (0.78 +/- 0.03) was significantly reduced by PVI.DHP as compared to that of group A (3.49 +/- 1.15, P < 0.01). The pancreatic tissue levels (microgram/g. tissue) 30 min after drug infusion of group A (61.2 +/- 13.4) were slightly lower than those in group B (88.9 +/- 27.8), although not statistically significant. However, tissue levels of group B in the liver (27.3 +/- 9.2) and heart (1.8 +/- 0.8) were significantly lower than those of group A (liver; 52.3 +/- 18.5, heart; 4.9 +/- 0.6, P < 0.05). In conclusion, PVI.DHP achieved a significant reduction in systemic drug exposure during intraarterial chemotherapy. Therefore, we consider that this system will allow dose escalation of ADR during intraarterial chemotherapy for pancreatic body and tail cancers.


[Evaluation of selenium consumption by Mongolian residents].
Selenium is one of the essential elements which adequate consumption is strictly necessary for human health. Despite unfavorable geographical position of Mongolia and registered cases of selenium deficiency diseases among domestic animals in some provinces of the country there are still no concrete data of selenium content in objects of the environment in this region. The aim of the present work was the evaluation of selenium consumption levels by adults from different provinces of Mongolia and the development of methods of prophylactic for the selenium status optimization. Detection of selenium deficiency in Mongolia was caused by inadequate selenium content in foodstuffs. Determined mean consumption levels were equal to 41.8±4.9 μg/day for males and 34.1±3.1 μg/day for females. The main reason of low selenium content in the diet was its deficiency in native foodstuffs: selenium concentrations in meat of domestic animals μg/kg d.w.) reached 109-296 in beef, 94-200 in mutton, 120-225 in horseflesh and 124-197 in goat's flash, values did not differ between each other statistically (p>0.05). The exception were samples of horseflash with selenium concentration exceeding 400 μg/kg d.w. from Gov-Altai province. Selenium content in wheat was in the range 6-36μg/kg d.w., with the lowest levels in Dornod, Ucs and Selenge provinces. Selenium content in eggs was equal 6.7-7.8 μg/egg. The correction of selenium deficiency is recommended to achieve using preparations of Astragalus Mongolicus from Bulgan province with selenium concentration 278±26μg/kg d.w. Besides this utilization of Mongolicum Tricholoma Mushrooms (from the vicinity of Ulaanbaatar and from Zavkhan province) seems to be highly promising due to high selenium concentrations (616±26 μg/kg d.w. and 352±17μg/kg d.w. respectively).


Genetic-molecular characterization of backcross generations for sexual conversion in papaya (Carica papaya L.).
The low number of improved cultivars limits the expansion of the papaya crop, particularly because of the time required for the development of new varieties using classical procedures. Molecular techniques associated with conventional procedures accelerate this process and allow targeted improvements. Thus, we used microsatellite markers to perform genetic-molecular characterization of papaya genotypes obtained from 3 backcross generations to monitor the inbreeding level and parental genome proportion in the evaluated genotypes. Based on the analysis of 20 microsatellite loci, 77 genotypes were evaluated, 25 of each generation of the backcross program as well as the parental genotypes. The markers analyzed were identified in 11 of the 12 linkage groups established for papaya, ranging from 1 to 4 per linkage group. The average values for the inbreeding coefficient were 0.88 (BC1S4), 0.47 (BC2S3), and 0.63 (BC3S2). Genomic analysis revealed average values of the recurrent parent genome of 82.7% in BC3S2, 64.4% in BC1S4, and 63.9% in BC2S3. Neither the inbreeding level nor the genomic proportions completely followed the expected average values. This demonstrates the significance of molecular analysis when examining different genotype values, given the importance of such information for selection processes in breeding programs.


Comparison of cholinergic activation and desensitization at snake twitch and slow muscle fibre end-plates.
Characteristics of receptor-channel activation and desensitization have been compared at voltage-clamped snake slow and twitch fibre end-plates maintained in an isotonic potassium propionate solution. Miniature end-plate current (m.e.p.c.) decay was slower and less voltage dependent at slow fibre end-plates than at twitch fibre end-plates. The peak m.e.p.c. amplitude versus voltage relationship and reversal potential were similar at the two end-plate types. Acetylcholine-induced noise and m.e.p.c.s were recorded at slow fibre end-plates. At most slow fibres the spectral density was not adequately fitted by a single Lorentzian function. Rather, the observed spectral density was greater at high frequencies than the values predicted using the m.e.p.c. decay rate. The noise could be well described by the sum of two Lorentzian functions, one of which corresponded to a single Lorentzian function with the corner frequency determined by the m.e.p.c. decay rate. The shape of the carbachol concentration-peak end-plate current relationship was similar at both slow and twitch fibre end-plates. However, for all concentrations tested, the peak carbachol-induced end-plate current (e.p.c.carb.) value was markedly less at slow fibre end-plates than at twitch fibre end-plates. The onset of desensitization was determined using two methods. The first concerned analysis of the time course of decay of the e.p.c.carb. from a peak value during the sustained application of agonist. The second involved a double-perfusion technique in which a 'desensitizing' dose was applied for varying intervals before the application of a second 'test' dose of carbachol. With both methods the development of desensitization at both end-plate types was dependent on carbachol concentration and duration of exposure. At each end-plate type the time course of desensitization onset often exhibited two components; one with a time constant of seconds and a slower component having time constants in the range of tens to hundreds of seconds. The slope of the relationship between carbachol concentration and equilibrium desensitization at slow and twitch fibre end-plates was close to two, suggesting that two molecules of agonist are probably bound during the development of desensitization. However, for all concentrations tested, desensitization developed more rapidly and to a greater extent at twitch fibre end-plates than at slow fibre end-plates. The voltage dependence of the 3 min steady-state desensitization produced by 108 microM-carbachol was very similar (approximately -0.0250 mV-1) at both fibre types.(ABSTRACT TRUNCATED AT 400 WORDS)


