Jejunal graft conduits after esophagectomy.
The jejunum is uniquely suitable for esophageal reconstruction because it is relatively abundant, does not require a formal preparation, is typically free of disease, has similar luminal size compared to the esophagus, has intrinsic peristalsis, and may not undergo senescent lengthening to the extent that colon does. To obtain data to determine the outcomes of jejunal interposition for esophageal replacement, electronic databases were searched, including MEDLINE (Ovid SP), Scopus, EMBASE (Ovid SP), Science Direct's full-text database, and the Cochrane Library from January 1990 to September 2013. Two-hundred and forty-six abstracts were reviewed and an article search was performed on selected abstracts. Additional references from article bibliographies were included as appropriate. A thorough search of the literature demonstrates the widespread use of jejunum, either as a free, pedicled, or free- and pedicled-graft with acceptable results. Any region of the esophagus can be replaced by jejunum, whether it is distal esophagus as a Merendino procedure for a vagal-sparing esophagectomy and segmental jejunal reconstruction connected to stomach, mid-thoracic esophagus as a pedicled jejunal interposition or free flap, cervical esophagus as a free segmental interposition, or the entire length as a long-segment super-charged pedicled jejunal interposition. When used, the jejunum is either pedicled, augmented ("super-charged"), a free segment (requiring microvascular anastomosis of artery and vein), or a combination of the above.


[The treatment of metabolic syndrome].
The metabolic syndrome is a common syndrome affecting 20%-25% of the population whose features include abdominal obesity, dyslipidemia, arterial hypertension, hyperglycemia, hyperinsulinemia/insulin resistance, renal dysfunction and microalbuminuria. All these components of the syndrome are known cardiovascular risk factors. There is also clear evidence that the presence of metabolic syndrome presents an increased risk of development of diabetes. Therefore, the treatment of metabolic syndrome should be of great importance for preventing the complications. The pharmacological treatment of metabolic syndrome includes the use of several groups of drugs such as antihypertensives, oral antidiabetics, insulin, statins/fibrates as well as anti-obesity drugs.


Palmitoylation of influenza virus proteins.
During and after their synthesis, the envelope proteins of influenza viruses are extensively modified by glycosylation, disulfide-bond formation, oligomerisation and proteolytical cleavage. These modifications have an enormous impact on folding and transport of the proteins to the plasma membrane and are also crucial for the infectivity and pathogenicity of the resulting virus particles. Here we summarize the results of 25 years of research on the linkage of fatty acids to proteins (palmitoylation), a modification we discovered with viral glycoproteins including the influenza virus spike proteins. The fundamental biochemistry of the attachment of fatty acids to the hemagglutinin (HA) and to the ion-channel M2 is described which has been instrumental in revealing similar modifications in cellular proteins. Finally, the functional consequences of palmitoylation for entry of viruses into target cells by HA-mediated membrane fusion and for assembly and release of virus particles from infected cells are discussed.


n-Butanol partitioning into phase-separated heterogeneous lipid monolayers.
Cellular adaptation to elevated alcohol concentration involves altering membrane lipid composition to counteract fluidization. However, few studies have examined the biophysical response of biologically relevant heterogeneous membranes. Lipid phase behavior, molecular packing, and elasticity have been examined by surface pressure-area (π-A) analysis in mixed monolayers composed of saturated dipalmitoylphosphatidylcholine (DPPC) and unsaturated dioleoylphosphatidylcholine (DOPC) as a function of DOPC and n-butanol concentration. n-Butanol partitioning into DPPC monolayers led to lipid expansion and increased elasticity. Greater lipid expansion occurred with increasing DOPC concentration, and a maximum was observed at equimolar DPPC:DOPC consistent with n-butanol partitioning between coexisting liquid expanded (LE, DOPC) phases and liquid condensed (LC, DPPC) domains. This led to distinct changes in the size and morphology of LC domains. In DOPC-rich monolayers the effect of n-butanol adsorption on π-A behavior was less pronounced due to DOPC tail kinking. These results point to the importance of lipid composition and phase coexistence on n-butanol partitioning and monolayer restructuring.


Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.
We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.


Myocardial perfusion defects and associated systemic ventricular dysfunction in congenitally corrected transposition of the great arteries.
Patients with systemic ventricles of right ventricular morphology are at high risk of contractile dysfunction, the cause of which has not been fully elucidated. To assess whether ischaemia or infarction contributes to ventricular impairment in unoperated patients with uncomplicated congenitally corrected transposition of the great arteries (TGA) by studying myocardial perfusion and function. Paediatric and adult congenital cardiac clinics of a tertiary referral centre. Five patients with congenitally corrected TGA but without associated structural cardiac defects (aged 3.5 to 34 years). Maximal exercise stress testing using standard or modified Bruce protocols. Sestamibi (technetium-99m methoxy isobutyl isonitrile) scanning after isotope injection at maximal exercise and rest. Maximum exercise capacity; right ventricular myocardial perfusion, regional wall motion, and thickening; right ventricular ejection fraction. The two youngest patients (3.5 and 11 years) had normal exercise capacity for age, while the others had reduced exercise performance. Sestamibi scanning showed reversible myocardial ischaemia in four patients and fixed defects indicating infarction in five. Irreversible defects were mostly associated with impaired wall motion and thickening. The ejection fraction was normal (65%) in the youngest patient but < 55% in the others (mean (SD) 47(11)%). Patients with unoperated congenitally corrected TGA have a high prevalence of myocardial perfusion defects, with consequent abnormalities of regional wall motion and thickening, and impaired ventricular contractility. These data suggest that ischaemia and infarction are important in the pathogenesis of ventricular failure in this condition.


Exploring mothers' perspectives of an intensive home visiting program in Australia: a qualitative study.
Intensive nurse home visiting programs are an early childhood, population based intervention that target vulnerable families. Programs are dependent on the relationship between home visitor and mother to bring about change. Few studies have focused on investigating parents' perspectives of these programs using qualitative methods and none in the Australian context. The aim of this qualitative study was to explore and describe mothers' perspectives of an intensive nurse home visiting program in South Australia. Eight in-depth interviews were conducted with mothers receiving the program. The findings indicated the role of a trusting relationship between nurse and participant as well as shared decision making was central to program engagement and led to participant perceptions of increasing control over their role as parents. However, a clear distinction was made by the mothers: that they engaged in a relationship, not a program.


Evaluation of deformable image registration between external beam radiotherapy and HDR brachytherapy for cervical cancer with a 3D-printed deformable pelvis phantom.
In this study, we developed a 3D-printed deformable pelvis phantom for evaluating spatial DIR accuracy. We then evaluated the spatial DIR accuracies of various DIR settings for cervical cancer. A deformable female pelvis phantom was created based on patient CT data using 3D printing. To create the deformable uterus phantom, we first 3D printed both a model of uterus and a model of the internal cavities of the vagina and uterus. We then made a mold using the 3D printed uterus phantom. Finally, urethane was poured into the mold with the model of the internal cavities in place, creating the deformable uterus phantom with a cavity into which an applicator could be inserted. To create the deformable bladder phantom, we first 3D printed models of the bladder and of the same bladder scaled down by 2 mm. We then made a mold using the larger bladder model. Finally, silicone was poured into the mold with the smaller bladder model in place to create the deformable bladder phantom with a wall thickness of 2 mm. To emulate the anatomical bladder, water was poured into the created bladder. We acquired phantom image without applicator for EBRT. Then, we inserted the applicator into the phantom to simulate BT. In this situation, we scanned the phantom again to obtain the phantom image for BT. We performed DIR using the two phantom images in two cases: Case A, with full bladder (170 ml) in both EBRT and BT images; and Case B with full bladder in the BT image and half-full bladder (100 ml) in the EBRT image. DIR was evaluated using Dice similarity coefficients (DSCs) and 31 landmarks for the uterus and 25 landmarks for the bladder. A hybrid intensity and structure DIR algorithm implemented in RayStation with four DIR settings was evaluated. On visual inspection, reasonable agreement in shape of the uterus between the phantom and patient CT images was observed for both EBRT and BT, although some regional disagreements in shape of the bladder and rectum were apparent. The created phantom could reproduce the actual patient's uterus deformation by the applicator. For both Case A and B, large variation was seen in landmark error among the four DIR parameters. In addition, although DSCs were comparable, moderate differences in landmark error existed between the two different DIR parameters selected from the four DIR parameters (i.e., DSC = 0.96, landmark error = 13.2 ± 5.7 mm vs. DSC = 0.97, landmark error = 9.7 ± 4.0 mm). This result suggests that landmark error evaluation might thus be more effective than DSC for evaluating DIR accuracy. Our developed phantom enabled the evaluation of spatial DIR accuracy for the female pelvic region for the first time. Although the DSCs are high, the spatial errors can still be significant and our developed phantom facilitates their quantification. Our results showed that optimization is needed to identify suitable DIR settings. For determining suitable DIR settings, our method of evaluating spatial DIR accuracy using the 3D-printed phantom may prove helpful.


