A re-assessment of sucrose signaling involved in cluster-root formation and function in phosphate-deficient white lupin (Lupinus albus).
Apart from substrate functions, a signaling role of sucrose in root growth regulation is well established. This raised the question whether sucrose signals might also be involved in formation of cluster-roots (CRs) under phosphate (Pi) limitation, mediating exudation of phosphorus (P)-mobilizing root exudates, e.g. in Lupinus albus and members of the Proteaceae. Earlier studies demonstrated that CR formation in L. albus was mimicked to some extent by external application of high sucrose concentrations (25 mM) in the presence of extremely high P supply (1-10 mM), usually suppressing CR formation. In this study, we re-addressed this question using an axenic hydroponic culture system with normal P supply (0.1 mM) and a range of sucrose applications (0.25-25 mM). The 2.5 mM sucrose concentration was comparable with internal sucrose levels in the zone of CR initiation in first-order laterals of P-deficient plants (3.4 mM) and induced the same CR morphology. Similar to earlier studies, high sucrose concentrations (25 mM) resulted in root thickening and inhibition of root elongation, associated with a 10-fold increase of the internal sucrose level. The sucrose analog palatinose and a combination of glucose/fructose failed to stimulate CR formation under P-sufficient conditions, demonstrating a signal function of sucrose and excluding osmotic or carbon source effects. In contrast to earlier findings, sucrose was able to induce CR formation but had no effect on CR functioning with respect to citrate exudation, in vitro activity and expression of genes encoding phosphoenolpyruvate carboxylase, secretory acid phosphatase and MATE transporters, mediating P-mobilizing functions of CRs.


A cluster-randomized trial assessing the impact of school water, sanitation, and hygiene improvements on pupil enrollment and gender parity in enrollment.
We employed a cluster randomized trial design to measure the impact of a school based water, sanitation, and hygiene (WASH) improvement on pupil enrollment and on gender parity in enrollment, in primary schools in Nyanza Province, Kenya (2007-2009). Among schools with poor water access during the dry season, those that received a water supply, hygiene promotion and water treatment (HP&WT) and sanitation improvement, demonstrated increased enrollment (β=0.091 [0.009, 0.173] p=0.03), which translates to 26 additional pupils per school on average. The proportion of girls enrolled in school also increased by 4% (prevalence ratio (PR)=1.04 [1.00, 1.07] p=0.02). Among schools with better baseline water access during the dry season (schools that didn't receive a water source), we found no evidence of increased enrollment in schools that received a HP&WT intervention (β=0.016 [-0.039, 0.072] p=0.56) or the HP&WT and sanitation intervention (β=0.027 [-0.028, 0.082]p=0.34), and there was no evidence of improved gender parity (PR=0.99 [0.96, 1.02] p=0.59, PR=1.00 [0.97, 1.02] p=0.75, respectively). Our findings suggest that increased school enrollment and improved gender parity may be influenced by a comprehensive WASH program that includes an improved water source; schools with poor water access during the dry season may benefit most from these interventions.


Oxygen delivery for ambulatory patients. How the Micro-Trach increases mobility.
Transtracheal oxygen delivery with the Micro-Trach is state-of-the-art treatment for patients requiring long-term oxygen therapy. The Micro-Trach diminishes dyspnea because it bypasses the anatomic dead space in the respiratory tract. It eliminates the waste of oxygen that escapes from the nose and mouth when a nasal cannula is used. Therefore, a small oxygen container lasts longer, increasing the patient's mobility. The patient's appetite improves because oxygen is not diverted during deglutition, and the senses of smell and taste are restored. Rehabilitation is enhanced through increased mobility and improved nutrition. Transtracheal instillation of saline solution cleanses the respiratory tract and stimulates coughing, opening occluded air passages. There are fewer lung infections and hospitalizations for infective exacerbations of disease. Prescribed saline solution, mucolytics, and antibiotics can also be instilled through the Micro-Trach to treat cystic fibrosis. This use and others are still being explored.


X chromosome insertion in the MLL gene in a case of childhood acute myeloblastic leukemia.
Band 11q23 is known to be involved in translocations and insertions with a variety of partner chromosomes. These lead to MLL rearrangement, resulting in a fusion with numerous genes. We report here the case of a 5-month-old boy presenting with hemianopsia and severe diffuse intravascular coagulopathy in whom a diagnosis of acute myeloblastic leukemia (AML) French-American-British M4 classification was made. Conventional cytogenetic techniques showed an ins(11;X) (q23;q28q12). Fluorescent in situ hybridization (FISH) with whole chromosome paints confirmed this finding. Using a specific probe, the MLL gene was found to be disrupted, a portion of the X chromosome being inserted between the 5' and 3' regions of the MLL gene. Although some cases of insertion involving chromosomes X and 11 have been reported in AML, this appears to be the first case involving band Xq28. We postulate that this chromosomal rearrangement led to the fusion of the 5' region of the MLL gene with a yet unidentified gene located in band Xq28.


Quantum dynamics of NH(a(1)Delta)+H reactions on the NH(2) A (2)A(1) surface.
We present the Born-Oppenheimer dynamics of the depletion reaction NH(a(1)Delta)+H(')-->N((2)D)+H(2) and of the exchange one NH(a(1)Delta)+H(')-->NH(')(a(1)Delta)+H, using the real wavepacket and flux methods and an accurate NH(2)(A (2)A(1)) surface. We report coupled-channel reaction probabilities, cross sections, and rate constants, taking into account Coriolis couplings. Because the surface is barrierless and strongly bound, probabilities have small centrifugal thresholds and present sharp and large resonances, associated with long-lived collision complexes. Large J's enhance the high-energy reactivity and favor the exchange reaction, owing to the negative Coriolis couplings, and to K that inhibits depletion but not exchange. Coriolis couplings are important in the collision complexes, and the centrifugal sudden approximation thus gives large errors. Cross sections are large at the threshold and minimal at intermediate collision energies and increase moderately at larger energies. Exchange is preferred, and both reactions are inhibited by the NH rotational excitation. Finally, the present rate constants are in good agreement with previous experimental and semiclassical results.


HSC70 is required for infectious bursal disease virus (IBDV) infection in DF-1 cells.
Infectious bursal disease (IBD) is a highly contagious infectious disease that causes severe immunosuppression and damage to the bursa of Fabricius in chickens. Several proteins involved in IBD virus (IBDV) infection, such as surface immunoglobulin M, integrin, annexin A2 and chicken heat shock protein 90, have been identified. However, the main protein that plays key roles in virus infection has not yet been confirmed. DF-1 cell line was transfected with the pcDNA-VP2 plasmid and analyzed by immunofluorescence assay. The proteins reacted with VP2 of IBDV in DF-1 cells were pulldown with the monoclonal antibody and identified by mass spectrometry. Heat shock cognate protein 70 (HSC70), one of these proteins, was selected to be investigated in the function in IBDV infection by specific antibody and its inhibitor. The DF-1 cell line was transfected with the pcDNA-VP2 plasmid, and expression of IBDV VP2 in DF-1 cells was confirmed by immunofluorescence assays. Heat shock cognate protein 70 (HSC70) was one of the proteins identified by coimmunoprecipitation using a monoclonal antibody (2H11) against VP2 and mass spectrometry analysis. IBDV infection in DF-1 cells was strongly inhibited by both an anti-HSC70 antibody and a HSC70 inhibitor (VER155008). These results suggest that HSC70 may be an essential factor for IBDV infection.


Risk factors for recurrent hemorrhage after successful mesenteric arterial embolization.
The objective of this study was to describe the risk factors and to determine the outcomes after recurrent gastrointestinal hemorrhage after successful mesenteric arterial embolization A retrospective analysis was undertaken of a single-center experience with mesenteric arterial embolization performed for gastrointestinal hemorrhage over a 5-year period. Statistical analyses including Student's t test and Fisher's exact test were used to compare results. For the years 2001 through 2005, 36 patients (10 women; average age, 60.8 years) underwent 37 technically successful mesenteric embolizations for acute gastrointestinal hemorrhage. Two (5.4%) cases required surgical intervention for cessation of hemorrhage, and six (16.2%) patients died during their hospitalization after technically successful embolization. Nine (24.3%) patients experienced in-hospital rehemorrhage, and of these, five (55.6%) died. Risk factors for rehemorrhage included intra-abdominal malignancy (P < 0.05), transfusion requirement greater than 10 units before angiography (P < 0.05), and the source of hemorrhage other than solitary gastroduodenal artery hemorrhage (P < 0.05). The failure of initial embolization was associated with an increased incidence of death (55.6% vs 5.0%; P < 0.05) and operative intervention to cease hemorrhage (P < 0.05). The failure of technically successful mesenteric embolization is not uncommon and is associated with identifiable risk factors. Risk factor awareness should assist in patient selection for and timing of mesenteric embolization.


The safety of high-dose vitamin E supplementation in healthy Japanese male adults.
We administered high-dose vitamin E to healthy adult male volunteers and assessed the safety of such supplementation. Fourteen volunteers received daily 1,200 IU of vitamin E (800 mg of D-alpha-tocopherol) for 28 d and eight controls were also enrolled. The volunteers treated with vitamin E showed no abnormalities during the study period. The alpha-tocopherol concentrations of plasma and platelets were markedly elevated by vitamin E treatment, but there were no significant differences in platelet aggregation, coagulation, and the clinical parameters between the two groups. In conclusion, a high dose of vitamin E for 28 d had no adverse effects in healthy men.


Efficient synthesis of 2-substituted-1,2,3-triazoles.
In this three-component reaction, alkynes undergo a copper(I)-catalyzed cycloaddition with sodium azide and formaldehyde to yield 2-hydroxymethyl-2 H-1,2,3-triazoles, which are useful intermediates that can be readily converted to polyfunctional molecules. The hydroxymethyl group can also be removed, providing convenient access to N H-1,2,3-triazoles. The reaction is experimentally simple and readily scalable.