Knockdown of Ras-Related Protein 25 (Rab25) Inhibits the In Vitro Cytotoxicity and In Vivo Antitumor Activity of Human Glioblastoma Multiforme Cells.
Ras-related protein 25 (Rab25) is a member of the Rab family, and it has been reported to play an important role in tumorigenesis. However, its direct involvement in human glioblastoma multiforme (GBM) is still unclear. The aim of the current study was to investigate the potential role of Rab25 in the growth, proliferation, invasion, and migration of human GBM. Our results showed that Rab25 expression was significantly higher in human GBM cell lines compared with a normal astrocyte cell line. In vitro functional studies revealed that knockdown of Rab25 reduced cell proliferation and inhibited invasion and migration of GBM cells. In vivo experiments showed that knockdown of Rab25 attenuated the tumor growth in nude mice. Finally, knockdown of Rab25 significantly inhibited the phosphorylation levels of PI3K and AKT in GBM cells. Taken together, these findings indicate that Rab25 may act as a tumor promoter in human GBM and that approaches to target Rab25 may provide a novel strategy to treat this disease.


Utilizing the Oxygen Reduction Reaction in Particle Impact Electrochemistry: A Step toward Mediator-Free Digital Electrochemical Sensors.
The current blockade particle impact method opens a route toward highly parallelized single-entity electrochemical assays. An important limitation is, however, that a redox mediator must be present in the sample, which can detrimentally interfere with molecular recognition processes. Dissolved O2 that is naturally present in aqueous solutions under ambient conditions can in principle serve as a suitable mediator via the oxygen reduction reaction (ORR). Here, we demonstrate the validity of this concept by performing current blockade experiments to capture and detect individual microparticles at Pt microelectrodes using solely the ORR. The readout modality is independent of the absolute O2 concentration, allowing operation under varying conditions. We further determine how the trajectories of individual microparticles are influenced by the combination of electrophoresis and electroosmotic flows and how these can be utilized to provide continuous detection of cationic particles in water for environmental monitoring.


Prevalence and Related Factors of Euthyroid Sick Syndrome in Children with Untreated Cancer According to Two Different Criteria
In this study, we evaluated the frequency of euthyroid sick syndrome (ESS) among patients with childhood cancer and its association with the stage of disease, nutritional parameters and cytokines levels. Eighty newly diagnosed children were included in the study. ESS was assessed in two different ways. According to criteria 1 ESS was present if free triiodothyronine (fT3) was below the lower limit and free thyroxine was within the normal or low limits, thyroid-stimulating hormone (TSH) was in the normal range. According to criteria 2, in addition to the above, it was required that reverse triiodothyronine (rT3) be performed and was higher than normal limits. Three of our pediatric patients had subclinical hypothyroidism and two had subclinical hyperthyroidism. Out of 75 patients, ESS was identified in 14 (17.3%) according to criteria 1 and in eight (10.6%) according to criteria 2. Only fT3 levels were significantly different in the ESS (+) and ESS (-) groups (p<0.05) according to criteria 1. A significantly negative correlation between interleukin (IL)-6 and fT3 was found, according to both sets of criteria. tumor necrosis factor alpha was negatively correlated with fT3 levels only in the criteria 1 group. There were no correlations between IL-1β and fT3, free thyroxine, rT3 and TSH levels. ESS may occur in childhood cancer and thyroid function testing should be performed routinely when cancer is diagnosed.


Comparable Injury to the Indirect Head of the Rectus Femoris During Interportal and Periportal Capsulotomy: A Cadaveric Study.
There is concern for maintaining the integrity of the reflected head of the rectus femoris during arthroscopic hip joint access. Because of the proximity to the indirect head of the rectus femoris (IHRF), capsulotomy technique and capsular closure during routine hip arthroscopy may play a role in postoperative tendinitis. To quantify the extent of injury sustained to the IHRF during interportal versus periportal capsulotomy for routine arthroscopic hip joint access. Controlled laboratory study. A cadaveric study was conducted using 20 fresh-frozen cadaveric hips, in which hip joint access through a periportal capsulotomy (n = 10) or interportal capsulotomy (n = 10) was performed. Capsular closure followed by a layered dissection to the capsuloligamentous complex of the hip joint was then performed to localize the IHRF. Suture proximity to the tendon, tendon disruption, and the IHRF footprint was documented to the nearest 0.01 mm using digital calipers. Statistical analysis was performed using unpaired Student t tests. The mean capsulotomy length for the interportal specimens was 19.27 ± 3.25 mm, and the mean medial and lateral capsulotomy length for the periportal specimens was 4.47 ± 1.60 and 4.26 ± 0.89 mm, respectively. There was violation of the tendon in 3 of 10 interportal specimens and 4 of 10 periportal specimens. There was no significant difference in the closest suture measured to the IHRF for specimens with versus without tendon violation, for either interportal or periportal capsulotomy. We found comparable outcomes with regard to violation of the IHRF between interportal and periportal capsulotomy, with no significant difference in suture proximity to the IHRF in specimens with or without tendon violation. There remains no consensus on the ideal method by which to avoid iatrogenic damage to the IHRF. Our findings provide insight that may lead to future advances in surgical care, such that protection of the tendon during routine hip arthroscopy may allow for improved postoperative rehabilitation and strength.


