Implementing an intervention to reduce use of antibiotics for suspected urinary tract infection in nursing homes - a qualitative study of barriers and enablers based on Normalization Process Theory.
Overuse of antibiotics in the elderly population is contributing to the global health problem of antibiotic resistance. Hence, it is important to improve prescribing practices in care facilities for elderly residents. In nursing homes, urinary tract infection (UTI) is the most common reason for antibiotic prescription but inappropriate prescriptions are frequent. In order to reduce the use of antibiotics for suspected urinary tract infection in this context, a complex intervention based on education as well as tools for reflection and communication had been developed and trialed in a group of nursing homes. The presents study explored the barriers and enablers in implementing this complex intervention. After the intervention trial period, a qualitative interview study was performed in six of the nursing homes that had received the intervention. The study included 12 informants: One senior manager, four nurses, six healthcare assistants, and one healthcare helper. Normalization Process Theory was used to structure the interviews as well as the analysis. The intervention was well received among the informants in terms of its purpose and content. The initial educational session had altered the informants' perceptions of UTI and of the need for adopting a different approach to suspected UTIs. Also, the study participants generally experienced that the intervention had positively impacted their practice. The most important barrier was that some of the interventions' clinical content was difficult to understand for the staff. This contributed to some problems with engaging all relevant staff in the intervention and with using the observation tool correctly in practice. Here, nurses played a key role in the implementation process by regularly explaining and discussing the intervention with other staff. The results suggest that it is possible to implement more evidence-based practices concerning antibiotics use in nursing homes by employing a combination of educational activities and supportive tools directed at nursing home staff.


Investigating Potential Modes of Actions of Mimusops kummel Fruit Extract and Solvent Fractions for Their Antidiarrheal Activities in Mice.
Fruits of Mimusops kummel A. DC. (Sapotaceae) are traditionally used for the treatment of diarrhea. The present study aimed at investigating modes of actions of this fruits for antidiarrheal action to guide future drug development process. Fractions of chloroform, n-butanol, and water were obtained from 80% methanol extract, which was prepared by maceration. Antidiarrheal activities and the modes of actions were investigated in mice. In castor oil induced diarrheal model, the extract delayed onset of diarrhea and reduced number and weight of feces at all tested doses significantly. In this model all fractions significantly delayed onset of diarrhea at all tested doses. Charcoal meal test showed that the extract and all the fractions produced a significant antimotility effect at all tested doses. Enteropooling test showed that the extract as well as n-butanol and aqueous fractions at all tested doses produced a significant decline in volume and weight of intestinal contents, whereas chloroform fraction had substantial effect only at high dose. This study demonstrated that the extract and solvent fractions produced antidiarrheal activities due to dual inhibitory effect, intestinal motility, and fluid secretion, with the aqueous fraction being the most active among fractions in three models.


Manufacturing Clinical Grade Recombinant Adeno-Associated Virus Using Invertebrate Cell Lines.
Recombinant adeno-associated virus (rAAV) vectors are proving to be a reliable gene transfer system for several clinical applications, with an increasing body of evidence supporting safety and efficacy. Realizing the clinical and commercial potential of rAAV depends on a reliable source of high-quality, well-characterized rAAV lots. This requirement has been very challenging to achieve due to limits of manufacturing platforms, lot-to-lot variability, or differences in the rigor applied to quality-control assays. In addition to reliable, high-quality vectors, limited quantities of rAAV have hampered clinical development and discouraged investigations into applications that require large therapeutic doses or quantities needed to treat large patient populations. A minimal number of vector production runs should be sufficient to support all phases of clinical development, including non-clinical, pharmacological, and toxicological studies, as well as clinical studies and commercial supply. The production platform using the Sf9 invertebrate cell line has emerged as a scalable and economical source of rAAV. Access to larger quantities of rAAV has now enabled evaluation of gene therapeutics for diseases that require large doses per patient or diseases with large patient populations. The only licensed rAAV product, Glybera, was produced in Sf9 cells, and other rAAV products are in clinical trials in the United States and Europe. The development of the Sf9 rAAV genetics, processes, and overview of the current system are described.


Curupira-1 and Curupira-2, two novel Mutator-like DNA transposons from the genomes of human parasites Schistosoma mansoni and Schistosoma japonicum.
Transposons of the Mutator superfamily have been widely described in plants, but only recently have metazoan organisms been shown to harbour them. In this work we describe novel Mutator superfamily transposons from the genomes of the human parasites Schistosoma mansoni and S. japonicum, which we name Curupira-1 and Curupira-2. Curupira elements do not have Terminal Inverted Repeats (TIRs) at their extremities and generate Target Site Duplications (TSDs) of 9 base pairs. Curupira-2 transposons code for a conserved transposase and SWIM zinc finger domains, while Curupira-1 elements comprise these same domains plus a WRKY zinc finger. Alignment of transcript sequences from both elements back to the genomes indicates that they are subject to splicing to produce mature transcripts. Phylogenetic analyses indicate that these transposons represent a new lineage of metazoan Mutator-like elements with characteristics that are distinct from the recently described Phantom elements. Description of these novel schistosome transposons provides new insights in the evolution of transposable elements in schistosomes.


Placental vascular obstructive lesions: risk factor for developing necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is a severe neonatal disease affecting particularly preterm infants. Its exact pathogenesis still remains unknown. In this study, we have compared the prevalence of vascular obstructive lesions in placentae of premature newborns which developed NEC and of a control group. We further compared separately the findings of placentae of infants of less than 30 weeks of gestation, the age group in which NEC occurs most frequently. We found signs of fetal vascular obstructive lesions in 65% of the placentae of preterm patients developing NEC, compared to only 17% of the placentae of preterm patients in the control group. In the age groups below 30 weeks of gestation, 58.5% of placentae of later NEC patients presented such lesions compared to 24.5% in the control group. The significant difference between NEC and control group suggests a strong association between fetal vascular obstructive lesions and NEC. Therefore, we propose that fetal vascular obstructive lesions might be considered as a risk factor for the development of NEC in premature infants.


Three-Dimensional Morphology Study of Capsule in Pseudophakic Eyes with High-Speed Swept-Source Optical Coherence Tomography.
To study the capsule morphology in pseudophakic eyes on the three-dimensional level using high-speed swept-source optical coherence tomography (SSOCT). This study collected patients with age-related cataract and divided them into two groups according to the anterior capsule and intraocular lens (IOL) optic relationship: total anterior capsule overlap (360°, Group-T) and partial anterior capsule overlap (<360°, Group-P). One standard SSOCT radial scanning was performed in all eyes at 1 day, 1 week, 1 month, and 3 months postoperatively. Thirty-two eyes from 25 patients were enrolled in the Group-T and 17 eyes from 13 patients in the Group-P. No eyes achieved complete adhesion between IOL optic and posterior capsule at 1 day after the surgery. However, the rate of complete adhesion was low (15/49, 30.6%) even at 3 months postoperatively and there was no statistically difference between Group-T and Group-P (21.9% vs. 47.1%, P > 0.05). At 1 day, 1 week, 1 month, and 3 months after the surgery, the capsule bend index (CBI) in the Group-T was 0.02 ± 0.09, 1.35 ± 1.48, 3.60 ± 0.54, and 3.88 ± 0.19, respectively. CBI rises linearly during the first month and the rise goes stable relatively with the great reduction of standard deviation in the following 2 months (All P < 0.05). The anterior capsule opening area and diameter were both reduced in the first month, and then they both became stable. With square-edge IOL, posterior capsule opacification risk is still high in most eyes at 3 months postoperatively for the complete adhesion of posterior capsule and IOL was only achieved in 30.6% eyes. IOL-in-bag may be driven by the significant capsule bag changes especially in the first month postoperatively.


A Community-Based Participatory Research Guided Model for the Dissemination of Evidence-Based Interventions.
Dissemination is a principle within community-based participatory research (CBPR); however, published research focuses on the dissemination of findings from CBPR projects but less on dissemination of interventions developed through CBPR approaches. To disseminate an evidence-based lifestyle intervention tailored for Native Hawaiians and other Pacific Islanders, the PILI 'Ohana Project (POP), an 11-year CBPR initiative, developed an innovative dissemination model. The community-to-community mentoring (CCM) model described in this paper extends the application of CBPR values and principles used in intervention development to intervention dissemination. The CCM model combines a CBPR orientation with the diffusion of innovation theory, the social cognitive theory, and key concepts from community organizing and community building to address the multilevel factors that influence uptake of an evidence-based intervention (EBI). Grounding the model in CBPR principles provides benefits for intervention dissemination and integrates a focus on community benefits and capacity building. By establishing co-equal, mutually beneficial relationships at the core of the CCM model, opportunities are created for building critical consciousness, community capacity, and social capital. More research is needed to determine the effectiveness of this model of intervention dissemination which may enhance diffusion of CBPR interventions and empower communities in the process.


Environmental Air Pollutants Affecting Skin Functions with Systemic Implications.
The increase in air pollution worldwide represents an environmental risk factor that has global implications for the health of humans worldwide. The skin of billions of people is exposed to a mixture of harmful air pollutants, which can affect its physiology and are responsible for cutaneous damage. Some polycyclic aromatic hydrocarbons are photoreactive and could be activated by ultraviolet radiation (UVR). Therefore, such UVR exposure would enhance their deleterious effects on the skin. Air pollution also affects vitamin D synthesis by reducing UVB radiation, which is essential for the production of vitamin D3, tachysterol, and lumisterol derivatives. Ambient air pollutants, photopollution, blue-light pollution, and cigarette smoke compromise cutaneous structural integrity, can interact with human skin microbiota, and trigger or exacerbate a range of skin diseases through various mechanisms. Generally, air pollution elicits an oxidative stress response on the skin that can activate the inflammatory responses. The aryl hydrocarbon receptor (AhR) can act as a sensor for small molecules such as air pollutants and plays a crucial role in responses to (photo)pollution. On the other hand, targeting AhR/Nrf2 is emerging as a novel treatment option for air pollutants that induce or exacerbate inflammatory skin diseases. Therefore, AhR with downstream regulatory pathways would represent a crucial signaling system regulating the skin phenotype in a Yin and Yang fashion defined by the chemical nature of the activating factor and the cellular and tissue context.