Value of Blood Cultures in the Management of Children Hospitalized with Community-Acquired Pneumonia.
Background and objectives Current guidelines for the management of community-acquired pneumonia (CAP) in children recommend obtaining a blood culture for children with moderate to severe pneumonia; yet, there is no guidance to assess the severity of the disease. Thus, a blood culture is obtained for the majority of children admitted with CAP, regardless of the severity of their symptoms. The study was designed to investigate and identify the prevalence of bacteremia in pediatric patients hospitalized with CAP and to evaluate the clinical and laboratory variables associated with bacteremia. Methods We conducted a medical record review of children aged from two months to 18 years diagnosed with CAP between January 1, 2013, and December 31, 2017, at our two urban tertiary centers. We used binary logistic regression analysis and chi-square tests to look at factors associated with blood culture positivity. Results A total of 464 patients were admitted with CAP. Blood cultures were obtained in 357 (76.9%) patients; 23 patients had repeated cultures. Fifteen patients had positive cultures: 5/380 (1.3%) were considered true positive results and 10/380 (2.6%) were considered contaminants. Intensive care unit (ICU) admission (OR 5.6 with 95% CI (1- 31), p<0.03), toxic appearance (OR 12.8 with 95% CI (1.3-125), p<0.01), and significantly elevated C-reactive protein (CRP) (>300 mg/L (p<0.01) were associated with bacteremia. Conclusion The prevalence of bacteremia among children admitted for CAP is low. The use of routine blood cultures should be reserved for children with moderate to severe pneumonia. Further studies are required to better risk-stratify children with CAP.


HLA-Bw54-DR4-DRw53-DQw4 haplotype controls nonresponsiveness to hepatitis-B surface antigen via CD8-positive suppressor T cells.
We have previously reported that in nonresponders to hepatitis-B (HB) vaccine there was an HLA-linked immune suppression gene for hepatitis-B surface antigen (Is-HBsAg) controlling the nonresponsiveness to HBsAg, through HBsAg-specific suppressor T cells, and that the Is-HBsAg was in strong linkage disequilibrium with the HLA-Bw54-DR4-DRw53 haplotype (1). We have now done the HLA typing on an additional 6 nonresponders, and using the system of T-cell proliferative response to HBsAg we found that the Is-HBsAg controlled the nonresponsiveness to HBsAg through HBsAg-specific suppressor T cells in nonresponders to HB vaccine who have HLA-Bw54-DR4-DRw53-DQw4 haplotype. T- and B-cell recognition of HB vaccines might play an important role at 3 to 5 weeks after the last immunization. Use of an anti-HLA monoclonal antibody has shown that the HLA-DR molecule plays an important role in helper T-cell proliferation in nonresponders, although the role of HLA-DQ molecule in nonresponders was unclear.


[Method of assessment of 137Cs biological availability in forest soil].
A method for quantitative assessment of 137Cs availability to plants in forest ecosystems on the basis of soil properties has been developed. It is shown that the experimental dependencies of 137Cs soil-to-plant transfer factor (TFag) for fern and bilberry on the bioavailability factor calculated on the basis of soil characteristics of root layer: 137Cs exchangeability, exchangeable Ca, effective selectivity coefficient, were satisfactory described by linear function. The advantage of the proposed method is that the necessary soil characteristics can be taken from the reference literature, evaluated using empirical correlations or determined with standard agrochemical procedures.


Federated health information architecture: Enabling healthcare providers and policymakers to use data for decision-making.
Health information systems (HIS) in India, as in most other developing countries, support public health management but fail to enable healthcare providers to use data for delivering quality services. Such a failure is surprising, given that the population healthcare data that the system collects are aggregated from patient records. An important reason for this failure is that the health information architecture (HIA) of the HIS is designed primarily to serve the information needs of policymakers and program managers. India has recognised the architectural gaps in its HIS and proposes to develop an integrated HIA. An enabling HIA that attempts to balance the autonomy of local systems with the requirements of a centralised monitoring agency could meet the diverse information needs of various stakeholders. Given the lack of in-country knowledge and experience in designing such an HIA, this case study was undertaken to analyse HIS in the Bihar state of India and to understand whether it would enable healthcare providers, program managers and policymakers to use data for decision-making. Based on a literature review and data collected from interviews with key informants, this article proposes a federated HIA, which has the potential to improve HIS efficiency; provide flexibility for local innovation; cater to the diverse information needs of healthcare providers, program managers and policymakers; and encourage data-based decision-making.


Microfluidic perfusion bioreactor for optimization of microalgal lipid productivity.
Nutrient deprivation in a batch process induces microbes to produce secondary metabolites while drastically constraining cellular growth. A microfluidic continuous perfusion system was designed and tested to culture microalgae, Chlamydomonas reinhardtii, under constant nutrient concentration slightly lower than normal condition. When cultured in 7.5%/7.5% of NH4+/PO42-, C. reinhardtii showed a 2.4-fold increase in TAG production with a 3.5-fold increase in biomass compared to level obtained under an only NH4+ depleted condition. The microfluidic continuous perfusion bioreactor with steady continuous nutrient flow can be used to optimize conditions for enhancing secondary metabolite production and increasing microbial biomass.


Escherichia coli stringent factor binds to ribosomes at a site different from that of elongation factor Tu or G.
The binding of Escherichia coli stringent factor to ribosomes has been studied; the reaction depends on 50S and 30S ribosomal subunits and poly(U) as messenger RNA. The ribosome-stringent factor complex is formed at 5-10 mM magnesium acetate; NH4 ions are inhibitory. Binding of the stringent factor to the 70S-mRNA complex is not stimulated by uncharged tRNA. The ribosomal binding site(s) for the stringent factor does not overlap with the one known for the elongation factor Tu (EF-Tu) or G (EF-G). Ribosomes carrying either EF-Tu or EF-G are active in binding the stringent factor; however, they are inactive in synthesizing guanosine 5'-triphosphate 3'-diphosphate (pppGpp) and guanosine 5'-diphosphate 3'-diphosphate (ppGpp). The latter result is due to the blockage of the ribosomal acceptor site by the aminoacyl-tRNA and/or elongation factors. That stringent and elongation factors do not compete for identical ribosomal region(s) is supported by: (1) the reverse experiments where ribosomes charged with the stringent factor are fully active in EF-Tu or EF-G dependent functions; (2) ribosomes that lack the two ribosomal proteins L7 and L12 known to be essential for EF-Tu and EF-G functions bind the stringent factor and are active in synthesizing pppGpp and ppGpp.


Effects of monosodium glutamate treatment on calretinin-immunoreactive neurons in hippocampus of postnatal rats.
Calretinin (CR) is a protein, which is present in GABAergic neurons and belongs to the calcium-binding proteins family. It may reduce the excitotoxicity phenomenon through its Ca2+ buffering properties. This phenomenon is due to the increase of calcium ions levels caused by the excess of glutamate—the main excitatory neurotransmitter. The aim of the study was to investigate alterations of calretinin-immunoreactivity in neurons of hippocampal CA1 region and dentate gyrus with hilus in 10 day-old rats treated with monosodium glutamate (MSG). Ten 7 day-old Wistar rats were used. The MSG-group consisted of 5 MSG-treated rats at a dose of 4 g/kg b.w. for 3 consecutive days and the second group consisted of 5 control animals. After euthanasia the brains containing hippocampus were dissected and embedded in paraffin blocks. The immunohistochemical peroxidase-antiperoxydase reaction was performed on tissue sections. The morphometric analyses of CR-immunopositive neurons: density, percentage ratio to the density of all cells and an assessment of digital immunostaining intensity were performed. The distribution of the CR-immunoreactive neurons in the hippocampus was irregular. In the MSG-group there were single cells, which were more intensely stained than in control animals. Some of cells contained processes of different length. The density of CR-immunopositive cells and their percentage ratio to the density of all cells did not change significantly after MSG treatment. However, there was a statistically significant increase in the staining intensity of CR-immunopositive cells. The obtained results indicate that CR-positive cells in P7-P10 rats are only slightly affected by MSG in CA1 region and dentate gyrus with hilus of the hippocampus.


Developing a method for assessing environmental sustainability based on the Google Earth Engine platform.
Environmental sustainability is the foundation and of great significance for the sustainable development of urban agglomerations. Taking the Beijing-Tianjin-Hebei urban agglomeration as an example, we developed a method to effectively assess long-term regional environmental sustainability based on the Google Earth Engine (GEE) platform. We used the GEE to obtain 5206 Landsat remote sensing images in the region from 1983 to 2016 and developed the comprehensive environmental index (CEI) to assess regional environmental sustainability based on the theme-oriented framework proposed by the United Nations Commission on Sustainable Development. We found that the environmental sustainability of the urban agglomeration showed a trend of first rising, then falling, and then rising again in the past 30 years. The average CEI increased from 0.621 to 0.631 from 1985 to 1990, dropped to the lowest value of 0.618 in 2000, and then rose to the highest value of 0.672 in 2015. In particular, the extent of areas in which environmental sustainability improved (56% of the region) was greater than the extent of areas in which environmental deterioration occurred. The environmental sustainability of Hengshui, Xingtai, and Cangzhou in the southeast of the region has been significantly improved. The method proposed in this study provides an automatic, rapid, and extensible way to assess regional environmental sustainability and provides a scientific reference for improving the sustainability of the regional environment.


Differential effects of community health worker visits across social and economic groups in Uttar Pradesh, India: a link between social inequities and health disparities.
Uttar Pradesh (UP) accounts for the largest number of neonatal deaths in India. This study explores potential socio-economic inequities in household-level contacts by community health workers (CHWs) and whether the effects of such household-level contacts on receipt of health services differ across populations in this state. A multistage sampling design identified live births in the last 12 months across the 25 highest-risk districts of UP (N = 4912). Regression models described the relations between household demographics (caste, religion, wealth, literacy) and CHW contact, and interactions of demographics and CHW contact in predicting health service utilization (> = 4 antenatal care (ANC) visits, facility delivery, modern contraceptive use). No differences were found in likelihood of CHW contact based on caste, religion, wealth or literacy. Associations of CHW contact with receipt of ANC and facility delivery were significantly affected by religion, wealth and literacy. CHW contact increased the odds of 4 or more ANC visits only among non-Muslim women, increased the odds of both four or more ANC visits and facility delivery only among lower wealth women, increased the odds of facility delivery to a greater degree among illiterate vs. literate women. CHW visits play a vital role in promoting utilization of critical maternal health services in UP. However, significant social inequities exist in associations of CHW visits with such service utilization. Research to clarify these inequities, as well as training for CHWs to address potential biases in the qualities or quantity of their visits based on household socio-economic characteristics is recommended.