The Potential Protective Effect of Mesencephalic Astrocyte-Derived Neurotrophic Factor on Post-Operative Delirium via Inhibiting Inflammation and Microglia Activation.
The increased inflammation is closely correlated with post-operative delirium (POD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) shows protective effect on inflammatory diseases. However, the relationship between MANF and POD is still undefined. This study aimed to explore the potential effect of MANF on POD. Pre- and post-operative levels of MANF and inflammatory cytokines were measured in serum from POD and non-POD patients by ELISA, as well as endogenous MANF in serum from healthy individuals with different ages. Endogenous MANF in mice brain from different ages was also measured. Abdominal surgery was performed for POD mice model. POD-like behavior changes in mice were evaluated using buried food test, open field test and Y maze test. Endogenous MANF was decreased in age-dependent manner in both humans and mice. The pre-operative level of MANF in serum from POD patients was lower compared with that in non-POD patients (p=0.016). MANF increase in serum after surgery was less in POD patients than that in non-POD patients (p<0.001). In mice, recombinant human MANF reversed the surgery-induced elongation of latency to eat food, increase in latency to center and increase in time in center in open field test, and also increase in duration in novel arm in Y maze test. In addition, MANF inhibited surgery-induced inflammation, microglial activation and M1 polarization in mice. The relative low MANF level may contribute to POD in the elderly. MANF has a protective role against POD-like behavior changes in mice.


Self-assembly modes of glycyrrhetinic acid esters in view of the crystal packing of related triterpene molecules.
The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are reported. X-ray crystallography revealed that despite differences in the size of the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of molecular self-assembly is similar in all three cases but differs significantly from that observed in other known GE esters. According to our analysis, the two basic patterns of self-assembly of GE esters observed in their unsolvated crystals correspond to two distinct orientations of the ester groups relative to the triterpene backbone. Moreover, comparison of the self-assembly modes of GE esters in their unsolvated forms with the supramolecular organization of GE and carbenoxolone in their solvated crystals revealed that ester substituents replace solvent molecules hydrogen bonded to the COOH group at the triterpene skeleton, resulting in similar packing arrangements of these compounds.


[Isolation and study of physico-chemical properties of alpha-amylase from Bacillus subtilis].
By chromatography on ultragel ACA-54 alpha-amylase was isolated from the enzymic preparation amylosubtilin G10x. As compared to the initial preparation, the specific activity of the purified enzyme per mg increased 25-fold. The major physico-chemical characteristics of alpha-amylase were determined. The molecular weight of the enzyme measured by gel-chromatography and electrophoresis was estimated to be 49,000. The isoelectric point determined by electrofocusing was found to be 5,2. Irreversible acid inactivation of the enzyme in the range of pH 2-5 was investigated. The reaction was found to develop in at least two stages.


Lesser Metatarsophalangeal Joint Pathology Addressed With Arthrodesis: A Case Series.
Lesser metatarsophalangeal joint pathology is a common condition facing the foot and ankle surgeon, often beginning as a mild subluxation of the toe and progressing to a full dislocation of the metatarsophalangeal joint. In severe or recalcitrant deformities, traditional conservative and surgical methods can fail to resolve the issue. We report on 4 patients with 5 severely dislocated lesser metatarsophalangeal joints with varied etiologies and comorbidities who underwent arthrodesis of these joints using screw and plate fixation. All patients achieved radiographic and clinical signs of union at an average of 16.4 weeks.


Effect of excisional wounding on DMBA-induced hamster tongue carcinogenesis.
The purpose of this study was to investigate histologically the effect of wounding on the hamster tongue after pretreatment with DMBA. The animals in which the tips of the tongues were pretreated with DMBA for 8 weeks, subsequently excised, and had no treatment or received applications of acetone, showed epithelial dysplasias. The animals which had the same pretreatment, excision, and received additional post-excision applications of DMBA for 9-13 days, developed squamous cell carcinomas. However, the animals which were pretreated with DMBA for 8 weeks but had no excision, did not show any pathologic changes, even though they received additional applications of DMBA for 9-13 days. The animals which received no pretreatment with DMBA for 8 weeks but had an excision, showed normal wound healing, even though they had a post-treatment with DMBA for 9-13 days. The results of the present study indicated that excisional wounding acted as a promotional stimulus in inducing the appearance of epithelial dysplasias or carcinomas of tongues initiated with the carcinogen DMBA.


