Image Encryption Using Elliptic Curves and Rossby/Drift Wave Triads.
We propose an image encryption scheme based on quasi-resonant Rossby/drift wave triads (related to elliptic surfaces) and Mordell elliptic curves (MECs). By defining a total order on quasi-resonant triads, at a first stage we construct quasi-resonant triads using auxiliary parameters of elliptic surfaces in order to generate pseudo-random numbers. At a second stage, we employ an MEC to construct a dynamic substitution box (S-box) for the plain image. The generated pseudo-random numbers and S-box are used to provide diffusion and confusion, respectively, in the tested image. We test the proposed scheme against well-known attacks by encrypting all gray images taken from the USC-SIPI image database. Our experimental results indicate the high security of the newly developed scheme. Finally, via extensive comparisons we show that the new scheme outperforms other popular schemes.


Unusual presentation of acute upper airway obstruction caused by an anterior mediastinal mass.
We report an unusual case of acute upper airway obstruction. Inhalation of a foreign body caused choking in a 5-yr-old child, but subsequent investigations revealed a large anterior mediastinal tumour, externally compressing the trachea and the main bronchi. Such a presentation may be deceptive and is important, as general anaesthesia may result in complete airway obstruction with fatal consequences.


[Principles of intensive care during the acute period of severe craniocerebral trauma in children].
Prospective analysis of the course of severe craniocerebral injury (CCI) in 37 children showed that the results of treatment depended on methods of intensive care. In children the outcome of CCI depends primarily on adequacy of maintaining effective cerebral bloodflow during the acute period of CCI irrespective of the terms and etiological factors of coma. Adequate cerebral perfusion pressure is attained with osmodiuretics, saluretics, and hemodynamic therapy. Hyperventilation is justified in cases with coma developing within 2 h after the injury; it should not lead to long (more than 1 h) decrease of PaCO2 below 28 mm Hg. The authors emphasize that every delayed decrease of consciousness after the injury should be thoroughly analyzed in order to rule out intracranial complications (epi/subdural and intracerebrai hematomas) in no more than 6 h, which is the maximal time allowed for decision making. Use of unapproved medical methods and drugs in children during acute period of severe CCI is ineffective and even hazardous, because it distracts the physician's attention to negligible details of treatment; in addition many of such drugs have side effects.


The effect of early to mid-gestational nutrient restriction on female offspring fertility and hypothalamic-pituitary-adrenal axis response to stress.
Primiparous ewes born as singletons to Rambouillet x Columbia crossbred ewes fed either 100% of NRC recommendations (control, Con; n = 7) or 50% of NRC (nutrient restricted, NR; n = 7) from d 28 through 78 postmating were utilized for this study. At 1 yr of age, a subset of ewes born to Con (n = 4) and NR (n = 4) mothers received jugular catheters and were subjected to a corticotrophin-releasing hormone (CRH)/arginine vasopressin (AVP) challenge, an ACTH challenge, and an isolation stress test, in which ACTH and cortisol responses were determined. A week after these challenges, estrus was monitored twice daily in all ewes from Con (n = 7) and NR mothers (n = 7). Once estrus was observed (d 0), daily blood samples were collected from ewes for progesterone through the subsequent estrus. Estrous detection and daily blood sampling were repeated during an estrous cycle in the next year, ewes were hand mated at the second estrus, and pregnancy was determined by delivery of a live lamb(s). Ewes from NR mothers tended (P = 0.10) to have a greater peak ACTH response after an intravenous CRH/AVP injection than ewes from Con mothers. The cortisol response of ewes to a CRH/AVP or ACTH challenge was not influenced by maternal nutrition. In contrast, ewes from Con mothers tended (P = 0.10) to release more ACTH in response to the isolation stress test and showed a greater (P = 0.04) cortisol release than ewes from NR mothers. Ewes from NR mothers exhibited decreased (P < 0.05) plasma progesterone in both yr 1 and 2 of the study compared with ewes from Con mothers. Furthermore, fewer (P < 0.0001) ewes from NR mothers produced a lamb (1 of 7) than ewes from Con mothers (7 of 7) during yr 2 of the study. These findings indicate that maternal undernutrition during early gestation may affect stress responses by the offspring, but has limited impact on hypothalamo-pituitary-adrenal sensitivity. Furthermore, offspring of NR ewes exhibited reduced progesterone secretion during the luteal phase of their estrous cycles and a markedly reduced fertility compared with offspring from Con ewes.


Development of an ultra-thin parallel plate ionization chamber for dosimetry in FLASH radiotherapy.
Conventional air ionization chambers (ICs) exhibit ion recombination correction factors that deviate substantially from unity when irradiated with dose per pulse magnitudes higher than those used in conventional radiotherapy. This fact makes these devices unsuitable for the dosimetric characterization of beams in ultra-high dose per pulse as used for FLASH radiotherapy. We present the design, development, and characterization of an ultra-thin parallel plate IC that can be used in ultra-high dose rate (UHDR) deliveries with minimal recombination. The charge collection efficiency (CCE) of parallel plate ICs was modeled through a numerical solution of the coupled differential equations governing the transport of charged carriers produced by ionizing radiation. It was used to find out the optimal parameters for the purpose of designing an IC capable of exhibiting a linear response with dose (deviation less than 1%) up to 10 Gy per pulse at 4 μ $\umu$ s pulse duration. As a proof of concept, two vented parallel plate IC prototypes have been built and tested in different ultra-high pulse dose rate electron beams. It has been found that by reducing the distance between electrodes to a value of 0.25 mm it is possible to extend the dose rate operating range of parallel plate ICs to ultra-high dose per pulse range, at standard voltage of clinical grade electrometers, well into several Gy per pulse. The two IC prototypes exhibit behavior as predicted by the numerical simulation. One of the so-called ultra-thin parallel plate ionization chamber (UTIC) prototypes was able to measure up to 10 Gy per pulse, 4 μ $\umu$ s pulse duration, operated at 300 V with no significant deviation from linearity within the uncertainties (ElectronFlash Linac, SIT). The other prototype was tested up to 5.4 Gy per pulse, 2.5 μ $\umu$ s pulse duration, operated at 250 V with CCE higher than 98.6% (Metrological Electron Accelerator Facility, MELAF at Physikalisch-Technische Bundesanstalt, PTB). This work demonstrates the ability to extend the dose rate operating range of ICs to ultra-high dose per pulse range by reducing the spacing between electrodes. The results show that UTICs are suitable for measurement in UHDR electron beams.


[Fournier's gangrene, a battle won. Traditional cures versus a polyhexanide solution].
This article won the top place in the Third Prontosan Scientific Prize in 2008. Fournier's Gangrene is a rare process having an unknown origin which affects soft tissue in the genital and perirectal area. The authors describe the case of a 61 year old patient suffering from this disease, the recommended treatment by the Nurses' Consulting Office for Bed Sores, or Decubitus Ulcers, and Chronic Skin Ulcerations, and the patient's evolution. The medical team carried out a complete evaluation of this patient and his/her injury and took a sample to make a surface culture from. After this initial evaluation, the medical team's first recommendation was to apply treatment consisting of using polyhexanide combined with a calcic alginate dressing to control oozing; the objective of this treatment is to clean and decontaminate the wound and to provide the optimum conditions for a correct cicatrisation process in the least time possible. After 58 days undergoing treatment, the affected area did not show any sign nor symptom of infection and was practically finished with the cicatrisation process. The use of polyhexanide, in this case, proved to be the ideal therapeutic option to clean, decontaminate and maintain the conditions optimum for a correct cicatrisation of this wound.


Surfactant induced autophobing.
Surfactant adsorption in a three-phase system and its influence on wetting properties are relevant in various applications. Here, we report a hitherto not observed phenomenon, namely the retraction of an aqueous drop on hydrophilic solid substrates (which we refer to as 'autophobing') in ambient oil containing water-insoluble fatty acids, caused by the deposition of these fatty acids from the ambient oil onto the solid substrate. AFM measurements confirm that the surfactant is deposited on the solid by the moving contact line. This leads to a more hydrophobic substrate, the retraction of the contact line and a concomitant increase in the contact angle. The deposition process is enabled by the formation of a reaction product between deprotonated fatty acids and Ca(2+) ions at the oil/water interface. We investigate how the transition to a new equilibrium depends on the concentrations of the fatty acids, the aqueous solute, the chain lengths of the fatty acid, and the types of alkane solvent and silica or mica substrates. This phenomenon is observed on both substrates and for all explored combinations of fatty acids and solvents and thus appears to be generic. In order to capture the evolution of the contact angle, we develop a theoretical model in which the rate of adsorption at the oil-water interface governs the overall kinetics of autophobing, and transfer to the solid is determined by a mass flux balance (similar to a Langmuir Blodgett transfer).


Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats.
1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O(2) consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the accelerated rate of ketone-body metabolism; however, we found no correlation between the decrease in glucose uptake in the diabetic state and the arteriovenous difference for ketone bodies. 12. The data also suggest that the rates of acetoacetate and 3-hydroxybutyrate utilization by brain are governed by their concentrations in plasma. 13. The finding of very low concentrations of acetoacetate and 3-hydroxybutyrate in brain compared with plasma suggests that diffusion across the blood-brain barrier may be the rate-limiting step in their metabolism.


The Arabidopsis CLAVATA2 gene encodes a receptor-like protein required for the stability of the CLAVATA1 receptor-like kinase.
The CLAVATA2 (CLV2) gene regulates both meristem and organ development in Arabidopsis. We isolated the CLV2 gene and found that it encodes a receptor-like protein (RLP), with a presumed extracellular domain composed of leucine-rich repeats similar to those found in plant and animal receptors, but with a very short predicted cytoplasmic tail. RLPs lacking cytoplasmic signaling domains have not been previously shown to regulate development in plants. Our prior work has demonstrated that the CLV1 receptor-like kinase (RLK) is present as a disulfide-linked multimer in vivo. We report that CLV2 is required for the normal accumulation of CLV1 protein and its assembly into protein complexes, indicating that CLV2 may form a heterodimer with CLV1 to transduce extracellular signals. Sequence analysis suggests that the charged residue in the predicted transmembrane domain of CLV2 may be a common feature of plant RLPs and RLKs. In addition, the chromosomal region in which CLV2 is located contains an extremely high rate of polymorphism, with 50 nucleotide and 15 amino acid differences between Landsberg erecta and Columbia ecotypes within the CLV2 coding sequence.


The role of lipid content in the infectivity of third-stage larvae of Heligmosomoides polygyrus.
The concurrent effects of aging on the lipid content of third-stage larvae (L3) of H.p. polygyrus and H.p. bakeri were described experimentally. It was shown that larval age was closely correlated with their infectivity. The infectivity of H. polygyrus in field and laboratory mice, as indicated by mean worm recovery, was significantly higher for one week old compared with 16 weeks old larvae. Image analysis has been used for the first time to quantify the lipid content of L3 of H. polygyrus with age. The proportion of lipid within infective larvae was reduced and their infectivity declined with age. It has also been found that larvae of H.p. polygyrus possess more lipid than H.p. bakeri suggesting that L3 larvae of H.p. polygyrus are physiologically different from those of H.p. bakeri and the additional lipid reserves assist in extending their survival time in the extremes of climatic conditions in the field.


The Rhodobacter sphaeroides 2.4.1 rho gene: expression and genetic analysis of structure and function.
The gene which encodes transcription termination factor Rho from Rhodobacter sphaeroides 2.4.1, the gram-negative facultative photosynthetic bacterium, has been cloned and sequenced. The deduced protein shows a high level of sequence similarity to other bacterial Rho factors, especially those from proteobacteria. However, several amino acid substitutions in the conserved ATP-binding site have been identified. When expressed in Escherichia coli, the R. sphaeroides rho gene relieves Rho-dependent polarity of the trp operon, indicating interference with the transcription termination machinery of E. coli. A truncated version of R. sphaeroides Rho (Rho') is toxic to a bacterium related to R. sphaeroides, Paracoccus denitrificans, and is lethal to R. sphaeroides. We suggest that toxicity is due to the ability of Rho' to form inactive heteromers with the chromosomally encoded intact Rho. We localized a minimal amino acid sequence within Rho which appears to be critical for its toxic effect and which we believe may be involved in protein-protein interactions. This region was previously reported to be highly conserved and unique among various Rho proteins. The lethality of rho' in R. sphaeroides together with our inability to obtain a null mutation in rho suggests that Rho-dependent transcription termination is essential in R. sphaeroides. This is analogous to what is observed for gram-negative E. coli and contrasts with what is observed for gram-positive Bacillus subtilis. The genetic region surrounding the R. sphaeroides rho gene has been determined and found to be different compared with those of other bacterial species. rho is preceded by orf1, which encodes a putative integral membrane protein possibly involved in cytochrome formation or functioning. The gene downstream of rho is homologous to thdF, whose product is involved in thiophene and furan oxidation.


Early recurrent feedback facilitates visual object recognition under challenging conditions.
Standard models of the visual object recognition pathway hold that a largely feedforward process from the retina through inferotemporal cortex leads to object identification. A subsequent feedback process originating in frontoparietal areas through reciprocal connections to striate cortex provides attentional support to salient or behaviorally-relevant features. Here, we review mounting evidence that feedback signals also originate within extrastriate regions and begin during the initial feedforward process. This feedback process is temporally dissociable from attention and provides important functions such as grouping, associational reinforcement, and filling-in of features. Local feedback signals operating concurrently with feedforward processing are important for object identification in noisy real-world situations, particularly when objects are partially occluded, unclear, or otherwise ambiguous. Altogether, the dissociation of early and late feedback processes presented here expands on current models of object identification, and suggests a dual role for descending feedback projections.


Maximal oxidative capacity during exercise is associated with skeletal muscle fuel selection and dynamic changes in mitochondrial protein acetylation.
Maximal exercise-associated oxidative capacity is strongly correlated with health and longevity in humans. Rats selectively bred for high running capacity (HCR) have improved metabolic health and are longer-lived than their low-capacity counterparts (LCR). Using metabolomic and proteomic profiling, we show that HCR efficiently oxidize fatty acids (FAs) and branched-chain amino acids (BCAAs), sparing glycogen and reducing accumulation of short- and medium-chain acylcarnitines. HCR mitochondria have reduced acetylation of mitochondrial proteins within oxidative pathways at rest, and there is rapid protein deacetylation with exercise, which is greater in HCR than LCR. Fluxomic analysis of valine degradation with exercise demonstrates a functional role of differential protein acetylation in HCR and LCR. Our data suggest that efficient FA and BCAA utilization contribute to high intrinsic exercise capacity and the health and longevity benefits associated with enhanced fitness.


Cholesterol accumulation in tissues of the Niemann-pick type C mouse is determined by the rate of lipoprotein-cholesterol uptake through the coated-pit pathway in each organ.
Niemann-Pick type C (NPC) disease is associated with the accumulation of unesterified cholesterol in nearly all tissues and with progressive neurodegeneration. A murine model of this disease, the NPC mouse, was used to determine whether this sequestered cholesterol represented sterol carried in low density lipoprotein (LDL) and chylomicrons (CMs) taken up into the tissues through the coated-pit pathway. By 7 weeks of age, the sterol pool in the NPC mice had increased from 2,165 to 5,669 mg/kg body weight because of the daily sequestration of 67 mg of cholesterol per kg in the various organs. This was 7-fold greater than the rate of accumulation in control mice. The rate of LDL clearance in the NPC mouse was normal (523 ml/day per kg) and accounted for the uptake of 78 mg/day per kg of cholesterol in LDL whereas 8 mg/day per kg was taken up from CMs. Deletion of the LDL receptor in NPC mice altered the concentration of unesterified cholesterol in every organ in a manner consistent with the changes also observed in the rate of LDL cholesterol uptake in those tissues. Similarly, altering the flow of cholesterol to the liver through the CM pathway changed the concentration of unesterified cholesterol in that organ. Together, these observations strongly support the conclusion that, in NPC disease, it is cholesterol carried in LDL and CMs that is sequestered in the tissues and not sterol that is newly synthesized and carried in high density lipoprotein.


Epidemiological analysis defining concurrent outbreaks of Serratia marcescens and methicillin-resistant Staphylococcus aureus in a neonatal intensive-care unit.
To describe the epidemiology, interventions, and molecular typing methods used during the investigation and control of concurrent outbreaks of Serratia marcescens and methicillin-resistant Staphylococcus aureus (MRSA) infections in a neonatal intensive-care unit (NICU). A 206-bed women's and infants' hospital with a 48-bed NICU. A 22-week, prospective, descriptive study of all NICU infants with S marcescens or MRSA infection or colonization. Repetitive polymerase chain reaction (rep PCR) and pulsed-field gel electrophoresis (PFGE), respectively, were applied to the typing of S marcescens and MRSA isolates. Infants with S marcescens or MRSA infection or colonization were placed in isolation; all other infants were cohorted. A multidisciplinary task force implemented education for all hospital and medical staff regarding policies essential for outbreak control. Changes in physical setting and patient contact procedure were required to promote adherence to existing policies. Two premature infants had S marcescens infection, and five were colonized; rep PCR verified that both invasive and three of five colonizing isolates were related genotypically. Five bacteremic and 10 MRSA-colonized infants were identified; PFGE confirmed that 12 of the isolates had similar electrophoretic patterns. S marcescens infection was eliminated from the NICU 3 weeks after interventions were initiated. MRSA infections also were eliminated, and MRSA colonization fell to below pre-outbreak rates within 8 weeks. Despite a 100% increase in NICU patient days per month during the subsequent 2 years, no further clusters of S marcescens or MRSA infection have occurred. Concurrent outbreaks of S marcescens and MRSA in an NICU were confirmed by genotyping of strains. Control was achieved by isolation and cohorting of patients and strict adherence to NICU policies and procedures.