Arterial pressure beat to beat characterization during post-occlusive reactive hyperemia.
In recent years, peripheral arterial tonometry (PAT, a non-invasive and reproducible technique) has gained considerable interest. In this sense, arterial capacity to react to vasoactive stimulus (induced by reactive hyperemia) is known as vascular reactivity (VR). Post ischemic beat to beat VR characterization was performed based on PAT measurements. Systolic Blood Pressure (SBP) and Augmentation index (AIx) variations were modeled, as a response to flow stimulus. Obtained R2 values were around 70% for VR while, to a lesser degree, AIx fit was about 50% Conclusion: Beat to Beat VR was described in terms of SBP and AIx behavior. Further studies are needed to determine the clinical usefulness of the proposed indicators.


Increasing prevalence of ciprofloxacin-resistant food-borne Salmonella strains harboring multiple PMQR elements but not target gene mutations.
Fluoroquinolone resistance in Salmonella has become increasingly prevalent in recent years. To probe the molecular basis of this phenomenon, the genetic and phenotypic features of fluoroquinolone resistant Salmonella strains isolated from food samples were characterized. Among the 82 Salmonella strains tested, resistance rate of the three front line antibiotics of ceftriaxone, ciprofloxacin and azithromycin was 10%, 39% and 25% respectively, which is significantly higher than that reported in other countries. Ciprofloxacin resistant strains typically exhibited cross-resistance to multiple antibiotics including ceftriaxone, primarily due to the presence of multiple PMQR genes and the blaCTX-M-65, blaCTX-M-55 blaCMY-2 and blaCMY-72 elements. The prevalence rate of the oqxAB and aac(6')-Ib-cr genes were 91% and 75% respectively, followed by qnrS (66%), qnrB (16%) and qnrD (3%). The most common PMQR combination observable was aac(6')-Ib-cr-oqxAB-qnrS2, which accounted for 50% of the ciprofloxacin resistant strains. Interestingly, such isolates contained either no target mutations or only a single gyrA mutation. Conjugation and hybridization experiments suggested that most PMQR genes were located either in the chromosome or a non-transferrable plasmid. To summarize, findings in this work suggested that PMQRs greatly facilitate development of fluoroquinolone resistance in Salmonella by abolishing the requirement of target gene mutations.


Consequences of severe epilepsy: psychosocial aspects.
Patients with severe epilepsy very often present a diversity of problems which interact with each other and with factors in the environment in subtle ways. Intellectual and social shortcomings as well as anxiety-related emotional problems are among the most common primary and secondary consequences seen in this patient group. Anxiety among the relatives, ignorance and prejudice in the general population often add to the patients' burdens. When seen from a developmental neuropsychological and psychological point of view the importance of early treatment must be stressed.


Effect of treadmill exercise on lumbar vertebrae in ovariectomized rats: anthropometrical and mechanical analyses.
The purpose of this study was to examine the preventive effect of exercise on lumbar vertebrae in ovariectomized rats. Three-month-old female Wistar rats were divided into 3 groups: control group (A, n = 10); non-exercised ovariectomized group (B, n = 7) and exercised ovariectomized group (C, n = 7). The rats from group C were subjected to treadmill exercise (15 m/minute in the initial six weeks and 19 m/minute in the next six weeks, 1 hour/day, 4 days/week) for 12 weeks. At death, the fourth lumbar vertebrae were removed and an anthropometrical analysis by a paquimeter and a mechanical compression test by a universal test machine were performed. After 12 weeks, the ovariectomy decreased the superior-inferior vertebral height and the maximal braking load in group B compared to group A, while the exercise increased the vertebral mass in group C compared to both groups A and B (rho< 0.01) and the stiffness compared to group B. We concluded the physical activity has an important role to prevent the osteopenia in lumbar vertebrae.


Pyridinium dihydrogenmonothiophosphate.
By reaction of pyridine dithiomonometaphosphoryl fluoride with ethyldiphenylphosphine in the presence of traces of water, we isolated crystals of the title compound, (I). In the structure of this salt, two kinds of hydrogen bonds were detected. They link N-H (part of the cation), as well as one O-H group (part of the anion), to the phosphoryl O atom of the anion. The donor-acceptor distances are 2.654 (1) and 2.568 (1) A, respectively. The P-O and P-S bond lengths are 1.514 (2) and 1.967 (1) A, respectively, which fall therefore in the range of a 1.5-fold bond.


Functional electrical stimulation to the abdominal wall muscles synchronized with the expiratory flow does not induce muscle fatigue.
[Purpose] Continuous electrical stimulation of abdominal wall muscles is known to induce mild muscle fatigue. However, it is not clear whether this is also true for functional electrical stimulation delivered only during the expiratory phase of breathing. This study aimed to examine whether or not intermittent electrical stimulation delivered to abdominal wall muscles induces muscle fatigue. [Subjects and Methods] The subjects were nine healthy adults. Abdominal electrical stimulation was applied for 1.5 seconds from the start of expiration and then turned off during inspiration. The electrodes were attached to both sides of the abdomen at the lower margin of the 12th rib. Abdominal electrical stimulation was delivered for 15 minutes with the subject in a seated position. Expiratory flow was measured during stimulus. Trunk flexor torque and electromyography activity were measured to evaluate abdominal muscle fatigue. [Results] The mean stimulation on/off ratio was 1:2.3. The declining rate of abdominal muscle torque was 61.1 ± 19.1% before stimulus and 56.5 ± 20.9% after stimulus, not significantly different. The declining rate of mean power frequency was 47.8 ± 11.7% before stimulus and 47.9 ± 10.2% after stimulus, not significantly different. [Conclusion] It was found that intermittent electrical stimulation to abdominal muscles synchronized with the expiratory would not induce muscle fatigue.


Developmental patterns of emotion regulation in toddlerhood: Examining predictors of change and long-term resilience.
Emotion regulation is critical for optimal functioning across a wide range of domains and may be even more important for individuals in high-risk environments. While evidence suggests that childhood is generally a period of emotion regulation growth and development, research is needed to examine factors that may contribute to deviations from a typical trajectory. In a prospective study of 1,905 children, latent class growth analysis (LCGA) was used to identify trajectory groups of emotion regulation across toddlerhood (age 14-36 months), examine predictors of those trajectory groups from child temperament, parenting behaviors, and environmental risk, and explore predictions of resilience in 5th grade from the identified groups. LGCA supported a three-class model, with a Stable Incline group, a Decline group, and a Catch-Up group. Child negative emotionality, positive and negative parenting, and environmental risk predicted group membership. These trajectory groups in toddlerhood were predictive of child resilient functioning in the 5th grade. Our findings highlight the importance of utilizing developmental models of emotion regulation and provide implications for prevention and early intervention services to enhance emotion regulation development in early childhood.


The use of information and communication technology in veterinary education.
The internet provides new opportunities to deliver distance and e-learning to the veterinary profession both at undergraduate and postgraduate levels. There are now numerous examples of successful computer-based educational projects in UK higher education, which provide useful models for veterinary science. This will present challenges for academics who will need to adapt their teaching methodologies and students who will have to develop new ways of learning. The future of Information and Communication Technologies (ICT) in the veterinary sector is difficult to predict but it is likely to have far reaching effects on the profession.


Gonadal steroids and energy availability during ovarian maturation stages of the Amazonian pirarucu Arapaima gigas (Teleostei: Osteoglossidae) in the wild.
The Amazonian pirarucu, Arapaima gigas, belongs to a phylogenetically basal group of teleosts (family Osteoglossidae). The commercial importance and the overexploited status of natural stocks of A. gigas brought the interest to rear it in the Amazon region, but rearing techniques are not fully understood to obtain reproduction success. Gonadal steroids (plasma and cephalic liquid), lipids and proteins (muscles, liver and ovary) of wild A. gigas females were analyzed during one year on Mexiana Island (Amazon Basin, Brazil) and ovarian maturation stages were described. The sexual gender determination method based on 11-ketostestosterone (11KT) and estradiol (E2) ratio was applied to check if the value is in agreement of the sex previously determined by direct observation. Adult females were classified into four reproductive stages according to ovary development stage: previtellogenic, maturation, mature, and regression/spawning. Immature females were also analyzed. All mature females were sampled during the rainy season. Lipids stored in the ventrecha (belly) are a possible source of this substrate for the developing ovary. Plasma steroid profile throughout A. gigas female reproductive stages is similar to that found in most teleosts, but plasma 11KT levels peaked at the mature stage, suggesting an important role of this androgen in female ovulation. The 11KT/E2 method was 100% efficient when sexing juveniles and adults at the beginning of their reproductive cycle and can successfully be applied to identify the sexual gender of animals. The steroid profile of the cephalic liquid suggests a possible role of this fluid as a pheromone, due to the high level of 17α-hydroxyprogesterone at the final stages of the reproductive cycle.


"Perfect" designer chromosome V and behavior of a ring derivative.
Perfect matching of an assembled physical sequence to a specified designed sequence is crucial to verify design principles in genome synthesis. We designed and de novo synthesized 536,024-base pair chromosome synV in the "Build-A-Genome China" course. We corrected an initial isolate of synV to perfectly match the designed sequence using integrative cotransformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated editing in 22 steps; synV strains exhibit high fitness under a variety of culture conditions, compared with that of wild-type V strains. A ring synV derivative was constructed, which is fully functional in Saccharomyces cerevisiae under all conditions tested and exhibits lower spore viability during meiosis. Ring synV chromosome can extends Sc2.0 design principles and provides a model with which to study genomic rearrangement, ring chromosome evolution, and human ring chromosome disorders.


The Globalisation of Cardiology and Cardiovascular Diseases in the World-Society-A Case Study with a Special Focus on Heart Failure.
While there has been a shift of attention in global health towards non-communicable diseases, we still know little about the social mechanisms that have allowed these diseases to emerge as topics of global concern. We employ a sociological approach to globalisation in order to reconstruct how cardiology, with our special focus being on heart failure research, has become global, and thereby placed cardiovascular diseases on the agenda of global health. Following sociological theories of world-society and world-polity, we identify a number of preconditions that had to be met so that the globalisation of cardiology could set in. Amongst them were technological innovations, the emergence of an organisational infrastructure on the national level, the appearance of cardiological journals, and an internationally standardised nomenclature. More recently, new drugs and treatment strategies, new specialist journals, and new international standards allowed the subspeciality of heart failure to globalise. Our findings are based on the history and sociology of cardiology, and on our analysis of a broad range of other documents, including scientific articles, guidelines, and policy documents. Additionally, our analysis included two datasets, one containing information on national cardiac societies, and the other containing data on publication output in cardiology.


