Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation.
Depleting the microenvironment of important nutrients such as arginine is a key strategy for immune evasion by cancer cells. Many tumors overexpress arginase, but it is unclear how these cancers, but not T cells, tolerate arginine depletion. In this study, we show that tumor cells synthesize arginine from citrulline by upregulating argininosuccinate synthetase 1 (ASS1). Under arginine starvation, ASS1 transcription is induced by ATF4 and CEBPβ binding to an enhancer within ASS1. T cells cannot induce ASS1, despite the presence of active ATF4 and CEBPβ, as the gene is repressed. Arginine starvation drives global chromatin compaction and repressive histone methylation, which disrupts ATF4/CEBPβ binding and target gene transcription. We find that T cell activation is impaired in arginine-depleted conditions, with significant metabolic perturbation linked to incomplete chromatin remodeling and misregulation of key genes. Our results highlight a T cell behavior mediated by nutritional stress, exploited by cancer cells to enable pathological immune evasion.


Chromosomally integrated conjugative plasmids are common in antibiotic-resistant Haemophilus influenzae.
Twenty-three highly antibiotic-resistant strains of Haemophilus influenzae and two of Haemophilus parainfluenzae without detectable large plasmids were examined for conjugative transfer of their resistance to H. influenzae strain Rd or to other strains. Very inefficient transfer was observed for 18 H. influenzae strains and 1 H. parainfluenzae strain. All H. influenzae transcipients carried a large plasmid, and they were in turn efficient donors of their resistances in standard conjugation crosses with isogenic recipients. This was not seen for the H. parainfluenzae transcipients. It is concluded that most of the original antibiotic-resistant cultures carried an integrated conjugative R plasmid which had been excised in a few cells in each population. It was these cells which transferred resistance in the primary crosses.


Effectiveness of Video Demonstration over Conventional Methods in Teaching Osteology in Anatomy.
Technology and its applications are the most happening things in the world. So, is it in the field of medical education. This study was an evaluation of whether the conventional methods can compete with the test of technology. A comparative study of traditional method of teaching osteology in human anatomy with an innovative visual aided method. The study was conducted on 94 students admitted to MBBS 2014 to 2015 batch of Travancore Medical College. The students were divided into two academically validated groups. They were taught using conventional and video demonstrational techniques in a systematic manner. Post evaluation tests were conducted. Analysis of the mark pattern revealed that the group taught using traditional method scored better when compared to the visual aided method. Feedback analysis showed that, the students were able to identify bony features better with clear visualisation and three dimensional view when taught using the video demonstration method. The students identified visual aided method as the more interesting one for learning which helped them in applying the knowledge gained. In most of the questions asked, the two methods of teaching were found to be comparable on the same scale. As the study ends, we discover that, no new technique can be substituted for time tested techniques of teaching and learning. The ideal method would be incorporating newer multimedia techniques into traditional classes.


Comprehensive transcriptome and WGCNA analysis reveals the potential function of anthocyanins in low-temperature resistance of a red flower mutant tobacco.
The anthocyanin is a protective substance in various plants, and plays important roles in resisting to low-temperature. Here, we explored transcriptome analysis of pink flower (as CK) and the natural mutant red flower (as research objects) under low-temperature conditions, and aimed to reveal the potential functions of anthocyanins and anthocyanin-related regulatory factors in resistance to low-temperature. Our results showed that most of the differentially expressed genes (DEGs) encoding key enzymes in the late stage of anthocyanin metabolism in the mutant were significantly up-regulated. Meanwhile, several genes significantly differentially expressed in CK or mutant were obtained by classification and analysis of transcription factors (TFs), phytohormones and osmoregulators. Additionally, WGCNA was carried out to mine hub genes resistanted to low-temperature stress in flavonoid pathway. Finally, one UFGT family gene, three MYB and one bHLH were obtained as the future hub genes of this study. Combined with the above information, we concluded that the ability of the red flower mutant to grow and develop normally at low-temperatures was the result of a combination of flavonoids and cold resistance genes.


Observations on levels of immunoglobulin M in confirmed cases of Trypanosoma rhodesiense infection in the Lambwe Valley.
By means of established single-diffusion techniques, immunoglobulin M (IgM) levels in the blood and cerebrospinal fluid of patients with confirmed Trypanosoma rhodesiense infections were studied at the time of parasitological diagnosis, while the patients were being treated with suramin and melarsoprol, and during post-treatment surveillance. During the 3-year study period the number of diagnosed cases in which there was a raised level of IgM in the blood varied considerably, depending on whether diagnosis was made early or late in the course of the infection. In some cases the blood IgM levels returned to normal during preliminary courses of treatment with suramin and in others by the end of a 1-month course of treatment with melarsoprol, while in some other cases they did not return to normal for about 2 years. Similar results were obtained for IgM in cerebrospinal fluid, except that if IgM could be detected at the start of treatment with melarsoprol it was still detectable at the end of treatment. However, cerebrospinal IgM usually disappeared after 2 years. The results indicate that IgM levels are a useful indicator in the diagnosis of the more chronic cases.


Land Ahoy! Understanding Submarine Command and Control During the Completion of Inshore Operations.
The aim of this study was to use multiple command teams to provide empirical evidence for understanding communication flow, information pertinence, and tasks undertaken in a submarine control room when completing higher- and lower-demand inshore operation (INSO) scenarios. The focus of submarine operations has changed, and submarines are increasingly required to operate in costal littoral zones. However, submarine command team performance during INSO is not well understood, particularly from a sociotechnical systems perspective. A submarine control-room simulator was built. The creation of networked workstations allowed a team of nine operators to perform tasks completed by submarine command teams during INSO. The Event Analysis of Systematic Teamwork method was used to model the social, task, and information networks and to describe command team performance. Ten teams were recruited for the study, affording statistical comparisons of how command-team roles and level of demand affected performance. Results indicated that the submarine command-team members are required to rapidly integrate sonar and visual data as the periscope is used, periodically, in a "duck-and-run" fashion, to maintain covertness. The fusion of such information is primarily completed by the operations officer (OPSO), with this operator experiencing significantly greater demand than any other operator. The OPSO was a bottleneck in the command team when completing INSO, experiencing similar load in both scenarios, suggesting that the command team may benefit from data synthesis tasks being more evenly distributed within the command team. The work can inform future control-room design and command-team ways of working by identifying bottlenecks in terms of information and task flow between operators.


Comparison of self-reported emotional and behavioural problems in adolescents from Greece and Finland.
To compare self-reported emotional and behavioural problems among Greek and Finnish adolescents. Youth Self-Report scores were analysed for 3373 Greek adolescents aged 18 years and 7039 Finnish adolescents aged 15-16 years from the general population in both countries. The impact of country, gender, place of residence, socioeconomic status (SES) and family stability on the scores was evaluated. Only country and gender yielded small to medium effect on the scores. Greek boys scored significantly higher than Finns on 10 of the 11 YSR syndromes, particularly on the anxious/depressed scale. Greek girls scored significantly lower than Finnish girls on the somatic complaints and delinquent behaviour scales. In general, girls scored higher than boys on both internalising and externalising problems. The gender by country interaction revealed that Finnish girls reported more externalising problems. The main differences marked in this comparison were the higher level of anxiety and depression in Greeks than Finns and the higher level of externalising problems in Finnish girls than boys. Cultural standards could play an important role in explaining these differences. Overall, it seems that only a small number of differences exist between a northern and southern European region.


Lupus nephritis in the absence of renal major histocompatibility complex class I and class II molecules.
MRL/Mp-lpr/lpr (MRL-lpr) mice develop an aggressive autoimmune disorder characterized by arthritis, vasculitis, and glomerulonephritis. Renal injury is associated with increased expression of major histocompatibility complex (MHC) molecules, as well as cytokines, adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1), and autoantibodies. By using either MHC Class I (MRL-lpr B2m-/-) or MHC Class II deficient (MRL-lpr Ab-/-) kidneys in a transplant model, we tested the role of renal expression of these molecules in the development of autoimmune renal injury. Kidneys from MRL-lpr B2m-/- or MRL-lpr Ab-/- mice as well as control wild-type mice transplanted into MRL-lpr wt/- recipients developed nephritis, CD4+ and CD8+ T cell infiltration, and heavy glomerular deposition of immunoglobulin. Spontaneously proliferating autoreactive T cells were found in wild-type MRL-lpr and MRL-lpr B2m-/- but not MRL-lpr Ab-/- mice. These results suggest that the absence of renal expression of either Class I or Class II molecules does not provide marked protection from autoimmune lupus nephritis and supports the possibility that protection from autoimmune disease in MRL-lpr Ab-1- mice is related to the loss of autoreactive MHC Class II-dependent CD4+ T cells.


Intention matters to make you (im)moral: Positive-negative asymmetry in moral character evaluations.
Is intention, even if unfulfilled, enough to make a person appear to be good or bad? In this study, we investigated the influence of unfulfilled intentions of an agent on subsequent moral character evaluations. We found a positive-negative asymmetry in the effect of intentions. Factual information concerning failure to fulfill a positive intention mitigated the morality judgment of the actor, yet this mitigation was not as evident for the negative vignettes. Participants rated an actor who failed to fulfill their negative intention as highly immoral, as long as there was an external explanation to its unfulfillment. Furthermore, both emotional and cognitive (i.e., informativeness) processes mediated the effect of negative intention on moral character. For the positive intention, there was a significant mediation by emotions, yet not by informativeness. Results evidence the relevance of mental states in moral character evaluations and offer affective and cognitive explanations to the asymmetry.