Pathogenesis and management of cancer-related insomnia.
Insomnia is the most common sleep disorder reported by cancer patients. Oncologists have noticed that alterations in sleep patterns are endemic among their patients, yet sleep problems are rarely assessed in a typical patient evaluation. Other concerns, such as morbidity and mortality, appear to take precedence. The cause of chronic sleep difficulties is multifaceted and up until recently, little attention has been given to the potential factors associated with the pathogenesis of cancer-related insomnia. The unique contributions of psychologic, medical, treatment side effects, environmental, behavioral, and pharmaceutical pathways on cancer-related insomnia cannot be ignored. This paper explores an overview of the incidence and severity of sleep disturbance in cancer patients, a review of the mechanisms of sleep, and the potential factors associated with the pathogenesis of cancer-related insomnia. Nurses, physicians, and other healthcare providers are in a unique position to greatly improve the quality of sleep in cancer patients. Cancer patients face many challenges; sleep problems do not have to be one of the necessary consequences associated with the cancer experience.


Atomic Mechanism of Hybridization-Dependent Surface Reconstruction with Tailored Functionality in Hexagonal Multiferroics.
The broken symmetry along with anomalous defect structures and charging conditions at multiferroics surface can alter both crystal structures and electronic configurations, bringing in emergent physical properties. Extraordinary surface states are induced into original mutually coupled order parameters in such strongly correlated oxides, which flourish in diverse properties but remain less explored. Here, we report the peculiar surface ferroelectric states and reconfigurable functionalities driven by the relaxation of surface and consequent changes in O 2p and Y 4d orbital (p-d) hybridization within a representative hexagonal multiferroics, YMnO3. An unprecedented surface reconstruction is achieved by tailored p-d hybridization coupling with in-plane oxygen vacancies, which is atomically revealed on the basis of the advantages of state-of-the-art aberration-corrected (scanning) transmission electron microscopy. Further ab initio density functional theory calculations verify the key roles of in-plane oxygen vacancies in modulating polarization properties and electronic structure, which should be regarded as the atomic multiferroic element. This surface configuration is found to induce tunable functionalities, such as surface ferromagnetism and conductivity. Meanwhile, the controversial origin of improper ferroelectricity that is unexpectedly free from critical size has also been atomically unraveled. Our findings provide new insights into the design and implementation of surface chemistry devices by simply controlling the oxygen stoichiometry, greatly advance our understandings of surface science in strongly correlated oxides, and enable exciting innovations and new technological functionality paradigms.


Graphyne nanotubes as electrocatalysts for oxygen reduction reaction: the effect of doping elements on the catalytic mechanisms.
The detailed density functional theory (DFT) calculations have been carried out to study the oxygen reduction reaction (ORR) activity and the mechanism on doped single-walled γ-graphyne nanotubes (GNTs). Four of the most commonly used doping elements, N, B, P, and S atoms, were used to investigate the doping effects. The calculated results indicate that doping GNTs with different elements could lead to different ORR catalytic mechanisms. The ORR catalyzed by both N- and B-GNTs is initiated by the end-on adsorption of O2 and is completed via an O-H2O dissociation mechanism, while the ORR on the P-GNT is initiated by the bridge adsorption of O2 and is completed via an O2 dissociation mechanism. The predicted catalytic performance of the doped GNT would decrease in the sequence N-GNT > B-GNT > P-GNT > S-GNT, based on the analysis of adsorption energies of ORR species and landscapes of ORR pathways. Electronic structure analysis shows that the high ORR activity of doped GNTs is directly related to the suitable HOMO levels and HOMO-LUMO energy gaps.


Influence of endogenous neuropeptide Y (NPY) on the sympathetic-parasympathetic interaction in the canine heart.
The purpose of this study was to examine the sympathetic-parasympathetic interactions on heart rate through release of neuropeptide Y (NPY) and its action on prejunctional NPY Y2 receptors on vagal and sympathetic nerve fibers. In other studies on various preparations and in various organs, attenuation of transmitter release has in fact been demonstrated through activation of the NPY Y2 receptor. In the present study on anesthetized dogs we examine, however, for the first time if vagal bradycardia is attenuated by endogenous NPY released during intense cardiac sympathetic stimulation. In addition, we explore if sympathetic transmitter release and heart rate, during moderate sympathetic stimulation, are affected through this receptor system. The significance of the NPY Y2 receptor was revealed by performing experiments before and after administration of its specific receptor antagonist BIIE0246. We found that attenuation of the bradycardia during vagal nerve stimulation was dose-dependently counteracted by BIIE0246 and that the tachycardia elicited by sympathetic stimulation remained unaffected after NPY Y2 receptor blockade. Thus, endogenous NPY appears to attenuate vagal bradycardia by stimulating prejunctional NPY Y2 receptors on cardiac vagal nerve terminals and, less efficiently, to attenuate transmitter release and tachycardia through a feedback loop on the cardiac sympathetic nerve fibers.


Effects of Blood Flow Restriction Training on Muscular Strength and Hypertrophy in Older Individuals: A Systematic Review and Meta-Analysis.
The combination of low-load resistance training with blood flow restriction (BFR) has recently been shown to promote muscular adaptations in various populations. To date, however, evidence is sparse on how this training regimen influences muscle mass and strength in older adults. The purpose of this systematic review and meta-analysis was to quantitatively identify the effects of low-load BFR (LL-BFR) training on muscle mass and strength in older individuals in comparison with conventional resistance training programmes. Additionally, the effectiveness of walking with and without BFR was assessed. A PRISMA-compliant systematic review and meta-analysis was conducted. The systematic literature research was performed in the following electronic databases from inception to 1 June 2018: PubMed, Web of Science, Scopus, CINAHL, SPORTDiscus and CENTRAL. Subsequently, a random-effects meta-analysis with inverse variance weighting was conducted. A total of 2658 articles were screened, and 11 studies with a total population of N = 238 were included in the meta-analysis. Our results revealed that during both low-load training and walking, the addition of BFR elicits significantly greater improvements in muscular strength with pooled effect sizes (ES) of 2.16 (95% CI 1.61 to 2.70) and 3.09 (95% CI 2.04 to 4.14), respectively. Muscle mass was also increased when comparing walking with and without BFR [ES 1.82 (95% CI 1.32 to 2.32)]. In comparison with high-load training, LL-BFR promotes similar muscle hypertrophy [ES 0.21 (95% CI - 0.14 to 0.56)] but lower strength gains [ES - 0.42 (95% CI - 0.70 to - 0.14)]. This systematic review and meta-analysis reveals that LL-BFR and walking with BFR is an effective interventional approach to stimulate muscle hypertrophy and strength gains in older populations. As BFR literature is still scarce with regard to potential moderator variables (e.g. sex, cuff pressure or training volume/frequency), further research is needed for strengthening the evidence for an effective application of LL-BFR training in older people.


Decoding of Ankle Flexion and Extension from Cortical Current Sources Estimated from Non-invasive Brain Activity Recording Methods.
The classification of ankle movements from non-invasive brain recordings can be applied to a brain-computer interface (BCI) to control exoskeletons, prosthesis, and functional electrical stimulators for the benefit of patients with walking impairments. In this research, ankle flexion and extension tasks at two force levels in both legs, were classified from cortical current sources estimated by a hierarchical variational Bayesian method, using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings. The hierarchical prior for the current source estimation from EEG was obtained from activated brain areas and their intensities from an fMRI group (second-level) analysis. The fMRI group analysis was performed on regions of interest defined over the primary motor cortex, the supplementary motor area, and the somatosensory area, which are well-known to contribute to movement control. A sparse logistic regression method was applied for a nine-class classification (eight active tasks and a resting control task) obtaining a mean accuracy of 65.64% for time series of current sources, estimated from the EEG and the fMRI signals using a variational Bayesian method, and a mean accuracy of 22.19% for the classification of the pre-processed of EEG sensor signals, with a chance level of 11.11%. The higher classification accuracy of current sources, when compared to EEG classification accuracy, was attributed to the high number of sources and the different signal patterns obtained in the same vertex for different motor tasks. Since the inverse filter estimation for current sources can be done offline with the present method, the present method is applicable to real-time BCIs. Finally, due to the highly enhanced spatial distribution of current sources over the brain cortex, this method has the potential to identify activation patterns to design BCIs for the control of an affected limb in patients with stroke, or BCIs from motor imagery in patients with spinal cord injury.


Function analysis of fish Tollip gene in response to virus infection.
Toll-interacting protein (Tollip) is one of the important regulatory proteins of Toll-like receptor (TLR) signaling pathways. In previous studies, a Tollip sequence of grouper (Epinephelus coioides) was identified and the signal transduction functions of Tollip were studied. However, the response of Tollip to virus infection has not been characterized from grouper. In the present paper, the Tollip homolog (EtTollip) from grouper (Epinephelus tauvina) was cloned and its immune response to Singapore grouper iridovirus (SGIV) was investigated. EtTollip shares significant similarities to other mammalian Tollips, which contain a centrally localized protein kinase C conserved region 2 (C2) domain and a C-terminal CUE domain. After challenging with SGIV, the expression levels of EtTollip were altered in the spleen and head kidney of grouper. EtTollip mainly aggregated in the cytoplasm in a condensed state and was also distributed on the membranes of GS cells. EtTollip significantly inhibited the activities of NF-κB and IFN-β luciferase reporter when transfected into grouper spleen (GS) cells. SGIV can increase the activities of NF-κB and IFN-β luciferase reporter, especially to IFN-β. When transfected EtTollip with EcMyd88, the activity of NF-κB was increased, while transfected EtTollip with EcIRF3, the activity of IFN-β was significantly increased. Over-expressed EtTollip inhibited the transcription of SGIV genes significantly in GS cells, and silencing of EtTollip with siRNA led to increase of SGIV genes loads. Taken together, the results provide new insights in to the importance of Tollip as evolutionarily conserved molecule for grouper innate immunity against virus infection.


Nano-liposomal zein hydrolysate for improved apoptotic activity and therapeutic index in lung cancer treatment.
Lung cancer is one of the most common cancers in the world with a high mortality rate. Zein is a protein compound whose protein isolate is not useful and whose protein hydrolysis produces biological activity. By encapsulating this bioactive compound inside the nanoparticles (NPs), it causes itself to reach the tumor site and destroy it rapidly. In this study, the effects of zein hydrolysate (ZH) and nano-liposomal ZH (N-ZH) were investigated on the human A549 cell line. Western blotting and cell cycle analyses showed that ZH and N-ZH caused cytotoxicity. They induced apoptosis via cell cycle arrest at the G0 phase, as well as significant increases in pro-apoptotic genes, such as Bax, caspase-3, -8, -9, and p53, accompanied with significant decreases in the anti-apoptotic marker Bcl-2. Based on the results, the cytotoxic and anticancer effects of N-ZH were higher than those of free ZH. In conclusion, liposomes improved the performance of ZH and dramatically reduced the IC50 value of ZH. These findings provided the experimental evidence that N-ZH with favorable anticancer activity can be used as a therapeutic agent and strategy for lung cancer treatment in future clinical trials.