Monitoring dynamic reactions of red blood cells to UHF electromagnetic waves radiation using a novel micro-imaging technology.
Multiple state-of-the-art techniques, such as multi-dimensional micro-imaging, fast multi-channel micro-spetrophotometry, and dynamic micro-imaging analysis, were used to dynamically investigate various effects of cell under the 900 MHz electromagnetic radiation. Cell changes in shape, size, and parameters of Hb absorption spectrum under different power density electromagnetic waves radiation were presented in this article. Experimental results indicated that the isolated human red blood cells (RBCs) do not have obviously real-time responses to the ultra-low density (15 μW/cm(2), 31 μW/cm(2)) electromagnetic wave radiation when the radiation time is not more than 30 min; however, the cells do have significant reactions in shape, size, and the like, to the electromagnetic waves radiation with power densities of 1 mW/cm(2) and 5 mW/cm(2). The data also reveal the possible influences and statistical relationships among living human cell functions, radiation amount, and exposure time with high-frequency electromagnetic waves. The results of this study may be significant on protection of human being and other living organisms against possible radiation affections of the high-frequency electromagnetic waves.


Comparison of the hemodynamic and hematologic toxicity of a protamine variant after reversal of low-molecular-weight heparin anticoagulation in a canine model.
Using the dog as an animal model, we developed an experimental preparation to compare hemodynamic and hematologic toxicity of anticoagulation reversal. Currently, protamine sulfate reversal of standard unfractionated heparin and low-molecular-weight heparin (LMWH) anticoagulation causes adverse side effects, including decreased systemic mean arterial pressure (MAP), decreased cardiac output (CO), decreased oxygen consumption (VO2), and thrombocytopenia. In addition, standard protamine is only marginally effective at reversing the factor Xa inhibition induced by LMWHs. We have produced protamine-like variant peptides to decrease the adverse responses attributed to standard protamine. The hemodynamic, hematologic, and coagulation effects of standard protamine and the protamine variant (+18RGD) were assessed after reversal of LMWH anticoagulation in anesthetized dogs. Flow probes and vascular catheters were surgically implanted for measurement of hemodynamic parameters including MAP, CO, VO2, and heart rate (HR). Hematologic studies (platelet and white blood cell counts) and coagulation studies (activated clotting time [ACT], activated partial thromboplastin time [aPTT], thrombin clotting time [TCT], antifactor Xa and antifactor IIa values) also were performed. The protamine variant +18RGD was less toxic, induced less thrombocytopenia, and was more effective in anticoagulation reversal than was standard protamine sulfate. Results of this study indicate that the dog may be a useful model for investigating important hemodynamic, hematologic, and coagulation parameters during reversal of LMWH anticoagulation by use of synthetic protamine variants.


A tale of two risks: smoking, diabetes and the subgingival microbiome.
Although smoking and diabetes have been established as the only two risk factors for periodontitis, their individual and synergistic impacts on the periodontal microbiome are not well studied. The present investigation analyzed 2.7 million 16S sequences from 175 non-smoking normoglycemic individuals (controls), smokers, diabetics and diabetic smokers with periodontitis as well as periodontally healthy controls, smokers and diabetics to assess subgingival bacterial biodiversity and co-occurrence patterns. The microbial signatures of periodontally healthy smokers, but not diabetics, were highly aligned with the disease-associated microbiomes of their respective cohorts. Diabetics were dominated by species belonging to Fusobacterium, Parvimonas, Peptostreptococcus, Gemella, Streptococcus, Leptotrichia, Filifactor, Veillonella, TM7 and Terrahemophilus. These microbiomes exhibited significant clustering based on HbA1c levels (pre-diabetic (<6.5%), diabetic (6.5-9.9%), diabetics >10%). Smokers with periodontitis evidenced a robust core microbiome (species identified in at least 80% of individuals) dominated by anaerobes, with inter-individual differences attributable largely to the 'rare biosphere'. Diabetics and diabetic smokers, on the other hand, were microbially heterogeneous and enriched for facultative species. In smokers, microbial co-occurrence networks were sparse and predominantly congeneric, while robust inter-generic networks were observed in diabetics and diabetic smokers. Smoking and hyperglycemia impact the subgingival microbiome in distinct ways, and when these perturbations intersect, their synergistic effect is greater than what would be expected from the sum of each effect separately. Thus, this study underscores the importance of early intervention strategies in maintaining health-compatible microbiomes in high-risk individuals, as well as the need to personalize these interventions based on the environmental perturbation.


Regulation of dopamine release from interplexiform cell processes in the outer plexiform layer of the carp retina.
The gamma-aminobutyric acid (GABA) antagonists bicuculline and picrotoxin stimulate a four- to fivefold increase in endogenous dopamine release from isolated intact carp retina. The release evoked by these agents is Ca2+ dependent, a finding suggesting a vesicular release. Using light microscopic autoradiography, we have localized the sites of dopamine release to the dopaminergic interplexiform cell processes of the outer plexiform layer, which synapse onto horizontal cells. Our findings support previous suggestions that the dopaminergic interplexiform cells receive GABAergic inhibitory input and that the effects of GABA antagonists on horizontal cells are mediated by dopamine release from the interplexiform cells.


Prenylated indole-terpenoids with antidiabetic activities from Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne.
Finding novel and effective suppression of hepatic glucagon response antidiabetic compounds is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. In this study, four new prenylated indole-terpenoids (1-4), named encindolenes I-L, as well as a known analogue (5), were isolated from the fungus Penicillium sp. HFF16from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the antidiabetic activity assay, compounds 1-5 could inhibit glucagon-induced hepatic glucose output with EC50 values of 67.23, 102.1, 49.46, 25.20, and 35.96 μM, respectively, and decrease the intracellular cAMP contents in primary hepatocytes.


Pancreatic ductal adenocarcinoma cell lines display a plastic ability to bi‑directionally convert into cancer stem cells.
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed when metastatic events have occurred. Cancer stem cells (CSCs) play an important role in tumor initiation, metastasis, chemoresistance and relapse. A growing number of studies have suggested that CSCs exist in a dynamic equilibrium with more differentiated cancer cells via a bi‑directional regeneration that is dependent on the environmental stimuli. In this investigation, we obtain, by using a selective medium, PDAC CSCs from five out of nine PDAC cell lines, endowed with different tumorsphere‑forming ability. PDAC CSCs were generally more resistant to the action of five anticancer drugs than parental cell lines and were characterized by an increased expression of EpCAM and CD44v6, typical stem cell surface markers, and a decreased expression of E‑cadherin, the main marker of the epithelial state. PDAC CSCs were able to re‑differentiate into parental cells once cultured in parental growth condition, as demonstrated by re‑acquisition of the epithelial morphology, the decreased expression levels of EpCAM and CD44v6 and the increased sensitivity to anticancer drugs. Finally, PDAC CSCs injected into nude mice developed a larger subcutaneous tumor mass and showed a higher metastatic activity compared to parental cells. The present study demonstrates the ability to obtain CSCs from several PDAC cell lines and that these cells are differentially resistant to various anticancer agents. This variability renders them a model of great importance to deeply understand pancreatic adenocarcinoma biology, to discover new biomarkers and to screen new therapeutic compounds.


Apixaban: a review of its use in the prevention of venous thromboembolism after knee or hip replacement surgery.
Apixaban (Eliquis™) is an orally active and selective direct inhibitor of factor Xa indicated for twice-daily use in the EU for the prevention of venous thromboembolism (VTE) in adults who have had knee or hip replacement surgery. In this article, the pharmacological, clinical efficacy and tolerability data relevant to the use of apixaban in this indication are reviewed. Oral apixaban is a generally effective and well tolerated thromboprophylactic agent for use after major orthopaedic surgery. In the large, randomized, double-blind, phase III, noninferiority trials known as ADVANCE-2 and -3, apixaban 2.5 mg twice daily initiated after surgery was generally more effective in preventing VTE in patients undergoing knee or hip replacement surgery than subcutaneous enoxaparin sodium initiated before surgery at the EU recommended dosage of 40 mg once daily, with apixaban conferring this benefit without significantly increasing the risk of bleeding. However, when the same apixaban regimen was compared with the US recommended dosage regimen of subcutaneous enoxaparin sodium (30 mg twice daily, initiated after surgery) in patients undergoing knee replacement surgery in the similarly designed ADVANCE-1 trial, the thromboprophylactic efficacy of apixaban did not meet primary endpoint noninferiority criteria, although apixaban was associated with fewer major or clinically relevant nonmajor bleeds (composite endpoint) than this enoxaparin sodium regimen. Additional comparative efficacy and tolerability data are required to definitively position apixaban with respect to other anticoagulants, including rivaroxaban and dabigatran etexilate. In the meantime, currently available clinical data indicate that apixaban is an emerging option for the prevention of VTE in patients undergoing knee or hip replacement surgery.


Self-assembly and glass-formation in a lattice model of telechelic polymer melts: Influence of stiffness of the sticky bonds.
Telechelic polymers are chain macromolecules that may self-assemble through the association of their two mono-functional end groups (called "stickers"). A deep understanding of the relation between microscopic molecular details and the macroscopic physical properties of telechelic polymers is important in guiding the rational design of telechelic polymer materials with desired properties. The lattice cluster theory (LCT) for strongly interacting, self-assembling telechelic polymers provides a theoretical tool that enables establishing the connections between important microscopic molecular details of self-assembling polymers and their bulk thermodynamics. The original LCT for self-assembly of telechelic polymers considers a model of fully flexible linear chains [J. Dudowicz and K. F. Freed, J. Chem. Phys. 136, 064902 (2012)], while our recent work introduces a significant improvement to the LCT by including a description of chain semiflexibility for the bonds within each individual telechelic chain [W.-S. Xu and K. F. Freed, J. Chem. Phys. 143, 024901 (2015)], but the physically associative (or called "sticky") bonds between the ends of the telechelics are left as fully flexible. Motivated by the ubiquitous presence of steric constraints on the association of real telechelic polymers that impart an additional degree of bond stiffness (or rigidity), the present paper further extends the LCT to permit the sticky bonds to be semiflexible but to have a stiffness differing from that within each telechelic chain. An analytical expression for the Helmholtz free energy is provided for this model of linear telechelic polymer melts, and illustrative calculations demonstrate the significant influence of the stiffness of the sticky bonds on the self-assembly and thermodynamics of telechelic polymers. A brief discussion is also provided for the impact of self-assembly on glass-formation by combining the LCT description for this extended model of telechelic polymers with the Adam-Gibbs relation between the structural relaxation time and the configurational entropy.