Analysis of the genetic diversity of Chinese native Cannabis sativa cultivars by using ISSR and chromosome markers.
Hemp (Cannabis sativa) is an important fiber crop, and native cultivars exist widely throughout China. In the present study, we analyzed the genetic diversity of 27 important Chinese native hemp cultivars, by using inter-simple sequence repeats (ISSR) and chromosome markers. We determined the following chromosome formulas: 2n = 20 = 14m + 6sm; 2n = 20 = 20m; 2n = 20 = 18m + 2sm; 2n = 20 = 16m + 4sm; and 2n = 20 = 12m + 8sm. The results of our ISSR analysis revealed the genetic relationships among the 27 cultivars; these relationships were analyzed by using the unweighted pair-group method based on DNA polymorphism. Our results revealed that all of the native cultivars showed considerable genetic diversity. At a genetic distance of 0.324, the 27 varieties could be classified into five categories; this grouping corresponded well with the chromosome formulas. All of the investigated hemp cultivars represent relatively primitive types; moreover, the genetic distances show a geographical distribution, with a small amount of regional hybridity.


Native Reversed-Phase Liquid Chromatography: A Technique for LCMS of Intact Antibody-Drug Conjugates.
The synthesis of antibody-drug conjugates (ADCs) using the interchain cysteines of the antibody inherently gives a mixture of proteins with varying drug-to-antibody ratio. The drug distribution profiles of ADCs are routinely characterized by hydrophobic interaction chromatography (HIC). Because HIC is not in-line compatible with mass spectrometry (MS) due to the high salt levels, it is laborious to identify the constituents of HIC peaks. An MS-compatible alternative to HIC is reported here: native reversed phase liquid chromatography (nRPLC). This novel technique employs a mobile phase 50 mM ammonium acetate for high sensitivity in MS and elution with a gradient of water/isopropanol. The key to the enhancement is a bonded phase giving weaker drug-surface interactions compared to the noncovalent interactions holding the antibody-drug conjugates together. The hydrophobicity of the bonded phase is varied, and the least hydrophobic bonded phase in the series, poly(methyl methacrylate), is found to resolve the intact constituents of a model ADC (Ab095-PZ) and a commercial ADC (brentuximab vedotin) under the MS-compatible conditions. The nRPLC-MS data show that all species, ranging from drug-to-antibody ratios of 1 to 8, remained intact in the column. Another desired advantage of the nRPLC is the ability of resolving multiple positional isomers of ADC that are not well-resolved in other chromatographic modes. This supports the premise that lower hydrophobicity of the bonded phase is the key to enabling online nRPLC-MS analysis of antibody-drug conjugates.


VirtualLeaf: an open-source framework for cell-based modeling of plant tissue growth and development.
Plant organs, including leaves and roots, develop by means of a multilevel cross talk between gene regulation, patterned cell division and cell expansion, and tissue mechanics. The multilevel regulatory mechanisms complicate classic molecular genetics or functional genomics approaches to biological development, because these methodologies implicitly assume a direct relation between genes and traits at the level of the whole plant or organ. Instead, understanding gene function requires insight into the roles of gene products in regulatory networks, the conditions of gene expression, etc. This interplay is impossible to understand intuitively. Mathematical and computer modeling allows researchers to design new hypotheses and produce experimentally testable insights. However, the required mathematics and programming experience makes modeling poorly accessible to experimental biologists. Problem-solving environments provide biologically intuitive in silico objects ("cells", "regulation networks") required for setting up a simulation and present those to the user in terms of familiar, biological terminology. Here, we introduce the cell-based computer modeling framework VirtualLeaf for plant tissue morphogenesis. The current version defines a set of biologically intuitive C++ objects, including cells, cell walls, and diffusing and reacting chemicals, that provide useful abstractions for building biological simulations of developmental processes. We present a step-by-step introduction to building models with VirtualLeaf, providing basic example models of leaf venation and meristem development. VirtualLeaf-based models provide a means for plant researchers to analyze the function of developmental genes in the context of the biophysics of growth and patterning. VirtualLeaf is an ongoing open-source software project (http://virtualleaf.googlecode.com) that runs on Windows, Mac, and Linux.


[Occupational hypersensitivity pneumonitis].
Hypersensitivity pneumonitis (HP) is a granulomatous disease of the lungs due to immune reactions following chronic inhalation of organic dusts or chemicals especially encountered in the occupational environment. The main purpose of this review is to report current concepts regarding aetiologies, epidemiology, diagnosis, treatment as well as legal aspects of HP. The following aspects will be focused: (1) increase in new etiological circumstances, especially occupational and news antigens, (2) for diagnosis, the major contribution of chest high resolution CT scan which often shows characteristic images but also recent developments in simple diagnostic criteria that may be used for an epidemiological approach, (3) importance of bronchial obstruction and even emphysema as a long term sequelae, finally (4) the possibility of continuing occupational activities in certain circumstances where preventive measures can be used. The increasing knowledge of etiological agents and circumstances as well as the development of secondary and especially primary preventive measures should lead to reduce the frequency of this disease and of its medico-social consequences.