Valvular heart disease in antiphospholipid syndrome.
Heart valve disease (HVD) is the most frequent cardiac manifestation in patients with antiphospholipid syndrome (APS), with prevalence of 30 %. The definition is based on the presence of thickening or vegetation of the valves (mainly mitral and aortic) as described by Libman and Sacks for patients with systemic lupus erythematosus (SLE). Transthoracic and/or transoesophageal echocardiography (TTE and TEE, respectively) enable early and accurate diagnosis and help avoid misdiagnosis as rheumatic valve disease. The presence of antiphospholipid antibodies (aPL) in SLE patients is associated with a threefold greater risk of HVD, confirming the crucial importance of these antibodies in the pathogenic process, leading to thrombotic manifestations on valves because of hypercoagulability. Natural history is characterized by worsening of HVD over time with an increased risk for stroke. APS patients undergoing valve-replacement surgery are at high risk of thrombotic and bleeding complications. Thus aPL-associated HVD has affects clinical management of APS patients.


Comparison of anthropometric, metabolic and dietary fatty acids profiles in lean and obese dyslipidaemic Asian Indian male subjects.
To compare obesity measures, metabolic profiles and dietary fatty acids in lean and obese dyslipideamic Asian Indian male subjects. Cross-sectional. Asian Indians living in the eastern part of India. One hundred and thirty (Group I: lean control, n=50; Group II: lean dyslipidaemic, n=40 and Group III: obese dyslipidaemic, n=40) Asian Indian male subjects (> or =30 years) living in the eastern part of India. Anthropometric measures namely height, weight, circumferences of waist (WC) and hip, lipids (total cholesterol (TC) and triglycerides (TG)), lipoproteins (high- (HDL) and low-density lipoproteins (LDL)), fasting plasma glucose (FPG) and dietary fatty acids were obtained from each participant. Obesity measures, that is, body mass index (BMI), waist-hip ratio (WHR) and conicity index (CI) were subsequently calculated from anthropometric measures. Obesity was defined as individuals having BMI> or =25 kg/m(2). SUBJECTS with one or more of the following conditions were considered as dyslipidaemic: TG> or =2.3 mmol/l, TC> or =6.2 mmol/l, or TC/HDL> or =4.4 mmol/l. Daily intake of nutrients as well as saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) were estimated by adding together all the foodstuffs consumed on weekly and monthly manner. Conversion of foodstuffs into nutrients was performed according to standard nutritive values of Indian foodstuffs. Analysis of variance with Scheffe's post hoc test revealed that Group I had significantly lower mean compared to both Group II and Group III for age, WC, WHR, CI, TC, TG, LDL, FPG, total carbohydrates intake and intake of trans fatty acids. On the other hand, Group I had significantly lower mean than Group III only for BMI as well as intake of total proteins, total fats, total energy and erucic acids. Although, Group I had significantly greater mean compared to both Group II and Group III for HDL, UFA/SFA, MUFA/SFA and PUFA/SFA. Pearson's partial correlations (controlling for age and total energy) revealed that central obesity measures (WC, WHR and CI) had significant association with dietary fatty acids and their ratios. Furthermore, partial correlations (controlling for age) also showed that the ratios of unsaturated to SFA had significant negative association with lipids, lipoproteins (except HDL) and plasma glucose. Discriminant function analysis revealed that overall 78% of all entries were positively (correctly) classified in three groups using fatty acids and their ratios. It seems rational to argue that while dealing with dyslipidaemic Asian Indians, clinicians should consider obesity measures, metabolic profiles and dietary fatty acids simultaneously to better comprehend the condition (s).


Hematological alterations and splenic T lymphocyte polarization at the crest of snake venom induced acute kidney injury in adult male mice.
Snake venom induced acute kidney injury (SAKI) is of great clinical relevance in tropical countries. Involvement of T cell, a key mediator of AKI and its remission, is least explored in SAKI. In the present study the in vivo hematological alterations and associated splenic T cell polarization is probed in order to investigate the immune response at the crest of Russell's viper venom (RVV) induced AKI in experimental murine model. Based on a dose and time kinetic study intra muscular injection dose of 20 μg RVV/100 gm body weight of mice and incubation period of 60 h was selected for induction of SAKI. Renal involvement in SAKI group was confirmed from oliguria, significantly elevated urinary microprotein (p < 0.001), decreased urinary creatinine (p = 0.003) and creatinine clearance (p < 0.001) compared to control. Hematological analyses revealed a significant neutrophilic leukocytosis (p < 0.001) associated with a reduced lymphocyte percentage (p < 0.001) favoring a state of acute inflammation in SAKI group. Immunophenotyping study of splenocytes showed a significant decrease in CD4+/CD8+ ratio (p < 0.001) with a significant increase in regulatory (CD25+FoxP3+) helper and cytotoxic subset of T cell (p < 0.001). Significant increase in IL-10+ regulatory helper and cytotoxic T cell (p < 0.001) further confirmed the internal milieu favoring immunosuppression. Apart from these the CD25-FoxP3+ reservoir regulatory T cells were also found to be significantly elevated in SAKI group compared to that of control (p < 0.001). Taken together, the results of the present study clearly indicated a state of acute inflammation and splenic T cell polarization towards regulatory subset at the crest of SAKI.


[Obese Hungary. Trend and prevalence of overweight and obesity in Hungary, 2015].
The prevalence of obesity is growing continuously worldwide, even in Hungary. Since 1988, when the first professional wide-range evaluation was performed, only limited data are available. Authors present the results of the ever largest Hungarian obesity-prevalence surveys, performed by family and occupational physicians. Data from 0.55% of the population above 18 year were registered in all geographical regions of Hungary (43,287 persons; 17,901 males and 25,386 females), close to the proper national representativeness. Age, body mass index, waist circumference, educational level, presence of hypertension and/or diabetes were analyzed statistically and compared with previous data. The overall prevalence rate of overweight and obesity among men was 40% and 32%, respectively, while overweight and obesity occurred in 32% of women. In the different age groups of men, the prevalence of overweight and obesity was: 32.7% and 18.2% in 18-34 years; 40.1% and 34.4% in 35-59 years; 43.5% and 38.8% in over 60 years, respectively. In the same age groups of women, overweight and obesity occurred in 19.6% and 15.7%, 36.8% and 38.7%, and 36.5% and 39.7%, respectively. Body mass index and waist-circumference were presented according to age, by decades and by type of residency as well. The highest ratio of overweight was registered among men with the highest educational level, while highest ratio of obesity among women having the lowest education. Obesity according to Body mass index and abdominal obesity was the highest in the villages, especially among females. Registered metabolic morbidities were strongly correlated with body mass index and both were inversely related to the level of urbanization. Over the previous decades, the ratio of the overweight and even the number of obese persons increased significantly, and it was most prominent among males, mainly in younger generation. Obesity means a serious medical, public health and economic problem, and it requires higher public awareness and political support. Orv. Hetil., 2016, 157(31), 1248-1255.


The Turkish Adaptation of the Ten-Item Personality Inventory.
Personality is one of the important domains of psychology, and it is an integration of emotional, cognitive, social and physical properties. In this study, we aimed to assess the applicability of the "Ten-Item Personality Inventory (TIPI)" which measures five basic personality traits in Turkish young people. Data from a total of 420 participants - 208 male (49.1%) and 212 female (50.9%) - were employed for the validity and reliability analyses. Of the participants, 230 (54,8%; mean age: 23.2 years; sd=1.6) were university students and the rest were not (n=190; 45.2%; mean age: 23.4 years; df=1.7). The mean age of the participants was 22.1 years (df=1.3), ranging from 18 to 25 years. Language validity (correlations between 0.92 and 0.97), exploratory factor analysis yielded 10 items and five-factor model explaining 65.21% of the variance. Confirmatory factor analyses (χ2/df: 2.20, GFI=0.95, AGFI=0.92, CFI=0.93, NNFI=0.91, RMR=0.04, and RMSEA=0.03), item analysis, and convergent validity results indicated that a five-factor solution with 10 items met the criteria standards for adequacy of fit among Turkish young people. The internal consistency (Openness to Experiences 0.83, Agreeableness 0.81, Emotional Stability 0.83, Conscientiousness 0.84, and Extraversion 0.86) and test-retest stability (=54; Openness to Experiences 0.89, Agreeableness 0.87, Emotional Stability 0.89, Conscientiousness 0.87, and Extraversion 0.88) revealed a moderate to acceptable reliabilities. The results demonstrated that the TIPI could be used in studies that evaluate personality in Turkish young people.


Sulfur K-Edge XAS Studies of the Effect of DNA Binding on the [Fe4S4] Site in EndoIII and MutY.
S K-edge X-ray absorption spectroscopy (XAS) was used to study the [Fe4S4] clusters in the DNA repair glycosylases EndoIII and MutY to evaluate the effects of DNA binding and solvation on Fe-S bond covalencies (i.e., the amount of S 3p character mixed into the Fe 3d valence orbitals). Increased covalencies in both iron-thiolate and iron-sulfide bonds would stabilize the oxidized state of the [Fe4S4] clusters. The results are compared to those on previously studied [Fe4S4] model complexes, ferredoxin (Fd), and to new data on high-potential iron-sulfur protein (HiPIP). A limited decrease in covalency is observed upon removal of solvent water from EndoIII and MutY, opposite to the significant increase observed for Fd, where the [Fe4S4] cluster is solvent exposed. Importantly, in EndoIII and MutY, a large increase in covalency is observed upon DNA binding, which is due to the effect of its negative charge on the iron-sulfur bonds. In EndoIII, this change in covalency can be quantified and makes a significant contribution to the observed decrease in reduction potential found experimentally in DNA repair proteins, enabling their HiPIP-like redox behavior.