Tunable GLUT-Hexose Binding and Transport via Modulation of Hexose C-3 Hydrogen-Bonding Capabilities.
The importance of the hydrogen bonding interactions in the GLUT-hexose binding process (GLUT=hexose transporter) has been demonstrated by studying the binding of structurally modified d-fructose analogues to GLUTs, and in one case its transport into cells. The presence of a hydrogen bond donor at the C-3 position of 2,5-anhydro-d-mannitol derivatives is essential for effective binding to GLUT5 and transport into tumor cells. Surprisingly, installation of a group that can function only as a hydrogen bond acceptor at C-3 resulted in selective recognition by GLUT1 rather than GLUT5. A fluorescently labelled analogue clearly showed GLUT-mediated transport and low efflux properties of the probe. This study reveals that a single positional modification of a 2,5-anhydro-d-mannitol derivative is sufficient to switch its binding preference from GLUT5 to GLUT1, and uncovers general scaffolds that are suitable for the potential selective delivery of molecular payloads into tumor cells via GLUT transport machinery.


Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway.
The aim of the present study was to gain insight into the molecular mechanism of gefitinib resistance in non-small cell lung cancer (NSCLC), and demonstrate whether long noncoding RNA (lncRNA) expression signatures differ between gefitinib-sensitive PC9 and gefitinib-resistant PC9 (PC9-R) cell lines. PC9 and PC9-R cells were treated with gefitinib and, after 48 h, proliferation and apoptosis were analyzed using a Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Microarray expression profiling of lncRNAs was undertaken in both PC9 and PC9-R cells, and the expression profiles were verified by reverse transcription quantitative-polymerase chain reaction. The EGFR/PI3K/AKT signaling pathway and mitochondrial apoptosis protein expression levels were assessed by western blot analysis. The PC9 cell line treated with gefitinib had a more significant effect on cell viability and apoptosis than the PC9-R cell line (P<0.05). Expression of various lncRNAs differed significantly between the two cell lines, and MIR31HG expression in particular was significantly higher in PC9-R cells. As expected, MIR31HG lncRNA knockdown sensitized PC9-R cells to gefitinib, and further experiments revealed that turning off the EGFR/PI3K/AKT signaling pathway activated expression of p53 in PC9-R cells transfected with si-MIR31HG. Furthermore, PC9-R cells transfected with si-MIR31HG induced cell apoptosis through the mitochondrial apoptosis pathway, and arrested the cell cycle in the G0/G1 phase. The results of the current study suggest that MIR31HG lncRNA levels in PC9-R cells are higher than in PC9 cells. Furthermore, overexpression of MIR31HG lncRNAs may contribute to gefitinib resistance in PC9-R cells through the EGFR/PI3K/AKT pathway, which impacts on cell proliferation, apoptosis and the cell cycle. MIR31HG lncRNA may therefore be a novel candidate biomarker for future therapeutic strategies involving EGFR-TKIs.


Factors Affecting the Prognosis of Patients with Acute Cerebrovascular Occlusion with High National Institutes of Health Stroke Scale Scores Treated with SWIM Technology.
We aimed to explore the factors affecting the prognosis of patients with acute cerebrovascular occlusion with high National Institutes of Health Stroke Scale (NIHSS) scores treated with the SWIM (Solitaire™ stent retriever-assisted thrombectomy with immediate mechanical aspiration) technique using an intracranial support catheter. A retrospective analysis was conducted in 72 patients with acute cerebrovascular occlusion who underwent SWIM surgery in the Affiliated Hospital of Chengde Medical University in China between January 2020 and June 2022. The patients were divided into a good prognosis group (Modified Rankin Score [mRS] 0 to 2; n = 30) and a poor prognosis group (mRS score 3 to 6; n = 42) on their mRS scores 3 months after surgery. The THRIVE (TICI, hemorrhage, reocclusion, infarction, vessel, and embolism) score at different time points before and after the SWIM procedure and the postoperative revascularization rate were compared in the 2 NIHSS score groups. Univariate and logistic regression analyses were performed to identify the risk factors that affected the prognosis of patients with acute cerebrovascular occlusion treated with the SWIM procedure. The NIHSS score difference at various time points after SWIM surgery in patients with low to moderate NIHSS scores was significantly higher than in patients with high NIHSS scores (P < .05). The postoperative revascularization rate in patients with high NIHSS scores was 74.36%, which was not significantly different from that in patients with low to moderate scores (84.85%; P > .05). The poor prognosis in patients with acute cerebrovascular occlusion after SWIM surgery was related to age, hypertension, NIHSS score, Glasgow Coma Scale (GCS) score, Essen Stroke Risk Score (ESRS), onset-to-treatment time (OTT) and Alberta Collateral Grading Scale (ACGS) score (P < .05). Logistic regression analysis showed that age, admission NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure (P < .05). The prognosis in patients with acute cerebrovascular occlusion with high NIHSS scores after SWIM surgery was poor. Advanced age, high NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure. Overall, incorporating these findings into clinical practice promotes personalized approaches, interdisciplinary collaboration and timely interventions to optimize outcomes in patients undergoing the SWIM procedure for acute cerebrovascular occlusion.


Feline leukemia virus-associated enteritis--a condition with features of feline panleukopenia.
Infection with feline leukemia virus (FeLV) was demonstrated immunohistologically in 218 necropsied cats suffering from enteritis. The animals were divided into three groups according to histopathological criteria. The first group exhibited the signs of feline panleukopenia in intestine, lymphoid tissues, and bone marrow. Only 1.6% of these animals were FeLV-infected. The animals of the second group had histopathological alterations as seen in cats suffering from feline panleukopenia, but these were found only in the intestine and not in lymphoid tissues or bone marrow. Of these 71.9% were infected with FeLV. The third group consisted of all other cats suffering from enteritis of which 6.3% were FeLV-positive. The association between FeLV infection and the lesions seen in the animals of group 1 (feline panleukopenia) and group 3 (other types of enteritis) is statistically not significant whereas the alterations exhibited by the cats of group 2 are significantly FeLV-associated. Cats with FeLV-associated enteritis (group 2) are of a mean age of about 2.5 years and are significantly older than animals with feline panleukopenia which are of a mean age of about half a year. Thus a FeLV-associated enteritis exists as a histopathologically recognizable condition which sometimes might be mistaken for feline panleukopenia in routine post-mortem investigations.


TARGETED REJECTION PREDICTS HASTENED ONSET OF MAJOR DEPRESSION.
Although severe life stress frequently precipitates the onset of major depression, little is known about the basic nature of stressors in this general category of adversity and how exposure to different life events might be related to clinical aspects of the disorder. We addressed this issue by introducing, and examining the effects of, targeted rejection (TR), which involves the exclusive, active, and intentional social rejection of an individual by others. Twenty-seven adults with major depressive disorder were administered an interview-based measure of life stress. Severe life events that occurred prior to the onset of depression were subsequently coded as TR or as non-TR. Participants who experienced a pre-onset severe TR event became depressed approximately three times faster than did their non-TR counterparts. These findings highlight the potential importance of TR as a marker of hastened depression onset and demonstrate how refining characterizations of stress may advance our understanding of depression.


Generalized similarity in finite range solar wind magnetohydrodynamic turbulence.
Extended or generalized similarity is a ubiquitous but not well understood feature of turbulence that is realized over a finite range of scales. The ULYSSES spacecraft solar polar passes at solar minimum provide in situ observations of evolving anisotropic magnetohydrodynamic turbulence in the solar wind under ideal conditions of fast quiet flow. We find a single generalized scaling function characterizes this finite range turbulence and is insensitive to plasma conditions. The recent unusually inactive solar minimum--with turbulent fluctuations down by a factor of approximately 2 in power--provides a test of this invariance.


Veillonella Intrapulmonary Abscess With Empyema.
A lung abscess is characterized as a clinical ailment arising from the localized suppurative necrosis of lung parenchyma. This condition primarily results from the complications of aspiration pneumonia due to anaerobic microorganisms originating from the oral cavity. Clinically, patients typically manifest symptoms such as fever, malaise, and a productive cough persisting over several weeks. The majority of lung abscess cases acquired within the community stem from anaerobic bacterial infections, often exhibiting a polymicrobial nature. We present a 51-year-old female with intrapulmonary abscess and empyema, with isolation of Veillonella species. She has a 25-pack-year smoking history. Two weeks prior to arrival at our facility, she experienced intermittent shortness of breath, fever, and subjective fever. Her primary care physician ordered an outpatient computed tomography (CT) which showed evidence of a large right-sided fluid collection. Initial chest X-ray at our facility revealed extensive opacification of the middle and right lower hemithorax, believed to be a large-sized pleural effusion with adjacent pneumonia or atelectasis. She was given a working diagnosis of right-sided empyema. Cardiothoracic surgery was consulted and video-assisted thoracoscopic surgery (VATS) was performed. A very large collection of grossly purulent material was evacuated and revealed a large intrapulmonary abscess. Over 400 cc of frank pus was collected and sent for microbiological analysis. Anaerobic culture demonstrated 3+ Peptostreptococcus species and 3+ Veillonella species. The genus Veillonella consists of a small, strictly anaerobic, gram-negative cocci that lacks flagella, spores, and capsules. This genus obtains energy from the utilization of short-chain organic acids that are present in the oral cavity and intestinal tract. Oral Veillonella is strongly associated with biofilms, causing human oral infectious diseases such as periodontitis and dental caries. Literature states that this organism has been isolated in a limited number of chronic pneumonitis cases. To date, the most common organism isolated from lung abscesses is Streptococcus in adult patients and Staphylococcus aureus in pediatric patients. We strive to elucidate the distinctive clinical presentation evident in this case, alongside a comprehensive understanding of the unusual pathogens identified in the disease's pathogenesis.