Mosaic allelic insulin-like growth factor 2 expression patterns reveal a link between Wilms' tumorigenesis and epigenetic heterogeneity.
Numerous observations link the loss of imprinting of insulin-like growth factor 2 (IGF2) and an overdosage of this growth factor gene with cancer, in general, and with Wilms' tumorigenesis, in particular. It is not known, however, if loss of imprinting correlates with specific stages of neoplasia or if allelic expression patterns vary within the tumor. By applying an allele-specific in situ hybridization technique to formalin-fixed thin sections, we show that the parental IGF2 alleles can be differentially expressed, not only in Wilms' tumors, but also in nephrogenic rests (which represent premalignant lesions) of Wilms' tumor patients. Moreover, a subpopulation of mesenchymal cells, which surrounds tumor nodules, expresses IGF2 biallelically irrespective of the imprinted state of IGF2 within the tumor. These data show that Wilms' tumorigenesis involves epigenetic heterogeneity as visualized by variable allelic IGF2 expression patterns.


COMT gene polymorphism is associated with declarative memory in adulthood and old age.
Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.


Birth preparedness and complication readiness - a qualitative study among community members in rural Tanzania.
Birth preparedness and complication readiness (BP/CR) strategies are aimed at reducing delays in seeking, reaching, and receiving care. Counselling on birth preparedness is provided during antenatal care visits. However, it is not clear why birth preparedness messages do not translate to utilisation of facility delivery. This study explores the perceptions, experiences, and challenges the community faces on BP/CR. A qualitative study design using Focused Group Discussions was conducted. Twelve focus group discussions were held with four separate groups: young men and women and older men and women in a rural community in Tanzania. Qualitative content analysis was used to analyse the data. The community members expressed a perceived need to prepare for childbirth. They were aware of the importance to attend the antenatal clinics, relied on family support for practical and financial preparations such as saving money for costs related to delivery, moving closer to the nearest hospital, and also to use traditional herbs, in favour of a positive outcome. Community recognised that pregnancy and childbirth complications are preferably treated at hospital. Facility delivery was preferred; however, certain factors including stigma on unmarried women and transportation were identified as hindering birth preparedness and hence utilisation of skilled care. Challenges were related to the consequences of poverty, though the maternal health care should be free, they perceived difficulties due to informal user fees. This study revealed community perceptions that were in favour of using skilled care in BP/CR. However, issues related to inability to prepare in advance hinder the realisation of the intention to use skilled care. It is important to innovate how the community reinforces BP/CR, such as using insurance schemes, using community health funds, and providing information on other birth preparedness messages via community health workers.


Expression of Frzb-1 during chick development.
We cloned the chick homolog of Xenopus and mouse Frzb-1, a secreted Wnt antagonist and performed in situ hybridizations to determine the pattern of cFrzb-1 expression in the developing chick embryo. At early stages, cFrzb-1 transcripts are located exclusively in the ectodermal layer corresponding to the neural plate. The labelling continues in the neural tube, but is always excluded from the floor plate. cFrzb-1 mRNA is expressed by migrating cephalic and truncal neural crest cells. Later, cFrzb-1 transcripts are found in a subset of neural crest derivatives such as cephalic cartilage, nerves and spinal ganglia. In addition to ectodermal derivatives, cFrzb-1 transcripts were also observed in mesodermal derivatives such as vertebral and limb cartilage, the adrenal cortex, the gonads, and a subpopulation of blood cells.


Novel mechanism for regulation of epidermal growth factor receptor endocytosis revealed by protein kinase A inhibition.
Current models put forward that the epidermal growth factor receptor (EGFR) is efficiently internalized via clathrin-coated pits only in response to ligand-induced activation of its intrinsic tyrosine kinase and is subsequently directed into a lysosomal-proteasomal degradation pathway by mechanisms that include receptor tyrosine phosphorylation and ubiquitylation. Herein, we report a novel mechanism of EGFR internalization that does not require ligand binding, receptor kinase activity, or ubiquitylation and does not direct the receptor into a degradative pathway. Inhibition of basal protein kinase A (PKA) activity by H89 and the cell-permeable substrate peptide Myr-PKI induced internalization of 40-60% unoccupied, inactive EGFR, and its accumulation into early endosomes without affecting endocytosis of transferrin and mu-opioid receptors. This effect was abrogated by interfering with clathrin function. Thus, the predominant distribution of inactive EGFR at the plasma membrane is not simply by default but involves a PKA-dependent restrictive condition resulting in receptor avoidance of endocytosis until it is stimulated by ligand. Furthermore, PKA inhibition may contribute to ligand-induced EGFR endocytosis because epidermal growth factor inhibited 26% of PKA basal activity. On the other hand, H89 did not alter ligand-induced internalization of EGFR but doubled its half-time of down-regulation by retarding its segregation into degradative compartments, seemingly due to a delay in the receptor tyrosine phosphorylation and ubiquitylation. Our results reveal that PKA basal activity controls EGFR function at two levels: 1) residence time of inactive EGFR at the cell surface by a process of "endocytic evasion," modulating the accessibility of receptors to stimuli; and 2) sorting events leading to the down-regulation pathway of ligand-activated EGFR, determining the length of its intracellular signaling. They add a new dimension to the fine-tuning of EGFR function in response to cellular demands and cross talk with other signaling receptors.


Controllable two- and three-state magnetization switching in single-layer epitaxial Pd1- x Fe x films and an epitaxial Pd0.92Fe0.08/Ag/Pd0.96Fe0.04 heterostructure.
We have investigated the low-temperature magnetoresistive properties of a thin epitaxial Pd0.92Fe0.08 film at different directions of the current and the applied magnetic field. The obtained experimental results are well described within an assumption of a single-domain magnetic state of the film. In a wide range of the appled field directions, the magnetization reversal proceeds in two steps via the intermediate easy axis. An epitaxial heterostructure of two magnetically separated ferromagnetic layers, Pd0.92Fe0.08/Ag/Pd0.96Fe0.04, was synthesized and studied with dc magnetometry. Its magnetic configuration diagram has been constructed and the conditions have been determined for a controllable switching between stable parallel, orthogonal, and antiparallel arrangements of magnetic moments of the layers.


Impact of congenital heart disease on outcomes among pediatric patients hospitalized for influenza infection.
Young children and those with chronic medical conditions are at risk for complications of influenza including cardiopulmonary compromise. Here we aim to examine risks of mortality, clinical complications in children with congenital heart disease (CHD) hospitalized for influenza. We analyzed data from in-hospital pediatric patients from 2003, 2006, 2009, 2012 and 2016 using the nationally representative Kids Inpatient Database (KID). We included children 1 year and older and used weighted data to compare the incidence of in-hospital mortality and rates of complications such as respiratory failure, acute kidney injury, need for mechanical ventilation, arrhythmias and myocarditis. Data from the KID estimated 125,470 children who were admitted with a diagnosis of influenza infection. Out of those, 2174(1.73%) patients had discharge diagnosis of CHD. Children with CHD who required hospitalization for influenza had higher in-hospital mortality (2.0% vs 0.5%), with an adjusted OR (aOR) of 2.8 (95% CI: 1.7-4.5). Additionally, acute respiratory failure and acute kidney failure were more likely among patients with CHD, with aOR of 1.8 (95% CI: 1.5-2.2) and aOR of 2.2 (95% CI: 1.5-3.1), respectively. Similarly, the rate of mechanical ventilatory support was higher in patients with CHD compared to those without, 14.1% vs 5.6%, aOR of 1.9 (95% CI: 1.6-2.3). Median length of hospital stay in children with CHD was longer than those without CHD [4 (IQR: 2-8) days vs. 2 (IQR: 2-4) days]. Outcomes were similar between those with severe vs non-severe CHD. Children with CHD who require hospital admission for influenza are at significantly increased risk for in-hospital mortality, morbidities, emphasizing the need to reinforce preventative measures (e.g. vaccination, personal hygiene) in this particularly vulnerable population.


[Pulmonary densities following a hysterectomy, caused by benign metastatic leiomyoma].
A 49-year-old woman, who had undergone a hysterectomy 17 years previously, was referred with thoracic pain located on the right side that had been present for several weeks. Thoracic imaging showed multiple pulmonary lesions on both sides. Histological investigation of a biopsy from one of these lesions revealed a benign metastatic leiomyoma. The patient was treated with gonadotropin-releasing hormone (GnRH) analogue. The lesions showed regression and the symptoms disappeared. Benign metastatic leiomyoma is a rare benign clinical entity in women of fertile age who have had a surgical intervention on the uterus because of uterus myomatosus. The therapeutic options are surgical resection, removal of the hormonal stimulus by administering progesterone or GnRH-analogues or bilateral ovariectomy.


Intervals between bone density testing.
There is a wide range of practices regarding times between bone density (BMD) measurements in osteopenic women. If decisions to treat osteoporosis are to be based on absolute fracture risk, then projections of fracture risk are a logical basis for determining appropriate intervals for BMD testing. Fracture risk depends mainly on age and BMD, and bone loss in older women is relatively constant at ∼1% annually, so it is possible to project fracture risk into the future and estimate when an individual's risk will approach the threshold for intervention. Modeling scenarios for a range of osteopenic baseline BMDs in 65-year-old women shows a remarkable consistency in the doubling time for Fracture Risk Assessment Tool (FRAX)-assessed fracture risk: 5 to 6 years. This estimate is of immediate relevance to clinical practice in that it can be used to determine how long to wait before reassessing BMD and fracture risk in women whose other risk factors are stable.