In situ biosurfactant production by Bacillus strains injected into a limestone petroleum reservoir.
Biosurfactant-mediated oil recovery may be an economic approach for recovery of significant amounts of oil entrapped in reservoirs, but evidence that biosurfactants can be produced in situ at concentrations needed to mobilize oil is lacking. We tested whether two Bacillus strains that produce lipopeptide biosurfactants can metabolize and produce their biosurfactants in an oil reservoir. Five wells that produce from the same Viola limestone formation were used. Two wells received an inoculum (a mixture of Bacillus strain RS-1 and Bacillus subtilis subsp. spizizenii NRRL B-23049) and nutrients (glucose, sodium nitrate, and trace metals), two wells received just nutrients, and one well received only formation water. Results showed in situ metabolism and biosurfactant production. The average concentration of lipopeptide biosurfactant in the produced fluids of the inoculated wells was about 90 mg/liter. This concentration is approximately nine times the minimum concentration required to mobilize entrapped oil from sandstone cores. Carbon dioxide, acetate, lactate, ethanol, and 2,3-butanediol were detected in the produced fluids of the inoculated wells. Only CO(2) and ethanol were detected in the produced fluids of the nutrient-only-treated wells. Microbiological and molecular data showed that the microorganisms injected into the formation were retrieved in the produced fluids of the inoculated wells. We provide essential data for modeling microbial oil recovery processes in situ, including growth rates (0.06 +/- 0.01 h(-1)), carbon balances (107% +/- 34%), biosurfactant production rates (0.02 +/- 0.001 h(-1)), and biosurfactant yields (0.015 +/- 0.001 mol biosurfactant/mol glucose). The data demonstrate the technical feasibility of microbial processes for oil recovery.


Aspects of the relationship between cognitive theories and therapies of depression.
Cognitive theories of depression are examined with respect to the relationship between cognition and affect, the assumption that cognitions are accessible and open to modification, and the adequacy of cognitive accounts of the onset and maintenance of depression. The role of social and familial factors in maintaining depression and the extent to which negative cognitions may be based on accurate perceptions of the social milieu are considered. The relationship between cognitive therapy for depression and cognitive theories of depression is noted.


In vitro evaluation of dual carbapenem combinations against carbapenemase-producing Enterobacteriaceae.
This study aimed to analyse the in vitro activity of dual combinations of carbapenems against Klebsiella pneumoniae producing the main carbapenemase types. MIC values of the carbapenems, imipenem, meropenem, ertapenem and doripenem were determined alone and in dual combinations for 20 clinical K. pneumoniae isolates producing representative carbapenemases, i.e. OXA-48 (n = 6), NDM-1 (n = 4), NDM-1 + OXA-48 (n = 2) and KPC-2 (n = 8). MICs were also determined for Escherichia coli recombinant strains with or without permeability defects producing NDM-1, OXA-48 or KPC-2. In vitro synergy combination testing was performed using the microdilution and chequerboard techniques. Fractional inhibitory concentration indexes were calculated to determine whether the combinations were synergistic, indifferent or antagonistic. All carbapenemase producers were resistant to the tested carbapenems, with most isolates showing MICs of carbapenems >32 mg/L. None of the combinations was antagonistic. For KPC producers, synergistic combinations were observed with imipenem/ertapenem (5/8 isolates), imipenem/doripenem (4/8), imipenem/doripenem (4/8), meropenem/doripenem (3/8) and ertapenem/doripenem (3/8), while no synergy was observed with meropenem/ertapenem. For OXA-48 producers, synergies were observed with imipenem/ertapenem and with imipenem/meropenem for both isolates tested. Notably, combining imipenem with a non-carbapenem β-lactam (cefalotin) did not give any synergistic result. No synergy was observed for all NDM-1 and NDM-1+OXA-48 producers. Time-kill assays confirmed most of the data obtained by chequerboard testing. The data strongly support the hypothesis that dual carbapenem combinations might be effective against serine-β-lactamase producers (KPC, OXA-48). The imipenem-containing combinations appeared to be the most efficient.


Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.
The inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with the identification of side effects resulting from chronic Dll4/Notch blockade. Alternatively, we explored the endothelial Dll4 overexpression using different mouse tumor models. We used a transgenic mouse model of endothelial-specific Dll4 overexpression, previously produced. Growth kinetics and vascular histopathology of several types of solid tumors was evaluated, namely Lewis Lung Carcinoma xenografts, chemically-induced skin papillomas and RIP1-Tag2 insulinomas. We found that increased Dll4/Notch signaling reduces tumor growth by reducing vascular endothelial growth factor (VEGF)-induced endothelial proliferation, tumor vessel density and overall tumor blood supply. In addition, Dll4 overexpression consistently improved tumor vascular maturation and functionality, as indicated by increased vessel calibers, enhanced mural cell recruitment and increased network perfusion. Importantly, the tumor vessel normalization is not more effective than restricted vessel proliferation, but was found to prevent metastasis formation and allow for increased delivery to the tumor of concomitant chemotherapy, improving its efficacy. By reducing endothelial sensitivity to VEGF, these results imply that Dll4/Notch stimulation in tumor microenvironment could be beneficial to solid cancer patient treatment by reducing primary tumor size, improving tumor drug delivery and reducing metastization. Endothelial specific Dll4 overexpression thus appears as a promising anti-angiogenic modality that might improve cancer control.


Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner.
The mouse cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine. However, the neurotransmitters released by cortical ChAT+ neurons and their synaptic connectivity are unknown. We show that the nearly all cortical ChAT+ neurons in mice are specialized VIP+ interneurons that release GABA strongly onto other inhibitory interneurons and acetylcholine sparsely onto layer 1 interneurons and other VIP+/ChAT+ interneurons. This differential transmission of ACh and GABA based on the postsynaptic target neuron is reflected in VIP+/ChAT+ interneuron pre-synaptic terminals, as quantitative molecular analysis shows that only a subset of these are specialized to release acetylcholine. In addition, we identify a separate, sparse population of non-VIP ChAT+ neurons in the medial prefrontal cortex with a distinct developmental origin that robustly release acetylcholine in layer 1. These results demonstrate both cortex-region heterogeneity in cortical ChAT+ interneurons and target-specific co-release of acetylcholine and GABA.


Mitochondrial and microsatellite DNA analyses showed comparative genetic diversity between parent and offspring populations of Korean black rockfish in a hatchery facility.
The black rockfish, Sebastes inermis (Sebastidae), is an important commercial fishery resource in Korea. As a preliminary investigation into the effect of artificial reproduction in a hatchery facility, the genetic divergence between parent and offspring populations of black rockfish was accessed using 10 polymorphic nuclear microsatellite DNA loci and a mitochondrial (mt) control gene. All loci that were screened showed marked polymorphisms. mtDNA control region sequences were also highly variable. Of approximately 350 base pairs (bp) sequenced, 52 variable sites, comprising 56 base substitutions, were found among 233 individuals. Offspring populations showed less genetic variability than the parent population in terms of numbers of microsatellite alleles and mtDNA haplotypes, as well as mtDNA haplotype diversity. Statistical analysis of the fixation index (ΦST and F(ST)) and analysis of molecular variance using both DNA markers showed significant genetic differences between the parent and offspring populations. These results suggest that random genetic drift and/or inbreeding events, as well as artificial selection and founder effects, occurred when the offspring strain was reproduced in a hatchery facility despite thousands of males and females from different hatcheries being maintained for artificial reproduction. Therefore, it is necessary to improve current hatchery programs by monitoring genetic variation in both the broodstock and progeny and controlling inbreeding within stocks in commercial breeding facilities to maintain the production of high-quality black rockfish. This information will be useful for determining suitable guidelines for establishing and maintaining cultured stocks and the aquaculture industry of S. inermis.


The immunological response of llamas (Lama glama) following experimental infection with Mycobacterium bovis.
Llamas were experimentally infected with Mycobacterium bovis in order to evaluate the axillary skin test and the ELISA as diagnostic procedures for tuberculosis in llamas (Lama glama). Six llamas were given a single intratracheal challenge with 1 of 2 doses of a recent field isolate of M. bovis and 2 llamas were left as noninfected controls. This resulted in a progressive disease in some animals with 1 mortality as early as 68 d post-infection (PI). The tuberculin skin test, at the axillary site, was positive in 4 of 5 infected llamas at 80 d PI. At 143 d PI, all 3 surviving lamas were positive, including the one which had not responded at 80 d PI. The application of skin and serological tests throughout the course of this experiment adds support for the need to further evaluate the skin test and its anamnestic effect on serodiagnosis since serological responses were generally not observed in the absence of skin testing or antibiotic treatment. The wide variation in M. bovis antigens recognized by the serological response would indicate that a diagnostic panel should include multiple antigens such as MPB70 and lipoarabinomannan (LAM). While skin testing or serology alone may be of limited value to diagnose tuberculosis in llamas, together they may offer an enhanced potential for immunodiagnosis of tuberculosis.


Quantifying gene network connectivity in silico: scalability and accuracy of a modular approach.
Large, complex data sets that are generated from microarray experiments, create a need for systematic analysis techniques to unravel the underlying connectivity of gene regulatory networks. A modular approach, previously proposed by Kholodenko and co-workers, helps to scale down the network complexity into more computationally manageable entities called modules. A functional module includes a gene's mRNA, promoter and resulting products, thus encompassing a large set of interacting states. The essential elements of this approach are described in detail for a three-gene model network and later extended to a ten-gene model network, demonstrating scalability. The network architecture is identified by analysing in silico steady-state changes in the activities of only the module outputs, communicating intermediates, that result from specific perturbations applied to the network modules one at a time. These steady-state changes form the system response matrix, which is used to compute the network connectivity or network interaction map. By employing a known biochemical network, the accuracy of the modular approach and its sensitivity to key assumptions are evaluated.