Effects of School Physical Education on the Exercise Habits of Children and Adolescents: An Empirical Analysis Using China Health and Nutrition Survey Data.
Since 2002, the Chinese Ministry of Education has conducted reform in the physical education (PE) curriculums of schools in China, with a focus on shifting from sports skills to regular participation in physical activity (PA) and promoting health. The aim of the study, therefore, is to examine the effects of school PE on the exercise habits of children and adolescents in China over time. Data based on 5941 observations of 3708 individuals aged 6 to 17 were collected from the China Health and Nutrition Survey (CHNS) for the period 2004 to 2015. The data were analyzed using the fixed-effect Logit model and the random-effect Tobit model. The likelihood of exercising outside of school is 20.2% higher for students who have school PE than those who do not. Our study found that increasing the duration of PE at school by 100%, increases the duration of out-of-school PA by 22.3%. The variety of the types of sports schools offer encourages students to participate in out-of-school physical activity. The likelihood of students exercising outside of school increases by 5.6% when 1 more exercise type is provided in school PE. In addition, soccer, basketball, badminton, and volleyball education increases students' participation in after-school exercises. Soccer and basketball education, in particular, improves the duration of after-school PA. To form exercise habits in children and adolescents, we encourage the promotion of a variety of physical activities in schools, especially team sports such as soccer and basketball.


Genetic and BMI risks for predicting blood pressure in three generations of West African Dogon women.
The study of genetic polymorphisms and body mass index (BMI) among African women in Africa and in the United States contributes to our understanding of the genetic and environmental risk factors for hypertension. African American women have the highest prevalence of hypertension and obesity compared to other ethnic groups in the United States. Using a cross-sectional research design, we examined the effects of genetic and environmental risks of single nucleotide polymorphisms (SNPs) and BMI on blood pressure (BP) among three generations of West African Dogon women (N = 199). We genotyped six SNPs located in the candidate genes known to be related to hypertension. We tested the associations between these SNPs and systolic BP (SBP) and diastolic BP (DBP) with Fisher's exact tests, chi-square tests for independence, and multivariable linear mixed models. The SNP rs8179526 (SLC4A5) was significantly associated with SBP adjusted for age, age(2), and BMI (p = .02). The "C" allele variant of rs8179526 (allele frequency of 0.445) was associated with higher SBP. This SNP did not deviate from the Hardy-Weinberg equilibrium (HWE) with p value of .772. The SNP × BMI interaction effects associated with SBP and DBP were not significant. rs8179526 is located on the SLC4A5 gene on chromosome 2. SLC4A5 encodes a protein that transports sodium and bicarbonate across cell membranes while regulating cellular pH and contains several SNPs linked to elevated BP. Knowledge of the SNP's effect on hypertension among West African women can help health practitioners educate their patients about genetic risks of developing hypertension.


An intermediate level of approximation for computing the dual descriptor.
At present, there are two levels of approximation to compute the dual descriptor (DD). The first uses the total electronic density of the original system along with the electronic densities of the system with one more electron and one less electron, but this procedure is time consuming and normal termination of computation of total electronic densities is not guaranteed. The second level of approximation uses only the electronic densities of frontier molecular orbitals, HOMO and LUMO, to avoid the former approximation; however, the orbital relaxation implicitly included in the first level of approximation is absent in the second, thus risking an incorrect interpretation of local reactivity. Between the lowest occupied molecular orbital (LOMO) and the highest unoccupied molecular orbital (HUMO), a framework to provide an expression of the DD in terms of the electronic densities of all molecular orbitals (except HUMO and LOMO) has been proposed to be implemented by programmers as a computational code. This methodology implies another level of approximation located between the conventional approximation methods mentioned above. In this study, working equations have been oriented toward molecular closed- and open-shell systems. In addition, the mathematical expression for a closed-shell system was applied to acetylene in order to assess the capability of this approach to generate the DD.


A review of radiographic lines and angles used in orthopedics.
This paper reviews many of the most common lines and angles used in the evaluation of skeletal radiographs. The descriptions and accompanying figures are organized by anatomic location and radiographic projection view. The method of drawing the line or measuring the angle, as well as the expected range of normal and the significance of an abnormal measurement, are included.


Long-Term Fipronil Treatment Induces Hyperactivity in Female Mice.
Fipronil is an insecticide widely used for veterinary and agricultural purposes. While its insecticidal properties mostly rely on its high affinity antagonistic activity on insect γ aminobutyric acid (GABA) receptors, fipronil and its main metabolite fipronil sulfone nevertheless display non-negligible affinity for mammalian GABAA receptor. As several environmental toxicants have been shown to raise the risk of developing various neurodegenerative disorders, the aim of this study was to evaluate whether long-term low dose administration of fipronil could lead to cognitive deficiencies. Our results indicate that long-term fipronil treatment leads to behavioral perturbations in mice, indicating an accumulative effect of sustained exposure to low dose of fipronil. Although no memory impairment was observed during the course of our study, we noticed a significant hyperlocomotion behavior after 43 weeks of weekly fipronil administration, which is consistent with its direct effect on the GABAergic system.


Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes.
Pyrroloquinoline quinone (PQQ) has been shown to protect primary cultured hippocampal neurons from glutamate-induced cell apoptosis by scavenging reactive oxygen species (ROS) and activating phosphatidylinositol-3-kinase (PI3K)/Akt signaling. We investigated the downstream pathways of PI3K/Akt involved in PQQ protection of glutamate-injured hippocampal neurons. Western blot analysis indicated that PQQ treatment following glutamate stimulation triggers phosphorylation of glycogen synthase kinase 3β, accompanied by maintenance of Akt activation. Immunostaining and quantitative RT-PCR revealed that PQQ treatment promotes nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), and up-regulates mRNA expression of Nrf2 and the antioxidant enzyme genes, heme oxygenase-1 and glutamate cysteine ligase catalytic in glutamate-injured hippocampal neurons; this is a process dependent on the PI3K/Akt pathway, as evidenced by blocking experiments with PI3K inhibitors. In addition, increased ROS production and decreased glutathione levels in glutamate-injured hippocampal neurons were found to be reduced by PQQ treatment. Collectively, our findings suggest that PQQ exerts neuroprotective activity, possibly through PI3K/Akt-dependent activation of Nrf2 and up-regulation of antioxidant genes. However, the ability of PQQ to scavenge ROS was not totally regulated by PI3K/Akt signaling; possibly it is governed by other mechanisms.


Methodologies toward Efficient and Stable Cesium Lead Halide Perovskite-Based Solar Cells.
In an attempt to replace thermally vulnerable organic perovskites, considerable research effort has recently been focused on the development of all-inorganic perovskites in the field of photovoltaics. The preceding studies demonstrated that cesium lead halide perovskites are promising candidates for thermally stable and efficient solar cell materials. Here, the recent progress in cesium lead halide perovskite-based solar cells is summarized. Whether organic cations are essential for the superiority of halide perovskites is controversial. However, more than 13% efficient solar cells have been successfully fabricated by employing cesium lead halide perovskites in a short amount of time. The state-of-the-art materials engineering techniques will help to achieve a remarkable photovoltaic performance comparable to that of organic perovskites. In addition, improved understanding of the intrinsic photophysical behaviors will provide new insights that will facilitate further improvements in solar cell applications.


Investigating the safety and operational benefits of mixed traffic environments with different automated vehicle market penetration rates in the proximity of a driveway on an urban arterial.
Traffic congestion is monotonically increasing, especially in large cities, due to rapid urbanization. Traffic congestion not only deteriorates traffic operation and degrades traffic safety, but also imposes costs to the road users. The concerns associated with traffic congestion increase when considering more complicated situations such as unsignalized intersections and driveways at which maneuvers are entirely dependent upon drivers' judgment. Urban arterials are characterized by closely spaced signalized and unsignalized intersections and high traffic volumes, which make them a priority while analyzing traffic safety and operation. Autonomous Vehicles (AV) provide ample opportunities to overcome the aforementioned challenges. In essence, this study evaluates the impact of various AV Market Penetration Rates (MPR) on the safety and operation of urban arterials in proximity of a driveway under different traffic levels of service (LOS). Twenty-four separate scenarios were developed using VISSIM, considering six AV MPRs of 0 %, 10 %, 25 %, 50 %, 75 %, and 100 %, and four LOS including A, B, C, and D. Various operational and safety measures were analyzed including traffic density, traffic speed, traffic conflict (rear-end and lane-changing), and driving volatility. The trajectory and lane-based analysis of the traffic density indicates that MPR significantly improves the overall traffic density for all the scenarios, especially under high traffic LOS. Additionally, by increasing the MPR and decreasing the traffic volume of the network, the mean speed increases significantly by up to 6 %. Exploring the safety of the scenarios indicates that by increasing the MPR from 0% to 100 % for all the LOS, the number of rear-end conflicts and lane-changing conflicts decreases 84 %-100 % and 42 %-100 %, respectively. Moreover, assessing the longitudinal driving volatility measures, which represent risky driving behaviors, showed that higher MPRs significantly reduce some of the driving volatility measures and enhance safety.