Differential expression of thrombospondin (THBS1) in tumorigenic and nontumorigenic prostate epithelial cells in response to a chromatin-binding soy peptide.
The chemopreventive properties of the chromatin-binding soy peptide, lunasin, are well documented, but its mechanism of action is unclear. To elucidate the mechanism by which lunasin reduces tumor foci formation in cultured mammalian cells, nontumorigenic (RWPE-1) and tumorigenic (RWPE-2) human prostate epithelial cells were treated with lunasin followed by gene expression profiling and characterization of the chromatin acetylation status for certain chemopreventive genes. The genes HIF1A, PRKAR1A, TOB1, and THBS1 were upregulated by lunasin in RWPE-1 but not in RWPE-2 cells. Using histone acetyltransferase (HAT) assays with acid-extracted histones as templates, we showed that lunasin specifically inhibited H4K8 acetylation while enhanced H4K16 acetylation catalyzed by HAT enzymes p300, PCAF, and HAT1A. These results suggest a novel mechanism for lunasin-dependent upregulation of gene expression. Chromatin immunoprecipitation (ChIP) revealed hypoacetylation of H4K16 in RWPE-2 cells, specifically at the 5' end of THBS1 containing a CpG island. Moreover, bisulfite PCR (BSP) and subsequent DNA sequencing indicated that this CpG island was hypomethylated in RWPE-1 but hypermethylated in RWPE-2 cells. Histone hypoacetylation and DNA hypermethylation in the 5' region of THBS1 may explain the inability of lunasin to upregulate this gene in RWPE-2 cells.


Flow-cytometric detection of terminal deoxynucleotidyl transferase and other intracellular antigens in combination with membrane antigens in acute lymphatic leukemias.
Development of a new fixation procedure allowed flow-cytometric analysis of nuclear and other intracellular antigens in acute lymphatic leukemia (ALL). A short fixation of the cells with buffered formaldehyde acetone (BFA) rendered the cell membrane permeable, allowing the monoclonal antibodies (MoAbs) to penetrate the cell. Through this method, a rapid analysis of intracellular antigens, specific for acute lymphatic leukemia [such as terminal deoxynucleotidyl transferase (TdT), immunoglobulin M (IgM) heavy chain, and antigens recognized by the CD22 or CD3 MoAbs) was performed by flow cytometry. The surface antigens remained intact after this fixation procedure, enabling simultaneous detection of membrane and intracellular antigens. The binding of biotinylated antibodies against several B- and T-lymphoid membrane antigens was detected with streptavidin-phycoerythrin (red fluorescence), whereas the intracellular antigens were stained with FITC-labeled polyclonal antibodies, or indirectly with FITC-labeled goat anti-mouse IgG (green fluorescence). Through this combination of markers, minor cell populations can be detected and a rapid and quantitative immunodiagnosis can be performed.


Magnetic resonance imaging findings after uneventful continuous infusion neuraxial analgesia: a prospective study to determine whether epidural infusion produces pathologic magnetic resonance imaging findings.
Magnetic resonance imaging (MRI) is considered the preferred diagnostic tool to determine whether postepidural neurologic symptoms are due to hematoma or abscess. However, there is currently no published information regarding the normal appearance of a MRI after a continuous epidural infusion. In this prospective cohort study, we defined the characteristic appearance of MRI findings after uneventful epidural analgesia. Thirty women were prospectively enrolled to undergo a lumbar MRI after labor and delivery. The study group consisted of 15 women who received neuraxial analgesia with a combined spinal epidural technique followed by continuous epidural infusion, whereas the control group included 15 women who delivered without receiving neuraxial analgesia. All patients received a MRI within 12 h of delivery via a 1.5T scanner. MRIs were reviewed by two neuroradiologists who were blinded to the patient's study group allocation and asked to document the presence or absence of fluid collection, air collection, or soft tissue abnormalities. There were no radiologically significant fluid collections, hematomas, or mass effects noted on the thecal sac of any of the 30 MRI studies. A small amount of epidural air was seen in 77% of MRI studies after epidural analgesia, but there was no indention on the thecal sac. The lack of significant collections or mass effects seen in the MRIs of our patients after continuous infusion of epidural analgesia suggests that the presence of these findings in a patient with new neurologic symptoms after administration of epidural analgesia should be considered pathologic and warrant immediate attention.


Community disassembly and disease: realistic-but not randomized-biodiversity losses enhance parasite transmission.
Debates over the relationship between biodiversity and disease dynamics underscore the need for a more mechanistic understanding of how changes in host community composition influence parasite transmission. Focusing on interactions between larval amphibians and trematode parasites, we experimentally contrasted the effects of host richness and species composition to identify the individual and joint contributions of both parameters on the infection levels of three trematode species. By combining experimental approaches with field surveys from 147 ponds, we further evaluated how richness effects differed between randomized and realistic patterns of species loss (i.e. community disassembly). Our results indicated that community-level changes in infection levels were owing to host species composition, rather than richness. However, when composition patterns mirrored empirical observations along a natural assembly gradient, each added host species reduced infection success by 12-55%. No such effects occurred when assemblages were randomized. Mechanistically, these patterns were due to non-random host species assembly/disassembly: while highly competent species predominated in low diversity systems, less susceptible hosts became progressively more common as richness increased. These findings highlight the potential for combining information on host traits and assembly patterns to forecast diversity-mediated changes in multi-host disease systems.


Compressive Force With 2-Screw and 3-Screw Subtalar Joint Arthrodesis With Headless Compression Screws.
Joint compression is an essential element of successful arthrodesis. Although subtalar joint compression generated by conventional screws has been quantified in the laboratory, compression obtainable with headless screws that rely on variable thread pitch to achieve bony contact has not been assessed. This study measured subtalar joint compression achieved by 2 posteriorly placed contemporary headless, variable-pitch screws, and quantified additional compression gained by placing a third screw anteriorly. Ten, unpaired fresh-frozen cadaveric subtalar joints were fixed sequentially using 2 diverging posterior screws (one directed into the talar dome, the other into the talar neck), 2 parallel posterior screws (both ending in the talar dome), and 2 parallel screws with an additional anterior screw inserted from the plantar calcaneus into the talar neck. Joint compression was quantified directly during screw insertion using a novel custom-built measuring device. The mean compression generated by 2 diverging posterior screws was 246 N. Two parallel posterior screws produced 294 N of compression, and augmentation of that construct with a third, anterior screw increased compression to 345 N (P < .05). Compression subsequent to 2-screw fixation was slightly less than that reported previously for subtalar joint fixation with 2 conventional lag screws, but was comparable when a third screw was added. Under controlled testing conditions, 2 tapered, variable-pitch screws generated somewhat less compression than previously reported for 2-screw fixation with conventional headed screws. A third screw placed anteriorly increased compression significantly. Because headless screws are advantageous where prominent screw heads are problematic, such as the load-bearing surface of the foot, their effectiveness compared to other screws should be established to provide an objective basis for screw selection. Augmenting fixation with an anterior screw may be desirable when conditions for fusion are suboptimal.


Occupational health problems among nurses.
Nurses are an integral component of the health care delivery system. In discharging their duties, nurses encounter a variety of occupational health problems which may be categorized into biological hazards, chemical hazards, physical hazards, and psychosocial hazards. A review of some examples of each of these four types of hazards is presented in this article. Particular attention has been devoted to hepatitis B, acquired immunodeficiency syndrome, tuberculosis, cytotoxic drugs, anesthetic agents, needlestick injury, back pain, and stress.


Vertically oriented nanoporous block copolymer membranes for oil/water separation and filtration.
The separation of oil from water and filtration of aqueous solutions and dispersions are critical issues in the processing of waste and contaminated water treatment. Membrane-based technology has been proven as an effective method for the separation of oil from water. In this research, novel vertical nanopores membrane, via oriented cylindrical block copolymer (BCP) films, suitable for oil/water filtration has been designed, fabricated and tested. We used a ∼100 nm thick model poly(styrene-block-methymethacrylate) (PS-b-PMMA) BCP as the active top nanofiltration layer, processed using a roll-to-roll (R2R) method of cold zone annealing (CZA) to obtain vertical orientation, followed by ultraviolet (UV) irradiation selective etch of PMMA cylinders to form vertically oriented nanopores as a novel feature compared to meandering nanopores in other reported BCP systems. The cylindrical nanochannels are hydrophilic, and have a uniform pore size (∼23 nm), a narrow pore size distribution and a high nanopore density (∼420 per sq. micron). The bottom supporting layer is a conventional microporous polyethersulfone (PES) membrane. The created asymmetric membrane is demonstrated to be effective for oil/water extraction with a modestly high throughput rate comparable to other RO/NF membranes. The molecular weight dependent filtration of a water soluble polymer, PEO, demonstrates the broader applications of such membranes.


The F-box protein FBXO7 positively regulates bone morphogenetic protein-mediated signaling through Lys-63-specific ubiquitination of neurotrophin receptor-interacting MAGE (NRAGE).
Parkinson's disease (PD) is characterized by progressive midbrain dopaminergic neuron degeneration and the formation of intracellular protein aggregates, referred to as Lewy bodies. F-box only protein 7 (FBXO7) gene mutations are closely associated with progression of the autosomal recessive form of familial PD. FBXO7 encodes a component of Skp1, cullin, F-box ubiquitin ligase complexes; however, its cellular targets, including substrates and regulators, are not yet clarified. To identify potential substrates of FBXO7, we performed a yeast two-hybrid screen of a human fetal brain library and identified neurotrophin receptor-interacting MAGE protein (NRAGE) as a novel FBXO7-binding partner. We found that FBXO7 interacts with NRAGE and mediates Lys-63-linked poly-ubiquitination of NRAGE in mammalian cells. FBXO7 overexpression accelerates formation of NRAGE-TAK1-TAB1 complexes, whereas FBXO7 knockdown correspondingly decreases complex formation. In addition, BMP4 stimulation enhances NRAGE ubiquitination through FBXO7 and facilitates endogenous NRAGE-TAK1-TAB1 complex formation. Furthermore, FBXO7 positively regulates formation of the BMP receptor-NRAGE-TAK1-TAB1 complex, and up-regulates NF-κB activity. Taken together, our results suggest that FBXO7 affects BMP4-mediated signaling through proteasome-independent ubiquitination of NRAGE and augments formation of downstream signaling components.