Unified treatment of chemical and van der Waals forces via symmetry-adapted perturbation expansion.
We propose a symmetry-adapted perturbation theory (SAPT) expansion of the intermolecular interaction energy which in a finite order provides the correct values of the constants determining the asymptotics of the interaction energy (the van der Waals constants) and is convergent when the energy of the interacting system is submerged in the continuum of Pauli-forbidden states-the situation common when at least one of the monomers has more than two electrons. These desirable features are achieved by splitting the intermolecular electron-nucleus attraction terms of the Hamiltonian into regular (long-range) and singular (short-range) parts. In the perturbation theory development, the regular part is treated as in the conventional polarization theory, which guarantees the correct asymptotics of the interaction energy, while the singular part is weakened sufficiently by an application of permutational symmetry projectors so that a convergent perturbation series is obtained. The convergence is demonstrated numerically, for both the chemical and van der Waals minima, by performing high-order calculations of the interaction energy of the ground-state lithium and hydrogen atoms-the simplest system for which the physical ground state is submerged in the Pauli-forbidden continuum. The obtained expansion enables a systematic extension of SAPT calculations beyond second order with respect to the intermolecular interaction operator.


Ti/Ti4O7 Anodes for Efficient Electrodeposition of Manganese Metal and Anode Slime Generation Reduction.
Preventing lead-based anodes from causing high-energy consumption, lead pollution, and harmful anode slime emission is a major challenge for the current electrolytic manganese metal industry. In this work, a Ti4O7-coated titanium electrode was used as anode material (Ti/Ti4O7 anode) in manganese electrowinning process for the first time and compared with a lead-based anode (Pb anode). The Ti/Ti4O7 anode was used for galvanostatic electrolysis; the cathodic current efficiency improved by 3.22% and energy consumption decreased by 7.82%. During 8 h of electrolysis, it reduced 90.42% solution anode slime and 72.80% plate anode slime formation. Anode product characterization and electrochemical tests indicated that the Ti/Ti4O7 anode possesses good oxygen evolution activity, and γ-MnO2 has a positive catalytic effect on oxygen evolution reaction (OER), which inhibited anode Mn2+ oxidation reaction and reduced the formation of anode slime. In addition, the low charge-transfer resistance, high diffusion resistance, and dense MnO2 layer of the anode blocked the diffusion path of Mn3+ in the system and inhibited the formation of anode slime. The Ti/Ti4O7 anode exhibits excellent electrochemical performance, which provides a new idea for the selection of novel anodes, energy savings and emission reduction, and the establishment of a new mode of clean production in the electrolytic manganese metal industry.


Radiological pitfalls associated with the diagnosis of usual interstitial pneumonia pattern on high-resolution computed tomography and associated findings: experience from a single Italian center.
The diagnostic algorithm for idiopathic pulmonary fibrosis (IPF) based on high-resolution computed tomography (HRCT) findings and multidisciplinary discussion (MDD) has been well established. To identify the causes of disagreement between non-thoracic and thoracic radiologist involved in MDD for the imaging diagnosis of usual interstitial pneumonia (UIP) patterns and associated findings on HRCT and to improve the understanding of IPF by non-expert radiologists through a more systematic approach to HRCT. This study included 68 patients who underwent MDD for suspected IPF. We compared the first reports generated before MDD by non-expert radiologists with the CT pattern and associated findings of IPF reported by thoracic radiologist involved in MDD. Regarding the diagnosis of CT pattern by non-expert radiologists, 30/68 patients received a discordant diagnosis, and in another 28 reports, all features of the CT pattern were described without reaching a diagnostic conclusion. The first report was concordant in only 10 patients. For 63 cases in which associated findings were reported by expert radiologists in MDD, we documented discrepancies in 47 cases where associated findings were considered absent by the first non-thoracic radiologist. We found significant discrepancies in the imaging diagnosis of UIP patterns and associated findings on HRCT between non-expert and thoracic radiologists included in MDD. Therefore, in this study, we analyzed and suggested diagnostic strategies to improve non-expert radiologists' approach to HRCT.


High CO2 absorption by diamino protic ionic liquids using azolide anions.
For the first time, several low-viscosity diamino protic ionic liquids (DPILs), based on azolides as anions (pyrazolide, imidazolide and triazolide) have been synthesised, characterised and evaluated for CO2 capture. The results reveal that these ionic liquids rapidly absorb CO2 to more than 20% w/w pointing towards equimolar absorption.


Cooperative interactions in supramolecular aggregates: linear and nonlinear responses in calix[4]arenes.
The linear and nonlinear optical polarizabilities of donor-acceptor (D-pi-A) chromophores in confined geometries of calix[4]arenes are investigated through a model for interacting polar-polarizable molecules. Both the linear polarizability (alpha) and the first hyperpolarizability (beta) decrease with increasing the interdipolar angle, as expected in the oriented-gas picture. However, within the polar-polarizable model we predict deviations from the additive result, irrespective of the interdipolar angle. Depending on the nature of the chromophore, electrostatic intermolecular interactions between polar and polarizable chromophores lead to cooperative damping or enhancement of the optical responses. Specifically, for chromophores whose ground state is dominated by the neutral D-pi-A structure both alpha and beta are suppressed with respect to the prediction of the oriented-gas model, whereas the opposite holds true for chromophores whose ground state is dominated by the zwitterionic D(+)-pi-A(-). These results explain recent experimental data on a calix[4]arene functionalized with a donor-acceptor dye for nonlinear optical applications. Density functional theory calculations on the relevant crystal structure further support our interpretation.


Bowenoid papulosis and squamous cell carcinoma of the genitalia: suspected sexual transmission.
The human papillomavirus causes a variety of genital lesions: condyloma acuminatum, bowenoid papulosis (carcinoma in situ), and squamous cell carcinoma. Only condylomata have been documented to be sexually transmitted. We report clinical and histopathologic evidence of suspected female to male transmission of bowenoid papulosis to the penis from a woman with condylomata acuminata, squamous cell carcinoma in situ, and focally invasive squamous cell carcinoma of the vulva. These findings indicate a need for thorough clinical and histopathologic evaluation of any anogenital lesions resembling condylomata and occurring in sexual partners. Conservative yet thorough destruction of bowenoid papulosis and squamous cell carcinoma in situ appears to be the treatment of choice.


Monoclonal antibodies specific for beta-adrenergic ligands.
After somatic cell fusion between splenocytes of immunized BALB/c mice and NS-1 myeloma cells, eight clones were obtained secreting anti-alprenolol antibodies as characterized by means of an ELISA. Four of these were subcloned and were studied further. The association constant for alprenolol ranged from 1.9 X 10(6) M-1 to 24 to 10(6) M-1. Competitive inhibition of [3H]-l-dihydroalprenolol binding revealed cross-reactivity with beta-adrenergic ligands, with a higher avidity for antagonists than for agonists. Two of the antibodies had a higher affinity for the l-isomer than for the d-isomer. The most stereospecific of these antibodies showed only affinity for beta-adrenergic antagonists and for the agonist isoproterenol. The other recognized both beta-adrenergic antagonists and agonists; it also showed an increase in tryptophan fluorescence after ligand binding. This property was used for the physicochemical study of the hapten-antibody interaction.


Differential roles of the universal stress proteins of Escherichia coli in oxidative stress resistance, adhesion, and motility.
The universal stress protein (UspA) superfamily encompasses a conserved group of proteins that are found in bacteria, archaea, and eukaryotes. Escherichia coli harbors six usp genes--uspA, -C, -D, -E, -F, and -G--the expression of which is triggered by a large variety of environmental insults. The uspA gene is important for survival during cellular growth arrest, but the exact physiological role of the Usp proteins is not known. In this work we have performed phenotypic characterization of mutants with deletions of the six different usp genes. We report on hitherto unknown functions of these genes linked to motility, adhesion, and oxidative stress resistance, and we show that usp functions are both overlapping and distinct. Both UspA and UspD are required in the defense against superoxide-generating agents, and UspD appears also important in controlling intracellular levels of iron. In contrast, UspC is not involved in stress resistance or iron metabolism but is essential, like UspE, for cellular motility. Electron microscopy demonstrates that uspC and uspE mutants are devoid of flagella. In addition, the function of the uspC and uspE genes is linked to cell adhesion, measured as FimH-mediated agglutination of yeast cells. While the UspC and UspE proteins promote motility at the expense of adhesion, the UspF and UspG proteins exhibit the exact opposite effects. We suggest that the Usp proteins have evolved different physiological functions that reprogram the cell towards defense and escape during cellular stress.


Rare Pseudotumor in Ceramic-On-Ceramic Total Hip Replacement with Concomitant Fungal Periprosthetic Joint Infection: A Case Report.
BACKGROUND Total hip replacement (THR) is a commonly performed treatment for severe osteoarthritis. In this report, we present the case of a woman who unfortunately suffered 2 severe but rare complications of THRs: a pseudotumor formation on a Delta ceramic-on-ceramic bearing and a fungal periprosthetic joint infection (PJI). CASE REPORT In early 2016, a 63-year-old woman underwent an elective left total hip replacement with ceramic-on-ceramic bearing due to severe osteoarthritis. In 2021, she suffered 2 unprovoked DVTs. Therefore, ultrasound (US) Doppler imaging of the left lower limb was performed, which showed a mass close to the iliac vein. After magnetic resonance imaging (MRI) to further examine the mass, a pseudotumor was confirmed. Revision surgery was performed, after which positive swabs for fungal infection were identified, but were not clinically correlated. A few years before, a deep buccal fungal infection was suspected and treated, but never confirmed. The pseudotumor was confirmed by histology samples. A few weeks later, the patient presented again with symptoms of infection, and 2 debridement, antibiotics, and implant retention (DAIR) procedures were performed, in which further positive swabs of Candida parapsilosis were obtained. Currently, the patient is on conservative therapy with long-term antifungal medication since she refused a staged procedure due to personal circumstances. CONCLUSIONS In conclusion, this case report documents the first ever reported pseudotumor associated with a ceramic-on-ceramic bearing THR with concomitant fungal PJI. Although it is unlikely for a person to develop 2 rare complications without them being connected, no causal link could be established.


HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases.
HIV-1 co-opts several host machinery to generate a permissive environment for viral replication and transmission. In this work we reveal how HIV-1 impacts the host translation and intracellular vesicular trafficking machineries for protein synthesis and to impede the physiological late endosome/lysosome (LEL) trafficking in stressful conditions. First, HIV-1 enhances the activity of the master regulator of protein synthesis, the mammalian target of rapamycin (mTOR). Second, the virus commandeers mTOR-associated late endosome/lysosome (LEL) trafficking and counteracts metabolic and environmental stress-induced intracellular repositioning of LEL. We then show that the small Rag GTPases, RagA and RagB, are required for the HIV-1-mediated LEL repositioning that is likely mediated by interactions between the Rags and the viral proteins, Gag and Vif. siRNA-mediated depletion of RagA and RagB leads to a loss in mTOR association to LEL and to a blockade of viral particle assembly and release at the plasma membrane with a marked concomitant reduction in virus production. These results show that HIV-1 co-opts fundamental mechanisms that regulate LEL motility and positioning and support the notion that LEL positioning is critical for HIV-1 replication.