Gross anatomy of the deep perivertebral musculature in horses.
To determine the gross morphology of the multifidus, longus colli, and longus thoracis muscles in the cervical and cranial thoracic portions of the equine vertebral column. 15 horse cadavers. The vertebral column was removed intact from the first cervical vertebra (C1) to the seventh thoracic vertebra (T7). After removing the superficial musculature, detailed anatomic dissections of the multifidus, longus colli, and longus thoracis muscles were performed. The multifidus cervicis muscle consisted of 5 bundles/level arranged in lateral, medial, and deep layers from C2 caudally into the thoracic portion of the vertebral column. Fibers in each bundle attached cranially to a spinous process then diverged laterally, attaching caudally on the dorsolateral edge of the vertebral lamina and blending into the joint capsule of an articular process articulation after crossing 1 to 4 intervertebral joints. The longus colli muscle had ventral, medial, and deep layers with 5 bundles/level from C1 to C5 that attached cranially to the ventral surface of the vertebral body, diverged laterally and crossed 1 to 4 intervertebral joints, then attached onto a vertebral transverse process as far caudally as C6. The longus thoracis muscle consisted of a single, well-defined muscle belly from C6 to T5-T6, with intermediate muscular attachments onto the ventral aspects of the vertebral bodies, the intervertebral symphyses, and the craniomedial aspects of the costovertebral joint capsules. Results indicated that there were multiple, short bundles of the multifidus cervicis, multifidus thoracis, and longus colli muscles; this was consistent with a function of providing sagittal plane intersegmental vertebral column stability.


[New psychopharmacological approaches in mental health as applied by the Israel Defense Forces].
In the past decade there have been far-reaching developments in psychopharmacology. Previously, only a few classes of medication were at the disposal of psychiatrists, as many had serious side effects that limited their use. Now our psychopharmacological armamentarium has grown considerably, allowing for greater choice of treatment in the military. We review these developments, and discuss the special considerations to be taken into account when treating soldiers with psychiatric medication. We discuss suitable medication for ongoing outpatient treatment, as well as the standard list of medication currently used by units deployed in the field. Advances in psychopharmacologic treatment should enable more soldiers to serve safely in the military with fewer restrictions on their duties.


The effects of intensive short-term dynamic psychotherapy on depressive symptoms, negative affect, and emotional repression in single treatment-resistant depression: A randomized controlled trial.
Intensive short-term dynamic psychotherapy (ISTDP) is theorized to reduce negative affect by challenging patients' defense mechanisms so that they can experience and work through attachment-trauma-related emotions. While ISTDP has been shown to decrease depressive symptoms in single treatment-resistant depression (TRD), it has not been established whether negative affect and emotional repression are reduced, as theorized. Next to depressive symptoms, this retrospectively registered (https://osf.io/v46gy) randomized controlled trial, therefore, examined the effects of ISTDP on emotional repression and negative affect in adults with TRD. Eighty-six adults with major depressive disorder, who had not responded to at least one trial of antidepressants were randomized to 20 sessions of ISTDP (N = 43) or a waitlist control condition (N = 43). Mixed-effect models on the intention-to-treat sample showed that compared to the control condition, ISTDP resulted in significantly lower posttreatment levels of depressive symptoms (d = -1.73), emotional repression (d = -1.91), and negative affect (d = -1.45). Similarly, ISTDP resulted in significantly lower levels of depressive symptoms (d = -2.67), emotional repression (d = -2.69), and negative affect (d = -1.85) at the 3-month follow-up. These results support the evidence base of ISTDP by showing that it can decrease depressive symptoms, emotional repression, and negative affect in TRD. Future studies should assess whether these effects are specific to ISTDP. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Protocol: Optimised methodology for isolation of nuclei from leaves of species in the Solanaceae and Rosaceae families.
In this study, a protocol is described for rapid preparation of an enriched, reasonably pure fraction of nuclear proteins from the leaves of tobacco (Nicotiana tabacum), potato (Solanum tuberosum) and apple (Malus domestica). The protocol gives reproducible results and can be carried out quickly in 2 hours. Tissue extracts clarified with filtration were treated with non-ionic detergent (Triton X-100) to lyse membranes of contaminating organelles. Nuclei were collected from a 60% Percoll layer of density gradient following low-speed centrifugation. Western blot analysis using antibodies to marker proteins of organelles indicated that the nuclear protein fractions were highly enriched and free or nearly free of proteins from the endoplasmic reticulum and chloroplasts.


Fabrication of broadband poly(vinylidene difluoride-trifluroethylene) line-focus ultrasonic transducers for surface acoustic wave measurements of anisotropy of a (100) silicon wafer.
This paper investigates a new method for fabrication of broadband line-focus ultrasonic transducers by sol-gel spin-coating the poly(vinylidene difluoride-trifluroethylene) [P(VDF-TrFE)] copolymer film on a concave fine-polished beryllium copper backing. The ferroelectric hysteresis loops of the P(VDF-TrFE) films spin-coated from different molar ratios of VDF/TrFE, 77/23 and 55/45, were measured to select the better mixture. Owing to the better acoustic matching to water, compared with lead zirconate titanate (PZT), the fabricated transducers show relatively wide bandwidth of approximately 50 MHz with high central frequency of 60 MHz obtained at the focal plane when a fused-quartz acts as a reflecting target. Each one of the two finished transducers has a focal length of 5mm and a full aperture angle of 90°. After applying the specially developed digital signal processing algorithm to the defocusing experiment data, which is called V(f,z) analysis method based on two-dimensional fast Fourier transform (2-D FFT), the operating frequency can extend from several MHz to over 90 MHz. Surface acoustic wave (SAW) velocities of a typical (100) silicon wafer was measured along various directions between [100] and [010] to represent the anisotropic features.


What do you want to be? The strategic question behind your patient grouping decision.
How you group your patients has a lot to do with your strategic goals. It is the first step in creating an "operations strategy" that fits with your external strategy. As the Concentric Rings diagram suggests, the rest of your organizational design is based on this key decision. In today's changing environment, answering the question "What do we want to do?" is the first step. Your answer to this question could drastically shift your priorities and influence your trade-offs during your Patient Focused restructuring efforts. It is, however, only the first step. More than ever before, driving your overall strategy into your restructured design will be the key to your success and will "make or break" your Patient Focused program.


Introducing a method of in vitro testing of different anchoring systems used for female incontinence and prolapse surgery.
To develop a method for in vitro testing to compare different intracorporeal anchoring systems (AS) used, for example, in single-incision slings or vaginal meshes. Intracorporeal fixation needs reliable anchorage systems, which keep the implant in the operative and early postoperative phase in place. Up to now, the impact of the design of current anchor systems and their capability to provide sufficient retention forces is not known. Four AS ("PelFix", "Surelift", "TFS", and "MiniArc") were evaluated in an animal model and a ballistic gelatine model with pull-out tests. We performed ANOVA with post hoc Bonferroni. Results were presented as mean values whereby a significance level of <0.05 was considered significant. The four systems showed significantly different pull-out forces. Depending on mesh structure, size, and form of the AS, mechanical strain resulted in deformation with local peak stresses. Under the condition of form stability, relative differences of pull-out forces did not change in different tissues. Reliable testing of different AS in their ability to keep mesh implants in place can be done in animal models and in especially designed ballistic gelatine. These methods of testing will help to modify AS in novel pelvic floor implants.


The regulatory and transcriptional landscape associated with carbon utilization in a filamentous fungus.
Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level.


Amino-acid sequence of the cytochrome c from the yeast Hansenula anomala. Identification of three methylated positions.
The cytochrome c of the yeast Hansenula anomala has been purified and sequenced. A combination of automatic and manual sequencing methods was used on the whole protein and on fragments obtained by cyanogen bromide cleavage and proteolytic fragmentation. The cytochrome presents an amino-terminal extension of six residues and the C-terminal one-residue deletion typical of plant and fungal cytochrome c. Lysines 72 and 73 are trimethylated, lysine 55 partly monomethylated and partly dimethylated. Positions 73 and 55 have never been found methylated before.


Interleukin-10 and articular cartilage: experimental therapeutical approaches in cartilage disorders.
Interleukin (IL)-10 is a well known anti-inflammatory and immunoregulatory cytokine, mainly released by, and acting on cells of the immune system such as monocytes, macrophages, T cells, NK cells, and B cells. IL-10 is also produced by a few connective tissue cell types including chondrocytes and is involved in processes such as connective tissue extracellular matrix remodelling, although it's exact function in articular cartilage remains unclear. This review article summarizes after a short insight into functions of IL-10 in the immune system most of the published literature on the role of IL-10 in articular cartilage homeostasis and disorders. A critical analysis of the present literature was undertaken leading to a survey of the significance of IL-10 in rheumatoid arthritis (RA), osteoarthritis (OA) and blood induced cartilage damage with particular focus on the direct impact of IL-10 on chondrocyte biology. IL-10 is up-regulated in RA and OA and therapeutic effects of IL-10 in experimental arthritis using several gene therapeutic approaches were reported, mainly through an immune cell mediated immunosuppression mechanism. Recently, a direct anti-inflammatory, -catabolic and -apoptotic potential of IL-10 in cartilage was described, suggesting a chondroprotective effect of IL-10, not only in RA and OA, but also in non-RA and non-systemic cartilage disorders. Chondroprotection by IL-10 may be a promising tool in arthritis therapy, as IL-10 plays a role in joint and cartilage immunoregulation and homeostasis. However, a crucial problem remains to be the optimisation of local and continuous therapeutic effective levels of IL-10 administration in the joint.


Cutaneous malignant neoplasms in patients with renal transplants.
There is an increased risk of developing cutaneous neoplasms in patients with renal transplants who are receiving immunosuppressive therapy. We studied 523 consecutive white patients who had received renal transplants at a Canadian medical center. Malignant neoplasms developed in 7.5% of these patients, and 72% of these neoplasms were cutaneous in origin. Compared with the general population, the rate of development of all skin cancers, squamous cell carcinoma, and basal cell carcinoma was 3.2, 18.4, and 1.4 times, respectively. In our study the squamous cell carcinoma to basal cell carcinoma ratio was 2.3:1, compared with 0.2:1 in the general population. There was no significant difference in the site of development of skin cancer in patients with renal transplants compared with the general population. There was, however, a propensity for the development of multiple skin cancers at an earlier age, especially on sun-exposed areas. The results of this study have been compared with those of other world medical centers.