MrTPS3 and MrTPS20 Are Responsible for β-Caryophyllene and α-Pinene Production, Respectively, in Red Bayberry (Morella rubra).
Red bayberry is a sweet, tart fruit native to China and grown widely in the south. The key organic compounds forming the distinctive aroma in red bayberry, are terpenoids, mainly β-caryophyllene and α-pinene. However, the key genes responsible for different terpenoids are still unknown. Here, transcriptome analysis on samples from four cultivars, during fruit development, with different terpenoid production, provided candidate genes for volatile organic compound (VOC) production. Terpene synthases (TPS) are key enzymes regulating terpenoid biosynthesis, and 34 TPS family members were identified in the red bayberry genome. MrTPS3 in chromosome 2 and MrTPS20 in chromosome 7 were identified as key genes regulating β-caryophyllene and α-pinene synthesis, respectively, by qRT-PCR. Subcellular localization and enzyme activity assay showed that MrTPS3 was responsible for β-caryophyllene (sesquiterpenes) production and MrTPS20 for α-pinene (monoterpenes). Notably, one amino acid substitution between dark color cultivars and light color cultivars resulted in the loss of function of MrTPS3, causing the different β-caryophyllene production. Our results lay the foundation to study volatile organic compounds (VOCs) in red bayberry and provide potential genes for molecular breeding.


Successful endoscopic hemostasis for bleeding from an acquired ileal diverticulum.
We herein report successful endoscopic hemostasis in a patient with a bleeding from acquired ileal diverticulum. A 65-year-old woman was introduced to our hospital after the sudden onset of painless hematochezia. When emergency colonoscopy was performed, the site of bleeding could not be identified because of extensive blood pooling in the colon and ileocecal region. After admission, repeat colonoscopy with a transparent hood device after bowel preparation disclosed oozing of blood from an ileal diverticulum approximately 15 cm proximal to the ileocecal junction. We performed endoscopic therapy with injection of a hypertonic saline-epinephrine solution and placement of additional hemoclips in the diverticulum. Since the latter treatment, the patient had no recurrent hematochezia, and occult blood tests in stool had been negative. In cases of lower gastrointestinal bleeding, bleeding from an acquired ileal diverticulum should be considered and the terminal ileum carefully observed.


Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function.
The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias.


Analyzing the Content Found on Fellowship Websites for Adult Congenital Heart Disease.
The Adult Congenital Heart Disease (ACHD) fellowship is a two-year fellowship that can be done by physicians who have finished their internal medicine residency and cardiology fellowship. This study evaluated the accessibility and provided information on the websites of the ACHD fellowship programs to identify potential areas of improvement for future fellowship applicants. Analysis of 25 ACHD fellowship program websites was conducted based on 34 criteria under three main categories: recruitment information, education and research information, and incentive information. This study found that many evaluated ACHD program websites lacked information regarding recruitment. Specifically, information regarding mentorship opportunities, hospital statistics/number of beds, selection process, and interview dates, leaving out crucial details on what to expect during the matching process. Additionally, more information on education and research is beneficial for applicants to sufficiently compare ACHD fellowship programs and make more informed decisions about which programs they would like to apply to. Information on academic stipends, evaluation criteria, expected caseload, moonlighting opportunities, elective opportunities, rotation schedules, call requirements, and types of procedures were all limited across multiple websites. Lastly, incentive information was found to be insufficient across most ACHD fellowship websites. Incentive information included fellow wellness, harassment policies, parental leave, salary, benefits, and vacation/sick leave. This study shows that ACHD fellowship programs need to supply more information on their websites to provide applicants with details to help them choose the fellowship program that corresponds best with their career goals. Expanding upon information regarding recruitment, education, research, and incentives will provide applicants with a strong understanding of ACHD fellowship programs and what they can expect throughout their education. In return, this will help ACHD fellowship programs attract stronger applicants, ultimately improving the quality of their respective programs.


Synthesis, microwave-assisted polymerization, and polymer properties of fluorinated 2-phenyl-2-oxazolines: a systematic study.
We present a detailed systematic study of the synthesis and ability of fluorinated 2-phenyl-2-oxazolines to undergo polymerization. The synthesis of these compounds is based on a two-step procedure that gives the desired 2-oxazolines in moderate-to-good yields. All the compounds were fully characterized by IR and NMR ((1)H, (13)C, and (19)F) spectroscopy, mass spectrometry, and elemental analysis. The 2-oxazolines were subsequently used as monomers for living cationic ring-opening polymerization (CROP) with microwave irradiation as the heat source (T=140 degrees C), nitromethane as the solvent, and methyl tosylate as the initiator. The linear first-order kinetic plots of the polymerizations accompanied by a linear increase of the molecular weight with conversion and low polydispersity index (PDI) values (generally below 1.30) indicate a living polymerization mechanism. The resulting polymerization rates reflect a strong sensitivity to the quantity of fluorine substituents in general and the presence or absence of ortho-fluoro substituents of the phenyl ring in particular. All the polymers were isolated and characterized by size-exclusion chromatography and MALDI-TOF mass spectrometry. Finally, a detailed investigation of selected polymer properties was performed by using differential scanning calorimetry, thermogravimetric analysis, and contact-angle measurements, thus resulting in structure-property relationships. Whereas the thermal properties of the polymers are mostly influenced by the presence of ortho-fluoro substituents, the surface properties are mainly determined by the presence of para- and/or meta-fluoro substituents.


Crocin Ameliorates Diabetic Nephropathy through Regulating Metabolism, CYP4A11/PPARγ, and TGF-β/Smad Pathways in Mice.
Crocin is one of the main components of Crocus sativus L. and can alleviate oxidative stress and inflammation in diabetic nephropathy (DN). However, the specific mechanism by which crocin treats DN still needs to be further elucidated. In the present study, a mouse model of DN was first established to investigate the therapeutic effect of crocin on DN mice. Subsequently, non-targeted metabolomics techniques were used to analyze the mechanisms of action of crocin in the treatment of DN. The effects of crocin on CYP4A11/PPARγ and TGF-β/Smad pathway were also investigated. Results showed that crocin exhibited significant therapeutic and anti-inflammatory, and anti-oxidative effects on DN mice. In addition, the non-targeted metabolomics results indicated that crocin treatment affected several metabolites in kidney. These metabolites were mainly associated with biotin metabolism, riboflavin metabolism, and arachidonic acid metabolism. Furthermore, crocin treatment upregulated the decreased levels of CYP4A11 and phosphorylated PPARγ, and reduced the increased levels of TGF-β1 and phosphorylated Smad2/3 in the kidneys of DN mice. In conclusion, our study validated the considerable therapeutic, anti-inflammatory, and antioxidative impacts of crocin on DN mice. The mechanism of crocin treatment may be related to the regulation of biotin riboflavin and arachidonic acid metabolism, the activation of CYP4A11/PPARγ pathway, and the inhibition of TGF-β/Smad pathway in the kidney.


Oblique Pyramid Microstructure-Patterned Flexible Sensors for Pressure and Visual Temperature Sensing.
Flexible tactile sensors have garnered considerable attention in diverse fields. Among them, the sensors integrated with multifunctional tactile sensing features can simultaneously detect various stimuli, such as pressure and temperature, and are thus suitable for practical applications. However, integrating multiple sensor modalities within a solitary pixel invariably encounters various limitations encompassing interplay among disparate sensors, intricate structural design demands, and the complexities and high costs associated with fabrication. Herein, we harness a visual sensing mechanism to synergize with electric sensors, thereby realizing a tactile sensor reliant on thermochromic microstructures for simultaneous pressure and temperature sensing. The thermal distribution could be easily displayed by the color change of the sensor, avoiding inference between the sensing units, which is beneficial for low-cost mass fabrication. A capacitor sensor with dual-scale oblique pyramid microstructures in its dielectric layer is used for the pressure sensing function, resulting in improved sensitivity and an extended measurement range. This innovative tactile sensor design offers insights into tactile sensing mechanisms, paving the way for cost-effective, high-performance, and multimodal sensor fabrication.


Development of selection strategies for genetic improvement in production traits of Mecheri sheep based on a Bayesian multi trait evaluation.
The progression of genetic selection techniques to enhance farm animal performance traits is guided by the present level of genetic variation and maternal impact in each trait, as well as the genetic association between traits. This study was conducted on a population of Mecheri sheep maintained from 1980 to 2018 at Mecheri Sheep Research Station, Pottaneri, India, to determine variance and covariance components, as well as genetic parameters for various production performance traits. A total of 2616 lambs, produced by 1044 dams and 226 sires, were examined in the study and the production traits of Mecheri sheep assessed include birth weight (BW), weaning weight (WW), six-month weight (SMW), nine-month weight (NMW), and yearling weight (YW). The Bayesian approach, using the Gibbs sampler, analyzed six animal models with different combinations of additive direct and maternal additive effects. Direct genetics, maternal genetics, and residual effects models were the major contributors to total phenotypic variation for all the production traits studied. Direct heritability estimates of birth weight, WW, SMW, NMW, and YW were 0.25, 0.20, 0.12, 0.14, and 0.13, respectively. The maternal heritability estimated for BW, WW, SMW, NMW, and YW were 0.17, 0.10, 0.12, 0.14, and 0.14, respectively. The maternal effects had a major impact on the pre-weaning production traits. The genetic correlations estimated between different pairs of production traits studied ranged from 0.19 to 0.93. The body weight at birth exhibited a higher genetic relationship with weaning weight than post-weaning growth characteristics, and the genetic correlation between weaning weight and post-weaning attributes was moderate to high (0.52 to 0.72). Based on the additive genetic variance in weaning weight and the correlation estimates of weaning weight with post-weaning traits, weaning weight was proposed as a selection criterion for improving growth traits in Mecheri sheep.