ANDROGENETICS AND TRIPLOIDS FROM AN INTERACTING PARTHENOGENETIC HYBRID AND ITS ANCESTORS IN STICK INSECTS.
Populations of unisexual organisms are often assumed to be genetically invariant (clones) and destined to a short existence on an evolutionary timescale. Unisexual organisms are most often obligate parthenogens and, by definition, ought to be completely isolated reproductively from related bisexual organisms. The assumption of complete reproductive isolation between amphimictic ancestors and thelytokous hybrids is common to most hypotheses on the evolution of sex and its adaptive significance. Stick insects of the genus Bacillus however provide evidence for reproductive interactions between allodiploid parthenogens and their ancestors, because pure species progeny (androgenetics) and triploid descendants are produced. These findings demonstrate that, through androgenesis, offspring of parthenogenetic hybrid females can contribute specimens of both sexes to the fathering species when fertilized by syntopic ancestral males and the parthenogenetic egg of strictly clonal females, when fertilized, allows a third genome to be added to the allodiploid chromosome set. These triploid genomes promote further genetic diversification and evolution of the unisexual populations through the formation of new clones by recombination during the changed maturation mode of allotriploid eggs. All this argues for much more complex breeding systems and evolutionary pathways than are usually assumed for hybrid unisexual organisms.


At-home bleaching: pulpal effects and tooth sensitivity issues, part II.
The most common side effect of at-home bleaching is transient tooth sensitivity. Despite its high frequency, this phenomenon is not well understood. This is the second of a two-part Critical Appraisal on tooth sensitivity associated with at-home bleaching. The first installment reviewed articles that focus on the incidence of sensitivity, long-term effects of bleaching, and related pulpal concerns. This installment also covers pulpal concerns, as well as the prevention of sensitivity during at-home whitening treatments.


Allergic asthma: a tale of many T cells.
Asthma is a common immune-mediated disorder characterized by reversible airway inflammation, mucus production, and variable airflow obstruction with airways hyperresponsiveness (AHR). In most cases the airway inflammation characteristic of asthma is thought to result from an allergic-type reaction to an inhaled substance from the environment (so-called allergic asthma). In allergic asthma, allergen exposure stimulates eosinophilic inflammation of the airways associated with infiltration of T cells. Although the recruitment of eosinophils into the airways is an important component in the pathogenesis of asthma, the trafficking of T lymphocytes into the airways is now believed to establish and orchestrate the asthmatic inflammatory response. This review explores the roles of various T cell subsets in the pathogenesis of allergic airway inflammation and highlights the contributions of these cells in regulating asthma.


Biosynthesis and intracellular transport of a membrane glycoprotein (plgp57) of the prelysosome compartment.
We have characterized the biosynthesis and intracellular transport of a membrane glycoprotein, designated plgp57, which is found predominantly in the prelysosome compartment (PLC) of Madin-Darby bovine kidney cells. In pulse-chase experiments, plgp57 was found to be initially synthesized as a 35 kDa precursor which was modified to yield a diffuse approximately 57 kDa mature form. Digestion with endoglycosidase H (endo H) demonstrated that the 35 kDa precursor contained three endo H-sensitive, high mannose-type oligosaccharides which became modified to endo H-resistant, complex-type sugars on the approximately 57 kDa mature form. Labelling cells in the presence of tunicamycin and treatment of the 35 kDa precursor with endo H revealed that plgp57 has a core protein of 24 kDa to which three N-asparagine-liked oligosaccharides are attached. Other experiments indicated that plgp57 could be differentially glycosylated on a common 24 kDa core protein in different cell types. The half-lives of the glycosylated and non-glycosylated forms of plgp57 were approximately 18 and approximately 13 h, respectively. Glycosylated and non-glycosylated plgp57 exhibited similar steady-state intracellular distributions, indicating that targeting of plgp57 to the PLC does not require carbohydrate address markers. Pulse-labeling of cells followed by organelle fractionation at various chase times revealed a t1/2 = approximately 1 h for the transit of newly synthesized plgp57 to the PLC. Finally, amino terminal sequencing of plgp57 revealed the similarity of this protein to the CD63/ME491 family of membrane glycoproteins.


Zinc phosphide poisoning with unusual radiologic findings.
Accidental/suicidal ingestion of metal phosphides (e.g., zinc phosphide found in rodenticides) should be suspected in patients with sudden-onset abdominal pain, refractory hypotension, and metabolic acidosis. CT angiography may show radiopaque substance in the stomach and early enhancement of the inferior vena cava and contrast in right side of the heart.


How to Extract Climate Variability from Tree-Rings.
Tree rings have been used to reconstruct climatological variables in many locations around the world. Moreover, tree-rings can provide valuable insights into climatic variability of the last few centuries and, in some areas, several millennia. Despite the important development, that dendrochronology has had in recent decades to study the dendroclimatic potential of a large number of species present in different ecosystems, much remains to be done and explored. In addition to this, in the last few years more people (students, teachers and researchers) around the world are interested in implementing this science to extend the timeline of climate information backwards and understand how climate has changed on scales of decades, centuries or millennia. Therefore, the objective of this work is to describe the general aspects and basic steps needed to conduct a tree-ring climate reconstruction, from site selection and field sampling to laboratory methods and data analysis. In this method's video and manuscript, the general basis in tree-ring climatic reconstructions is explained so newcomers and students can use it as an available guide into this field of research.


Inguinal pain syndrome. The influence of intraoperative local administration of 0.5% bupivacaine on postoperative pain control following Lichtenstein hernioplasty. A prospective case-control study.
With current technological advancement and availability of synthetic materials used in inguinal hernia repair, a recurrence after first intervention is not a common and important adverse event. On the other hand, however, some patients complain about chronic pain of the operated site after surgeries using a polypropylene mesh. Many patients are constrained to a prolonged use of analgesics and increased frequency of control visits, which may eventually result in loss of trust in the operator. Every surgical intervention is associated with the risk of immediate or delayed complications. Genitofemoral neuralgia is associated with dysfunction of peripheral nerves passing through the inguinal canal or the surrounding tissue and it is a chronic, troublesome and undesired complication of an inguinal hernia repair. The possibility of minimizing chronic inguinal pain by proper management during herniorraphy should be considered in all cases of an inguinal canal reconstruction. The aim of the study was to investigate whether an intraoperative injection of 0.5% bupivacaine into the operated site (preemptive analgesia) has an influence on the postoperative pain assessed on the day of operation as well as the 1st and 2nd postoperative day after Lichtenstein hernioplasty of an inguinal, scrotal or recurrent hernia. In the studied population, we attempted to identify risk factors affecting pain level after surgical repair of an inguinal, scrotal or recurrent hernia. During the period between December 2015 and May 2016, 133 patients with preoperative diagnosis of an inguinal (81.95%, n=109), scrotal (13.53%, n=18) or recurrent hernia (4.51%, n=6) underwent an elective intervention and were randomly allocated to the group, which intraoperatively received 20 mL of 0.5% bupivacaine locally in selected anatomical points of the inguinal canal. In the group with preoperative diagnosis of an inguinal hernia, this intervention was applied in 56.88% of cases (n=62). In the case of scrotal or recurrent hernia, a similar intervention was applied in 41.67% (n=10) of patients. During the hospital stay, pain was assessed four times a day using the NRS numeric scale. All patients received preoperative antibiotic prophylaxis, and, during observation, analgesics and low-molecular-weight heparin were used. In the studied group, risk factor were identified, which affect the pain level associated with surgical treatment of an inguinal hernia. Mean pain level score according to the NRS scale (0-10) for an inguinal hernia was 4.17 on day 0 (standard deviation 2.22; minimum 0; maximum 10). On day 1 - 2.86 (standard deviation 1.86; minimum 0; maximum 8). On day 2 - 0.84 (standard deviation 1.21; minimum 0; maximum 5). The values of those parameters for a scrotal and recurrent hernia were as follows: on day 0 - 3.67 (standard deviation 1.76; minimum 0; maximum 7). On day 1 - 3.79 (standard deviation 1.67; minimum 0; maximum 7). On day 2 - 2.25 (standard deviation 1.54; minimum 0; maximum 4). Intraoperative application of 20 mL 0.5% bupivacaine did not reduce the postoperative pain on the postoperative day 0, 1, 2. Among independent risk factors exacerbating pain, the following variables were identified: local complications of the operated site including edema, ecchymosis and hematoma of the inguinal region. More frequent dressing changes were directly correlated with an increased pain sensation. Postoperative urethral catheterization due to urinary retention was associated with an increased pain immediately after surgery. In the case of intraoperative diagnosis of concurrent direct and indirect hernia (so-called pantaloon hernia), less intense pain was observed on postoperative day 0. Other parameters such as age, sex, duration of operation, duration of hospitalization and wound drainage did not influence the pain sensation. Local injection of an analgesic into the operated site was not associated with the reduction of pain assessed on postoperative day 0, 1 and 2 after an isolated inguinal, scrotal or recurrent hernia repair. Pathologies of the operated site such as edema, ecchymosis or hematoma were associated with an increased pain sensations on observation. Also, postoperative urinary retention and urethral catheterization increased the pain sensation after an inguinal hernia repair. A lack of wound complications significantly decreased the pain sensation during the immediate postoperative period after hernia repair.


Involvement of the thalamic parafascicular nucleus in mesial temporal lobe epilepsy.
Mesial temporal lobe epilepsy (MTLE) is characterized by focal seizures, associated with hippocampal sclerosis, and often resistance to antiepileptic drugs. The parafascicular nucleus (PF) of the thalamus is involved in the generation of physiological oscillatory rhythms. It receives excitatory inputs from the cortex and inhibitory inputs from the basal ganglia, a system implicated in the control of epileptic seizures. The aim of this study was to examine the involvement of the PF in the occurrence of hippocampal paroxysmal discharges (HPDs) in a chronic animal model of MTLE in male mice. We recorded the local field potential (LFP) and the extracellular and intracellular activity of hippocampal and PF neurons during spontaneous HPDs in vivo. The end of the HPDs was concomitant with a slow repolarization in hippocampal neurons leading to an electrical silence. In contrast, it was associated in the PF with a transient increase in the power of the 10-20 Hz band in LFPs and a depolarization of PF neurons resulting in a sustained firing. We tested the role of the PF in the control of HPDs by single 130 Hz electrical stimulation of this nucleus and bilateral intra-PF injection of NMDA and GABA(A) antagonist and agonist. High-frequency PF stimulation interrupted ongoing HPDs at an intensity devoid of behavioral effects. NMDA antagonist and GABA(A) agonist suppressed hippocampal discharges in a dose-dependent way, whereas NMDA agonist and GABA(A) antagonist increased HPDs. Altogether, these data suggest that the PF nucleus plays a role in the modulation of MTLE seizures.