Ab initio design of potent anti-MRSA peptides based on database filtering technology.
To meet the challenge of antibiotic resistance worldwide, a new generation of antimicrobials must be developed. This communication demonstrates ab initio design of potent peptides against methicillin-resistant Staphylococcus aureus (MRSA). Our idea is that the peptide is very likely to be active when the most probable parameters are utilized in each step of the design. We derived the most probable parameters (e.g., amino acid composition, peptide hydrophobic content, and net charge) from the antimicrobial peptide database by developing a database filtering technology (DFT). Different from classic cationic antimicrobial peptides usually with high cationicity, DFTamP1, the first anti-MRSA peptide designed using this technology, is a short peptide with high hydrophobicity but low cationicity. Such a molecular design made the peptide highly potent. Indeed, the peptide caused bacterial surface damage and killed community-associated MRSA USA300 in 60 min. Structural determination of DFTamP1 by NMR spectroscopy revealed a broad hydrophobic surface, providing a basis for its potency against MRSA known to deploy positively charged moieties on the surface as a mechanism for resistance. Our ab initio design combined with database screening led to yet another peptide with enhanced potency. Because of the simple composition, short length, stability to proteases, and membrane targeting, the designed peptides are attractive leads for developing novel anti-MRSA therapeutics. Our database-derived design concept can be applied to the design of peptide mimicries to combat MRSA as well.


Electron-electron interactions and the paired-to-nematic quantum phase transition in the second Landau level.
In spite of its ubiquity in strongly correlated systems, the competition of paired and nematic ground states remains poorly understood. Recently such a competition was reported in the two-dimensional electron gas at filling factor ν = 5/2. At this filling factor a pressure-induced quantum phase transition was observed from the paired fractional quantum Hall state to the quantum Hall nematic. Here we show that the pressure-induced paired-to-nematic transition also develops at ν = 7/2, demonstrating therefore this transition in both spin branches of the second orbital Landau level. However, we find that pressure is not the only parameter controlling this transition. Indeed, ground states consistent with those observed under pressure also develop in a sample measured at ambient pressure, but in which the electron-electron interaction was tuned close to its value at the quantum critical point. Our experiments suggest that electron-electron interactions play a critical role in driving the paired-to-nematic transition.


The recycling of Mn-Zn ferrite wastes through a hydrometallurgical route.
A novel recycling route using acid leaching, reduction, purification, co-precipitation and traditional ceramic process was applied to process the Mn-Zn ferrite wastes and prepare the corresponding high permeability soft magnetic product. Above 95% of Fe, Mn, Zn in the waste materials could be recycled in the form of Mn-Zn ferrite products through the hydrometallurgical route. The comprehensive properties of Mn-Zn ferrite prepared from wastes by this route have broader frequency characteristics, higher resistivity, lower loss coefficient and temperature coefficient as compared to the A102 product (Acme Electronics Corporation, Taiwan). Moreover, the cost of this recycling technology has economical advantage over the traditional ceramic process, which holds a promising industrial application.


A Bayesian method for inferring quantitative information from FRET data.
Understanding biological networks requires identifying their elementary protein interactions and establishing the timing and strength of those interactions. Fluorescence microscopy and Förster resonance energy transfer (FRET) have the potential to reveal such information because they allow molecular interactions to be monitored in living cells, but it is unclear how best to analyze FRET data. Existing techniques differ in assumptions, manipulations of data and the quantities they derive. To address this variation, we have developed a versatile Bayesian analysis based on clear assumptions and systematic statistics. Our algorithm infers values of the FRET efficiency and dissociation constant, Kd, between a pair of fluorescently tagged proteins. It gives a posterior probability distribution for these parameters, conveying more extensive information than single-value estimates can. The width and shape of the distribution reflects the reliability of the estimate and we used simulated data to determine how measurement noise, data quantity and fluorophore concentrations affect the inference. We are able to show why varying concentrations of donors and acceptors is necessary for estimating Kd. We further demonstrate that the inference improves if additional knowledge is available, for example of the FRET efficiency, which could be obtained from separate fluorescence lifetime measurements. We present a general, systematic approach for extracting quantitative information on molecular interactions from FRET data. Our method yields both an estimate of the dissociation constant and the uncertainty associated with that estimate. The information produced by our algorithm can help design optimal experiments and is fundamental for developing mathematical models of biochemical networks.


Immunohistochemical studies on fibrillin in amyloidosis, lichen ruber planus and porphyria.
The pathogenesis of macular amyloidosis and lichen amyloidosis remains unsolved and the primary amyloid fibril protein(s) has not yet been identified. Ultrastructural association of skin amyloid with elastin associated microfibrils has been noted earlier. The presence of fibrillin in conjunction with such microfibrils was recently demonstrated immunohistochemically. The presence of fibrillin immunoreactivity in the amyloid deposits in skin biopsies from 3 patients with macular amyloidosis and 3 patients with lichen amyloidosis was studied, using monoclonal anti-fibrillin antibodies. For comparison, skin specimens were studied from five patients with lichen ruber planus, four patients with erythropoietic protoporphyria and from a patient with myeloma-associated cutaneous amyloidosis. Renal specimens from two cases of the amyloid A type of renal amyloidosis also were investigated. There was no immunostaining either of the keratin bodies in specimens of lichen ruber planus, the cutaneous PAS-positive vascular deposits in patients with erythropoietic protoporphyria, or the amyloid deposits in specimens of systemic amyloidosis and it was faint or absent in amyloid deposits in the specimens from patients with lichen amyloidosis. In contrast, distinct fibrillin immunoreactivity could be demonstrated in amyloid deposits in specimens from patients with macular amyloidosis. It was sometimes absent in deposits located in the upper part of the papillary dermis, close to the dermal epidermal junction zone, while consistently strong in deposits located lower down in the dermis. The results suggest that fibrillin or part of the fibrillin molecule may be present in some of the amyloid deposits in specimens of macular amyloidosis.


To explore the prevalence and outcomes of advance care planning for patients with left ventricular assist devices: A review.
To explore the prevalence and outcomes of advance care planning for patients with left ventricular assist devices: a review. End-stage heart failure is associated with significant symptom burden at rest. Left ventricular assist devices are not curative; nevertheless, they alleviate symptoms and prolong survival. Evidence suggests that most patients with left ventricular assist devices and their families do not have open discussions regarding end-of-life wishes until catastrophic complications arise. Therefore, it is important to understand reasons for this, so healthcare professionals such as nurses can facilitate the process. A mixed-studies integrative review with a narrative synthesis of the evidence. PRISMA guidelines were followed for reporting systematic qualitative reviews. A search of four electronic data in January 2018 and a hand search yielded 139 citations; seven studies met the review eligibility criteria. Methodological quality of the selected studies was evaluated, and data were extracted and compiled. Three themes were identified: prevalence and feasibility of advanced care planning, advance care planning developed for patients with device support, patients' and caregivers' perceptions of advanced care planning discussions. Advanced care planning is underused routinely implemented in left ventricular device centres. Pre-implantation advanced care planning is feasible and results in the highest rate of documented advance decisions which are useful for both patients and their loved ones in cases of complications. Strong evidence that left ventricular assist-specific advanced care planning is recommended for all left ventricular assist device patients to enable their treatment preferences in case of incurable complications. Palliative care services should collaborate with nurses in designing and facilitating advanced care planning for delisted transplant patients. Patients with left ventricular devices awaiting heart transplant and those waiting for myocardium healing are underrepresented in the current studies. Research on the optimal timing of advanced care planning in these groups of patients is indicated. There is a need for improved approaches to advanced care planning for and with people with left ventricular devices.


Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish.
Epilepsy is a devastating neurological condition exhibited by repeated spontaneous and unpredictable seizures afflicting around 70 million people globally. The basic pathophysiology of epileptic seizures is still elusive, reflecting an extensive need for further research. Developing a novel animal model is crucial in understanding disease mechanisms as well as in assessing the therapeutic target. Most of the pre-clinical epilepsy research has been focused on rodents. Nevertheless, zebrafish disease models are relevant to human disease pathophysiology hence are gaining increased attention nowadays. The current study for the very first time developed a pilocarpine-induced chronic seizure-like condition in adult zebrafish and investigated the modulation in several neuroinflammatory genes and neurotransmitters after pilocarpine exposures. Seizure score analysis suggests that compared to a single dose, repeated dose pilocarpine produces chronic seizure-like effects maintaining an average seizure score of above 2 each day for a minimum of 10 days. Compared to the single dose pilocarpine treated group, there was increased mRNA expression of HMGB1, TLR4, TNF-α, IL-1, BDNF, CREB-1, and NPY; whereas decreased expression of NF-κB was upon the repeated dose of pilocarpine administration. In addition, the epileptic group demonstrates modulation in neurotransmitters levels such as GABA, Glutamate, and Acetylcholine. Moreover, proteomic profiling of the zebrafish brain from the normal and epileptic groups from LCMS/MS quantification detected 77 and 13 proteins in the normal and epileptic group respectively. Summing up, the current investigation depicted that chemically induced seizures in zebrafish demonstrated behavioral and molecular alterations similar to classical rodent seizure models suggesting the usability of adult zebrafish as a robust model to investigate epileptic seizures.