Healthcare utilization and economic burden of myopia in urban China: A nationwide cost-of-illness study.
China contributes to a significant proportion of the myopia in the world. The study aims to investigate the utilization of various correction methods and health service in urban China, and to estimate the cost of myopia treatment and prevention. In addition, we aimed to estimate the cost of productivity loss due to myopia. The study was a cross-sectional investigation carried out in urban areas in three provinces located in the east (Shanghai), middle (Anhui) and west part (Yunnan) of China, in 2016. A total of 23819 people aged between 5 to 50 years were included. Health utilization and the cost of myopia were analyzed from patients' perspective. The total number of people with myopia in the urban China was estimated to be 143.6 million. The correction rate was 89.5%, 92.1%, and 92.7% for Anhui, Shanghai, and Yunnan (χ2 = 19.5, P < 0.01). Over the recent year, 20.6%, 16.8%, and 28.8% of myopic subjects visited hospital due to myopia, in Anhui, Shanghai and Yunnan. The annual cost of treatment and prevention of myopia was 10.1 billion US dollar (US$, floating from 9.2 to 11.2 billion US$), and the cost per person was 69US$. The annual cost of loss of productivity was estimated to be 6.7 billion US$ for those with mild to moderate visual impairment (floating from 6.1 to 7.4 billion US$), and 9.4 billion US$ (floating from 8.5 to 10.4 billion US$) for those with severe visual impairment to blindness. Therefore, the total economic burden of myopia was estimated as 173.6 billion CNY (26.3 billion US$). The present study shows that myopia leads to substantial economic burden in China. The loss of productivity caused by myopia is an important part of the disease burden compared to the cost of correction and treatment paid by individuals. Therefore, the focus of myopia prevention and control should be to decrease the myopia prevalence, and prevent the uncorrected refractive errors and the irreversible damage of visual acuity by high myopia.


Late onset hepatic failure: clinical, serological and histological features.
The clinical, laboratory and histological features of 47 patients with what is defined as late onset hepatic failure are reviewed. Twenty-five of the patients were female and 22 male with a median age of 45 years. Hepatic dysfunction was severe as evidenced by the prolongation of prothrombin time (median = 32 sec, range = 17 to 120 sec). In only four cases was a viral etiology proven (2 hepatitis B, 2 hepatitis A) although the similarity of the clinical features to patients with fulminant viral hepatitis--apart from the longer period of illness prior to the onset of encephalopathy (median = 9 weeks, range = 8 to 24 weeks)--made non-A, non-B infection a possibility in the remainder. There were also similarities to chronic active hepatitis with low titer antibodies to smooth muscle or antinuclear factor in 17% and elevation of the serum IgG in 49%. Liver biopsy in 5 of 8 survivors more than 1 year after initial presentation showed chronic active hepatitis in three. Lobular inflammatory infiltrate, bridging necrosis and multilobular collapse were the features of the acute stage of illness in both the survivors and fatal cases. The patients given corticosteroids did not have a statistically significant improvement in survival, and overall mortality for the series was 81%. Hepatic transplantation, successfully performed in one patient, would appear to offer the best chance of survival for the majority of these patients.


Advances on the Study of Diurnal Flower-Opening Times of Rice.
The principal goal of rice (Oryza sativa L.) breeding is to increase the yield. In the past, hybrid rice was mainly indica intra-subspecies hybrids, but its yield has been difficult to improve. The hybridization between the indica and japonica subspecies has stronger heterosis; the utilization of inter-subspecies heterosis is important for long-term improvement of rice yields. However, the different diurnal flower-opening times (DFOTs) between the indica and japonica subspecies seriously reduce the efficiency of cross-pollination and yield and increase the cost of indica-japonica hybrid rice seeds, which has become one of the main constraints for the development of indica-japonica hybrid rice breeding. The DFOT of plants is adapted to their growing environment and is also closely related to species stability and evolution. Herein, we review the structure and physiological basis of rice flower opening, the factors that affect DFOT, and the progress of cloning and characterization of DFOT genes in rice. We also analyze the problems in the study of DFOT and provide corresponding suggestions.


Development of 16 novel EST-SSR markers for species identification and cross-genus amplification in sambar, sika, and red deer.
Deer genera around the globe are threatened by anthropogenic interference. The translocation of alien species and their subsequent genetic introgression into indigenous deer populations is particularly harmful to the species of greatest conservation concern. Products derived from deer, including venison and antler velvet, are also at risk of fraudulent labeling. The current molecular markers used to genetically identify deer species were developed from genome sequences and have limited applicability for cross-species amplification. The absence of efficacious diagnostic techniques for identifying deer species has hampered conservation and wildlife crime investigation efforts. Expressed sequence tag-simple sequence repeat (EST-SSR) markers are reliable tools for individual and species identification, especially in terms of cross-species genotyping. We conducted transcriptome sequencing of sambar (Rusa unicolor) antler velvet and acquired 11,190 EST-SSRs from 65,074 newly assembled unigenes. We identified a total of 55 unambiguous amplicons in sambar (n = 45), which were selected as markers to evaluate cross-species genotyping in sika deer (Cervus nippon, n = 30) and red deer (Cervus elaphus, n = 46), resulting in cross-species amplification rates of 94.5% and 89.1%, respectively. Based on polymorphic information content (>0.25) and genotyping fidelity, we selected 16 of these EST-SSRs for species identification. This marker set revealed significant genetic differentiation based on the fixation index and genetic distance values. Principal coordinate analysis and STRUCTURE analysis revealed distinct clusters of species and clearly identified red-sika hybrids. These markers showed applicability across different genera and proved suitable for identification and phylogenetic analyses across deer species.