Under-hyped and over-hyped drug-dietary supplement interactions and issues.
Complementary and alternative medicine utilization continues to abound, as does the use of prescription medications. Thus, real and hypothetical concerns exist for potential drug-dietary supplement interactions. Several supplements, including kava and St. John's Wort, have the potential for adverse medication interactions, but there are also several supplements, such as fish oil, garlic, ginkgo, pygeum, and saw palmetto, whose adverse potential may have been embellished. Still, there are other common supplements, such as vitamin D, that are enjoying an impressive amount of attention and consumption but their potential for current or future toxicity seems considerable and concerning, especially with individuals with multiple non-communicating practitioners. Regardless, it is important to continue to monitor dietary supplements (not just herbal products) that may have interaction and toxicity issues, and to also educate patients and clinicians on other supplements that do not have these issues despite an earlier concern and avoidance based on a minimal number of laboratory studies or case reports.


Effects of alterations in auditory feedback and speech rate on stuttering frequency.
This study investigated the effects of altered auditory feedback on stuttering frequency during speech production at two different speech rates, Nine stutterers, who exhibited at least 5% dysfluency during a reading task, served as subjects. They read eight different passages (each 300 syllables in length) while receiving four conditions of auditory feedback: nonaltered, masking, delayed, and frequency altered. For each auditory feedback condition, subjects read at both a normal and a fast rate. Results indicated that stuttering frequency was significantly decreased during conditions of delayed and frequency altered auditory feedback at both speech rates (p < 0.05). These findings refute the notion that a slowed speech rate is necessary for fluency enhancement under conditions of altered auditory feedback. Considering previous research and the results of this study, it is proposed that there may be two interdependent factors that are responsible for fluency enhancement: alteration of auditory feedback and modification of speech production.


Large Intra-subject Variability in Caffeine Pharmacokinetics: Randomized Cross-over Study of Single Caffeine Product.
Background Average bioequivalence has been criticized for not adequately addressing individual variations. Importance of subjects' blinding in bioequivalence studies has not been well studied. We explored the extent of intra-subject pharmacokinetic variability and effect of drug-ingestion unawareness in subjects taking single caffeine product. Methods A single-dose randomized cross-over design was used to compare pharmacokinetics of 200 mg caffeine, described as caffeine (overt) or as placebo (covert). Maximum concentration (Cmax), Cmax first time (Tmax), area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or to Tmax of overt caffeine (AUCOverttmax), and Cmax/AUCI were calculated blindly using standard non-compartmental method. Percentages of individual covert/overt ratios that are outside the ±25% range were determined. Covert-vs-overt effect on caffeine pharmacokinetics was evaluated by 90% confidence interval (CI) and 80.00-125.00% bioequivalence range. Results 32 healthy subjects (6% females, mean (SD) age 33.3 (7.2) year) participated in the study (28 analysed). Out of the 28 individual covert/overt ratios, 23% were outside the ±25% range for AUCT, 30% for AUCI, 20% for AUCOverttmax, 30% for Cmax, and 43% for Tmax. There was no significant covert-vs-overt difference in any of the pharmacokinetic parameters studied. Further, the 90% CIs for AUCT, AUCI, Cmax, AUCOverttmax, and Cmax/AUCI were all within the 80.00-125.00% bioequivalence range with mean absolute deviation of covert/overt ratios of 3.31%, 6.29%, 1.43%, 1.87%, and 5.19%, respectively. Conclusions Large intra-subject variability in main caffeine pharmacokinetic parameters was noted when comparing an oral caffeine product to itself. Subjects' blinding may not be important in average bioequivalence studies.


The Small Molecules Targeting Ubiquitin-Proteasome System for Cancer Therapy.
The ubiquitin-proteasome system (UPS) is the major pathway for degrading the intracellular proteins. The 2004 Nobel Prize in Chemistry was awarded to Rose, Hershko, and Ciechanover to highlight the fundamental importance of UPS. The alterations in this process have been shown to contribute to the cancer progression. Hence, UPS has become a popular target for developing chemotherapeutics against tumours. The application of bortezomib showed high efficiency in treating haematological malignancies by interfering with UPS activity. Many compounds are being screened and evaluated in recent pharmacological advances, either as single agents or in synergy with other drugs, and more to be revealed. In the present review, we exhibit the crucial ingredients involved in UPS and discuss the current situation of small molecules targeting various components of ubiquitination pathway in cancer treatment.


A role for radiation in the treatment of hairy cell leukemia complicated by massive lymphadenopathy: a case report.
A patient with leukemic reticuloendotheliosis is described who two years following splenectomy developed massive retroperitoneal, abdominal, and mediastinal lymphadenopathy. Therapeutic intervention was necessary because the bulky tumor masses produced disabling pain in the back and chest regions. Low-dose radiation to the involved fields produced prompt regression of the adenopathy along with dramatic pain relief. This case suggests that hairy cells may be quite sensitive to radiation, and this therapeutic modality should be considered, especially when local problems are present.


Potential functional replacement of the plastidic acetyl-CoA carboxylase subunit (accD) gene by recent transfers to the nucleus in some angiosperm lineages.
Eukaryotic cells originated when an ancestor of the nucleated cell engulfed bacterial endosymbionts that gradually evolved into the mitochondrion and the chloroplast. Soon after these endosymbiotic events, thousands of ancestral prokaryotic genes were functionally transferred from the endosymbionts to the nucleus. This process of functional gene relocation, now rare in eukaryotes, continues in angiosperms. In this article, we show that the chloroplastic acetyl-CoA carboxylase subunit (accD) gene that is present in the plastome of most angiosperms has been functionally relocated to the nucleus in the Campanulaceae. Surprisingly, the nucleus-encoded accD transcript is considerably smaller than the plastidic version, consisting of little more than the carboxylase domain of the plastidic accD gene fused to a coding region encoding a plastid targeting peptide. We verified experimentally the presence of a chloroplastic transit peptide by showing that the product of the nuclear accD fused to green fluorescent protein was imported in the chloroplasts. The nuclear gene regulatory elements that enabled the erstwhile plastidic gene to become functional in the nuclear genome were identified, and the evolution of the intronic and exonic sequences in the nucleus is described. Relocation and truncation of the accD gene is a remarkable example of the processes underpinning endosymbiotic evolution.


Moderate Sedation Changes for Bronchoscopy in 2017.
The reimbursement for procedures using moderate (conscious) sedation has changed significantly as of January 1, 2017. Due to the increasing use of anesthesia services to provide moderate sedation during endoscopy, the Centers for Medicare & Medicaid Services made the decision to remove work relative value units from many of the services requiring moderate sedation, including the bronchoscopy codes. If a bronchoscopist provides moderate sedation to a patient without using anesthesia services or another qualified provider, that work (and revenue) can be reclaimed by using the relevant codes. An understanding of the recent changes in coding and billing is essential for appropriate reimbursement.


Topical coapplication of hyaluronan with transdermal drug delivery enhancers attenuates inflammatory and neuropathic pain.
We have previously shown that intradermal injection of high-molecular-weight hyaluronan (500-1200 kDa) produces localized antihyperalgesia in preclinical models of inflammatory and neuropathic pain. In the present experiments, we studied the therapeutic effect of topical hyaluronan, when combined with each of 3 transdermal drug delivery enhancers (dimethyl sulfoxide [DMSO], protamine or terpene), in preclinical models of inflammatory and neuropathic pain. Topical application of 500 to 1200 kDa hyaluronan (the molecular weight range used in our previous studies employing intradermal administration), dissolved in 75% DMSO in saline, markedly reduced prostaglandin E 2 (PGE 2 ) hyperalgesia, in male and female rats. Although topical 500- to 1200-kDa hyaluronan in DMSO vehicle dose dependently, also markedly, attenuated oxaliplatin chemotherapy-and paclitaxel chemotherapy-induced painful peripheral neuropathy (CIPN) in male rats, it lacked efficacy in female rats. However, following ovariectomy or intrathecal administration of an oligodeoxynucleotide antisense to G-protein-coupled estrogen receptor (GPR30) mRNA, CIPN in female rats was now attenuated by topical hyaluronan. Although topical coadministration of 150 to 300, 300 to 500, or 1500 to 1750 kDa hyaluronan with DMSO also attenuated CIPN, a slightly lower-molecular-weight hyaluronan (70-120 kDa) did not. The topical administration of a combination of hyaluronan with 2 other transdermal drug delivery enhancers, protamine and terpene, also attenuated CIPN hyperalgesia, an effect that was more prolonged than with DMSO vehicle. Repeated administration of topical hyaluronan prolonged the duration of antihyperalgesia. Our results support the use of topical hyaluronan, combined with chemically diverse nontoxic skin penetration enhancers, to induce marked antihyperalgesia in preclinical models of inflammatory and neuropathic pain.


[The historiography of Arabic medicine and the challenges of the XXI century].
This is a critical review of the work and methods of past and present Western historians of Arabic medicine. It points out traditional errors, prejudices and limitations, and proposes to modernize the way we approach this field of research. Up to now, many Western scholars have deemed that Arabic medicine could be understood by knowing the important theoretical treatises (even in unreliable translations) and by reading the frequently outdated secondary literature. Modern research must turn to the texts that reflect the actual medical practices, focus on social aspects of medicine or reflect the actual medical practices, focus on social aspects of medicine or the interaction of learned and folkloric medicine, and must even try to find out the truth about the questionable statements we read in our textbooks. The field urgently needs interdisciplinary and international cooperation and wider diffusion of the recent bibliography.