Granular cell tumor in a premenstrual female breast.
Granular cell tumor is an exceedingly rare pediatric breast mass, derived from Schwann cells which are most commonly observed in the oral cavity, skin, and subcutaneous tissue. When they occur in the breast, they can mimic intrinsic breast masses. Most cases are benign, but malignant cases have been reported. We present a case of a premenstrual, African-American 9 year old female with a painful right breast mass originally felt to be an epidermal inclusion cyst. An ultrasound was performed 17 months after original presentation which demonstrated a 1 cm well-circumscribed solid ovoid mass. Despite the relatively small size and benign imaging appearance of the mass, surgical resection was performed for symptom relief given the associated pain. This is the first known case of granular cell tumor of the breast in a premenstrual female.


[Intervention to reduce adolescents sexual risk behaviors: a randomized controlled trial].
To test the efficacy of a behavioral intervention designed to decrease risk sexual behaviors for HIV/AIDS and unplanned pregnancies in Mexican adolescents. Randomized controlled trial with four follow ups; 832 adolescents recruited from high schools, age 14-17, were randomly assigned to the experimental or control group. The six hour intervention used active learning strategies, and was delivered in two sessions on two consecutive Saturdays. The study was carried out in Monterrey, Mexico, 2002-2005. GEE analysis indicated no differences in sexual relationships intentions between the two conditions, however, the experimental group had higher intentions to use condoms and contraceptives (mean differences 0.15 and 0.16, CI 95%) in the next three months, as compared with the control group. Theoretical variables, such as control beliefs, were significant mediators of the intervention. The behavioral intervention represents an important effort in promoting safe sexual behaviors among Mexican adolescents.


Social olfaction in marine mammals: wild female Australian sea lions can identify their pup's scent.
Historically, anatomical evidence has suggested that marine mammals are anosmic or at best microsmatic, i.e. absent or reduced olfactory capabilities. However, these neuroanatomical considerations may not be appropriate predictors for the use of olfaction in social interactions. Observations suggest that pinnipeds may use olfaction in mother-pup interactions, accepting or rejecting pups after naso-nasal contact. Such maternal-offspring recognition is a favourable area for investigating the involvement of odours in social recognition and selectivity, as females are evolutionarily constrained to direct resources to filial young. However, there is no experimental, morphological or chemical evidence to date for the use of olfaction in social contexts and for individual odour recognition abilities in pinnipeds. Here, we report unequivocal evidence that Australian sea lion (Neophoca cinerea) females can differentiate between the odour of their own pup and that of another, in the absence of any other distinguishing cues. This study demonstrates individual olfactory recognition in a free-ranging wild mammal and is clear evidence of the social function of olfaction in a marine mammal.


Occurrence and expression of glutathione-S-transferase-encoding bphK genes in Burkholderia sp. strain LB400 and other biphenyl-utilizing bacteria.
The gene bphK of Burkholderia sp. strain LB400 has previously been shown to be located within the bph locus, which specifies the degradation of biphenyl (BP) and chlorobiphenyls, and to encode a glutathione S-transferase (GST) which accepts 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. The specific physiological role of this gene is not known. It is now shown that the gene is expressed in the parental organism and that GST activity is induced more than 20-fold by growth of the strain on BP relative to succinate when these compounds serve as sole carbon source. Approximately the same induction factor was observed for 2,3-dihydroxybiphenyl 1,2-dioxygenase activity, which is encoded by the 5'-adjacent bphC gene. This suggests that the expression of bphK is coregulated with the expression of genes responsible for the catabolism of BP. A bphK probe detected only a single copy of the gene in strain LB400. A spontaneous BP- mutant of the organism neither gave a signal with the bphK probe nor showed CDNB-accepting GST activity, suggesting that this activity is solely encoded by bphK. Complementation of the mutant with a bph gene cluster devoid of bphK restored the ability to grow on BP, indicating that bphK is not essential for utilization of this carbon source. BphK activity proved to be almost unaffected by up to 100-fold differences in proton concentration or ionic strength. The enzyme showed a narrow range with respect to a variety of widely used electrophilic GST substrates, accepting only CDNB. A number of established laboratory strains as well as novel isolates able to grow on BP as sole carbon and energy source were examined for BphK activity and the presence of a bphK analogue. CDNB assays, probe hybridizations and PCR showed that several, but not all, BP degraders possess this type of GST activity and/or a closely related gene. In all bacteria showing BphK activity, this was induced by growth on BP as sole carbon source, although activity levels differed by up to 10-fold after growth on BP and by up to 60-fold after growth on succinate. This resulted in a variation of induction factors between 2 and 30. In the majority of bphK+ bacteria examined, the gene appeared to be part of LB400-like bph gene clusters. DNA sequencing revealed almost complete identity of bphK genes from five different bph gene clusters. These results suggest that bphK genes, although not essential, fulfill a strain-specific function related to the utilization of BPs by their host organisms. The usefulness of BphK as a reporter enzyme for monitoring the expression of catabolic pathways is discussed.


[Expression of different HIV-1 phenotypic subpopulations through the natural history of the infection].
Multiple viral subpopulations coexist in an HIV infected patient with dynamics of selection established between them. In order to get insight on the phenotype of these subpoblations, and its relation with disease progression, we have studied the biological variability of HIV-1 in 113 patients. Variability was related with CD4+ T lymphocyte counts, clinical status, way of viral transmission and antiretroviral treatment. 113 patients (80 adults and 33 children) were studied for HIV-1 isolation in cocultures of infected and non infected lymphocytes. Viral replication was evaluated as rapid (R)/slow (S) or high (H)/low (L). Syncytia formation was estimated in MT2 cell line (SI/NSI). The tropism toward lymphocytes and monocytes (LM) was studied on H9 and U937 cell lines. Up to 86.7% of viral isolates were R, 56.6% were H and 49.6% were SI. These percentages increased with disease progression. Eight viral strains were R/H/NSI cocultivated in MT2 cells and SI in cocultured lymphocytes (NSI/SI), which may be considered as a new phenotype. All the SI isolates and all the R/H (SI and NSI) isolates were LM. Three categories were established: R/H/SI/LM, R/H/NSI/LM and S/L/NSI/NLM. The first two categories corresponded to patients with CD4+ T lymphocytes <200 x 10(6)/I (56%, 50%). The third category corresponded to patients with > 500 x 10(6)/I (53.3%). Viral replication and SI phenotype, independently, are useful markers for severity of HIV infection. The biological differences among NSI of the 3 viral phenotype categories, including the new subgroup NSI/SI, may indicate the existence of more pathogenic NSI subpopulations.


Analysis of the primary structure and promoter function of a pyruvate decarboxylase gene (PDC1) from Saccharomyces cerevisiae.
The PDC1 gene of Saccharomyces cerevisiae, encoding pyruvate decarboxylase was sequenced. The gene contains an open reading frame of 1647 base pairs. The codon usage shows the same strong bias as found for some other glycolytic enzymes. Transcription starts mainly at -30 and terminates 100 base pairs downstream of the termination codon. In some strains a second termination site, 46 base pairs upstream of the stop codon was observed. The function of the promoter region was analyzed by fusion to the bacterial structural gene encoding beta-lactamase (bla). On multicopy plasmid or integrated in the genome, the expression of the bla gene showed the regulation of the authentic PDC1 gene.


Regulation of human CYP11B2 and CYP11B1: comparing the role of the common CRE/Ad1 element.
In humans, the final steps in corticosteroid production results from the activity of aldosterone synthase in the glomerulosa and 11beta-hydroxylase in the fasciculata. The regional expression of these isozymes is believed to result from transcriptional regulation of the aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes. Previous studies suggest that the primary cis-element needed for agonist enhanced transcription of the CYP11B genes shares high sequence similarity to a consensus cAMP Response Element (CRE). Here the role of the CRE/Adl was studied. Reporter constructs prepared with the 5'flanking DNA of hCYP11B2 and hCYP11B1 were transfected into NCI-H295R (H295R) adrenocortical tumor cells. Both hCYP11B2 and hCYP11B1 driven reporter constructs responded in a similar manner to treatment with angiotensin II, potassium, dbcAMP, or forskolin. Mutation of the hCYP11B1 CRE/Adl element decreased basal reporter expression and decreased response to agonist. Mutation of the hCYP11B2 CRE/Adl element caused a loss of basal expression but retained response to agonist suggesting a role for other cis-elements in hormonal regulation of hCYP11B2. In addition, both cis-elements were able to form complexes with in vitro prepared CRE binding (CREB) protein, activating transcription factor (ATF)-1 and ATF-2 in mobility shift assays. However, only the ATF-2 complex migrated similarly to a complex seen using H295R nuclear extract. Taken together these data suggest that the CRE/Adl element plays an important role in the transcriptional regulation of both hCYP11B genes but does not play an important role in the regional distribution of the two isozymes within the adrenal.