Effect of toluene on Pseudomonas stutzeri ST-9 morphology - plasmolysis, cell size, and formation of outer membrane vesicles.
Isolated toluene-degrading Pseudomonas stutzeri ST-9 bacteria were grown in a minimal medium containing toluene (100 mg·L(-1)) (MMT) or glucose (MMG) as the sole carbon source, with specific growth rates of 0.019 h(-1) and 0.042 h(-1), respectively. Scanning (SEM) as well as transmission (TEM) electron microscope analyses showed that the bacterial cells grown to mid-log phase in the presence of toluene possess a plasmolysis space. TEM analysis revealed that bacterial cells that were grown in MMT were surrounded by an additional "material" with small vesicles in between. Membrane integrity was analyzed by leakage of 260 nm absorbing material and demonstrated only 7% and 8% leakage from cultures grown in MMT compared with MMG. X-ray microanalysis showed a 4.3-fold increase in Mg and a 3-fold increase in P in cells grown in MMT compared with cells grown in MMG. Fluorescence-activated cell sorting (FACS) analysis indicated that the permeability of the membrane to propidium iodide was 12.6% and 19.6% when the cultures were grown in MMG and MMT, respectively. The bacterial cell length increased by 8.5% ± 0.1% and 17% ± 2%, as measured using SEM images and FACS analysis, respectively. The results obtained in this research show that the presence of toluene led to morphology changes, such as plasmolysis, cell size, and formation of outer membrane vesicles. However, it does not cause significant damage to membrane integrity.


Microtubule configuration and membranous vesicle transport in elongating fiber cells of the rat lens.
This study examines the microtubule configuration and its close association with the Golgi complex and Golgi-derived membranous vesicles in elongating fiber cells of the rat lens. Since fiber cells elongate tremendously during lens differentiation, we hypothesize that a microtubule-based motor system exists in the elongating fiber cells for transporting important membrane proteins and organelles to the target regions for cell growth. The newly synthesized membrane proteins are known to be transported from the trans-Golgi network in the form of vesicles to the target plasma membrane. By thin-section TEM, we observed a large number of vesicles of various sizes and shapes randomly distributed throughout the cytoplasm of elongating fiber cells. Both Golgi complex and vesicles exhibited characteristic normal structural features seen in other cell types and thus represented real vesicular organelles in the fiber cells. A large number of microtubules were regularly arranged into bundles parallel to the long axis of fiber cells as examined in both longitudinal and cross-section views. Many of these microtubules were closely associated or in intimate contact with the Golgi complex and vesicles in elongating fiber cells. The microtubule polarity assay revealed that microtubules exhibited a unidirectional polarity for the entire length of fiber cells as examined in both anterior and posterior cortical fiber segments. Namely, the minus end of microtubules was towards the anterior lens pole while the plus end was headed towards the posterior pole. This suggests that multiple molecular motors such as kinesin and dynein are needed for carrying the vesicles to both lens poles, since conventional kinesin is known to transport vesicular organelles towards the plus end whereas cytoplasmic dynein carries them towards the minus end of microtubules. By immunoblot analysis, we indeed detected the presence of both kinesin (120 kD) and dynein (70 kD) in homogenate prepared from lens cortical fibers. Moreover, immunogold TEM demonstrated that the aquaporin 0 (formally MIP26) antibody was localized on the membranous vesicles as well as plasma membranes of the cortical fiber cells. This study suggests that a microtubule-based motor system exists in the lens and plays an important role in transporting membrane proteins such as aquaporin 0 in the vesicles during fiber cell differentiation and elongation.


Listeriosis during pregnancy.
Listeriosis is a rare foodborne illness caused by Listeria monocytogenes. It can be transmitted by consuming contaminated ready-to-eat food, long shelf-life products, deli meats, and soft cheeses. Listeria has a predilection to affect immunocompromised patients, elderly people, pregnant women and neonates. In particular, pregnant women are at ~18 times greater risk of infection than general population due to specific pregnancy-related suppressed cell-mediated immunity and placental tropism of L. monocytogenes. The purpose of this review is to summarize the current knowledge regarding listeriosis during pregnancy. A literature search on Medline and Embase was done for articles about listeriosis during pregnancy. A detailed review of published data on epidemiology, pathogenesis, diagnosis, treatment and prevention of listeriosis during pregnancy was performed. Listeriosis during pregnancy encompasses maternal, fetal and neonatal disease. Maternal listeriosis during pregnancy usually presents as a mild febrile illness. Fetal listeriosis has a high mortality rate of 25-35%, depending on the gestational age at the time of infection. Neonatal listeriosis may present as sepsis or meningitis with severe sequels and high case fatality rate of 20%. Adequate treatment of maternal listeriosis prevents and treats fetal disease and it is of imminence importance in the treatment of the neonates. Amoxicillin or ampicillin are the first line of treatment alone or in combination with gentamicin, followed by trimethoprim/sulfamethoxazole. Pregnancy-associated listeriosis should be considered as a cause of fever during pregnancy and appropriate treatment should be initiated preemptively. Prevention remains the best way to control listeriosis and should be reinforced among patients, health care professionals, and regulatory agencies.


Depth-resolved optimization of a real-time sensorless adaptive optics optical coherence tomography.
Sensorless adaptive optics optical coherence tomography (AO-OCT) is a technology to image retinal tissue with high resolution by compensating ocular aberrations without wavefront sensors. In this Letter, a fast and robust hill-climbing algorithm is developed to optimize five Zernike modes in AO-OCT with a numerical aperture between that of conventional AO and commercial OCT systems. The merit function is generated in real time using graphics processing unit while axially tracking the retinal layer of interest. A new method is proposed to estimate the largest achievable field of view for which aberrations are corrected uniformly in sensorless AO-OCT.


Clozapine reduces rehospitalization among schizophrenia patients.
A number of studies have reported reduced rehospitalization for patients on clozapine. This article adds to that literature by mining the clozapine database at Hillside Hospital. The sample consisted of 81 schizophrenia patients who entered Hillside on a typical neuroleptic and then had their medication changed to clozapine. We ascertained the number of inpatient hospitalizations before starting clozapine and compared this with the number of hospitalizations after starting clozapine. We also followed an age- and gender-matched comparison group of other schizophrenia patients who entered Hillside at approximately the same time. Results indicate that the mean number of rehospitalizations while on a typical neuroleptic was 2.03 (1.93)/year, whereas it was only .56 (.97/year after the commencement of clozapine treatment; t(80) = 5.78, p < .001. A 95% confidence interval for the superiority of clozapine over standard neuroleptic treatment as measured in rehospitalizations/year is (1.0, 2.0). The decrease in hospitalization rate of .4 (1.6)/year (pre-index date minus post-index date) for the comparison group was also statistically significant [t(80) = 2.3, p < .03]; the 95% confidence interval for this decrease over time is (.1, .8). The pre-post change was much greater for the clozapine patients than comparison patients. A 2 x 2 repeated measures analysis of variance (ANOVA) contrasting the comparison group to the clozapine patients both before and after the index date indicates a significant time by group interaction (F(1.80) = 22.35, p < .001), thus documenting the greater relative decrease in rehospitalization rate in the clozapine group.


Analysis of Risk Factors for Intraoperative Hypotension in Cesarean Section and Poor Prognosis of Neonates.
To analyze the risk factors of intraoperative hypotension in cesarean section women and poor prognosis of neonates. The clinical data of 1071 cesarean section women admitted to The Affiliated Jiangning Hospital of Nanjing Medical University from January 2021 to December 2021 were retrospectively analyzed. They were divided into hypotension group (n = 472) and normal control group (n = 599) according to whether there was hypotension during operation. The correlations between the clinical data of cesarean section and the occurrence of intraoperative hypotension and poor prognosis of neonates were analyzed by logistic regression analysis. Receiver operating curve (ROC) was drawn and the area under the curve (AUC) was calculated. Logistic regression analysis results showed that BMI ≥30 kg/m2, infant weight ≥3500 g, spinal anesthesia, puncture site L2-3, bupivacaine dose>10 mg, ropivacaine dose>50 mg, and perfusion index≥4 were the risk factor for intraoperative hypotension in cesarean section (p < 0.01) and BMI ≥30 kg/m2, umbilical cord around neck, spinal anesthesia, and perfusion index≥4 were risk factors for poor prognosis of neonates (p < 0.01). The AUC of ROC for BMI to diagnose intraoperative hypotension in cesarean section women was 0.6240 (95% CI: 0.59-0.66, p < 0.01), the sensitivity was only 30.20% (95% CI: 26.73%-35.02%), and the specificity was 87.65% (84.77%-90.04%), and the AUC of BMI for the diagnosis of poor prognosis of neonates was 0.5647 (95% CI: 0.5013-0.6280, p = 0.049), and the sensitivity was 51.19% (95% CI: 40.69%-61.59%), and the specificity was 64.34% (61.30%-67.26%). The AUC of perfusion index for the diagnosis of intraoperative hypotension in cesarean section women was 0.8333 (95% CI: 0.8081-0.8584, p < 0.01), the sensitivity was 94.49% (95% CI: 92.05%-96.21%), and the specificity was 73.12% (69.43%-76.52%); the AUC of perfusion index for the diagnosis of ROC with poor prognosis of neonates was 0.6164 (95% CI: 0.5538-0.6791, p < 0.01), the sensitivity was 70.24% (95% CI: 59.75%-78.96%), and the specificity was 50.86% (47.75%-53.97%). The prediction model established by BMI, infant weight, anesthesia method, puncture site, anesthetic drug dose, and perfusion index has guiding value for clinical prediction of cesarean section maternal hypotension. The prediction model established by BMI, umbilical cord around neck, anesthesia method, and perfusion index has guiding value for clinical prediction of poor prognosis of neonates.


[Factors related to myasthenic crisis in myasthenia gravis patients with oropharyngeal involvement during hospitalization].
Objective: To investigate the factors related to myasthenic crisis (MC) in myasthenia gravis patients (MG) with oropharyngeal involvement during hospitalization. Methods: The clinical data of 99 MG patients with oropharyngeal involvement who were admitted to Beijing Tongren Hospital from 2018 to 2020 were retrospectively reviewed. There were 52 males and 47 females, aged 17-89 (55±15) years old, with a disease duration of 1-240 [10 (4, 36)] months. Multivariable logistic regression analysis was used to determine the factors associated with MC. Results: A total of 19 (19.19%) patients developed into MC during hospitalization. Multivariate logistic regression analysis showed that age of hospitalization ≥ 60 years old (OR=31.378, 95%CI: 3.868-254.557, P=0.001), type B and C thymoma (OR=29.175, 95%CI: 2.986-285.016, P=0.004), excess oropharyngeal secretions (OR=12.649, 95%CI: 2.057-77.783, P=0.006) and infections (OR=9.539, 95%CI: 1.345-67.645, P=0.024) were independently related to MC in MG patients with oropharyngeal involvement. Conclusions: Older age, malignant thymoma, excess oropharyngeal secretions and infection are independently related to MC in MG patients with oropharyngeal involvement during hospitalization. Therefore, great attention should be paid to this type of MG patients, and increased oropharyngeal secretions and various infections should be actively treated, so as to reduce the occurrence of MC.