Treatment of malignant hypercalcaemia.
Hypercalcaemia is a common paraneoplastic syndrome caused by the production by tumours of several factors which affect bone resorption and/or tubular calcium reabsorption. Antihypercalcaemic therapy in cancer patients involves rehydration manoeuvres, as well as the use of a variety of available drugs which inhibit bone resorption, namely plicamycin, calcitonin, bisphosphonates and gallium nitrate. While plicamycin is currently out of use because of its considerable toxicity, bisphosphonates have become the standard therapy in hypercalcaemia of malignancy (HM). These compounds are potent inhibitors of bone resorption but they do not affect tubular calcium reabsorption, which limits their efficacy in humoral HM (HHM) cases. In these patients, gallium nitrate should be the therapy of choice. Among the available bisphosphonates, pamidronate administered in a single infusion of 90 mg, normalises serum calcium levels in > 90% of HM patients. A recently introduced bisphosphonate, zoledronate, is likely to replace pamidronate as a first-line therapy in these patients. The effectiveness of calcitonin in HM treatment is limited, although it seems to be useful at the outset in cases with severe symptomatic hypercalcaemia. Future treatment options of HM are likely to include new bone resorption inhibitors, for example, naturally-occurring osteoprotegerin, or alternate approaches aimed at reducing the tumour production of parathyroid hormone-related protein with noncalcaemic analogues of calcitriol or ras-isoprenylation inhibitors. The development of putative therapeutic agents targeted to inhibit distal calcium reabsorption should be valuable in the management of HHM cases.


The Latest Evolution in Virtual Surgical Planning: Customized Reconstruction Plates in Free Fibula Flap Mandibular Reconstruction.
Virtual surgical planning has contributed to technical advancements in free fibula flap mandible reconstruction. The authors present the largest comparative study on the latest modification of this technology: the use of patient-specific, preoperatively customized reconstruction plates for fixation. A retrospective chart review was performed on all patients undergoing mandibular reconstruction with virtually planned free fibula flaps at a single institution between 2008 and 2018. Patient demographics, perioperative characteristics, and postoperative outcomes were reviewed. Reconstructions using traditional fixation methods were compared to those using prefabricated, patient-specific reconstruction plates. A total of 126 patients (mean age, 48.5 ± 20.3 years; 61.1 percent male) underwent mandibular reconstruction with a free fibula flap. Mean follow-up time was 23.5 months. A customized plate was used in 43.7 percent of cases. Reconstructions with patient-specific plates had significantly shorter total operative times compared with noncustomized fixation methods (643.0 minutes versus 741.7 minutes; p = 0.001). Hardware complications occurred in 11.1 percent of patients, with a trend toward a lower rate in the customized plate group (5.5 percent versus 15.5 percent; p = 0.091). Multivariate regression showed that the use of customized plates was a significant independent predictor of fewer overall complications (p = 0.03), shorter operative time (p = 0.014), and shorter length of stay (p = 0.001). Compared to traditional fixation methods, patient-specific plates are associated with fewer complications, shorter operative times, and reduced length of stay. The use of customized reconstruction plates increases efficiency and represents the latest technological innovation in mandibular reconstruction. Therapeutic, III.


Seawater-driven forward osmosis for pre-concentrating nutrients in digested sludge centrate.
Seawater-driven forward osmosis to enrich nutrients from sludge centrate and reduce membrane fouling is demonstrated. Due to enrichment and pH increase in the feed solution, without appropriate control measure, nutrient precipitation can occur directly on the membrane surface causing severe membrane fouling and reducing nutrient enrichment efficiency. Indeed without agitating the feed, there was less precipitation on the membrane surface, compared to with agitation. In addition, increase in the membrane area over permeate volume ratio significantly reduced the filtration time and nutrient precipitation. A novel technique to maintain the draw solution (DS) at an acidic condition was developed to improve nutrient enrichment and reduce membrane fouling. By using this technique and a high membrane surface to permeate volume ratio, nutrient enrichment similar to the theoretical efficiency was successfully demonstrated. Our technique reduced the filtration time to achieve 70% water recovery by over 90% (compared to unbuffered seawater as the DS, small membrane area, and feed agitation), as a result of significantly less membrane fouling. The amount of phosphorus precipitate on the membrane surface decreased by more than 10 times. The enrichment of ammonia and phosphorus as a function of water recovery was similar to the theoretical calculation, indicating negligible nutrient loss due to precipitation.


Preventive midline laparotomy closure with a new bioabsorbable mesh: an experimental study.
Incisional hernia formation is one of the most frequent complications of midline laparotomies requiring reoperation. The aim of this study was to evaluate the safety and efficacy of prophylactically placing a biodegradable mesh within the incision site at closure in a rat model. A 4-cm full-thick midline laparotomy was made in Sprague-Dawley rats along the linea alba and closed by inserting a commercially available web of synthetic polymers (polyglycolic acid-trimethylene carbonate) that are slowly degraded by the body. Host tissue reaction was evaluated ex vivo and compared with that obtained in suture-only-treated rats. Specimens were harvested at 1, 3, and 6mo after surgery and divided for histologic and zymographic analyses and uniaxial material testing. A group of intact nonoperated animals were included to serve as a reference. The excised tissue explants revealed that the performance of the synthetic device was good and resulted in enhanced fibroproliferation, gelatinolytic activity, and angiogenesis within the repair site as compared with the suture-only procedure. Lastly, tensile strength augmented over the suture-only condition. The preventive introduction of an absorbable mesh stimulates new tissue ingrowth and performance relative to suture repair without prosthesis, probably contributing to eventually reinforce the tension line. These results have a clinical potential in abdominal wall closure, especially in patients with multiple risk factors such as those treated for aortic reconstructive surgery, without the short- and long-term complications related to permanent grafts. However, data are preliminary and should be confirmed with longer follow-ups.


Complete Genome Sequence of Escherichia coli Phage Paul.
Escherichia coli is both a commensal and a pathogen in humans and other animals. Here, we describe the isolation of E. coli strain 4s bacteriophage Paul. The complete 79,429-bp genome was annotated and demonstrates similarity with phieco32viruses, as does its prolate podophage morphology.


Detection of Benign and Malignant Tumors in Skin Empowered with Transfer Learning.
Skin cancer is a major type of cancer with rapidly increasing victims all over the world. It is very much important to detect skin cancer in the early stages. Computer-developed diagnosis systems helped the physicians to diagnose disease, which allows appropriate treatment and increases the survival ratio of patients. In the proposed system, the classification problem of skin disease is tackled. An automated and reliable system for the classification of malignant and benign tumors is developed. In this system, a customized pretrained Deep Convolutional Neural Network (DCNN) is implemented. The pretrained AlexNet model is customized by replacing the last layers according to the proposed system problem. The softmax layer is modified according to binary classification detection. The proposed system model is well trained on malignant and benign tumors skin cancer dataset of 1920 images, where each class contains 960 images. After good training, the proposed system model is validated on 480 images, where the size of images of each class is 240. The proposed system model is analyzed using the following parameters: accuracy, sensitivity, specificity, Positive Predicted Values (PPV), Negative Predicted Value (NPV), False Positive Ratio (FPR), False Negative Ratio (FNR), Likelihood Ratio Positive (LRP), and Likelihood Ratio Negative (LRN). The accuracy achieved through the proposed system model is 87.1%, which is higher than traditional methods of classification.


Percutaneous nerve electrical stimulation for fatigue caused by chemotherapy for cervical cancer.
This retrospective study investigated the effectiveness of percutaneous nerve electrical stimulation (PNES) for fatigue caused by chemotherapy for cervical cancer survivors.Totally, 83 cases of fatigue caused by chemotherapy for cervical cancer survivors were analyzed. All these cases were assigned to a treatment group (n = 43), and a control group (n = 40). Patients in the treatment group received PNES, while the subjects in the control group were on waiting list. The treatment was applied once daily for a total of 6 weeks. The primary endpoint was fatigue. It was evaluated by the Multidimensional Fatigue Inventory (MFI), and Fatigue Questionnaire (FQ). The secondary endpoints consisted of anxiety and depression. They were measured by the Hospital Anxiety and Depression Scale (HADS). All outcomes were measured before and after 6-week treatment.After treatment, PNES did not show significant difference in fatigue relief, measured by MFI (General fatigue, P = .31; Physical fatigue, P = .44; Activity, P = .36; Motivation, P = .55; Mental fatigue, P = .49), and FQ (Mental fatigue, P = .29; Physical fatigue, P = .35); and the reduction of anxiety and depression, measured by the HADS (Anxiety, P = .21; Depression, P = .17) after 6 weeks treatment between 2 groups.This study demonstrated that PNES may not benefit for cervical cancer survivors with fatigue caused by chemotherapy after 6-week treatment.


Decarboxylative Fluorination of Electron-Rich Heteroaromatic Carboxylic Acids with Selectfluor.
A transition-metal-free decarboxylative fluorination of electron-rich five-membered heteroaromatics, including furan-, pyrazole-, isoxazole-, thiophene-, indole-, benzofuran- and indazolecarboxylic acids, with Selectfluor is reported. Fluorinated dimer products were observed for nitrogen-containing heteroaromatic carboxylic acids, such as indole and pyrazole. An effective method has been developed to synthesize the monomer of 2- and 3-fluoroindoles with Li2CO3 as base at low temperature.


Detection and measurement of noncoincidence between the principal axes of the g-matrix and zero-field splitting tensor using multifrequency powder EPR spectroscopy: application to cis-[(NH(3))(2)Pt(1-MeU)(2)Cu(H(2)O)(2)](SO(4)) x 4.5H(2)O (1-MeU = monoanion of 1-methyluracil).
Multifrequency continuous wave EPR spectra (4-34 GHz) on a powder of the title compound are consistent with a spin-triplet state. This arises from interaction between centrosymmetrically related pairs of copper(II) ions in the solid. The spectra at all frequencies have been simulated with a single set of spin-Hamiltonian parameters. The results show that there is noncoincidence between the principal axes of the g-matrices on each copper center and those of the zero-field splitting (D) tensor. This noncoincidence is a single rotation of 33 degrees +/- 2 degrees. The parameters from the powder spectra have been verified by a subsequent single-crystal EPR study which yielded the spin-Hamiltonian parameters g(XX) = 2.074, g(YY) = 2.093, g(ZZ) = 2.385, D(XX) = +/-0.0228 cm(-1), D(YY) = +/-0.0211 cm(-1), D(ZZ) = -/+0.0439 cm(-1) with Euler angles of alpha = 179 degrees, chi = 33.4 degrees, and gamma = 328 degrees. Analysis of the zero-field splitting tensor in terms of exchange indicates that the interaction between the pairs of copper(II) ions is almost entirely dipolar in origin. This study shows that multifrequency EPR spectroscopy on powders, coupled with spectrum simulation, can detect and measure noncoincidence between the principal axes of the g-matrix and zero-field splitting tensor, and does not necessarily require the presence of metal hyperfine interactions.


Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ.
Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The results revealed that the amorphous Ca-polyP particles promote the growth/viability of mesenchymal stem cells, as well as the osteogenic and chondrogenic differentiation of the bone marrow cells in rat femur explants, as revealed by an upregulation of the expression of the transcription factors SOX9 (differentiation towards osteoblasts) and RUNX2 (chondrocyte differentiation). In parallel to this bone anabolic effect, incubation of the femur explants with these particles significantly reduced the expression of the gene encoding the osteoclast bone-catabolic enzyme, cathepsin-K, while the expression of the tartrate-resistant acid phosphatase remained unaffected. The gene expression data were supported by the finding of an increased mineralization of the cells in the femur explants in response to the Ca-polyP particles. Finally, we show that the hybrid particles of polyP complexed with zoledronic acid exhibit both the cytotoxic effect of the bisphosphonate and the morphogenetic and mineralization inducing activity of polyP. Our results suggest that the Ca-polyP nano/microparticles are not only a promising scaffold material for repairing long bone osteo-articular damages but can also be applied, as a hybrid with zoledronic acid, as a drug delivery system for treatment of bone metastases. The polyP particles are highlighted as genuine, smart, bioinspired nano/micro biomaterials.


FDA Approves Drug Combo for Kidney Cancer.
The FDA has approved the combination of lenvatinib and everolimus to treat advanced or metastatic renal cell carcinoma. The approval marks the first time that tyrosine kinase and mTOR inhibitors have been combined successfully as second-line treatment for renal cell carcinoma following prior VEGF-targeted therapy.


Association between nonalcoholic fatty liver disease and coronary artery disease complexity in patients with acute coronary syndrome: a pilot study.
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with acute coronary syndrome (ACS). We assessed the association between NAFLD and SYNTAX Score (SS) in patients with ACS. Eighty consecutive patients with ACS were enrolled. Patients were evaluated using ultrasound to detect NAFLD and hepatosteatosis stage. The prevalence of NAFLD was 81.2%; median SS was 15. The SS was significantly higher in patients with NAFLD (18 ± 8 vs. 11 ± 5, P = .001). Univariate analysis showed that the stage of NAFLD correlated with SS (r = .6, P < .001). In multivariate binary logistic analysis, increased age (odds ratio [OR], 1.05; 95% confidence interval [CI],1.00-1.10) and presence of NAFLD (OR, 13.20; 95% CI, 2.52-69.15) were independent factors associated with supramedian SS. In conclusion, among patients with ACS, those with NAFLD have more complex CAD as assessed by SS.


Metabolome-wide association study of phenylalanine in plasma of common marmosets.
Little systematic knowledge exists concerning the impacts of cumulative lifelong exposure, termed the exposome, on requirements for nutrients. Phenylalanine (Phe) is an essential dietary amino acid with an aromatic ring structure similar to endogenous metabolites, dietary compounds and environmental agents. Excess plasma Phe in genetic disease or nutritional deficiency of Phe has adverse health consequences. In principle, structurally similar chemicals interfering with Phe utilization could alter Phe requirement at an individual level. As a strategy to identify components of the exposome that could interfere with Phe utilization, we tested for metabolites correlating with Phe concentration in plasma of a non-human primate species, common marmosets (Callithrix jacchus). The results of tests for more than 5,000 chemical features detected by high-resolution metabolomics showed 17 positive correlations with Phe metabolites and other amino acids. Positive and negative correlations were also observed for 33 other chemicals, which included matches to endogenous metabolites and dietary, microbial and environmental chemicals in database searches. Chemical similarity analysis showed many of the matches had high structural similarity to Phe. Together, the results show that chemicals in marmoset plasma could impact Phe utilization. Such chemicals could contribute to early lifecycle developmental disorders when neurological development is vulnerable to Phe levels.


Broadband orbital angular momentum transmission using a hollow-core photonic bandgap fiber.
We present the viability of exploiting a current hollow-core photonic bandgap fiber (HC-PBGF) to support orbital angular momentum (OAM) states. The photonic bandgap intrinsically provides a large refractive index spacing for guiding light, leading to OAM transmission with low crosstalk. From numerical simulations, a broad OAM±1 mode transmission window with satisfied effective index separations between vector modes (>10-4) and low confinement loss (<3 dB/km) covering 240 nm bandwidth is observed. The OAM purity (defined as normalized power weight for OAM mode) is found to be affected by the modal effective area. Simulation results also show HC-PBGF based OAM transmission is immune to fabrication inaccuracies near the hollow core. This work illustrates that HC-PBGF is a competitive candidate for high-capacity communication harnessing OAM multiplexing.


Correlation of CD4 counts with renal disease in HIV positive patients.
To correlate CD 4 counts with albuminuria and glomerular lesions in patients infected with human immunodeficiency virus (HIV), we studied 104 HIV positive patients (68 males, 36 females) of whom 100 patients were infected by heterosexual contact, 3 by transfusion, and 1 by i.v. drug abuse. We screened over nine months for albuminuria by urine dip stick method, and performed renal biopsy on patients with albuminuria 2+ or more. Histological examination was accomplished by light microscopy in all and by electron microscopy when it was feasible. Albuminuria was observed in 29 (27%) patients, and it revealed a significant negative correlation with CD4 count (p<0.01). Patients with CD4 cells <350 cells/mm(3) disclosed a 3.5 fold increased risk of albuminuria as compared with patients with CD4 >350 cells/mm(3). There was no significant correlation between proteinuria and the duration of infection from the time of diagnosis. Albuminuria also demonstrated a significant negative correlation with the levels of hemoglobin (p<0.05). In addition, low numbers of CD4 cells were associated with lower levels of hemoglobin (p<0.001). Only 10 patients received renal biopsies, and the results revealed HIV-associated nephropathy (HIVAN) in 7 (70%) patients, chronic tubulointerstitial nephritis in 1, membranous glomerulopathy in 1, and diffuse proliferative glomerulonephritis in 1. Acute renal failure was present in 5 patients, of whom four had a pre renal component and one had multiorgan dysfunction syndrome. We conclude that our study demonstrates that both proteinuria and HIVAN are common in HIV infected patients. Proteinuria has a negative correlation with the CD4 counts and hemoglobin levels.


Effect of flunixin meglumine on Escherichia coli heat-stable enterotoxin-induced diarrhea in calves.
In a study to evaluate the effect of flunixin meglumine on secretory diarrhea, 11 calves were assigned to 3 groups: group 1 (n = 3) served as controls, group-2 calves (n = 4) were given 2.2 mg of flunixin meglumine/kg, IM at 7 AM and 3 PM, and group-3 calves (n = 4) were given 2.2 mg of flunixin meglumine/kg, IM at 7 AM, 11 AM, and 3 PM. All calves were given approximately 200 micrograms of heat-stable Escherichia coli enterotoxin (STa) orally at 8 AM. Mean cumulative fecal output for groups 1, 2, and 3 was 1,331.0 +/- 317.2 g, 1,544.3 +/- 154.4 g, and 785.5 +/- 276.5 g, respectively. There was a significant (P less than 0.05) reduction in mean fecal output in group-3 calves, compared with that in groups 1 and 2. Calves in group 2 tended to have a delay, but not a reduction, in their fecal output. At 12 hours, hemoconcentration was significantly (P less than 0.05) greater in group-1 calves than in group-2 or group-3 calves.


Housekeeping sortase facilitates the cell wall anchoring of pilus polymers in Corynebacterium diphtheriae.
Many surface proteins in Gram-positive bacteria are covalently linked to the cell wall through a transpeptidation reaction catalysed by the enzyme sortase. Corynebacterium diphtheriae encodes six sortases, five of which are devoted to the assembly of three distinct types of pilus fibres--SrtA for the SpaA-type pilus, SrtB/SrtC for the SpaD-type pilus, and SrtD/SrtE for the SpaH-type pilus. We demonstrate here the function of SrtF, the so-called housekeeping sortase, in the cell wall anchoring of pili. We show that a multiple deletion mutant strain expressing only SrtA secretes a large portion of SpaA polymers into the culture medium, with concomitant decrease in the cell wall-linked pili. The same phenotype is observed with the mutant that is missing SrtF alone. By contrast, a strain that expresses only SrtF displays surface-linked pilins but no polymers. Therefore, SrtF can catalyse the cell wall anchoring of pilin monomers as well as pili, but it does not polymerize pilins. We show that SrtA and SrtF together generate wild-type levels of the SpaA-type pilus on the bacterial surface. Furthermore, by regulating the expression of SpaA in the cell, we demonstrate that the SrtF function becomes critical when the SpaA level is sufficiently high. Together, these findings provide key evidence for a two-stage model of pilus assembly: pilins are first polymerized by a pilus-specific sortase, and the resulting fibre is then attached to the cell wall by either the cognate sortase or the housekeeping sortase.


Reevaluating the Impact of Epstein-Barr Virus Noncoding RNAs on the Interferon Response.
The necessity of viruses to modulate the innate immune response often dictates the outcome of viral infection. As such, viruses encode many factors that undermine these potent antiviral responses. A recent study by Bouvet et al. (M. Bouvet, S. Voigt, T. Tagawa, M. Albanese, et al., mBio 12:e03440-20, 2021, https://doi.org/10.1128/mBio.03440-20) revisits the impact of virus-encoded noncoding RNAs on key components of the interferon pathway and sheds light on how the extensive biological functions of Epstein-Barr virus (EBV) microRNAs (miRNAs) are on targeting both the induction and signaling cascades of interferon.


Brain biopsy in patients with CLIPPERS syndrome: why and when.
CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an inflammatory disorder of the central nervous system (CNS), predominantly involving the brainstem with a characteristic magnetic resonance imaging (MRI) appearance and clinical and radiological responsiveness to glucocorticosteroids. Yet diagnostic biomarkers are missing and other immune-mediated, (para-) infectious and malignant causes mimic CLIPPERS-like MRI presentations. We report the case of a 51-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. After 7 months, however, treatment failed, and he had a biopsy-confirmed diagnosis of a CNS B-cell lymphoma. Clinical and MRI signs of CLIPPERS include a wide spectrum of differential diagnoses which often arise only later during the course of disease. Similar to the case presented here, delayed diagnosis and specific therapy may contribute to an unfavorable outcome. Hence, we propose that in the absence of other diagnostic markers, brain biopsy should be performed as early as possible in CLIPPERS patients.