Presacral extramedullary hematopoiesis in thalassemia intermedia.
Extramedullary hematopoiesis is manifested by several clinical hematologic disorders including beta-thalassemia major and thalassemia intermedia. We report an unusual case of extramedullary hematopoiesis, which presented as a painful presacral mass in a patient with beta-thalassemia intermedia. The diagnosis was confirmed by a needle biopsy guided by computed tomography. The patient responded well to radiation therapy to the sacral region.


Seasonal changes in the activity of serum alkaline phosphatase.
This paper reports a seasonal variation in alkaline phosphatase (ALP) levels in the serum, with low values occurring in summer and high in winter. These variations were found both in indoor and outdoor workers and in a group of elderly women in a long-stay ward. The seasonal change in ALP was in the opposite direction to the seasonal change in the serum levels of 25-hydroxyvitamin D. No such change was seen in the serum levels of gamma-glutamyltransferase. It is suggested that the seasonal change in plasma ALP could be due to changes in the bone isoenzyme. Serum levels of calcium remained unchanged; the change in ALP may reflect a homeostatic mechanism controlling plasma calcium, which compensates for seasonal variations in vitamin D supply.


Background incidence rates of hospitalisations and emergency department visits for thromboembolic and coagulation disorders in Ontario, Canada for COVID-19 vaccine safety assessment: a population-based retrospective observational study.
The objective of this study was to estimate background rates of selected thromboembolic and coagulation disorders in Ontario, Canada. Population-based retrospective observational study using linked health administrative databases. Records of hospitalisations and emergency department visits were searched to identify cases using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada diagnostic codes. All Ontario residents. Incidence rates of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, deep vein thrombosis, pulmonary embolism, idiopathic thrombocytopaenia, disseminated intravascular coagulation and cerebral venous thrombosis during five prepandemic years (2015-2019) and 2020. The average annual population was 14 million with 51% female. The mean annual rates per 100 000 population during 2015-2019 were 127.1 (95% CI 126.2 to 127.9) for ischaemic stroke, 22.0 (95% CI 21.6 to 22.3) for intracerebral haemorrhage, 9.4 (95% CI 9.2 to 9.7) for subarachnoid haemorrhage, 86.8 (95% CI 86.1 to 87.5) for deep vein thrombosis, 63.7 (95% CI 63.1 to 64.3) for pulmonary embolism, 6.1 (95% CI 5.9 to 6.3) for idiopathic thrombocytopaenia, 1.6 (95% CI 1.5 to 1.7) for disseminated intravascular coagulation, and 1.5 (95% CI 1.4 to 1.6) for cerebral venous thrombosis. Rates were lower in 2020 than during the prepandemic years for ischaemic stroke, deep vein thrombosis and idiopathic thrombocytopaenia. Rates were generally consistent over time, except for pulmonary embolism, which increased from 57.1 to 68.5 per 100 000 between 2015 and 2019. Rates were higher for females than males for subarachnoid haemorrhage, pulmonary embolism and cerebral venous thrombosis, and vice versa for ischaemic stroke and intracerebral haemorrhage. Rates increased with age for most of these conditions, but idiopathic thrombocytopaenia demonstrated a bimodal distribution with incidence peaks at 0-19 years and ≥60 years. Our estimated background rates help contextualise observed events of these potential adverse events of special interest and to detect potential safety signals related to COVID-19 vaccines.


The counterfeit self: the deceptive costs of faking it.
Although people buy counterfeit products to signal positive traits, we show that wearing counterfeit products makes individuals feel less authentic and increases their likelihood of both behaving dishonestly and judging others as unethical. In four experiments, participants wore purportedly fake or authentically branded sunglasses. Those wearing fake sunglasses cheated more across multiple tasks than did participants wearing authentic sunglasses, both when they believed they had a preference for counterfeits (Experiment 1a) and when they were randomly assigned to wear them (Experiment 1b). Experiment 2 shows that the effects of wearing counterfeit sunglasses extend beyond the self, influencing judgments of other people's unethical behavior. Experiment 3 demonstrates that the feelings of inauthenticity that wearing fake products engenders-what we term the counterfeit self-mediate the impact of counterfeits on unethical behavior. Finally, we show that people do not predict the impact of counterfeits on ethicality; thus, the costs of counterfeits are deceptive.


Agrobacterium T-DNA integration into the plant genome can occur without the activity of key non-homologous end-joining proteins.
Non-homologous end joining (NHEJ) is the major model proposed for Agrobacterium T-DNA integration into the plant genome. In animal cells, several proteins, including KU70, KU80, ARTEMIS, DNA-PKcs, DNA ligase IV (LIG4), Ataxia telangiectasia mutated (ATM), and ATM- and Rad3-related (ATR), play an important role in 'classical' (c)NHEJ. Other proteins, including histone H1 (HON1), XRCC1, and PARP1, participate in a 'backup' (b)NHEJ process. We examined transient and stable transformation frequencies of Arabidopsis thaliana roots mutant for numerous NHEJ and other related genes. Mutants of KU70, KU80, and the plant-specific DNA Ligase VI (LIG6) showed increased stable transformation susceptibility. However, these mutants showed transient transformation susceptibility similar to that of wild-type plants, suggesting enhanced T-DNA integration in these mutants. These results were confirmed using a promoter-trap transformation vector that requires T-DNA integration into the plant genome to activate a promoterless gusA (uidA) gene, by virus-induced gene silencing (VIGS) of Nicotiana benthamiana NHEJ genes, and by biochemical assays for T-DNA integration. No alteration in transient or stable transformation frequencies was detected with atm, atr, lig4, xrcc1, or parp1 mutants. However, mutation of parp1 caused high levels of T-DNA integration and transgene methylation. A double mutant (ku80/parp1), knocking out components of both NHEJ pathways, did not show any decrease in stable transformation or T-DNA integration. Thus, T-DNA integration does not require known NHEJ proteins, suggesting an alternative route for integration.


Strengthening exercises for old cruciate ligament tears.
Fifty-three consecutive patients with troublesome old cruciate ligament lesions underwent a 3-month thigh and calf muscle training program. Before training, the diagnosis was established by arthroscopy and clinical examination under anesthesia. Significant improvement in strength, performance, knee score, and activity level took place; the majority were improved and declined surgery. A period of strength training is recommended before the decision to undertake surgery for cruciate ligament injury.


Structural changes of gut microbiota in Parkinson's disease and its correlation with clinical features.
The aim of this study was to compare the structure of gut microbiota in Parkinson's disease (PD) patients and healthy controls; and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia (P=0.018), Faecalibacterium (P=0.048) and Ruminococcus (P=0.019) were significantly decreased in PD compared to healthy controls. The putative pathobionts from the genera Escherichia-Shigella (P=0.038), Streptococcus (P=0.01), Proteus (P=0.022), and Enterococcus (P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.


Considering Readout to Understand Working Memory.
While working memory (WM) allows us to store past information, its function is to guide future behavior. Given this role, the tight link between how WMs are maintained and how they are read out to be transformed into context-appropriate actions remains relatively unexplored. Beyond helping us understand memory-guided behavior, focusing on WM readout may also help us better understand the neural basis of memory maintenance.


Gold nanoparticles stabilize peptide-drug-conjugates for sustained targeted drug delivery to cancer cells.
Peptide-drug-conjugates (PDCs) are being developed as an effective strategy to specifically deliver cytotoxic drugs to cancer cells. However one of the challenges to their successful application is the relatively low stability of peptides in the blood, liver and kidneys. Since AuNPs seem to have a longer plasma half-life than PDCs, one approach to overcoming this problem would be to conjugate the PDCs to gold nanoparticles (AuNPs), as these have demonstrated favorable physico-chemical and safety properties for drug delivery systems. We set out to test whether PEG coated-AuNPs could provide a suitable platform for the non-covalent loading of pre-formed PDCs and whether this modification would affect the bioavailability of the PDCs and their cytotoxicity toward target cancer cells. Peptides specifically internalized by A20 murine lymphoma cells were isolated from a phage library displaying 7mer linear peptides. Peptide specificity was validated by flow cytometry and confocal microscopy. PDCs were synthesized containing a selected peptide (P4) and either chlorambucil (Chlor), melphalan (Melph) or bendamustine (Bend). Gold nanoparticles were sequentially coated with citrate, PEG-6000 and then PDC (PDC-PEG-AuNP). The physico-chemical properties of the coated particles were analyzed by electrophoresis, TEM, UV-VIS and FTIR. Stability of free and PDC-coated AuNP was determined. Biopanning of the phage library resulted in discovery of several novel peptides that internalized into A20 cells. One of these (P4) was used to synthesize PDCs containing either Chlor, Melph or Bend. All three PDCs specifically killed A20 target cells, however they had short half-lives ranging from 10.6 to 15.4 min. When coated to PEG-AuNPs, the half-lives were extended to 21.0-22.3 h. The PDC-PEG-AuNPs retained cytotoxicity towards the target cells. Moreover, whereas pre-incubation for 24 h of free PDCs almost completely abolished their cytotoxic activity, the PDC-PEG-AuNPs were still active even after 72 h pre-incubation. Peptide-drug-conjugates hold potential for improving the target efficacy of chemotherapeutic drugs, however their short half-lives may limit their application. This hurdle can be overcome by easily conjugating them to gold nanoparticles. This conjugation also opens up the possibility of developing slow release formulations of targeted drug delivery systems containing PDCs.