Michelson-Morley analogue for electrons using trapped ions to test Lorentz symmetry.
All evidence so far suggests that the absolute spatial orientation of an experiment never affects its outcome. This is reflected in the standard model of particle physics by requiring all particles and fields to be invariant under Lorentz transformations. The best-known tests of this important cornerstone of physics are Michelson-Morley-type experiments verifying the isotropy of the speed of light. For matter, Hughes-Drever-type experiments test whether the kinetic energy of particles is independent of the direction of their velocity, that is, whether their dispersion relations are isotropic. To provide more guidance for physics beyond the standard model, refined experimental verifications of Lorentz symmetry are desirable. Here we search for violation of Lorentz symmetry for electrons by performing an electronic analogue of a Michelson-Morley experiment. We split an electron wave packet bound inside a calcium ion into two parts with different orientations and recombine them after a time evolution of 95 milliseconds. As the Earth rotates, the absolute spatial orientation of the two parts of the wave packet changes, and anisotropies in the electron dispersion will modify the phase of the interference signal. To remove noise, we prepare a pair of calcium ions in a superposition of two decoherence-free states, thereby rejecting magnetic field fluctuations common to both ions. After a 23-hour measurement, we find a limit of h × 11 millihertz (h is Planck's constant) on the energy variations, verifying the isotropy of the electron's dispersion relation at the level of one part in 10(18), a 100-fold improvement on previous work. Alternatively, we can interpret our result as testing the rotational invariance of the Coulomb potential. Assuming that Lorentz symmetry holds for electrons and that the photon dispersion relation governs the Coulomb force, we obtain a fivefold-improved limit on anisotropies in the speed of light. Our result probes Lorentz symmetry violation at levels comparable to the ratio between the electroweak and Planck energy scales. Our experiment demonstrates the potential of quantum information techniques in the search for physics beyond the standard model.


Epigenetic abnormalities associated with a chromosome 18(q21-q22) inversion and a Gilles de la Tourette syndrome phenotype.
Gilles de la Tourette syndrome (GTS) is a potentially debilitating neuropsychiatric disorder defined by the presence of both vocal and motor tics. Despite evidence that this and a related phenotypic spectrum, including chronic tics (CT) and Obsessive Compulsive Disorder (OCD), are genetically mediated, no gene involved in disease etiology has been identified. Chromosomal abnormalities have long been proposed to play a causative role in isolated cases of GTS spectrum phenomena, but confirmation of this hypothesis has yet to be forthcoming. We describe an i(18q21.1-q22.2) inversion in a patient with CT and OCD. We have fine mapped the telomeric aspect of the rearrangement to within 1 Mb of a previously reported 18q22 breakpoint that cosegregated in a family with GTS and related phenotypes. A comprehensive characterization of this genomic interval led to the identification of two transcripts, neither of which was found to be structurally disrupted. Analysis of the epigenetic characteristics of the region demonstrated a significant increase in replication asynchrony in the patient compared to controls, with the inverted chromosome showing delayed replication timing across at least a 500-kb interval. These findings are consistent with long-range functional dysregulation of one or more genes in the region. Our data support a link between chromosomal aberrations and epigenetic mechanisms in GTS and suggest that the study of the functional consequences of balanced chromosomal rearrangements is warranted in patients with phenotypes of interest, irrespective of the findings regarding structurally disrupted transcripts.


The Misclassification of Diffuse Gliomas: Rates and Outcomes.
The integrated histopathologic and molecular diagnoses of the 2016 WHO classification of central nervous system tumors have revolutionized patient care by improving diagnostic accuracy and reproducibility; however, the frequency and consequences of misclassification of histologically diagnosed diffuse gliomas are unknown. Patients with newly diagnosed ICD-O-3 (International Classification of Diseases) histologically encoded diffuse gliomas from 2010-2015 were identified from the National Cancer Database, the misclassification rates and overall survival (OS) of which were assessed by WHO grade and 1p/19q status. In addition, misclassification rates by isocitrate dehydrogenase (IDH), ATRX, and p53 statuses were examined in an analogous multi-institutional cohort of registry-encoded diffuse gliomas. Of 74,718 patients with diffuse glioma, only 74.4% and 78.8% of molecularly characterized WHO grade II and III oligodendrogliomas were in fact 1p/19q-codeleted. In addition, 28.9% and 36.8% of histologically encoded grade II and III "oligoastrocytomas", and 6.3% and 8.8% of grade II and III astrocytomas had 1p/19q-codeletion, thus molecularly representing oligodendrogliomas if also IDH mutant. OS significantly depended on accurate WHO grading and 1p/19q status. On the basis of 1p/19q, IDH, ATRX, and p53, the misclassification rates of histologically encoded oligodendrogliomas, astrocytomas, and glioblastomas are approximately 21%-35%, 6%-9%, and 9%, respectively; with significant clinical implications. Our findings suggest that when compared with historical histology-only classified data, in national registry, as well as, institutional databases, there is the potential for false-positive results in contemporary trials of molecularly classified diffuse gliomas, which could contribute to a seemingly positive phase II trial (based on historical comparison) failing at the phase III stage. Critically, findings from diffuse glioma clinical trials and historical cohorts using prior histology-only WHO schemes must be cautiously reinterpreted.


The problem-oriented approach to sports injury evaluations.
The problem-oriented approach to sports injury evaluations is used successfully throughout the United States by various health care providers, and can be used by certified athletic trainers to enhance the evaluation and management of sports injuries. The problem-oriented medical record is used successfully to provide effective communications and as a learning tool in health-related education. In this paper, I present a problem-oriented system for evaluating and keeping medical records on sports injuries. The process of collecting data through interviews and organizing that information is the focus.


Bartonella henselae in small Indian mongooses (Herpestes auropunctatus) from Grenada, West Indies.
Many mammals are established hosts for the vector borne bacterial genus, Bartonella. Small Indian mongooses (Herpestes auropunctatus) have only been reported as a possible host for Bartonella henselae in southern Japan. Confirming Bartonella presence in mongooses from other regions in the world may support their role as potential reservoirs of this human pathogen. Specifically, documenting Bartonella in Caribbean mongooses would identify a potential source of zoonotic risk with mongoose-human contact in the New World. Using serological and molecular techniques, we investigated B. henselae DNA and specific antibody prevalence in 171 mongooses from all six parishes in Grenada, West Indies. Almost a third (32.3%, 54/167) of the tested mongooses were B. henselae seropositive and extracted DNA from 18/51 (35.3%) blood pellets were PCR positive for the citrate synthase (gltA) and/or the β subunit of RNA polymerase (rpoB) genes. All sequences were identical to B. henselae genotype I, as previously reported from Japan. This study confirms the role of small Indian mongooses as a natural reservoir of B. henselae in the New World.


Species specific differences in use of ANP32 proteins by influenza A virus.
Influenza A viruses (IAV) are subject to species barriers that prevent frequent zoonotic transmission and pandemics. One of these barriers is the poor activity of avian IAV polymerases in human cells. Differences between avian and mammalian ANP32 proteins underlie this host range barrier. Human ANP32A and ANP32B homologues both support function of human-adapted influenza polymerase but do not support efficient activity of avian IAV polymerase which requires avian ANP32A. We show here that the gene currently designated as avian ANP32B is evolutionarily distinct from mammalian ANP32B, and that chicken ANP32B does not support IAV polymerase activity even of human-adapted viruses. Consequently, IAV relies solely on chicken ANP32A to support its replication in chicken cells. Amino acids 129I and 130N, accounted for the inactivity of chicken ANP32B. Transfer of these residues to chicken ANP32A abolished support of IAV polymerase. Understanding ANP32 function will help develop antiviral strategies and aid the design of influenza virus resilient genome edited chickens.


Cloning of SEC61 homologues from Schizosaccharomyces pombe and Yarrowia lipolytica reveals the extent of functional conservation within this core component of the ER translocation machinery.
The Sec61 protein is required for protein translocation across the ER membrane in both yeast and mammals and is found in close association with polypeptides during their membrane transit. In Saccharomyces cerevisiae Sec61p is essential for viability and the extent of sequence similarity between the yeast and mammalian proteins (55% sequence identity) suggests that the role of Sec61p in the translocation mechanism is likely to be conserved. In order to further our understanding of the structure and function of Sec61p we have cloned homologues from both Schizosaccharomyces pombe and Yarrowia lipolytica. The S. pombe gene comprises six exons encoding a 479 residue protein which we have immunolocalised to the endoplasmic reticulum. Sequence comparisons reveal that S. pombe Sec61p is 58.6% identical to that of S. cerevisiae. The deduced amino acid sequence of the Y. lipolytica protein shares 68.8% sequence identity with S. cerevisiae Sec61p. Gene disruption studies have shown that the SEC61 is required for viability in both S. pombe and Y. lipolytica demonstrating that the essential nature of this protein is not unique to S. cerevisiae. Moreover, heterologous complementation studies indicate that the Y. lipolytica SEC61 gene can complement a null mutation in S. cerevisiae. Sequence comparisons between the various eukaryotic Sec61p homologues reveal a number of highly conserved domains, including several transmembrane sequences and the majority of cytosolic loops. These comparisons will provide an important framework for the detailed analysis of interactions between Sec61p and other components of the translocation machinery and between Sec61p and translocating polypeptide chains.