Mycobacterium tuberculosis infection among persons who inject drugs in San Diego, California.
Persons who inject drugs (PWID) might be at increased risk for Mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (LTBI) due to their injection drug use. To determine prevalence and correlates of M. tuberculosis infection among PWID in San Diego, California, USA. PWID aged 18 years underwent standardized interviews and serologic testing using an interferon-gamma release assay (IGRA) for LTBI and rapid point-of-care assays for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Independent correlates of M. tuberculosis infection were identified using multivariable log-binomial regression. A total of 500 participants met the eligibility criteria. The mean age was 43.2 years (standard deviation 11.6); most subjects were White (52%) or Hispanic (30.8%), and male (75%). Overall, 86.7% reported having ever traveled to Mexico. Prevalence of M. tuberculosis infection was 23.6%; 0.8% were co-infected with HIV and 81.7% were co-infected with HCV. Almost all participants (95%) had been previously tested for M. tuberculosis; 7.6% had been previously told they were infected. M. tuberculosis infection was independently associated with being Hispanic, having longer injection histories, testing HCV-positive, and correctly reporting that people with 'sleeping' TB cannot infect others. Strategies are needed to increase awareness about and treatment for M. tuberculosis infection among PWID in the US/Mexico border region.


Oral health-related knowledge, attitude and practices among eunuchs (hijras) residing in Bhopal City, Madhya Pradesh, India: A cross-sectional questionnaire survey.
The current cross-sectional questionnaire survey was conducted to assess the oral health-related knowledge, attitude and practices among eunuchs (hijras) residing in Bhopal city, Madhya Pradesh, India. Based on a convenient non-probability snow ball sampling technique, all the self-identified eunuchs residing in the city of Bhopal who were present at the time of study and who fulfilled the selection criteria were approached. A cross section of the general population was also surveyed. An interviewer-based, predesigned, structured, close-ended 18-item questionnaire that had been designed based on the primary objective of the study was used. All the obtained data were analyzed using software, Statistical Package for Social Science version 20. According to 188 (86.2%) males, 187 (87.4%) females and 168 (81.2%) eunuchs, good oral health can improve the general health. Most of the study participants including 211 (98.6%) females, 210 (96.3%) males and 205 (99%) eunuchs use either tooth paste or tooth powder to clean their teeth. While, a majority of eunuchs, i.e., 113 (54.6%), were having habit of chewing smokeless tobacco containing products such as betel nut, betel quid, gutkha, etc., The difference in use of tobacco products was statistically significant. The information presented in this study adds to our understanding of the common oral hygiene practices which are performed among eunuch population. Efforts to increase the awareness of oral effects of tobacco use and to eliminate the habit are needed to improve oral and general health of this population.


Note: Mechanical etching of atomic force microscope tip and microsphere attachment for thermal radiation scattering enhancement.
This Note describes a mechanical etching technique which can be used to prepare silicon tips used in atomic force microscopy apparatus. For such devices, dedicated tips with specific shapes are now commonly used to probe surfaces. Yet, the control of the tip morphology where characteristic scales are lower than 1 μm remains a real challenge. Here, we detail a controlled etching process of AFM probes apex allowing micrometer-sized sphere attachment. The technique used and influent parameters are discussed and SEM images of the achieved tips are given. Deceptive problems and drawbacks that might occur during the process are also covered.


Molecular and cellular effects of antisickling concentrations of alkylureas.
Alkylureas are capable of inhibiting sickling in vitro and the gelation of solutions of hemoglobin S at concentrations between 0.05 and 0.1 M with increasing effectiveness that is directly proportional to the length of the alkyl chain (butyl greater than propyl greater than ethyl greater than methyl). 6The inhibitory effect is independent of pH between 6.5 and 7.5 and is a process driven by entropy. The alkylureas at concentrations of 0.1 M have minimal effects on several erythrocyte functions. Oxygen equilibria, osmotic fragility, reduced glutathione content, and glutathione reductase activity are totally unaffected, while pyruvic kinase activity is decreased only by butylurea by about 20%, and glucose-6-phosphate dehydrogenase activity is decreased progressively to a maximum of 30% in direct proportion to the length of the alkyl chain. Alkylureas not only inhibit sickling but are also capable of desickling erythrocytes that have been maintained in the deoxygenated state. They have little effect on several erythrocyte functions at antisickling concentrations, but their toxicity must be evaluated before they can be examined as potential therapeutic agents for the treatment or prevention of acute episodes in sickle cell anemia.


Cell-free protein synthesis systems derived from cultured mammalian cells.
We present a technology for the production of target proteins using novel cell-free systems derived from cultured human K562 cells and Chinese hamster ovary (CHO) cells. The protocol includes the cultivation of cells, the preparation of translationally active lysates, and the cell-free synthesis of desired proteins. An efficient expression vector based on the internal ribosome entry site (IRES) from the intergenic region (IGR) of the cricket paralysis virus (CrPV) was constructed for both systems. The coupled batch-based platforms enable the synthesis of a broad range of target proteins such as cytosolic proteins, secreted proteins, membrane proteins embedded into endogenous microsomes, and glycoproteins. The glycosylation of erythropoietin demonstrates the successful performance of posttranslational modifications in the novel cell-free systems. Protein yields of approximately 20 μg/ml (K562-based cell-free system) and 50 μg/ml (CHO-based cell-free system) of active firefly luciferase are obtained in the coupled transcription-translation systems within 3 h. As a result, both cell-free protein synthesis systems serve as powerful tools for high-throughput proteomics.