Distribution and implications of beta-endorphin and ACTH-immunoreactive cells in the intermediate lobe of the hypophysis in healthy equids.
The distribution of cells that stain positive for beta-endorphin and ACTH immunoreactivity was studied in the pars intermedia (PI) of the hypophysis in 3 healthy horses and 2 healthy ponies. Serial sections treated with commercial antibodies generated against beta-endorphin or ACTH were processed for immunocytochemical studies, using the avidin biotin immunoperoxidase-complex method. Distribution patterns of cells reacting with antibodies were similar in cells from all equids. Cells immunostained for ACTH were numerous and widely distributed in the PI. Cells immunopositive for ACTH probably contain corticotrophin-like intermediate lobe peptide that cross-reacts with antisera to ACTH. Cells immunopositive for beta-endorphin were fewer in number and had a more limited distribution in the PI. Most beta-endorphin-positive cells were located along the border of the PI adjacent to the lobus nervosus and had abundant eosinophilic cytoplasm when stained with hematoxylin and eosin. Cells with prominent eosinophilic cytoplasm were not common in other areas of the PI. When serial sections were examined, cells that stained positive for beta-endorphin immunoreactivity also appeared positive for ACTH.


Hesperetin-5,7,3'-O-Trimethylether Dually Inhibits Phosphodiesterase 3/4 and Methacholine-Induced Airway Hyperresponsiveness in Sensitized and Challenged Mice.
Hesperetin-5,7,3'-O-trimethylether (HTME), a synthetic liposoluble hesperetin, has been reported to be a dual phosphodiesterase (PDE)3/4 inhibitor. We investigated its inhibitory effects on methacholine (MCh)-induced airway hyperresponsiveness (AHR) and its potential for treating atypical asthma and COPD. FlexiVent system was used to determine AHR in ovalbumin (OVA) sensitized and challenged mice. Determination of cytokines was performed by using mouse T helper (Th)1/Th2 cytokine CBA kits, and of total immunoglobulin (Ig)E and OVA-specific IgE using ELISA kits. The number of inflammatory cells was counted using a hemocytometer. Xylazine/ketamine-induced anesthesia was to assess nausea, vomiting, and gastric hypersecretion in these mice. HTME dually and competitively inhibited PDE3/4 activities in the Lineweaver-Burk analysis. HTME (30 and 100 μmol/kg) dose-dependently and significantly decreased the airway resistance (RL) and increased lung dynamic compliance (Cdyn) values induced by MCh. It significantly suppressed numbers of total inflammatory cells and neutrophils, and levels of cytokines in bronchoalveolar lavage fluid (BALF). HTME dose-dependently and significantly inhibited total and OVA-specific IgE levels in the BALF and serum. However, HTME did not influence xylazine/ketamine-induced anesthesia. HTME exerted anti-inflammatory and bronchodilator effects and may be useful in treating chronic obstructive pulmonary disease and allergic atypical asthma with no gastrointestinal side effects.


Neuronal intranuclear inclusion disease: report on a case originally diagnosed as dopa-responsive dystonia with Lewy bodies.
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with a heterogeneous clinical picture characterized by the presence of eosinophilic intranuclear inclusions in neuronal and glial cells. We describe a case, reported 12 years ago as dopa-responsive dystonia (DRD) with Lewy body pathology. Pathological re-examination has led to a revised diagnosis of neuronal intranuclear inclusion disease. This rare condition, which may be diagnosed in life with a full thickness rectal biopsy, needs to be considered in the differential diagnosis of any case presenting as progressive juvenile parkinsonism (JP) or dystonia.


Work and rest sleep schedules of 227 European truck drivers.
To investigate the sleep-wake behavior and performance of a random sample of European truck drivers. The drivers completed a questionnaire concerning sleep-wake habits and disorders experienced during the previous 3 months. In addition, they were asked to complete a sleep and travel log that included their usual work and rest periods during the previous two days. They answered questions concerning working conditions and reported their caffeine and nicotine intake during their trips. A total of 227 drivers, mean age 37.7+/- 8.4 years (96.2% acceptance rate), participated in the study. The drivers were found to have a fairly consistent total nocturnal sleep time during their work week, but on the last night at home prior to the new work week there was an abrupt earlier wake-up time associated with a decrease in nocturnal sleep time. Of the drivers, 12.3% had slept less than 6 h in the 24 h previous to the interview and 17.1% had been awake more than 16 h. Shifting sleep schedules between work and rest periods can generate long episodes of wakefulness. This type of sleep deprivation is rarely investigated. Its is usually not taken into consideration when creating work schedules, but affects the performance of drivers. Unsuspected shifts occur at the onset of a new workweek. Sleep hygiene education for professional drivers is still far from perfect.


Effects of biofertilizers on the growth, leaf physiological indices and chlorophyll fluorescence response of spinach seedlings.
Chemcial fertilizer as the main strategy for improving the vegetable yields was excessively applied in recent years which led to progressively serious soil problems such as the soil acidification. According the situation, five different biofertilizer treatments [no fertilizer (CK), inoculations of Bacillus subtilis (Bs, T1), combination of Bs and Bacillus mucilaginosus (Bs+Bm, T2), Bs and Bacillus amyloliquefaciens (Bs+Ba, T3), and Bm+Ba (T4)] were conducted to investigate the effect of the growth, leaf physiological indices, and chlorophyll fluorescence of spinach seedlings in the growth chamber. The growth and physiological indices of the spinach seedlings attained a maximum under the T2 treatments. Under the T2 treatment, the ABS/RC (Absorption flux per RC), TR0/RC (Trapping flux per RC), and ET0/RC (Electron transport flux per RC) was significantly increased, while the DI0/RC [Dissipated energy flux per RC (at t = 0)] was decreased. The OJIP curve was improved under of the inoculations of fertilizers, and the increasing range was the largest under the T2 treatment. The leaf light response curve (LC) was also significantly increased under the T2 treatment. The plant growth characteristics [leaf length (LL), leaf weight (LW), plant height (PH)] were positively correlated with the J-I-P test chlorophyll fluorescence parameters [PIABS (Performance index for energy conservation from exciton to the reduction of intersystem electron acceptors), φP0 (Maximum quantum yield of primary photochemistry), φE0 (Quantum yield of electron transport), ψ0 (The probability that a trapped exciton moved an electron in electron transport chain further than QA-), TR0/RC, and ET0/RC] while negatively correlated with φD0 (Quantum yield of energy dissipation) and DI0/RC. The leaf physiological characteristics [SP (soluble protein concentrations), SC (soluble carbohydrate concentrations), Chl a (chlorophyll a), Chl b (chlorophyll b), Chl a+b, Chl a/b, and WP (water potential)] were positively correlated with the J-I-P test chlorophyll fluorescence parameters (PIABS, φP0, φE0, ψ0, ABS/RC, TR0/RC, and ET0/RC) while negatively correlated with φD0 and DI0/RC. These results indicated that the combination of Bs+Bm inoculations promoted the growth of the spinach and improved the adaptability of the vegetable to acid soil while Ba inoculation didn't have any effects to plants.


Analysis of Nursing Effect of Comprehensive Nursing Intervention on Hemodialysis Patients with Uremia.
Uremic pruritus affects 50-90% of hemodialysis patients, making it one of the most frequent medical issues among this group. Pruritus can lead to skin infections, desquamation, pathological skin changes, sleep problems, anxiety, depression, and social problems. The epidemic of uremia pneumonia has put a lot of stress on hemodialysis patients, resulting in negative feelings. As a result, during the prevention and control of uremia, rigorous management and improved nursing intervention are critical. During the uremia disease outbreak, this study will examine and assess the impact of clinically refined nurse intervention on patients receiving maintenance hemodialysis.


Effect of blood glucose concentrations on admission in non-diabetic versus diabetic patients with first acute myocardial infarction on short- and long-term mortality (from the MONICA/KORA Augsburg Myocardial Infarction Registry).
The aim of this study was to investigate the association between increased admission glucose in nondiabetic (ND) patients and in patients with type 2 diabetes mellitus (T2DM) with first acute myocardial infarctions (AMIs) and 28-day as well as 1- and 3-year case fatality. The Monitoring Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) myocardial infarction registry database in Augsburg, Germany, was used, and 1,631 patients without and 659 patients with T2DM (aged 25 to 74 years) who were admitted from 1998 to 2003 with first AMIs were included. Mortality follow-up was carried out in 2005. ND patients with AMIs with admission glucose >152 mg/dl (top quartile) compared with those in the bottom quartile had an odds ratio of 2.82 (95% confidence interval [CI] 1.30 to 6.12) for death within 28 days after multivariate adjustment; correspondingly, patients with T2DM with admission glucose >278 mg/dl (top quartile) compared with those in the bottom quartile (<152 mg/dl) showed a nonsignificantly increased odds ratio of 1.45 (95% CI 0.64 to 3.31). After the exclusion of patients who died within 28 days, a nonsignificantly increased relative risk (RR) was seen between admission blood glucose and 1-year mortality in ND subjects (RR 2.71, 95% CI 0.90 to 8.15), whereas no increased RR was found in subjects with diabetes (RR 0.99, 95% CI 0.34 to 2.82). After 3 years, there was no increased risk for death in patients with high admission blood glucose levels, neither for ND patients nor for those with T2DM. In conclusion, elevated admission blood glucose is associated with increased short-term mortality risk in patients with AMIs, particularly in ND subjects. These patients constitute a high-risk group needing aggressive, comprehensive polypharmacotherapy.