Renal transplantation after thoracic duct drainage.
Forty-seven patients treated by at least 28 days of thoracic duct drainage (TDD) before cadaveric renal transplant are compared with 63 patients treated with standard immunosuppression. The TDD patients were begun on half the dosage of steroids, and at 30 days were receiving approximately two-thirds the dose that the non-TDD patients received. Acute rejection occurred in 35% of the TDD group, as compared with 61% of the non-TDD group. Graft survival in the TDD patients was twice as good as the non-TDD patients at all time intervals. The patient survival rates were not significantly different between the two groups. TDD pretransplant favorably affects cadaveric renal allograft survival for at least five years.


Nutrient intakes of dependent and apparently independent nursing home patients.
The nutrient intake of 20 independent and 18 dependent elderly persons is assessed in nursing home long-stay wards of a Melbourne geriatric teaching hospital. An assessment of the specific nutrient densities of the diet and comparison with recommended nutrient densities indicates that, not only is nutrient intake compromised because of low intakes of food energy, but also the quality of the diet is unsatisfactory. In institutional studies, those aged persons receiving supervision at meal times consume a more adequate diet than those able to feed themselves.


[Primary malignant fibrous histiocytoma of the lung].
A chance finding of a sheet-like, dorsal opacification in the left lower lung field of a 77-year-old nonsmoking woman was at first misdiagnosed as tuberculosis because mycobacteria were demonstrated in bronchial secretion. Before it was shown that they were atypical mycobacteria, only facultatively pathogenic, tuberculostatic treatment was started. But both radiologically and clinically the patient's condition deteriorated, with fever and enlargement of the pulmonary lesion. The left lower lobe was resected on suspicion of a chronic pneumonia with consolidation and ultimately abscess formation. The preliminary histological diagnosis of the resected lobe was of a small-cell bronchial carcinoma, stage pT3N0Mx. Further immunohistochemical tests, however, revealed a malignant fibrous histiocytoma which is extremely rare in the lung.


Blood Disorders in Patients Undergoing Transcatheter Aortic Valve Replacement: A Review.
Transcatheter aortic valve replacement (TAVR) is well established for treating patients with severe aortic stenosis considered at intermediate to high surgical risk. Blood disorders such as anemia, thrombocytopenia, and acquired type 2A von Willebrand disease are relatively frequent in TAVR candidates, and multiple studies to date have highlighted their potential clinical association with mortality and/or bleeding complications post-TAVR. The present review provides an overview of various blood disorders observed pre- and post-TAVR, with special focus on their incidence, etiology, clinical association, and management.


Photoredox mediated nickel catalyzed C(sp3)-H thiocarbonylation of ethers.
The first direct C(sp3)-H thiocarbonylation reaction is achieved by visible light photoredox/Ni dual catalysis. The thioester group of thiobenzoate is transferred to the α-oxy carbon of various cyclic/acyclic ethers, which is the opposite to the commonly expected chemical reactivity involving acyl group transfer via the weaker C(acyl)-S activation. Through mechanistic studies, we proposed that the reaction is initiated by photocatalytic reduction and fragmentation of the thioester into an acyl radical and a thiolate. A nickel complex binds to the thiolate and induces the decarbonylation of the acyl radical to form an aryl radical, which abstracts hydrogen from the α-oxy carbon of the ether. The resulting α-oxy C(sp3) centered radical re-binds to the (RS)(CO)Ni complex, which undergoes CO migratory insertion and reductive elimination to give the desired thioester product.


Cocaine exposure enhances permissiveness of quiescent T cells to HIV infection.
In vivo and in vitro exposure to stimulants has been associated with increased levels of HIV infection in PBMCs. Among these lymphocyte subsets, quiescent CD4(+) T cells make up the majority of circulating T cells in the blood. Others and we have demonstrated that HIV infects this population of cells inefficiently. However, minor changes in their cell state can render them permissive to infection, significantly impacting the viral reservoir. We have hypothesized that stimulants, such as cocaine, may perturb the activation state of quiescent cells enhancing permissiveness to infection. Quiescent T cells isolated from healthy human donors were exposed to cocaine and infected with HIV. Samples were harvested at different time-points to assess the impact of cocaine on their susceptibility to infection at various stages of the HIV life cycle. Our data show that a 3-day exposure to cocaine enhanced infection of quiescent cells, an effect that appears to be mediated by σ1R and D4R. Overall, our results indicate that cocaine-mediated effects on quiescent T cells may increase the pool of infection-susceptible T cells. The latter underscores the impact that stimulants have on HIV-seropositive individuals and the challenges posed for treatment.


Magnetizable solid-phase fluoroimmunoassay of thyroxine by a sequential addition technique.
We describe a simple fluoroimmunoassay for the determination of thyroxine concentrations in serum. The method, "sequential addition, separation fluoroimmunoassay," involves both thyroxine labeled with fluorescein and magnetizable cellulose/iron oxide particles to which antibodies to thyroxine have been covalently linked. Serum sample or standard is incubated with an excess of the solid-phase antibody; the particles, which now carry most of the antigen in the sample, are sedimented onto a magnet and the supernate, which contains endogenous fluorophores and other interfering factors, is removed and discarded. Excess labeled thyroxine is then added, and, after incubation, the fluorescence in the supernate (free fraction), which is related directly to the amount of thyroxine in the sample is measured. For the whole procedure, including fluorometry, each sample is treated entirely within disposable polystyrene test tubes. Correlation studies with two different radioimmunoassays showed good agreement.


[A cohort study on the difference of stroke incidence between urban and rural populations and related influential factors].
A longitudinal prospective study was carried out in a cohort of 1 809 persons aged 35 to 74 at entry, including 778 subjects from urban and 1 031 from rural areas. The average annual age-adjusted incidence of stroke was 95.7/10(4) in urban group during a 15-year-period from 1979 to 1994, which was significantly lower than that in rural areas (183.1/10(4) during a 11-year-period from 1983 to 1994. According to the results through multivariate regression analysis and comparative study of risk factors between urban and rural group at baseline examination, it was suggested that in addition to age, factors as drinking habit, smoking, ECG abnormality and elevated systolic blood pressure (in female) were important parameters causing the difference of incidence between urban and rural groups. Other than those factors mentioned above, low level of serum cholesterol in rural population was also suspected as a possible factor positively influencing the development of stroke.


A limited contribution of Ca2+ current facilitation to paired-pulse facilitation of transmitter release at the rat calyx of Held.
Recent studies have suggested that transmitter release facilitation at synapses is largely mediated by presynaptic Ca(2+) current facilitation, but the exact contribution of Ca(2+) current facilitation has not been determined quantitatively. Here, we determine the contribution of Ca(2+) current facilitation, and of an increase in the residual free Ca(2+) concentration ([Ca(2+)](i)) in the nerve terminal, to paired-pulse facilitation of transmitter release at the calyx of Held. Under conditions of low release probability imposed by brief presynaptic voltage-clamp steps, transmitter release facilitation at short interstimulus intervals (4 ms) was 227 +/- 31% of control, Ca(2+) current facilitation was 113 +/- 4% of control, and the peak residual [Ca(2+)](i) was 252 +/- 18 nm over baseline. By inferring the 'local' [Ca(2+)](i) transients that drive transmitter release during these voltage-clamp stimuli with the help of a kinetic release model, we estimate that Ca(2+) current facilitation contributes to approximately 40% to paired-pulse facilitation of transmitter release. The remaining component of facilitation strongly depends on the build-up, and on the decay of the residual free [Ca(2+)](i), but cannot be explained by linear summation of the residual free [Ca(2+)](i), and the back-calculated 'local' [Ca(2+)](i) signal, which only accounts for approximately 10% of the total release facilitation. Further voltage-clamp experiments designed to compensate for Ca(2+) current facilitation demonstrated that about half of the observed transmitter release facilitation remains in the absence of Ca(2+) current facilitation. Our results indicate that paired-pulse facilitation of transmitter release at the calyx of Held is driven by at least two distinct mechanisms: Ca(2+) current facilitation, and a mechanism independent of Ca(2+) current facilitation that closely tracks the time course of residual free [Ca(2+)](i).


An analytical approach to characterize morbidity profile dissimilarity between distinct cohorts using electronic medical records.
We describe a two-stage analytical approach for characterizing morbidity profile dissimilarity among patient cohorts using electronic medical records. We capture morbidities using the International Statistical Classification of Diseases and Related Health Problems (ICD-9) codes. In the first stage of the approach separate logistic regression analyses for ICD-9 sections (e.g., "hypertensive disease" or "appendicitis") are conducted, and the odds ratios that describe adjusted differences in prevalence between two cohorts are displayed graphically. In the second stage, the results from ICD-9 section analyses are combined into a general morbidity dissimilarity index (MDI). For illustration, we examine nine cohorts of patients representing six phenotypes (or controls) derived from five institutions, each a participant in the electronic MEdical REcords and GEnomics (eMERGE) network. The phenotypes studied include type II diabetes and type II diabetes controls, peripheral arterial disease and peripheral arterial disease controls, normal cardiac conduction as measured by electrocardiography, and senile cataracts.