Challenges with robotic low anterior resection.
Dramatic improvements in the local recurrence rate of patients with rectal cancer have been observed after the introduction of the embriologically-based concept of total mesorectal excision by Heald more than 30 years ago. During the last decades, advances in multimodal treatment have further contributed to improve outcomes, but surgery still play a major role. Laparoscopic surgery for rectal cancer has been validated in randomized controlled trials to be oncologically as safe and effective as the open approach with better short-term postoperative outcomes. Nevertheless, laparoscopic low anterior resection continues to be challenging because of technical constraints and a steep learning curve. Robotic surgery may potentially offer significant advantages in rectal cancer surgery thanks to its technological features. This paper summarizes the current available evidence and highlights the most challenging aspects of robotic low anterior resection, with supporting data from the literature and from the authors' nearly ten-year experience in the field.


The effect of antioxidant therapy on colonic inflammation in the rat.
Under normal physiological conditions, chemical and antioxidant defenses protect tissues from the damaging effects of reactive oxygen metabolites (ROM). It has been proposed that ROMs are involved in the development of tissue injury in many inflammatory diseases and also in patients with colitis. In the present study we aimed to investigate the effects of antioxidant therapy on the extent of colonic inflammation and ROM levels in the injured tissues in a trinitrobenzene sulfonic acid-induced colitis model in the rat. Sprague-Dawley rats were pretreated with the antioxidants superoxide dismutase (30,000 U/kg s.c.) or catalase (400,000 U/kg s.c.) prior to induction of colitis and they were decapitated 24 h (acute group) or 6 days (chronic group) after the induction of colitis (each group consists of eight to ten rats). Pretreatment with the antioxidants reduced the macroscopic damage score significantly in both acute and chronic groups compared with untreated colitis groups, whereas they reduced the microscopic damage score and colonic wet weight only in the chronic group. The chemiluminescence assay - a technique to assess the presence of reactive oxygen species in the tissues - values of the groups pretreated with the antioxidants showed a tendency to decrease compared with the untreated colitis group, but they were not statistically significant. Based on these findings, pretreatment with the antioxidants superoxide dismutase or catalase has beneficial effects on the extent of colonic inflammation, particularly in the chronic period, and this may support the importance of antioxidant therapy to reduce the severity of inflammatory bowel disease in humans.


Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease.
Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ1-42), total-tau (t-tau), and phosphorylated tau (p-tau181p), as well as with positron emission tomography (PET) using [(11)C]Pittsburgh compound-B ([(11)C]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [(11)C]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD. To determine concordance and classification accuracy of CSF biomarkers and [(11)C]PIB PET in a cohort of patients with MCI and AD. 68 patients (MCI, n = 33; AD, n = 35) underwent [(11)C]PIB PET and CSF sampling. Cutoffs of >1.41 ([(11)C]PIB), <450 pg/mL-and a more lenient cutoff of 550 pg/mL-(Aβ1-42), <6.5 (Aβ1-42/p-tau181p), and 1.14 (Aβ1-42/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI). Concordance between [(11)C]PIB and Aβ1-42 was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using Aβ1-42 <550 pg/mL, or Aβ1-42 to tau ratios. Logistic regression showed that classification accuracy of [(11)C]PIB, between sMCI and pMCI, was superior to Aβ1-42 (73% versus 58%), Aβ1-42/t-tau (63%), and Aβ1-42/p-tau181p (65%). In the present study, [(11)C]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of Aβ1-42 or Aβ1-42/tau. Discordance between PET and CSF markers for Aβ1-42 suggests they cannot be used interchangeably, as is currently the case.


Proteome adaptations in Ethe1-deficient mice indicate a role in lipid catabolism and cytoskeleton organization via post-translational protein modifications.
Hydrogen sulfide is a physiologically relevant signalling molecule. However, circulating levels of this highly biologically active substance have to be maintained within tightly controlled limits in order to avoid toxic side effects. In patients suffering from EE (ethylmalonic encephalopathy), a block in sulfide oxidation at the level of the SDO (sulfur dioxygenase) ETHE1 leads to severe dysfunctions in microcirculation and cellular energy metabolism. We used an Ethe1-deficient mouse model to investigate the effect of increased sulfide and persulfide concentrations on liver, kidney, muscle and brain proteomes. Major disturbances in post-translational protein modifications indicate that the mitochondrial sulfide oxidation pathway could have a crucial function during sulfide signalling most probably via the regulation of cysteine S-modifications. Our results confirm the involvement of sulfide in redox regulation and cytoskeleton dynamics. In addition, they suggest that sulfide signalling specifically regulates mitochondrial catabolism of FAs (fatty acids) and BCAAs (branched-chain amino acids). These findings are particularly relevant in the context of EE since they may explain major symptoms of the disease.


Detection of Legionnaires disease bacteria by direct immunofluorescent staining.
Antisera and fluorescein isothiocyanate conjugates prepared for five strains of the Legionnaires bacteria were tested in both homologous and heterologous staining reactions with 10 isolates of the organism from patients in seven geographic areas. The strains were related but not identical as judged by the results of direct immunofluorescence staining. The conjugates were successfully used to detect Legionnaires disease bacteria in Formalin-fixed lung scrapings, in histological sections, and in fresh lung tissue obtained at biopsy or autopsy. In addition, the labeled antibodies are valuable for staining suspected cultures of the bacterium and for searching for the source of these organisms in soil, water, and other environmental niches. The reagents are highly specific for detecting the Legionnaires organism in clinical specimens.


Determinants of non-nociceptive pain in Rheumatoid Arthritis.
Features suggestive of neuropathic pain (NP) have been described in RA in addition to nociceptive pain. We aimed to determine the clinical predictors of NP in RA patients and study its association with radiographic structural damage. Cross-sectional study was performed with RA patients followed at our Rheumatology department. Patients with diagnosed neuropathy of other origin, non-RA related risk factors for NP (e.g. diabetes mellitus) or fibromyalgia according to expert opinion were excluded. Demographic and clinical data were collected and disease activity/functional measures were evaluated. Two questionnaires were applied to assess NP: the Leeds Assessment of Neuropathic Symptoms (LANSS) and the painDETECT questionnaire (PDQ). Radiographs performed in up to 12 months before/after the evaluation were classified according to the modified van der Heijde Sharp´s method. Univariate and multivariate logistic regression were performed to identify the predictors of NP. 112 patients were included. 86 (77%) were women, with a mean (SD) age of 55.1 (10.8) years and median disease duration of 13 [2-41] years. 45 (40%) patients had NP by the LANSS (≥12) and 28% had a possible/likely NP in the PDQ (≥13). Female sex was predictive of NP by both tests and disease duration was inversely associated with LANSS NP. After adjusting for those two variables, pain VAS and TJC were positive predictors of NP by both tests. The same was not true for SJC, ESR or CRP levels. DAS28-CRP was significantly associated with PDQ NP, losing its statistical significance after adjustment for TJC and pain VAS. The HAQ score increased the odds of NP for both tests, independently of DAS 28-CRP. Positivity for ACPA and previous/current hydroxychloroquine treatment had lower odds of NP. 90 patients performed radiographic evaluation. Joint narrowing score was a significant negative predictor of LANSS NP. After adjusting for global radiographic score, current methotrexate treatment had lower odds of LANSS NP and previous/current leflunomide was a positive predictor of NP by both tests. NP was associated with disease activity/functional scores but not with objective inflammatory measures. Greater structural damage, increased disease duration and ACPA positivity did not seem to increase the odds of NP. Possible association of NP and underlying csDMARD treatment was uncovered.