Systemic Epstein-Barr virus infection associated with membranous nephropathy in children.
Epstein-Barr virus (EBV) infection can cause diverse renal manifestations ranging from microscopic hematuria to acute renal failure. Membranous nephropathy (MN) is an uncommon and usually secondary cause of nephrotic syndrome in children, and has been reported after chronic infections and antigenemia. We report two pediatric cases of secondary MN associated with acute and chronic systemic EBV infection. Patient 1 had a liver transplant for cirrhosis due to biliary atresia and developed chronic EB viremia. Membranous nephropathy occurred 3 years later and with aggressive therapy has partially subsided, in temporal association with a drop in blood EBV PCR levels. The other patient had a primary immunodeficiency and developed a lymphoproliferative disorder attributed to EBV. Nephrotic syndrome developed at initial presentation and was associated with MN on biopsy. The patient cleared the virus from blood, which was associated with eventual resolution of the MN. We postulate that EB viremia in patients lacking a fully competent immune system, but without a renal allograft, may create a susceptible environment for chronic systemic EB antigenemia that can then lead to immune-complex MN in the kidney. The association of EBV with renal histological changes consistent with MN has been suggested but not directly described before.


Utility of special drive campaign on substance use disorders in hard-to-reach communities in the fast urbanizing town of Solan, India.
Special drive campaigns on substance use disorders (SUDs) in India are usually organized in educational institutes, non-governmental organizations, or few selected localities. Hard to reach communities of construction, prison, and industrial sites quite often remain uncovered. During a month-long special drive in 2019, under a cross-sectional study, we reached these communities of Solan town through awareness camps and incorporated standardized screening tools for evaluating morbidity patterns of SUDs. Statistically significant relationship existed between 360 participants (90.8% males, 9.2% females; mean age of 33 years) and their educational levels with χ2 (1, n = 360) =130.59, P = 0.000. Fagerstrom's scale inferred very high nicotine dependence in 10.6%, 7.9%, and 2.4% of prisoners, industrial workers, and laborers, respectively. Whereas, Fagerstrom scale for smokeless tobacco revealed 31% of significant dependence potential amongst laborers. Alcohol use disorder identification test revealed 28 persons with harmful alcohol dependence. Drug abuse screening test revealed 13.6% of prisoners having moderate level drug abuse potential. The Kruskal-Wallis test showed a statistically significant difference, in levels and potential of substance use in construction, prison, and industrial sites. The study proved the utility of special drives in evaluating SUDs morbidity patterns in hard-to-reach communities.


Development of breeding values for susceptibility to virulent footrot in sheep: A strategy to accommodate variable disease progression at time of scoring.
Genetic evaluations utilising footrot scores from industry flocks in their essence, incorporate data from a wide range of challenge environments, resulting in potentially large differences in means, variances and distribution of scores across challenges. The date that commencement of infection occurs is generally unknown, and progression of the infection varies with the prevailing environmental and management conditions, virulence of the bacterium Dichelobacter nodosus, as well as the genetic potential and (permanent) environmental ability of animals to resist footrot. In practice, animals are unlikely to be repeatedly scored to identify the best time for comparison, or monitor development of disease progression. Furthermore, field challenges are limited by the need to treat animals before their welfare is compromised. Therefore, the duration and intensity of infection varies and this affects comparisons between animals for their susceptibility. Diseases such as footrot are characterised by multiple categorical scores reflecting clinical stages that describe the progression and relative impact of the disease. This provides the opportunity for the transformation of the data to a standardised prevalence. Scoring events from multiple footrot field challenges under a standardised protocol were used to establish a series of transition matrices to describe disease progression between scores over time. These transition matrices were used to standardise challenge events to the more severe scoring events, observed later in the challenge. The accuracy of the transition technique was tested by comparing the ranking of animals and sires against the observed scores. Transitioning the data from low disease prevalence to the higher prevalence at the subsequent scoring event improved the correlations between the scoring events, at the animal level, by upwards of 0.10 across challenges. The utilisation of a transition matrix to transform low prevalence disease challenges by taking into account the natural biological rate of progression through the clinical stages of the disease provides a more accurate technique to account for variation in disease prevalence. The transition technique increases the acceptable range of disease expression targeted by producers when scoring virulent footrot challenges reducing the need for repeat scoring and allowing earlier treatment and reducing the impact of the disease on the host animal.


Edge-based 3-D camera motion estimation with application to video coding.
Two classes of algorithms for modeling camera motion in video sequences captured by a camera are proposed. The first class can be applied when there is no camera translation and the motion of the camera can be adequately modeled by zoom, pan, and rotation parameters. The second class is more general in that it can be applied when the camera is undergoing a translation motion, as well as a rotation and zoom and pan. This class uses seven parameters to describe the motion of the camera and requires the depth map to be known at the receiver. The salient feature of both algorithms is that the camera motion is estimated using binary matching of the edges in successive frames. The rate distortion characteristics of the algorithms are compared with that of the block matching algorithm and show that the former provide performance characteristics similar to those of the latter with reduced computational complexity.


alpha-Glucan synthesis on a protein primer, uridine diphosphoglucose: protein transglucosylase I. Separation from starch synthetase and phosphorylase and a study of its properties.
It was found that the DEAE-cellulose-treated UDP-Glc:protein transglucosylase I catalyzing the first step (reaction 1) in the formation of alpha-glucan bound to protein in potato tuber is not only specific for the glucosyl donor but also for the endogenous acceptor. A single radioactive 38-kDa macromolecular component appeared during denaturing polyacrylamide gel electrophoresis of reaction 1 product. The labeled component is probably the polypeptide subunit of the endogenous acceptor which is being glucosylated. The radioactivity incorporated in reaction 1 product was isolated from a protease digest as a low-molecular-mass glucopeptide fraction. A beta-elimination reaction carried out in the presence of a reducing agent demonstrated that only one glucosyl moiety is transferred from UDP-Glc to the aminoacyl residue, thus forming an O-glucosidic linkage. 3H-labeled sodium borohydride showed that serine and threonine are involved in the peptide bond to glucose. Ion-exchange chromatography on DEAE-cellulose, affinity chromatography on concanavalin-A--Sepharose, gel filtration on Sephacryl S-300 and sucrose density gradient centrifugation failed to separate the enzyme catalyzing reaction 1 from the endogenous acceptor.


Cortical and brain stem changes in neural activity during static handgrip and postexercise ischemia in humans.
Static isometric exercise increases muscle sympathetic nerve activity (MSNA) and mean arterial pressure, both of which can be maintained at the conclusion of the exercise by occlusion of the arterial supply [postexercise ischemia (PEI)]. To identify the cortical and subcortical sites involved, and to differentiate between central command and reflex inputs, we used blood oxygen level-dependent (BOLD) functional MRI (fMRI) of the whole brain (3 T). Subjects performed submaximal static handgrip exercise for 2 min followed by 6 min of PEI; MSNA was recorded on a separate day. During the contraction phase, parallel increases in BOLD signal intensity occurred in the contralateral primary motor cortex and cerebellar nuclei and cortex; these matched the effort profile and ceased at the conclusion of the contraction. Progressive increases in the contralateral insula and primary and secondary somatosensory cortices, with progressive decreases in the perigenual anterior cingulate and midcingulate cortices, were sustained during the period of PEI and thus did not depend on central command. Discrete bilateral activation of the medial and lateral dorsal medulla was also observed during the contraction and PEI; we believe that these represent the nucleus tracts solitarius (NTS) and rostral ventrolateral medulla (RVLM), respectively. Given that metaboreceptor afferents are known to project to the NTS and that the RVLM is the primary output nucleus for MSNA, our data support that the metaboreflex is mediated by the medulla, whereas the somatosensory, insular, and anterior cingulate cortices are involved in the sensory and affective components of the maneuver.


Use of intercostal nerves for neurotization of the musculocutaneous nerve in infants with birth-related brachial plexus palsy.
The use of intercostal nerves (ICNs) for the neurotization of the musculocutaneous nerve (MCN) in adult patients with traumatic brachial plexus palsy has been well described. However, its use for brachial plexus palsy in infants has rarely been reported. The authors surgically created 31 ICN-MCN communications for birth-related brachial plexus palsy and present the surgical results. Thirty-one neurotizations of the MCN, performed using ICNs, were conducted in 30 patients with birth-related brachial plexus palsy. In most cases other procedures were combined to reconstruct all upper-extremity function. The mean patient age at surgery was 5.8 months and the mean follow-up period was 5.2 years. Intercostal nerves were transected 1 cm distal to the mammary line and their stumps were transferred to the axilla, where they were coapted directly to the MCN. Two ICNs were used in 26 cases and three ICNs in five cases. The power of the biceps muscle of the arm was rated Grade M4 in 26 (84%) of 31 patients. In the 12 patients who underwent surgery when they were younger than 5 months of age, all exhibited a grade of M4 (100%) in their biceps muscle power. These results are better than those previously reported in adults. Neurotization of the MCN by surgically connecting ICNs is a safe, reliable, and effective procedure for reconstruction of the brachial plexus in patients suffering from birth-related palsy.