The impact of cancer and chemotherapy during pregnancy on child neurodevelopment: A multimodal neuroimaging analysis.
This study applies multimodal MRI to investigate neurodevelopment in nine-year-old children born to cancer-complicated pregnancies. In this cohort study, children born after cancer-complicated pregnancies were recruited alongside 1:1 matched controls regarding age, sex and gestational age at birth (GA). Multimodal MRI was used to investigate whole-brain and subcortical volume, cortical structure (using surface-based morphometry), white matter microstructure (using fixel-based analysis) and functional connectivity (using resting-state blood-oxygen-level-dependant signal correlations). Graph theory probed whole-brain structural and functional organization. For each imaging outcome we conducted two group comparisons: 1) children born after cancer-complicated pregnancies versus matched controls, and 2) the subgroup of children with prenatal chemotherapy exposure versus matched controls. In both models, we used the covariate of GA and the group-by-GA interaction, using false-discovery-rate (FDR) or family-wise-error (FWE) correction for multiple comparisons. Exploratory post-hoc analyses investigated the relation between brain structure/function, neuropsychological outcome and maternal oncological/obstetrical history. Forty-two children born after cancer-complicated pregnancies were included in this study, with 30 prenatally exposed to chemotherapy. Brain organization and functional connectivity were not significantly different between groups. Both cancer and chemotherapy in pregnancy, as compared to matched controls, were associated with a lower travel depth, indicating less pronounced gyrification, in the left superior temporal gyrus (pFDR ≤ 006), with post-hoc analysis indicating platinum derivatives during pregnancy as a potential risk factor (p = .028). Both cancer and chemotherapy in pregnancy were related to a lower fibre cross-section (FCS) and lower fibre density and cross-section (FDC) in the posterior corpus callosum and its tapetal fibres, compared to controls. Higher FDC in the chemotherapy subgroup and higher FCS in the whole study group were observed in the anterior thalamic radiations. None of the psycho-behavioural parameters correlated significantly with any of the brain differences in the study group or chemotherapy subgroup. Prenatal exposure to maternal cancer and its treatment might affect local grey and white matter structure, but not functional connectivity or global organization. While platinum-based therapy was identified as a potential risk factor, this was not the case for chemotherapy in general. This project has received funding from the European Union's Horizon 2020 research and innovation program (European Research council, grant no 647,047), the Foundation against cancer (Stichting tegen kanker, grant no. 2014-152) and the Research Foundation Flanders (FWO, grants no. 11B9919N, 12ZV420N).


Positive and negative volume-outcome relationships in the geriatric trauma population.
In trauma populations, improvements in outcome are documented in institutions with higher case volumes. However, it is not known whether improved outcomes are attributable to the case volume within specific higher-risk groups, such as the elderly, or to the case volume among all trauma patients treated by an institution. To test the hypothesis that outcomes of trauma care for geriatric patients are affected differently by the volume of geriatric cases and nongeriatric cases of an institution. This retrospective cohort study using a statewide trauma registry was set in state-designated levels 1 and 2 trauma centers in Pennsylvania. It included 39 431 eligible geriatric trauma patients (aged >65 years) in the Pennsylvania Trauma Outcomes Study. In-hospital mortality, major complications, and mortality after major complications (failure to rescue). Between 2001 and 2010, 39 431 geriatric trauma patients and 105 046 nongeriatric patients were captured in a review of outcomes in 20 state-designated levels 1 and 2 trauma centers. Larger volumes of geriatric trauma patients were significantly associated with lower odds of in-hospital mortality, major complications, and failure to rescue. In contrast, larger nongeriatric trauma volumes were significantly associated with higher odds of major complications in geriatric patients. Higher rates of in-hospital mortality, major complications, and failure to rescue were associated with lower volumes of geriatric trauma care and paradoxically with higher volumes of trauma care for younger patients. These findings offer the possibility that outcomes might be improved with differentiated pathways of care for geriatric trauma patients.


[Wilms' tumors: the actual standpoint (author's transl)].
Treatment results in children with Wilms' tumors have remarkably improved during the past ten years. This is the most important aspect in modern Wilms' tumor research. Further, new etiologic factors have been identified. Modern diagnostic procedures (with special reference to an eventual preoperative treatment), aspects of "staging" and "grading", the changed prognosis and handling of bilateral tumors, the identification of infantile congeners of Wilms' tumors and the often realized optimal interdisciplinary cooperative treatment have allowed to design the former mostly fatal tumors as outstanding in clinical oncology. This paper summarizes the recent data available from the literature; several problems remain unresolved. Among open questions are a better preoperative diagnosis, standardization of treatment of stage-IV-patients, determination of the role of adriamycin in chemotherapy, and the comprehensive and thorough study of late effects.


Iron availability in an enteral feeding formulation by response surface methodology for mixtures.
The nutritional therapy with enteral diets has been getting specialized and those formulations to substitute the traditional diet for those patients who need to be fed by probe. This workís aim was to study the effect of the components of enteral diet formulation: fiber, calcium and medium-chain triglycerides, seeking optimize a formulation for the best dialysability of iron by Response Surface Methodology (RSM). The ingredients used for the formulations of the diet were chosen according to the ones commercialized in the modules of a standard enteral diet, with which it was made an experimental diet and the applicability of the experimental limits. The found results in the model have shown that it depends on the proportion of the nutrients that were manipulated in the experimental design. When the level curve was obtained for the iron dialysable, it could be verified that the binary interaction fiber-calcium was the one that presented more synergism for the appraised formulation. Before the analyzed facts, the best formulation of enteral diet optimized for the dialysability of the iron was the proportion of 60% of fiber and 40% of calcium, showing to be the best formulation of the enteral diet for the availability of the iron.


Variation in Procedural Sedation Practices Among Children's Hospitals.
Children often need procedural sedation for painful procedures. There are few data on type of provider, site of sedation, and agents used for procedural sedation in hospitals across the nation. The objective was to determine procedural sedation practices for hospitalized children outside the PICU and emergency department. Surveys were sent to 89 pediatric hospitalist (PH) leaders in hospitals belonging to the Child Health Corporation of America or the National Association of Children's Hospitals and Related Institutions. We received responses from 56 PHs (63%), of whom 49 (55%) completed the survey. PHs provided sedation in 18 hospitals. Provider, setting, and agents used for procedural sedation varied. The primary providers of procedural sedation for abscess incision and drainage, renal biopsy, joint aspiration, computed tomography, and MRI were anesthesiologists. A significantly greater percentage of hospitals where PHs did not provide procedural sedation used the operating room for abscess incision and drainage compared with hospitals where PHs provided procedural sedation (63% vs 28%, respectively). Postoperative/abscess dressing change, vesicocystourethrogram, and ≥1 painful procedure were performed without sedation in significantly greater percentage of hospitals where PHs did not provide procedural sedation compared with hospitals where PHs provided procedural sedation. There is variability in sedation practices in hospitals across the nation, which affects patient care and use of resources such as the operating room. In hospitals where PHs provide procedural sedation, there is less operating room use and fewer painful procedures for which no sedation is provided.


Tracing cranial nerve pathways (glossopharyngeal, vagus, and hypoglossal) in SIDS and control infants: a DiI study.
It has been proposed that Sudden Infant Death Syndrome (SIDS) might occur as a consequence of a developmental deficit associated with the cardiorespiratory and arousal control centers located within the brainstem. In this study 1.1' dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate (DiI) was used to investigate the trajectories of the glossopharyngeal and vagus nerves which carry essential afferent and efferent fiber tracts associated with cardiac and respiratory control and of the hypoglossal nerve which innervates the tongue, in SIDS (n = 14) and control (n = 7) infants. The postnatal development of the trajectories of these nerves was examined in non-SIDS brains and comparisons were then made with age-matched SIDS brains. The mean profile area of hypoglossal and dorsal motor neurons were also assessed. In controls, no major alterations were observed in the trajectories of axon bundles with increasing age (7 wk to 2 yr) in each of the nerves investigated although axon bundles appeared to increase in thickness with age. In SIDS cases (2 wk to 44 wk), the trajectories of the cranial nerves were not different from those seen in age-matched control cases. The mean profile area of hypoglossal and dorsal motor neurons was not significantly different between control and SIDS infants. We conclude that the DiI tracing technique can be used successfully to trace the pathways of cranial nerves in human infant fixed-tissue. Furthermore, if functional differences exist between SIDS and non-SIDS brains in the control of respiration, circulation, or arousal they do not appear to be related to markedly reduced or aberrant projections of the glossopharyngeal, vagus, or hypoglossal nerves.


Hyponatremia in patients with neurologic disorders.
The kidney and the brain play a major role in maintaining normal homeostasis of the extracellular fluid by neuroendocrine regulation of sodium and water balance. Therefore, disturbances of sodium balance are common in patients with central nervous system (CNS) disorders and clinicians should focus not only on the CNS lesion, but also on the potentially deleterious complications. Hyponatremia is the most common and important electrolyte disorder affecting patients with critical neurologic diseases. In these patients, the maladaptation to hyponatremia by impaired osmoregulation in pathologic lesions of brain may cause more aggressive cerebral edema and increased intracranial pressure due to hypoosmolality induced by hyponatremia. Furthermore, hyponatremia accompanied by CNS disorders has shown to increase delayed cerebral ischemia and mortality rates. Two main pathophysiologies of hyponatremia, excluding iatrogenic causes, are inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting (CSW) syndrome. Differential diagnosis between these two entities can be difficult due to considerable overlap in the laboratory findings and clinical situations. SIADH is in a volume expanded status due to inappropriately secreted arginine vasopressin (AVP) and requires water restriction. However, CSW syndrome is characterized by renal sodium wasting mainly due to increased natriuretic peptides resulting in volume depletion and follows appropriate secretion of AVP. Therefore, maintenance of volume status and sodium replacement is the mainstay of treatment in CSW syndrome. In this review, we aimed to describe the regulation of sodium and water balance, and pathophysiology, diagnosis and treatment of hyponatremia in neurologic patients, especially focusing on SIADH and CSW syndrome.