L-dopa therapy combined with peripheral decarboxylase inhibitor (MK-486) in Parkinsonism.
Eighteen patients with parkinsonism were treated with a combination of L-dopa and peripheral decarboxylase inhibitor, L-alphahydrazinomethyldopa (MK-486). Modification of L-dopa effect by MK-486 was also studied in parkinsonian patients as well as in cats. (1) Concentrations of dopa and dopamine in plasma and brain were measured in cats following intraperitoneal injection of L-dopa alone (100 mg/kg) or combined with MK-486 (10 mg/kg). Dopa levels in plasma and brain in the combination with MK-486 were three times as high as in L-dopa alone. Dopamine levels in caudate nucleus and putamen were increased nearly fourfold with the combination. (2) Plasma dopa and dopamine levels were measured in parkinsonian patients. Clinical pharmacological studies disclosed that a 1 : 10 ratio of MK-486 to L-dopa in dosage was preferable. (3) Maximum plasma dopa levels with the combination were four times those following L-dopa alone. Plasma dopa sustained a high level over a period of five hours. MK-486 markedly reduced plasma levels of dopamine. (4) There was no significant difference in dopa and dopamine levels in cerebrospinal fluid between L-dopa alone and a combination of MK-486, but dopamine levels in the CSF were still high at four hours after the combination of MK-486. (5) In clinical studies of eighteen patients with parkinsonism, the effectiveness of the combination therapy (mean dosage of L-dopa: 750 mg/day) was observed in all cases. Marked improvement was noted in 10 cases out of 15 (67%) with akinesia, in 12 cases out of 17 (71%) with rigidity and in six cases out of 14 (43%) with tremor. Maximum plasma dopa levels were higher in those cases with marked improvement, and were highest in patients with diskinesias as a side effect. (6) An addition of vitamin B6 did not show adverse effects. (7) Transient nausea and vomiting as a side effect, less severe than those experienced with L-dopa alone, were noted in five cases (28%). Dyskinesias in extremities, face, mouth and tongue were observed in six cases (33%). These dyskinesias were seen in a high percentage of cases with marked improvement and were never observed in the extremities contralateral to the side of thalamotomy.


[Oxidant stress in the pathogenesis of multiple sclerosis].
The problem of pathogenesis of multiple sclerosis is of great importance in modern neurology and its solution allows to determine a pathogenetic approach to treatment of this severe disease. Parameters of intensification of lipid peroxidation and indices of the state of enzymatic and non-enzymatic patterns in antioxidant defense system in different clinical forms and at different stages of MS course have been analyzed. The data obtained confirm the presence of oxidant stress in the development of pathological process in MS.


Distinctiveness and the attentional boost effect.
The typical pattern of results in divided attention experiments is that subjects in a full attention (FA) condition perform markedly better on tests of memory than subjects in a divided attention (DA) condition which forces subjects to split their attention between studying to-be-remembered stimuli and completing some peripheral task. Nevertheless, recent research has revealed an exception wherein stimuli presented concurrently with targets in a detection task are better remembered than stimuli which co-occur with distractors. Research on this phenomenon-the Attentional Boost Effect (ABE)-has demonstrated that the ABE is reduced or eliminated for words made distinct by their word frequency or orthographic properties-forms of secondary distinctiveness. However, it is unclear how primary distinctiveness effects may interact with the ABE. The current study observed how perceptual and semantic manipulations of primary distinctiveness via the isolation paradigm interact with the ABE, and revealed these interactions to be fundamentally different than those of secondary distinctiveness. Specifically, whereas the effects of secondary distinctiveness in earlier studies were found to be redundant with the ABE, the current study demonstrated that items characterized by primary distinctiveness enhanced memory performance independently of the ABE. (PsycINFO Database Record


n-Propyl gallate suppresses lipopolysaccharide-induced inducible nitric oxide synthase activation through protein kinase Cδ-mediated up-regulation of heme oxygenase-1 in RAW264.7 macrophages.
n-Propyl gallate is a synthetic phenolic antioxidant with potential anti-inflammatory effects. However, the underlying mechanism remains largely unknown. In the present study, we showed that n-propyl gallate increases the expression and activity of the heme oxygenase-1 (HO-1), a stress-inducible protein with potent anti-inflammatory activity, in RAW264.7 macrophages. The inhibition of the HO-1 activity by treatment with zinc (II) protoporphyrin IX (ZnPP) or by knockdown of the HO-1 expression with small interference RNA significantly reversed the inhibitory effect of n-Propyl gallate on activations of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). An additional mechanism study using inhibitors of signaling kinases revealed the involvement of protein kinase Cδ (PKCδ) in the expression of HO-1 induced by n-Propyl gallate. Consistent with these results, n-Propyl gallate increased the intracellular levels of phosphorylated PKCδ in concentration- and time-dependent manners. The inhibitory effects of n-Propyl gallate on LPS-induced iNOS expression and nitric oxide production were also significantly attenuated by pretreatment with the PKCδ inhibitor, rottlerin, or by transfection with PKCδ (K376R), a kinase-inactive form of PKCδ. Taken together, these findings provide the first evidence that n-Propyl gallate exerts its anti-inflammatory effect through PKCδ-mediated up-regulation of HO-1 in macrophages.


Validating a Series of Photonumeric Rating Scales for Use in Facial Aesthetics Using Statistical Analysis of Intra- and Inter-rater Reliability.
Growing demand for minimally invasive aesthetic procedures to correct age-related facial changes and optimize facial proportions has been met with innovation but has created an unmet need for objective assessment tools to evaluate results empirically. The purpose of this study is to establish the intra- and inter-rater reliability of ordinal, photonumeric, 4-, or 5-point rating scales for clinical use to assess facial aesthetics. Board-certified plastic surgeons and dermatologists (3 raters) performed live validation of jawline contour, temple volume, chin retrusion, nasolabial folds, vertical perioral lip lines, midface volume loss, lip fullness, and crow's feet dynamic- and at rest-rating scales over 2 rounds, 2 weeks apart. Subjects selected for live validation represented the range of scores and included 54 to 83 subjects for each scale. Test-retest reliability was quantitated through intra- and inter-rater reliability, determined from the mean weighted kappa and round 2 intraclass correlation coefficients, respectively. The clinical significance of a 1-grade difference was assessed through rater comparison of 31 pairs of side-by-side photographs of subjects with the same grade or a different grade on the developed scales. The study demonstrated substantial to near-perfect intra- and inter-rater reliability of all scales when utilized by trained raters to assess a diverse group of live subjects. Furthermore, the clinical significance of a 1-point difference on all the developed scales was established. The high test-retest reliability and intuitive layout of these scales provide an objective approach with standardized ratings for clinical assessment of various facial features.


Molecular detection, phylogenetic analysis, and identification of transcription motifs in feline leukemia virus from naturally infected cats in malaysia.
A nested PCR assay was used to determine the viral RNA and proviral DNA status of naturally infected cats. Selected samples that were FeLV-positive by PCR were subjected to sequencing, phylogenetic analysis, and motifs search. Of the 39 samples that were positive for FeLV p27 antigen, 87.2% (34/39) were confirmed positive with nested PCR. FeLV proviral DNA was detected in 38 (97.3%) of p27-antigen negative samples. Malaysian FeLV isolates are found to be highly similar with a homology of 91% to 100%. Phylogenetic analysis revealed that Malaysian FeLV isolates divided into two clusters, with a majority (86.2%) sharing similarity with FeLV-K01803 and fewer isolates (13.8%) with FeLV-GM1 strain. Different enhancer motifs including NF-GMa, Krox-20/WT1I-del2, BAF1, AP-2, TBP, TFIIF-beta, TRF, and TFIID are found to occur either in single, duplicate, triplicate, or sets of 5 in different positions within the U3-LTR-gag region. The present result confirms the occurrence of FeLV viral RNA and provirus DNA in naturally infected cats. Malaysian FeLV isolates are highly similar, and a majority of them are closely related to a UK isolate. This study provides the first molecular based information on FeLV in Malaysia. Additionally, different enhancer motifs likely associated with FeLV related pathogenesis have been identified.


Characterization of a deletion in the Hsp70 cluster in the bovine reference genome.
The 70 kilodalton heat shock proteins (Hsp70) are highly conserved molecular chaperones which have a crucial role in the stress response of the cell. In mammals, the Hsp70 proteins are encoded by a cluster of three genes: HSPA1A, HSPA1B and HSPA1L. In bovines, this cluster is located on chromosome 23 downstream of the major histocompatibility complex (BoLA). We detected inconsistencies in the location of markers on the Hsp70 genes reported in the literature that pointed to a potential deletion in the bovine reference genome UMD 3.1.1. An in silico analysis of the bovine genomic region of the Hsp70 cluster, using available information from public databases, confirmed the existence of a deletion of 11.1-kb spanning the HSPA1B gene and the intergenic region between HSPA1B and HSPA1A. Although we originally considered this an assembly error, it is most likely a particular condition of L1 Dominette 01449, the cow sequenced in the Bovine Genome Project. Moreover, we suggest a new classification of bovine Hsp70 sequences reported in NCBI and a reassignment of the location of SNPs from dbSNP that map to the deletion on BTA23. We also compared the location of selected transcription factor binding sites on the promoters of HSPA1A and HSPA1B. The results generated in the present work could be helpful to refine the reference genome of an important livestock species and also to understand the role and the regulation of the bovine Hsp70 genes.


Effect of recombinant human granulocyte colony-stimulating factor on Pneumocystis carinii infection in nude mice.
Repeated subcutaneous (s.c.) injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to Pneumocystis carinii (P. carinii)-infected balb/c nude (nu/nu) mice had no effects on the number of the P. carinii cysts in the lungs, despite neutrophilic infiltration in the tissues and a marked increase in blood neutrophil count. This finding indicates that neutrophils in the absence of T cells do not play an important role in the killing of P. carinii. However, survival periods of the rhG-CSF treated mice seemed to extend to some extent compared with the controls presumably because of the prevention of mixed bacterial infections.