Genetic definition of the substrate selectivity of outer membrane porin protein OprD of Pseudomonas aeruginosa.
Earlier studies proved that Pseudomonas aeruginosa OprD is a specific porin for basic amino acids and imipenem. It was also considered to function as a nonspecific porin that allowed the size-dependent uptake of monosaccharides and facilitation of the uptake of quinolone and other antibiotics. In the present study, we utilized P. aeruginosa strains with genetically defined levels of OprD to characterize the in vivo substrate selectivity of this porin. An oprD::omega interposon mutant was constructed by gene replacement utilizing an in vitro mutagenized cloned oprD gene. In addition, OprD was overexpressed from the lac promoter by cloning the oprD gene into the broad-host-range plasmid pUCP19. To test the substrate selectivity, strains were grown in minimal medium with limiting concentrations of the carbon sources glucose, gluconate, or pyruvate. In minimal medium with 0.5 mM gluconate, the growth rates of the parent strain H103 and its oprD::omega mutant H729 were only 60 and 20%, respectively, of that of the OprD-overexpressing strain H103(pXH2). In contrast, no significant differences were observed in the growth rates of these three strains on glucose or pyruvate, indicating that OprD selectively facilitated the transport of gluconate. To determine the role of OprD in antibiotic uptake, nine strains representing different levels of OprD and OprF were used to determine the MICs of different antibiotics. The results clearly demonstrated that OprD could be utilized by imipenem and meropenem but that, even when substantially overexpressed, it could not be significantly utilized by other beta-lactams, quinolones, or aminoglycosides. In addition, competition experiments confirmed that imipenem had common binding sites with basic amino acids in the OprD channel, but not with gluconate or glucose.


Sample transformation in online separations: how chemical conversion advances analytical technology.
While the advent of modern analytical technology has allowed scientists to determine the complexity of mixtures, it also spurred the demand to understand these sophisticated mixtures better. Chemical transformation can be used to provide insights into properties of complex samples such as degradation pathways or molecular heterogeneity that are otherwise unaccessible. In this article, we explore how sample transformation is exploited across different application fields to empower analytical methods. Transformation mechanisms include molecular-weight reduction, controlled degradation, and derivatization. Both offline and online transformation methods have been explored. The covered studies show that sample transformation facilitates faster reactions (e.g. several hours to minutes), reduces sample complexity, unlocks new sample dimensions (e.g. functional groups), provides correlations between multiple sample dimensions, and improves detectability. The article highlights the state-of-the-art and future prospects, focusing in particular on the characterization of protein and nucleic-acid therapeutics, nanoparticles, synthetic polymers, and small molecules.


Construction of a Generic and Evolutive Wheel and Lexicon of Food Textures.
In the context of data management and processing, food science needs tools to organize the results of diverse studies to make the data reusable. In sensory analysis, there are no classification or wheel of textural attributes that can be used to interpret the results of sensory studies. Research from the literature and databases was used to elaborate a list of attributes related to texture. With the help of a group of experts in food texture, work on these attributes and the related concepts was conducted to classify them into several categories, including intensity levels. The classification was represented as a texture wheel, completed by a generic lexicon of definitions of texture concepts. The work can be useful as a reference in texture attributes related to foods, and thanks to implementation in a general ontology based on food processing and observation, it can help query and interpret texture-related results from sensory studies.


Quantitative Proteome Profiling Reveals Cellobiose-Dependent Protein Processing and Export Pathways for the Lignocellulolytic Response in Neurospora crassa.
Filamentous fungi are intensively used for producing industrial enzymes, including lignocellulases. Employing insoluble cellulose to induce the production of lignocellulases causes some drawbacks, e.g., a complex fermentation operation, which can be overcome by using soluble inducers such as cellobiose. Here, a triple β-glucosidase mutant of Neurospora crassa, which prevents rapid turnover of cellobiose and thus allows the disaccharide to induce lignocellulases, was applied to profile the proteome responses to cellobiose and cellulose (Avicel). Our results revealed a shared proteomic response to cellobiose and Avicel, whose elements included lignocellulases and cellulolytic product transporters. While the cellulolytic proteins showed a correlated increase in protein and mRNA levels, only a moderate correlation was observed on a proteomic scale between protein and mRNA levels (R2 = 0.31). Ribosome biogenesis and rRNA processing were significantly overrepresented in the protein set with increased protein but unchanged mRNA abundances in response to Avicel. Ribosome biogenesis, as well as protein processing and protein export, was also enriched in the protein set that showed increased abundance in response to cellobiose. NCU05895, a homolog of yeast CWH43, is potentially involved in transferring a glycosylphosphatidylinositol (GPI) anchor to nascent proteins. This protein showed increased abundance but no significant change in mRNA levels. Disruption of CWH43 resulted in a significant decrease in cellulase activities and secreted protein levels in cultures grown on Avicel, suggesting a positive regulatory role for CWH43 in cellulase production. The findings should have an impact on a systems engineering approach for strain improvement for the production of lignocellulases.IMPORTANCE Lignocellulases are important industrial enzymes for sustainable production of biofuels and bio-products. Insoluble cellulose has been commonly used to induce the production of lignocellulases in filamentous fungi, which causes a difficult fermentation operation and enzyme loss due to adsorption to cellulose. The disadvantages can be overcome by using soluble inducers, such as the disaccharide cellobiose. Quantitative proteome profiling of the model filamentous fungus Neurospora crassa revealed cellobiose-dependent pathways for cellulase production, including protein processing and export. A protein (CWH43) potentially involved in protein processing was found to be a positive regulator of lignocellulase production. The cellobiose-dependent mechanisms provide new opportunities to improve the production of lignocellulases in filamentous fungi.


[Transcutaneous nerve stimulation as palliative treatment of pain].
The value of transcutaneous nerve stimulation (TNS) for palliative relief of pain is reviewed. The presumed mechanisms of effect are briefly described and a review of recent literature concerning TNS for acute and chronic pain, respectively, is presented. In addition, advice is given for the choice of apparatus and the technique employed is described. It is concluded that TNS may be tried with advantage in the treatment of a number of acute and chronic painful conditions of neurogenic/nocioceptive nature and that TNS has the advantage over e.g. acupuncture that the patient can administer the treatment himself.


The Value of Web-Based Patient Education Materials on Transarterial Chemoembolization: Systematic Review.
Thousands of web searches are performed related to transarterial chemoembolization (TACE), given its palliative role in the treatment of liver cancer. This study aims to assess the reliability, quality, completeness, readability, understandability, and actionability of websites that provide information on TACE for patients. The five most popular keywords pertaining to TACE were searched on Google, Yahoo, and Bing. General website characteristics and the presence of Health On the Net Foundation code certification were documented. Website assessment was performed using the following scores: DISCERN, Journal of the American Medical Association, Flesch-Kincaid Grade Level, Flesch Reading Ease Score, and the Patient Education Materials Assessment Tool. A novel TACE content score was generated to evaluate website completeness. The search yielded 3750 websites. In total, 81 website entities belonging to 78 website domains met the inclusion criteria. A medical disclaimer was not provided on 28% (22/78) of website domains. Health On the Net code certification was present on 12% (9/78) of website domains. Authorship was absent on 88% (71/81) of websites, and sources were absent on 83% (67/81) of websites. The date of publication or of the last update was not listed on 58% (47/81) of websites. The median DISCERN score was 47.0 (IQR 40.5-54.0). The median TACE content score was 35 (IQR 27-43). The median readability grade level was in the 11th grade. Overall, 61% (49/81) and 16% (13/81) of websites were deemed understandable and actionable, respectively. Not-for-profit websites fared significantly better on the Journal of the American Medical Association, DISCERN, and TACE content scores. The content referring to TACE that is currently available on the web is unreliable, incomplete, difficult to read, understandable but not actionable, and characterized by low overall quality. Websites need to revise their content to optimally educate consumers and support shared decision-making. PROSPERO International Prospective Register of Systematic Reviews CRD42020202747; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020202747.


Determination of protein degradation rates using a rumen in vitro system containing inhibitors of microbial nitrogen metabolism.
1. A previously reported rumen in vitro system (Broderick, 1978) was modified to include chloramphenicol (CAP) with hydrazine sulphate (HS) to give quantitative recovery of protein breakdown products. Degradation rates were determined by regression v. time of log proportion remaining undegraded (computed by subtracting from added nitrogen the amount of N recovered as ammonia and amino acids). Concentrations of reagents giving optimal N recoveries and estimated degradation rates for casein and expeller soya-bean-meal (SBM) were: 1.0 mM-HS, 30 micrograms CAP/ml, 2.0 mM-mercaptoethanol, 3.3 mg maltose/ml, when protein was added at 0.125 mg N/ml. 2. Digestion of azo-casein and azo-albumin, solubilization of radioactivity from 14C-labelled casein, ovalbumin and bovine serum albumin (BSA), and hydrolysis of benzoyl-L-tyrosine p-nitroanilide and benzoyl-L-arginine p-nitroanilide were not significantly decreased by HS and CAP. This suggests that the inhibitors did not reduce microbial proteolysis. 3. Mean fractional degradation rates (/h) were: 0.395 casein, 0.135 BSA, 0.159 solvent-SBM, 0.045 expeller-SBM, 0.061 meat meal, 0.070 lucerne (Medicago sativa) hay. Extents of protein escape, estimated assuming rumen passage of 0.06/h, were 13, 28, 56 and 40% for casein, solvent-SBM, expeller-SBM and lucerne hay respectively. This method appears more reliable for assessing rumen degradability than buffer N solubility and protein digestibility with ficin protease. 4. Azo-dye treatment slowed the rate of casein degradation, measured by ammonia plus amino acid release, but did not alter digestion of BSA. 5. The validity of the inhibitor in vitro method for estimating protein degradability, as well as potential problems in its application, are discussed. The complete procedure may be limited to laboratories with automated analytical equipment, but a simplified version of the method may be more generally applicable.