KRAS status predicted by pretreatment MRI radiomics was associated with lung metastasis in locally advanced rectal cancer patients.
Mutated KRAS may indicate an invasive nature and predict prognosis in locally advanced rectal cancer (LARC). We aimed to establish a radiomic model using pretreatment T2W MRIs to predict KRAS status and explore the association between the KRAS status or model predictions and lung metastasis. In this retrospective multicentre study, LARC patients from two institutions between January 2012 and January 2019 were randomly divided into training and testing cohorts. Least absolute shrinkage and selection operator (LASSO) regression and the support vector machine (SVM) classifier were utilized to select significant radiomic features and establish a prediction model, which was validated by radiomic score distribution and decision curve analysis. The association between the model stratification and lung metastasis was investigated by Cox regression and Kaplan‒Meier survival analysis; the results were compared by the log-rank test. Overall, 103 patients were enrolled (73 and 30 in the training and testing cohorts, respectively). The median follow-up was 38.1 months (interquartile range: 26.9, 49.4). The radiomic model had an area under the curve (AUC) of 0.983 in the training cohort and 0.814 in the testing cohort. Using a cut-off of 0.679 defined by the receiver operating characteristic (ROC) curve, patients with a high radiomic score (RS) had a higher risk for lung metastasis (HR 3.565, 95% CI 1.337, 9.505, p = 0.011), showing similar predictive performances for the mutant and wild-type KRAS groups (HR 3.225, 95% CI 1.249, 8.323, p = 0.016, IDI: 1.08%, p = 0.687; NRI 2.23%, p = 0.766). We established and validated a radiomic model for predicting KRAS status in LARC. Patients with high RS experienced more lung metastases. The model could noninvasively detect KRAS status and may help individualize clinical decision-making.


In the Alphaproteobacterium Hyphomicrobium denitrificans SoxR Serves a Sulfane Sulfur-Responsive Repressor of Sulfur Oxidation.
In organisms that use reduced sulfur compounds as alternative or additional electron donors to organic compounds, transcriptional regulation of genes for enzymes involved in sulfur oxidation is needed to adjust metabolic flux to environmental conditions. However, little is known about the sensing and response to inorganic sulfur compounds such as thiosulfate in sulfur-oxidizing bacteria. In the Alphaproteobacterium Hyphomicrobium denitrificans, one strategy is the use of the ArsR-SmtB-type transcriptional regulator SoxR. We show that this homodimeric repressor senses sulfane sulfur and that it is crucial for the expression not only of sox genes encoding the components of a truncated periplasmic thiosulfate-oxidizing enzyme system but also of several other sets of genes for enzymes of sulfur oxidation. DNA binding and transcriptional regulatory activity of SoxR are controlled by polysulfide-dependent cysteine modification. The repressor uses the formation of a sulfur bridge between two conserved cysteines as a trigger to bind and release DNA and can also form a vicinal disulfide bond to orchestrate a response to oxidizing conditions. The importance of the sulfur bridge forming cysteines was confirmed by site-directed mutagenesis, mass spectrometry, and gel shift assays. In vivo, SoxR interacts directly or indirectly with a second closely related repressor, sHdrR.


Evolutionary approaches to understanding the hypnotic experience.
Using Tinbergen's 4 why questions of causation, development, evolution, and function, the authors examine hypnosis from a larger, evolutionary perspective. Reasoning by analogy, they seek to view hypnosis in terms of an action pattern that represents a self-contained behavioral program although not as rigid as seen in lower organisms. In humans, such a program develops within the context of a long developmental sequence emphasizing social connections, imitation of significant figures, and the use of linguistic symbols to regulate both internal and external processes and actions. In terms of a mechanism, the authors speculate on the involvement of the cingulate cortex in achieving in hypnosis the experience of autonomous actions or analgesic sensory processes. Finally, they point to the fact that hypnotizability is associated with an ability to reduce the experience of pain, modulate the immune system, and achieve greater benefits of psychosocial therapies as a functional significance of the hypnotic experience.


Water-Borne Nanocoating for Rapid Inactivation of SARS-CoV-2 and Other Viruses.
The rise in coronavirus variants has resulted in surges of the disease across the globe. The mutations in the spike protein on the surface of the virion membrane not only allow for greater transmission but also raise concerns about vaccine effectiveness. Preventing the spread of SARS-CoV-2, its variants, and other viruses from person to person via airborne or surface transmission requires effective inactivation of the virus. Here, we report a water-borne spray-on coating for the complete inactivation of viral particles and degradation of their RNA. Our nanoworms efficiently bind and, through subsequent large nanoscale conformational changes, rupture the viral membrane and subsequently bind and degrade its RNA. Our coating completely inactivated SARS-CoV-2 (VIC01) and an evolved SARS-CoV-2 variant of concern (B.1.1.7 (alpha)), influenza A, and a surrogate capsid pseudovirus expressing the influenza A virus attachment glycoprotein, hemagglutinin. The polygalactose functionality on the nanoworms targets the conserved S2 subunit on the SARS-CoV-2 virion surface spike glycoprotein for stronger binding, and the additional attachment of guanidine groups catalyze the degradation of its RNA genome. Coating surgical masks with our nanoworms resulted in complete inactivation of VIC01 and B.1.1.7, providing a powerful control measure for SARS-CoV-2 and its variants. Inactivation was further observed for the influenza A and an AAV-HA capsid pseudovirus, providing broad viral inactivation when using the nanoworm system. The technology described here represents an environmentally friendly coating with a proposed nanomechanical mechanism for inactivation of both enveloped and capsid viruses. The functional nanoworms can be easily modified to target viruses in future pandemics, and is compatible with large scale manufacturing processes.


A participatory physical activity intervention in preschools: a cluster randomized controlled trial.
Previous studies on physical activity interventions in preschools have reported limited effectiveness. Participatory community-based approaches hold promise for increasing intervention effectiveness and involving parents as key stakeholders in a sustainable way. To assess whether a participatory parent-focused approach using parents as agents of behavioral change enhances the efficacy of a preschool physical activity (PA) intervention. Two-armed, cluster-RCT with preschool as unit of randomization and children as unit of analysis. 39 South German preschools applying for an existing state-sponsored PA program with 826 children (52% boys, aged 5.0±0.2 years), with 441 allocated to the intervention arm. Control preschools received a state-sponsored program consisting of twice-weekly gym classes over 6 months. In intervention preschools, this program was augmented by motivating parents to develop and implement their own project ideas for promoting children's PA. Primary outcomes included mean accelerometry counts and time spent in moderate- to vigorous-intensity PA or sedentary behavior. Secondary outcomes were BMI, percentage body fat, quality of life, sleep quality, and general health. Outcomes were measured at baseline and at 6 and 12 months in both study arms (time period: 2008-2010). Using an intention-to-treat-analysis, linear multilevel regression models assessed change over time and across study arms, adjusted for age, gender, season, and preschool location. Analysis was conducted in 2011. In 15 intervention preschools, parents implemented 25 PA projects. Compared with controls, intervention arm children were 11 minutes less sedentary per day (95% CI=5.39, 17.01, p=0.014); had significantly more mean accelerometry counts (1.4 counts/15 seconds [95% CI=0.22, 2.54], p=0.019); and showed benefits in perceived general health and quality of life. All other outcomes showed no difference between study arms. A participatory preschool intervention focusing on parents as agents of behavioral change may be able to promote PA and reduce sedentary behavior in preschoolers. These benefits may go beyond the effects of existing nonparticipatory interventions. This study is registered at clinicaltrials.gov NCT00987532.


Molecular basis for different levels of tet(M) expression in Streptococcus pneumoniae clinical isolates.
Seventy-four unrelated clinical isolates of Streptococcus pneumoniae harboring the tet(M) gene were studied. Seven strains with low tetracycline (Tc) MICs (0.25 to 0.5 μg/ml) were found to harbor truncated tet(M) alleles that were inactivated by different frameshift mutations. In contrast, five strains bore deletions in the tet(M) promoter region, among which four displayed increased Tc MICs (16 to 64 μg/ml). The same promoter mutations were detected in Tc-resistant mutants selected in vitro from various susceptible strains. Sequence analysis revealed that these deletions might impede the formation of the transcriptional attenuator located immediately upstream of tet(M). Expression in Enterococcus faecalis of a tet(M) reporter gene transcribed from these promoter mutants conferred a level of Tc resistance similar to that observed in the parental S. pneumoniae strains. These results show that different levels of Tc susceptibility found in clinical isolates of S. pneumoniae can be explained by frameshift mutations within tet(M) and by alterations of the upstream transcriptional attenuator.


Hepatic iron overload in blacks and whites: a comparative autopsy study.
Genetic susceptibility to iron loading is an important factor in the development of iron overload in Africans. This suggests that persons of African descent may be at risk to develop iron overload with its attendant complications, but relatively little is known about hepatic iron overload among blacks. The aim of this study was to compare the prevalence, histological features, and clinical correlates of hepatic iron overload in a group of autopsied black and white veterans. Hepatic iron concentrations (HIC) were determined on liver tissue from autopsies performed at the John Cochran Veterans Affairs Medical Center during the period 1993 to 1996. Clinical information was obtained from autopsy protocols. Sections from livers in which the HIC exceeded the upper limit of normal were examined histologically. Of 256 specimens, 99 were from blacks (39%), whereas 157 were from whites (61%). Thirty-one blacks (31%) had an elevated HIC versus 44 whites (28%) (ns). In the majority of these cases (18 blacks, 30 whites), the HIC was less than twice the upper limit of normal. Nine of 15 subjects with an HIC greater than twice the upper limit of normal and no evident cause of secondary iron overload were black. The prevalence of mild-to-moderate hepatic iron overload was similar in this group of black and white veterans. Because of the inherent limitations of autopsy studies, prospective assessment of iron stores in healthy blacks is needed to determine more accurately the prevalence and clinical significance of iron overload in this population.