Economic Consequences and Potentially Preventable Costs Related to Osteoporosis in the Netherlands.
Osteoporosis often does not involve symptoms, and so the actual number of patients with osteoporosis is higher than the number of diagnosed individuals. This underdiagnosis results in a treatment gap. To estimate the total health care resource use and costs related to osteoporosis in the Netherlands, explicitly including fractures, and to estimate the proportion of fracture costs that are linked to the treatment gap and might therefore be potentially preventable; to also formulate, on the basis of these findings, strategies to optimize osteoporosis care and treatment and reduce its related costs. In this retrospective study, data of the Achmea Health Database representing 4.2 million Dutch inhabitants were used to investigate the economic consequence of osteoporosis in the Netherlands in 2010. Specific cohorts were created to identify osteoporosis-related fractures and their costs. Besides, costs of pharmaceutical treatment regarding osteoporosis were included. Using data from the literature, the treatment gap was estimated. Sensitivity analysis was performed on the base-case results. A total of 108,013 individuals with a history of fractures were included in this study. In this population, 59,193 patients were using anti-osteoporotic medication and 86,776 patients were using preventive supplements. A total number of 3,039 osteoporosis-related fractures occurred. The estimated total costs were €465 million. On the basis of data presented in the literature, the treatment gap in our study population was estimated to vary from 60% to 72%. The estimated total costs corrected for treatment gap were €1.15 to €1.64 billion. These results indicate room for improvement in the health care policy against osteoporosis.


Does a Positive Response to Transforaminal Epidural Steroid Injection Identify Patients Who Can Avoid Surgery for Two Years?
Transforaminal epidural steroid injection (TFESI) is widely used to manage lumbar radiculopathy. In clinical settings, patients often undergo repeated transforaminal epidural injections with or without steroid administration. To examine whether a positive response to TFESI at the first month, can in clinical settings, identify patients with radiculopathy who can avoid surgery for two years. Study Design/Setting. This prospective observational study was conducted at an academic medical center. Individuals aged ≥20 years who had been referred to our pain center by spine surgeons were enrolled. All patients were assessed using the Numerical Rating Scale (NRS) at baseline and 1 month after the first TFESI. Patients were divided into two groups according to the NRS decrement: the positive response (PR) group achieved a ≥2.0 decrease on the NRS 1 month after the first TFESI compared to baseline and the no response (NR) group achieved a <2.0 decrease on the NRS. The incidence rates of surgery over two years were compared between the two groups. In addition, we calculated the hazard ratio of the PR group to the NR group regarding the incidence of surgery over two years using the Cox proportional hazard model, adjusting for baseline NRS. Seventy-six patients completed the two-year follow-up. In total, 8 and 68 patients had bilateral and unilateral radiculopathy, respectively. The PR and NR groups included 35 and 41 patients, respectively. The rate of surgery avoidance was 85.7% and 73.2% in the PR and NR groups, respectively. This difference was not statistically significant (p=0.26). After adjusting for baseline NRS, the hazard ratio of the PR group to the NR group regarding the incidence of surgery within two years was 0.35 (95% confidence interval: 0.11-1.11, p=0.08). A positive response to TFESI may not identify patients who can avoid surgery for two years.


Insights to ligand binding to the monoamine transporters-from homology modeling to LeuBAT and dDAT.
Understanding of drug binding to the human biogenic amine transporters (BATs) is essential to explain the mechanism of action of these pharmaceuticals but more importantly to be able to develop new and improved compounds to be used in the treatment of depression or drug addiction. Until recently no high resolution structure was available of the BATs and homology modeling was a necessity. Various studies have revealed experimentally validated binding modes of numerous ligands to the BATs using homology modeling. Here we examine and discuss the similarities between the binding models of substrates, antidepressants, psychostimulants, and mazindol in homology models of the human BATs and the recently published crystal structures of the Drosophila dopamine transporter and the engineered protein, LeuBAT. The comparison reveals that careful computational modeling combined with experimental data can be utilized to predict binding of molecules to proteins that agree very well with crystal structures.


Assessing the evidence on HMO performance.
HMOs contract to provide physician and hospital services to enrolled populations in return for fixed periodic payments. Total costs for HMO members are shown to be lower than for those enrolled in conventional insurance plans. But the explanation for this and related differences cannot be attributed solely to matters of efficiency, quality, or even consumer self-selection or physician satisfaction. Although public policy assumes that HMOs will encourage beneficial competitive responses by traditional health care providers, too little is known to predict the nature and extent of such probabilities.


Sickling of nucleated erythroid precursors from patients with sickle cell anemia.
The pathophysiology of sickle cell anemia is primarily explained in terms of the oxygen-dependent polymerization of sickle hemoglobin (HbS) followed by sickling of erythrocytes. Since the rate and extent of HbS polymerization depend on its intracellular concentration, it has been generally assumed that sickling occurs primarily in mature erythrocytes with their high intracellular hemoglobin concentration. In the present study, we investigated the propensity of nucleated erythroid precursors to undergo sickling; both cultured and fresh marrow-derived erythroid precursors from patients with homozygous sickle cell anemia were studied. The results revealed that upon deoxygenation cultured erythroblasts underwent characteristic morphological deformation in the form of fine, fragile, elongated spicules. Ultrastructural analysis demonstrated highly organized and tightly aligned hemoglobin fibers in the protruded regions. Bone marrow cells examined under partial or complete deoxygenated conditions displayed similar morphological changes. When cultured SS erythroid precursors were exposed to hydroxyurea or butyrate, drugs that may increase fetal hemoglobin (HbF) and inhibit intracellular polymerization, a significant decrease was observed in the propensity of these precursors to undergo sickling, accompanied by a three- to fivefold increase in HbF. These results suggest that, in addition to mature erythrocytes, nucleated erythroid precursors in the bone marrow have the capacity to undergo characteristic sickling as a result of HbS polymerization and may be involved in several aspects of the pathophysiology of sickle cell anemia. Treatment with HbF-stimulating drugs may benefit patients with this disease by inhibiting polymerization-induced sickling of erythroid precursors in the marrow as well as mature erythrocytes in the peripheral blood.


Pesticide contamination in groundwater bodies in the Júcar River European Union Pilot Basin (SE Spain).
The change from a traditional agricultural model to a modern, more productive one, coupled with population growth, has entailed an increased consumption of water, fertilizers and pesticides. This transformation has led to a greater risk of groundwater contamination. This study has analysed for this purpose a total of 314 samples (period 2010-2013). In addition, 332 samples from the Mancha Oriental groundwater body (period 2001-2003) were also examined in order to gain a better perspective on the temporal evolution of pesticides in groundwater bodies. Using this database, this study aims to characterize pesticide pollution and to examine possible processes. Triazine herbicides are the most common pesticides found and also appear in the highest concentrations, with terbuthylazine having a noteworthy concentration of 900 ng/L. The irrigated agriculture and the physicochemical properties of pesticides are the most important factors influencing the concentration and type of pesticides that can reach groundwater. The spatial distribution of nitrate and pesticides do not correspond as they would if the two behaved similarly. Pesticides can completely biodegrade before reaching the saturated zone, but it is also possible that their degradation products have not been analysed and, therefore, their concentrations are underestimated.


On the relative efficiency of model-assisted designs: a conditional approach.
In phase I dose-finding trials, model-assisted designs are a novel class of designs that combine the simplicity of algorithm-based methods with the superior performance of model-based methods. Examples of model-assisted designs include the modified toxicity probability (mTPI), Bayesian optimal interval (BOIN) and keyboard designs. To achieve simplicity, these model-assisted methods model only "local" data observed at the current dose, typically using a binomial model, to guide dose assignments. This potentially causes efficiency loss, however, by ignoring the data observed in other doses. To investigate this issue, we propose a conditional approach that utilizes the data from both current and adjacent (i.e., next higher or lower) doses to make the dose-assignment decisions. Specifically, we propose the conditional optimal interval (COIN) design, as the conditional approach extension of the BOIN design. We investigate the theoretical properties of the COIN design and conduct extensive numerical studies to examine its performance in comparison with existing model-assisted designs. We also present the conditional approach to the keyboard design. We observe that the conditional approach improves patient allocation, but yields similar maximum-tolerated dose (MTD) identification accuracy as the model-assisted designs, suggesting only minor efficiency loss using local data under the model-assisted designs.


Novel Loss-of-Function Mutations in NPR2 Cause Acromesomelic Dysplasia, Maroteaux Type.
Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare skeletal dysplasia characterized by severe disproportionate short stature, short hands and feet, normal intelligence, and facial dysmorphism. Homozygous or compound heterozygous mutations in the natriuretic peptide receptor 2 (NPR2) gene produce growth-restricted phenotypes. The current study was designed to identify and characterize NPR2 loss-of-function mutations in patients with AMDM and to explore therapeutic responses to recombinant growth hormone (rhGH). NPR2 was sequenced in two Chinese patients with AMDM via next generation sequencing, and in silico structural analysis or transcript analysis of two novel variants was performed to examine putative protein changes. rhGH treatment was started for patient 1. Three NPR2 mutations were identified in two unrelated cases: two compound heterozygous mutations c.1112G>A p.(Arg371Gln) and c.2887+2T>C in patient 1 and a homozygous mutation c.329G>A p.(Arg110His) in patient 2, yielding distinct phenotypes. RNA extracted from peripheral blood cells of patient 1 showed alternatively spliced transcripts not present in control cells. Homology modeling analyses suggested that the c.1112G>A p.(Arg371Gln) mutation disrupted the binding of NPR-B homodimer to its ligand (C-type natriuretic peptide) in the extracellular domain as a result of global allosteric effects on homodimer formation. Thus, c.2887+2T>C and c.1112G>A p.(Arg371Gln) in NPR2 were loss-of-function mutations. Furthermore, rhGH therapy in patient 1 increased the patient's height by 0.6SDS over 15 months without adversely affecting the trunk-leg proportion. The short-term growth-promoting effect was equivalent to that reported for idiopathic short stature. Overall, our findings broadened the genotypic spectrum of NPR2 mutations in individuals with AMDM and provided insights into the efficacy of rhGH in these patients.