Chlamydia control activities in Europe: cross-sectional survey.
Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe. The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire. Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816). A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes.


Sidestepping questions of legitimacy: how community representatives manoeuvre to effect change in a health service.
Empirical studies of community participation in health services commonly tie effectiveness to the perceived legitimacy of community representatives among health staff. This article examines the underlying assumption that legitimacy is the major pathway to influence for community representatives. It takes a different vantage point from previous research in its examination of data (primarily through 34 in-depth interviews, observation and recording of 26 meetings and other interactions documented in field notes) from a 3-year study of community representatives' action in a large health region in Australia. The analysis primarily deploys Michel de Certeau's ideas of Strategy and Tactic to understand the action and effects of the generally 'weaker players' in the spaces and places dominated by powerful institutions. Through this lens, we can see the points where community representatives are active participants following their own agenda, tactically capitalising on cracks in the armour of the health service to seize opportunities that present themselves in time to effect change. Being able to see community representatives as active producers of change, not simply passengers following the path of the health service, challenges how we view the success of community participation in health.


The cyclic AMP receptor protein, CRP, is required for both virulence and expression of the minimal CRP regulon in Yersinia pestis biovar microtus.
The cyclic AMP receptor protein (CRP) is a bacterial regulator that controls more than 100 promoters, including those involved in catabolite repression. In the present study, a null deletion of the crp gene was constructed for Yersinia pestis bv. microtus strain 201. Microarray expression analysis disclosed that at least 6% of Y. pestis genes were affected by this mutation. Further reverse transcription-PCR and electrophoretic mobility shift assay analyses disclosed a set of 37 genes or putative operons to be the direct targets of CRP, and thus they constitute the minimal CRP regulon in Y. pestis. Subsequent primer extension and DNase I footprinting assays mapped transcriptional start sites, core promoter elements, and CRP binding sites within the DNA regions upstream of pla and pst, revealing positive and direct control of these two laterally acquired plasmid genes by CRP. The crp disruption affected both in vitro and in vivo growth of the mutant and led to a >15,000-fold loss of virulence after subcutaneous infection but a <40-fold increase in the 50% lethal dose by intravenous inoculation. Therefore, CRP is required for the virulence of Y. pestis and, particularly, is more important for infection by subcutaneous inoculation. It can further be concluded that the reduced in vivo growth phenotype of the crp mutant should contribute, at least partially, to its attenuation of virulence by both routes of infection. Consistent with a previous study of Y. pestis bv. medievalis, lacZ reporter fusion analysis indicated that the crp deletion resulted in the almost absolute loss of pla promoter activity. The plasminogen activator encoded by pla was previously shown to specifically promote Y. pestis dissemination from peripheral infection routes (subcutaneous infection [flea bite] or inhalation). The above evidence supports the notion that in addition to the reduced in vivo growth phenotype, the defect of pla expression in the crp mutant will greatly contribute to the huge loss of virulence of this mutant strain in subcutaneous infection.


Post-ICU nutrition: the neglected side of metabolic support.
This review will focus on the neglected side of metabolic support in ICU survivors: nutritional therapy after critical illness. Knowledge of the evolution of the metabolism of patients that survived critical illness will be bundled, and current practices will be investigated. We will discuss some studies conducted to determine resting energy expenditure in ICU survivors and which identified barriers that cause interruptions in the feeding process based on published data between January 2022 and April 2023. Resting energy expenditure can be measured using indirect calorimetry, as predictive equations have proven to fail in their attempt to have good correlations with measured values. No guidelines or recommendations are available on post-ICU follow-up, including screening, assessment, dosing, timing, and monitoring of (artificial) nutrition. A limited number of publications shared treatment adequacy between 64-82% for energy (calories) and 72-83% for protein intake in a post-ICU setting. Loss of appetite, depression, and oropharyngeal dysphagia are the most prominent physiological barriers responsible for decreased feeding adequacy. Patients may be in a catabolic state during and after ICU discharge, with several factors impacting metabolism. Therefore, large prospective trials are needed to determine the physiological state of ICU survivors, determine nutritional requirements, and develop nutritional care protocols. Many barriers causing decreased feeding adequacy have already been identified, but solutions are scarce. This review depicts a variable metabolic rate among ICU survivors and a significant variation in feeding adequacy in-between world regions, institutions, and patient sub-phenotypes.


Aggression in borderline personality disorder: A multidimensional model.
This article proposes a multidimensional model of aggression in borderline personality disorder (BPD) from the perspective of the biobehavioral dimensions of affective dysregulation, impulsivity, threat hypersensitivity, and empathic functioning. It summarizes data from studies that investigated these biobehavioral dimensions using self-reports, behavioral tasks, neuroimaging, neurochemistry as well as psychophysiology, and identifies the following alterations: (a) affective dysregulation associated with prefrontal-limbic imbalance, enhanced heart rate reactivity, skin conductance, and startle response; (b) impulsivity also associated with prefrontal-limbic imbalance, central serotonergic dysfunction, more electroencephalographic slow wave activity, and reduced P300 amplitude in a 2-tone discrimination task; (c) threat hypersensitivity associated with enhanced perception of anger in ambiguous facial expressions, greater speed and number of reflexive eye movements to angry eyes (shown to be compensated by exogenous oxytocin), enhanced P100 amplitude in response to blends of happy versus angry facial expressions, and prefrontal-limbic imbalance; (d) reduced cognitive empathy associated with reduced activity in the superior temporal sulcus/gyrus and preliminary findings of lower oxytocinergic and higher vasopressinergic activity; and (e) reduced self-other differentiation associated with greater emotional simulation and hyperactivation of the somatosensory cortex. These biobehavioral dimensions can be nicely linked to conceptual terms of the alternative Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) model of BPD, and thus to a multidimensional rather than a traditional categorical approach.


Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.
Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration.


Motions of Allosteric and Orthosteric Ligand-Binding Sites in Proteins are Highly Correlated.
Allostery is the phenomenon in which a ligand binding at one site affects other sites in the same macromolecule. Allostery has important roles in many biological processes. Theoretically, all nonfibrous proteins are potentially allosteric. However, few allosteric proteins have been validated, and the identification of novel allosteric sites remains a challenge. The motion of residues and subunits underlies protein function; therefore, we hypothesized that the motions of allosteric and orthosteric sites are correlated. We utilized a data set of 24 known allosteric sites from 23 monomer proteins to calculate the correlations between potential ligand-binding sites and corresponding orthosteric sites using a Gaussian network model (GNM). Most of the known allosteric site motions showed high correlations with corresponding orthosteric site motions, whereas other surface cavities did not. These high correlations were robust when using different structural data for the same protein, such as structures for the apo state and the orthosteric effector-binding state, whereas the contributions of different frequency modes to motion correlations depend on the given protein. The high correlations between allosteric and orthosteric site motions were also observed in oligomeric allosteric proteins. We applied motion correlation analysis to predict potential allosteric sites in the 23 monomer proteins, and some of these predictions were in good agreement with published experimental data. We also performed motion correlation analysis to identify a novel allosteric site in 15-lipoxygenase (an enzyme in the arachidonic acid metabolic network) using recently reported activating compounds. Our analysis correctly identified this novel allosteric site along with two other sites that are currently under experimental investigation. Our study demonstrates that the motions of allosteric sites are highly correlated with the motions of orthosteric sites. Our correlation analysis method provides new tools for predicting potential allosteric sites.


Environmental Genome-Wide Association Reveals Climate Adaptation Is Shaped by Subtle to Moderate Allele Frequency Shifts in Loblolly Pine.
Understanding the genomic basis of local adaptation is crucial to determine the potential of long-lived woody species to withstand changes in their natural environment. In the past, efforts to dissect the genomic architecture in gymnosperms species have been limited due to the absence of reference genomes. Recently, the genomes of some commercially important conifers, such as loblolly pine, have become available, allowing whole-genome studies of these species. In this study, we test for associations between 87k SNPs, obtained from whole-genome resequencing of loblolly pine individuals, and 270 environmental variables and combinations of them. We determine the geographic location of significant loci and identify their genomic location using our newly constructed ultradense 26k SNP linkage map. We found that water availability is the main climatic variable shaping local adaptation of the species, and found 821 SNPs showing significant associations with climatic variables or combinations of them based on the consistent results of three different genotype-environment association methods. Our results suggest that adaptation to climate in the species might have occurred by many changes in the frequency of alleles with moderate to small effect sizes, and by the smaller contribution of large effect alleles in genes related to moisture deficit, temperature and precipitation. Genomic regions of low recombination and high population differentiation harbored SNPs associated with groups of environmental variables, suggesting climate adaptation might have evolved as a result of different selection pressures acting on groups of genes associated with an aspect of climate rather than on individual environmental variables.