[Prognostic value of dark cells and desmosomes in squamous cell carcinoma of the lung].
An electron microscopic study of 30 cases of squamous cell carcinoma of the lung of varying degree of cell differentiation was aimed at evaluating prognostic significance of ultrastructural features of tumor. A high level of dark cells was found to be associated with poor prognosis whereas the presence of well-formed and multiple cellular contacts (desmosomes) was in direct correlation with survival.


Bivariate segmentation of SNP-array data for allele-specific copy number analysis in tumour samples.
SNP arrays output two signals that reflect the total genomic copy number (LRR) and the allelic ratio (BAF), which in combination allow the characterisation of allele-specific copy numbers (ASCNs). While methods based on hidden Markov models (HMMs) have been extended from array comparative genomic hybridisation (aCGH) to jointly handle the two signals, only one method based on change-point detection, ASCAT, performs bivariate segmentation. In the present work, we introduce a generic framework for bivariate segmentation of SNP array data for ASCN analysis. For the matter, we discuss the characteristics of the typically applied BAF transformation and how they affect segmentation, introduce concepts of multivariate time series analysis that are of concern in this field and discuss the appropriate formulation of the problem. The framework is implemented in a method named CnaStruct, the bivariate form of the structural change model (SCM), which has been successfully applied to transcriptome mapping and aCGH. On a comprehensive synthetic dataset, we show that CnaStruct outperforms the segmentation of existing ASCN analysis methods. Furthermore, CnaStruct can be integrated into the workflows of several ASCN analysis tools in order to improve their performance, specially on tumour samples highly contaminated by normal cells.


[Influence of an additional movement task for the upper extremities on equilibrium maintenance in frontal and sagittal level in standing man].
The postural oscillations of standing man were studied during additional manual motor task that consisted of maintaining of the moving ball in the center of flat box. The movement of a center of pressure (CP) in frontal and sagittal plane were analyzed during standing on stable rigid support and on moving unstable support. The influence of the additional motor task on CP movement depend on level of support stability. Sagittal CP movement increased while the additional task was executed during standing on moving support but it did not when the support was stable. Frontal CP movement decreased when the additional task was executed during standing on stable support but it did not while the support was unstable. Thus execution of the additional motor task execution led to the reduction of efficacy of the postural control on the moving unstable support. This result suggests that the cortical influence on the postural mechanism was stronger during standing on moving support in comparison to the standing on the stable support.


The purification, composition and specificity of wheat-germ agglutinin.
1. The purification of wheat-germ agglutinin from commercial wheat germ is described. By ion-exchange chromatography three active proteins (isolectins) were separated, one of which was examined in detail. 2. The amino acid composition is unusual, as 20% of residues are half-cystine and 21% are glycine. Unlike most lectins and contrary to previous reports, this protein is not a glycoprotein. 3. The efficiency of various saccharides as inhibitors of the agglutination reaction was investigated and from this the specificity of the binding site was inferred. Of monosaccharides, only derivatives of glucose with a 2-acetamido group and a free 3-hydroxyl group are effective inhibitors, and glycosides of either anomeric configuration are bound. Oligosaccharides are much more powerful inhibitors of agglutination than are monosaccharides. 4. It is proposed that the binding site consists of three or four subsites with differing specificities, in a cleft in the molecule resembling that proposed for hen's-egg-white lysozyme.


Pressure-controlled ventilation for the long-range aeromedical transport of patients with burns.
Pressure-controlled ventilation is used to treat smoke inhalation injury to achieve adequate oxygenation and ventilation at lower peak inspiratory pressures. A portable pressure-controlled time-cycled transport ventilator permits this modality to be used in the field. We have examined the safety and efficacy of this ventilator for aeromedical transfer of thermally injured patients. Burn flight teams transported 146 intubated patients with thermal injury to the U.S. Army Burn Center with this system. The average extent of burn injury was 40.45% total body surface area with an average full-thickness injury of 25.29% total body surface area. The transport ventilator was used for 57 rotary wing and 89 fixed wing missions. The study group was transported a total of 86,889 miles without in-flight morbidity, mortality, or failure of ventilation. Arterial blood gas analysis at conclusion of flight demonstrated an arterial pH > or = 7.35 in 85% of the patients, an arterial partial pressure of carbon dioxide < or = 45 torr in 97%, and an arterial partial pressure of oxygen > or = 70 torr in 99%. Pressure-controlled ventilation performed by an experienced transport team with this ventilator is safe and effective for the long-range aeromedical transfer of intubated patients with burns.


Small molecular compounds in development for rheumatoid arthritis.
To provide an update on the development of small molecular compounds as novel therapeutics for the treatment of rheumatoid arthritis. The development of such orally available agents has long been hoped for in rheumatology; in the past year, it has become clear that the expectations are becoming fulfilled. Over the past year, a large number of clinical trials have been published or presented reporting positive therapeutic results with tyrosine kinase inhibitors, a large class of orally available drugs that are also being developed in other medical fields. This class of drugs includes the Janus kinase (JAK) inhibitors, and data on tofacitinib published during the past year have attested to the biologic-like efficacy of this drug and supported its subsequent U.S. Food and Drugs Administration (FDA) approval. Positive clinical trial results have also been reported for several other JAK inhibitors including baricitinib. Several other JAK inhibitors and other small molecular entities are also being developed in studies ranging from preclinical models to large clinical trials. Tyrosine kinase inhibition has emerged as a major new direction in rheumatoid arthritis therapy.


Magnetic-assisted robotic surgery: initial case series of reduced-port robotic prostatectomy.
Minimally invasive radical prostatectomy has rapidly been adopted as the primary means of surgical intervention for prostate cancer. Intraoperative tissue retraction relies on either gravity (via positioning) or use of additional ports and instrumentation. We report the use of a novel trocar-less magnetic retractor system to aid with tissue retraction. Three patients underwent robotic-assisted radical prostatectomy in the treatment of prostatic adenocarcinoma at a single tertiary care institution. All surgeries utilized the Levita™ Magnetic Surgical System (San Mateo, CA) without the use of a fourth robotic arm. The magnetic grasper was used to manipulate the bowel, peritoneum, seminal vesicles, and prostatic capsule. Demographic, pre-operative, and perioperative information were collected. No cases required placement of any additional ports. No intraoperative or immediate post-operative complications occurred. No tissue tearing or subjective tissue damage was noted by placement or removal of the magnetic retractor. Mean operative time was 216 ± 17 min and mean blood loss was 333 ± 57 mL. All patients were discharged to home on post-operative day 1. Robotic prostatectomy utilizing a magnetically anchored tissue grasper appears to be safe and effective while reducing the number of ports (fourth robotic arm) needed. Further investigation is warranted.


Outcomes of second revascularization procedures after stent implantation.
Drug-eluting stents (DES) reduce subsequent revascularization procedures. Although randomized trials have compared DES to brachytherapy and balloon angioplasty (PTCA) for in-stent restenosis, few long-term comparisons have been made to bare metal stents (BMS) or bypass surgery (CABG), particularly following second procedures. We sought to assess the association between revascularization modality and long-term clinical outcomes of patients receiving a second procedure for coronary artery disease. Between January 2000 and July 2005, 4,666 consecutive patients underwent initial coronary stent implantation (DES or BMS). From this population we identified 569 patients undergoing a second target vessel revascularization (DES, BMS, PTCA or CABG). Outcomes were assessed at 6, 12, and 24 months after the second procedure, with follow-up through September 2006. Adjusted cumulative incidence rates were calculated using inverse probability weighted estimators. We found that at 24 months, there were no significant differences in death or myocardial infarction for PTCA, BMS, DES, and CABG (17.7%, 14.9%, 7.5%, and 10.2%, p = 0.26[3dfl]). DES patients had lower rates of death or myocardial infarction or third target vessel procedures than patients receiving PTCA (14.6% vs. 30.0%, p = 0.01) and BMS (14.6% vs. 42.2%, p < 0.01), but rates similar to CABG patients (14.6% vs. 14.6%, p = 0.99). For patients undergoing a second revascularization procedure, PTCA, BMS, DES, and CABG are associated with a similar risk of death or nonfatal myocardial infarction. DES and CABG are associated with lower rates of third revascularization procedures compared to PTCA and BMS. Further studies are needed to determine the optimum application for CABG vs. DES as a second or third revascularization procedure.