Resilience in Extremely Preterm/Extremely Low Birth Weight Kindergarten Children.
Research on developmental outcomes of preterm birth has traditionally focused on adverse effects. This study investigated the prevalence and correlates of resilience in 146 extremely preterm/extremely low birth weight (EPT/ELBW) children (gestational age <28 weeks and/or birth weight <1000 g) attending kindergarten and 111 term-born normal birth weight (NBW) controls. Adaptive competence (i.e., "resilience" in the EPT/ELBW group) was defined by scores within grade expectations on achievement tests and the absence of clinically elevated parent ratings of child behavior problems. The "adaptive" children who met these criteria were compared to the "maladaptive" children who did not on child and family characteristics. Additional analyses were conducted to assess the conjoint effects of group (ELBW vs. NBW) and family factors on adaptive competence. A substantial minority of the EPT/ELBW group (45%) were competent compared to a majority of NBW controls (73%), odds ratio (95% confidence interval)=0.26 (0.15, 0.45), p<.001. Adaptive competence was associated with higher cognitive skills, more favorable ratings of behavior and learning not used to define adaptive competence, and more advantaged family environments in both groups, as well as with a lower rate of earlier neurodevelopmental impairment in the EPT/ELBW group. Higher socioeconomic status and more favorable proximal home environments were associated with competence independent of group, and group differences in competence persisted across the next two school years. The findings document resilience in kindergarten children with extreme prematurity and highlight the role of environmental factors as potential influences on outcome. (JINS, 2019, 25, 362-374).


Lithium treatment of affective disorders: effects of lithium on the inositol phospholipid and cyclic AMP signalling pathways.
The effects of lithium (Li+) on the adenylyl cyclase and inositol phospholipid receptor signalling pathways were compared directly in noradrenergic and carbachol stimulated rat brain cortical tissue slices. Li+ was a comparatively weak inhibitor of noradrenaline-stimulated cyclic AMP accumulation with an IC50 of approx. 20 mM. By contrast, half-maximal effects of Li+ on inositol monophosphate (InsP) accumulation in [3H]inositol labelled tissue slices occurred at about 1 mM. A similar IC50 for Li+ of about 1 mM was also obtained for noradrenaline-stimulated accumulation of CMP-phosphatidate (CMPPA), a sensitive indicator of intracellular inositol depletion, in tissue slices that had been prelabelled with [3H]cytidine. The effect of myo-inositol (inositol) depletion on the prolonged activity of phosphoinositidase C (PIC) was examined in carbachol-stimulated cortical slices using a novel mass assay for InsP. Exposure to a maximal dose of carbachol for 30 min in the presence of 5 mM Li+ caused a 10-fold increase in the level of radioactivity associated with the InsP fraction, but only a 2-fold increase in InsP mass. During prolonged incubations in the presence of both carbachol and Li+ the accumulation of InsP mass was enhanced if 30 mM inositol was included in the medium. The results are compatible with the inositol depletion hypothesis of Li+ action but do not support the concept that adenylyl cyclase or guanine nucleotide dependent proteins represent therapeutically relevant targets of this drug.


Feeding Practices and Effects on Transfusion-Associated Necrotizing Enterocolitis in Premature Neonates.
Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development. To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions. Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates. Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes. To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation. It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes.


Nonsequential modeling of laser diode stacks using Zemax: simulation, optimization, and experimental validation.
Modeling a real laser diode stack based on Zemax ray tracing software that operates in a nonsequential mode is reported. The implementation of the model is presented together with the geometric and optical parameters to be adjusted to calibrate the model and to match the simulated intensity irradiance profiles with the experimental profiles. The calibration of the model is based on a near-field and a far-field measurement. The validation of the model has been accomplished by comparing the simulated and experimental transverse irradiance profiles at different positions along the caustic formed by a lens. Spot sizes and waist location are predicted with a maximum error below 6%.


Single-Cell Transcriptome Sequencing and Proteomics Reveal Neonatal Ileum Dynamic Developmental Potentials.
The neonatal period is a crucial time during development of the mammalian small intestine. Moreover, neonatal development and maturation of the small intestine are exceptionally important for early growth, successful weaning, and postweaning growth and development, in order to achieve species-specific milestones. Although several publications recently characterized intestinal epithelial cell diversity at the single-cell level, it remains unclear how differentiation and molecular interactions take place between types and subtypes of epithelial cells during the neonatal period. A single-cell RNA sequencing (scRNA-seq) survey of 40,186 ileal epithelial cells and proteomics analysis of ileal samples at 6 time points in the swine neonatal period were performed. The results revealed previously unknown developmental changes: specific increases in undifferentiated cells, unique enterocyte differentiation, and time-dependent reduction in secretory cells. Moreover, we observed specific transcriptional factors, ligand-receptor pairs, G protein-coupled receptors, transforming growth factor β, bone morphogenetic protein signaling pathways, and gut mucosal microbiota playing vital roles in ileal development during the neonatal window. This work offers new comprehensive information regarding ileal development throughout the neonatal period. Reference to this data set may assist in the creation of novel interventions for inflammation-, metabolism-, and proliferation-related gut pathologies. IMPORTANCE We found previously unknown neonatal ileum developmental potentials: specific increases in undifferentiated cells, unique enterocyte differentiation, and time dependent reduction in secretory cells. Specific transcriptional factors (TFs), ligand-receptor pairs, G protein-coupled receptors, transforming growth factor β, bone morphogenetic protein signaling pathways, and the gut mucosal microbiota are involved in this process. Our results may assist in the creation of novel interventions for inflammation-, metabolism-, and proliferation-related gut pathologies.


Electric-dipole-induced universality for Dirac fermions in graphene.
We study electric dipole effects for massive Dirac fermions in graphene and related materials. The dipole potential accommodates towers of infinitely many bound states exhibiting a universal Efimov-like scaling hierarchy. The dipole moment determines the number of towers, but there is always at least one tower. The corresponding eigenstates show a characteristic angular asymmetry, observable in tunnel spectroscopy. However, charge transport properties inferred from scattering states are highly isotropic.


Mesenteric lymphoblast localization throughout the murine small intestine: temporal analysis relating intestinal length and lymphoblast division.
Mesenteric lymphoblasts (MLN) have a predilection to selectively localize in the lamina propria and epithelium of the small intestine. Using an adoptive transfer method, we examined the localization kinetics of these blasts in the intestinal wall with respect to their distribution from duodenum to terminal ileum and also assessed their mitotic activity by autoradiographic techniques. 3H-thymidine-labelled MLN cells were found throughout the small intestine by 6 hr post-transfer and reached a maximum frequency in this organ by 24 hr post-transfer. Donor blasts were most frequent in the duodenum and terminal ileum regions of the gut. Subsequently, the frequency of labelled cells throughout the intestinal wall declined to near zero. The apparent accumulation of MLN blasts in the gut was not related to either a temporary retention and departure from the pulmonary vasculature or to mitotic division of labelled cells in the gut wall. A model describing the relationship between MLN blast localization kinetics in various segments of the intestine was formulated.


Urinary excretion of plasma proteins in diabetic subjects. Increased excretion of kappa light chains in diabetic patients with and without proliferative retinopathy.
The urinary excretion of beta2-microglobulin, albumin, kappa light chains, transferrin, and IgG as well as their concentration ratios were assessed in 27 nondiabetic patients with proteinuria and in 72 IDDM patients, 41 with proliferative retinopathy (PR) and 31 without retinopathy, matched for age, duration of diabetes, and treatment. The mean excretions of albumin, transferrin, and IgG were similar in patients with nondiabetic proteinuria and in IDDM patients with PR and were significantly higher than in IDDM patients without retinopathy. Despite similar albumin excretion, the amount of excreted kappa light chains was significantly higher in IDDM patients than in patients with nondiabetic proteinuria, resulting in an elevated kappa chain/albumin ratio. Furthermore, diabetic subjects without microalbuminuria showed increased kappa chain/albumin ratio, indicating that increased urinary excretion of kappa chains may be an early sign of diabetic nephropathy. Determination of kappa light chain excretion may have clinical implications in the differentiation between proteinuria of diabetic and nondiabetic origin. The ratio kappa chain/albumin was independent of the excretion of beta2-microglobulin in patients with PR, suggesting that the reduced ability to reabsorb immunoglobulin light chains may occur earlier than that of beta2-microglobulin in the development of tubular dysfunction in insulin-dependent diabetes mellitus.


[Lipoprotein lipase and diabetic cardiomyopathy].
Lipoprotein lipase (LPL) hydrolyzes plasma triglyceride-rich lipoproteins into free fatty acids (FFA) to provide energy for cardiac tissue. During diabetes, cardiac energy supply is insufficient due to defected utilization of glucose. As a compensation of cardiac energy supply, FFAs are released through the hydrolysis of very low density lipoprotein (VLDL) and chylomicrons (CM) due to activation of LPL activity. In diabetic patients, activated LPL activity and elevated FFAs result in the intracellular accumulation of reactive oxygen species and lipids in myocardium and potentially induce the diabetic cardiomyopathy (DCM). The present review summarizes the regulatory mechanisms of myocardial LPL and the pathogenesis of DCM induced by LPL and provides novel therapeutic targets and pathways for DCM.


Assessing health impact assessment: multidisciplinary and international perspectives.
Health impact assessment (HIA) seeks to expand evaluation of policy and programmes in all sectors, both private and public, to include their impact on population health. While the idea that the public's health is affected by a broad array of social and economic policies is not new and dates back well over two centuries, what is new is the notion-increasingly adopted by major health institutions, such as the World Health Organisation (WHO) and the United Kingdom National Health Services (NHS)-that health should be an explicit consideration when evaluating all public policies. In this article, it is argued that while HIA has the potential to enhance recognition of societal determinants of health and of intersectoral responsibility for health, its pitfalls warrant critical attention. Greater clarity is required regarding criteria for initiating, conducting, and completing HIA, including rules pertaining to decision making, enforcement, compliance, plus paying for their conduct. Critical debate over the promise, process, and pitfalls of HIA needs to be informed by multiple disciplines and perspectives from diverse people and regions of the world.