Tissue motion--a disturbance in the laser-Doppler blood flow signal?
The tissue matrix in the human body is continuously in motion driven by forces generated by the circulatory and respiratory systems. The linear velocities recorded can be as high as 300 microm/s. The question raised: is the motion of tissue matrix generating an error signal in laser-Doppler (LD) recordings that is misinterpreted as solely a blood flow signal. The problem is studied by using a physical model demonstrating the contribution from a flow channel and, in addition, from a linear motion of the flow tube. Measurements of skin motion in the forearm have been performed. The corresponding spectra have been compared with blood flow spectra recorded with the LD method at the same sites. The two types of spectra overlap each other indicating that motion induced signals can be interpreted as a flow signal. The "blood flow" contribution from tissue motion varies strongly with the site studied.


Robust Fusion of Diffusion MRI Data for Template Construction.
Construction of brain templates is generally carried out using a two-step procedure involving registering a population of images to a common space and then fusing the aligned images to form a template. In practice, image registration is not perfect and simple averaging of the images will blur structures and cause artifacts. In diffusion MRI, this is further complicated by intra-voxel inter-subject differences in fiber orientation, fiber configuration, anisotropy, and diffusivity. In this paper, we propose a method to improve the construction of diffusion MRI templates in light of inter-subject differences. Our method involves a novel q-space (i.e., wavevector space) patch matching mechanism that is incorporated in a mean shift algorithm to seek the most probable signal at each point in q-space. Our method relies on the fact that the mean shift algorithm is a mode seeking algorithm that converges to the mode of a distribution and is hence robust to outliers. Our method is therefore in effect seeking the most probable signal profile at each voxel given a distribution of signal profiles. Experimental results show that our method yields diffusion MRI templates with cleaner fiber orientations and less artifacts caused by inter-subject differences in fiber orientation.


Low-FODMAP Diet Is Associated With Improved Quality of Life in IBS Patients-A Prospective Observational Study.
The low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet is effectively manages irritable bowel syndrome (IBS) symptoms. Long-term low-FODMAP studies rarely report quality of life (QoL). We aimed to determine the effect of low-FODMAP diet on long-term QoL, gastrointestinal (GI) and non-GI symptoms in IBS patients. A prospective observational study of IBS patients referred for low-FODMAP dietary advice was performed. The primary outcome of QoL and secondary outcomes of GI symptoms, anxiety/depression, fatigue, sleep quality, and happiness were obtained at baseline, 6 weeks (T6), and 6 months (T26). 111 patients were recruited. 91.0%, 71.6%, and 50.5% of participants completed baseline, T6, and T26 assessments, respectively. There were significant improvements in QoL from baseline at T6 and T26 (both P < 0.001). Significant reductions were seen in GI symptoms at T6 and T26 (both P < 0.001), fatigue at T6 and T26 (both P < 0.003), and anxiety at T6 and T26 (both P < 0.007), compared with baseline. A significant reduction was seen for depression (P < 0.010) from baseline at T26, and a significant increase was seen for both happiness and vitality (both P < 0.04) from baseline at T26. There was a significant correlation between GI symptom response and change in QoL, anxiety, depression, and fatigue (all P < 0.034). Low-FODMAP diet was associated with improved long-term QoL and GI symptoms, reduced fatigue and anxiety/depression, and increased happiness and vitality. These data support a wider range of benefits for IBS patients consuming a low-FODMAP diet.


Projected Retained Ability Score (PRAS): A New Methodology for Quantifying Absolute Change in Norm-Based Psychological Test Scores Over Time.
A limitation of norm-based ability test scores is that they can only be used to evaluate relative change (compared with change in the norm sample), as opposed to absolute (raw) change in performance from Time 1 to Time 2. To address this limitation, a novel method (Projected Retained Ability Score [PRAS]) was developed to characterize absolute change in norm-based ability test scores. The PRAS method was applied to Differential Ability Scales®-Second Edition (DAS-II) General Conceptual Ability (GCA) scores in three cases of children with the neurodegenerative condition mucopolysaccharidosis type II (MPS II) who were assessed at two visits, 16 to 23 months apart. Although all three cases showed declines in norm-based GCA scores, the PRAS method revealed differences in absolute change in performance. The PRAS method allows for differentiation of slower-than-average improvement or stabilization versus deterioration of cognitive ability when norm-based scores decline from Time 1 to Time 2.


Spatiotemporal expression of tmie in the inner ear of rats during postnatal development.
The circling (cir/cir) mouse is a murine model for human nonsyndromic deafness DFNB6. Transmembrane inner ear (tmie) is the causative gene and its mutation through deletion of a 40-kilobase genomic region including tmie leads to deafness. The function of Tmie is unknown. To better understand the function of Tmie, we focused on the spatiotemporal expression of tmie in the rat cochlea by using a Tmie-specific antibody. Results showed that tmie expression was prominent in early postnatal rat cochleas in the stereocilia bundles of hair cells. The Tmie signal spread from the stereocilia to the hair cell body region and on to organ of Corti cells. No Tmie signal was observed in cell nuclei; Tmie was localized to the cytoplasm. Because Tmie is predicted to have 1 or 2 transmembrane domains, we postulate that it is localized to membrane-based organelles or the plasma membrane. Our results imply that Tmie exists in the cytoplasm and may have a key role in the maturation and structure of stereocilia bundles in developing hair cells. After hair cell maturation, Tmie is thought to be involved in the maintenance of organ of Corti cells.


Ontological journeys: The lifeworld of opium across the Afghan-Iranian border in/out of the pharmacy.
How can we conceive alternative policy models that embrace the empirical potentialities emerging from the lifeworld of drugs? The article reflects on this question, concluding that to reassess and to reinvent current policies on drugs, we need to think with a political ontology. Incidentally, the article also responds to the critique dismissing ontological inquiries as obstructing - or, at best, not informing - alternative drug policies. In an archaeological approach inspired by the work of Giorgio Agamben, the article unearths the case study of opium maintenance programme in Iran (1969-79), a forgotten policy experiment in an understudied and yet crucial geo-cultural environment for the global study of drugs. Mobilising the conceptual framework of ontological journeys, the article recomposes the lifeworld of opium within the horizons of transformative cultural practices, international borders, policy regimes and public ethics. Here, the materiality of drug consumption under the maintenance policy links with the changes in opium's transnational political economy and with shifting regimes of health and bioethical orthodoxy. Ontological journeys, hence, develop in a fluid space and time, making it possible to illuminate the lifeworld of drugs in places and times hitherto deserted by global policy studies. In building theoretical reflections upon a non-Western case, the article also incites the possibility of theory beyond Eurocentric knowledge and Euromerican cases. In this way, the article's purpose is to analyse the be-coming of opium beyond 'good' or 'evil', as a 'medicine' or a 'drug' and its real or perceived classification as 'licit' or 'illicit' across the Afghan-Iranian border. In conclusion, the article reflects upon the significance of this forgotten policy experiment, understood as an ontological journey, for contemporary drug policy and drug studies, but also for reinventing notions of care, welfare and health.


Dysregulation of miR-431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis.
The level of microRNA (miR)-431 was found to be markedly up-regulated in intestinal tissue of necrotizing enterocolitis (NEC). The objective of this study was to identify the target gene of miR-431 and to investigate the role of the miR-431-FOXA1 axis in the pathophysiology of NEC. The target gene of miR-431 was identified by in silico target prediction bioinformatics, luciferase assay, and Western blotting. Effects of miR-431 on downstream expression signals, cell proliferation, and apoptosis were investigated by overexpression in Caco-2 cells upon stimulation by LPS or lipoteichoic acid (LTA). FOXA1 was identified as the target gene of miR-431. Overexpression of miR-431 in Caco-2 cells significantly inhibited FOXA1, ESRRG, and HNF4A and activated IL-6, LGR5, NFKB2, PLA2G2A, PRKCZ, and TNF. IL-8 and - 10 were enhanced when costimulated with LPS or LTA. These potential downstream genes were also significantly dysregulated in primary NEC tissues compared with surgical-control tissues. Overexpression of miR-431 significantly decreased proliferation and increased apoptosis of Caco-2 cells. A proposed network of miR-431-FOXA1 interaction with LPS and LTA receptors demonstrates dysregulation of transcription factors, inflammatory mediators, epithelium tight junction regulators, and cell proliferation and apoptosis signals. The miR-431-FOXA1 axis could in part be responsible for the intensification of the inflammatory response in NEC tissues and contribute to the proinflammatory pathophysiology.-Wu, Y. Z., Chan, K. Y. Y., Leung, K. T., Lam, H. S., Tam, Y. H., Lee, K. H., Li, K., Ng, P. C. Dysregulation of miR-431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis.


Students' academic engagement during COVID-19 times: a mixed-methods study into relatedness and loneliness during the pandemic.
The COVID-19 outbreak forced higher education students to study online-only. Previous research indicates that forced solitude or loneliness can cause a variety of problems for students, among which is reduced academic engagement. The Basic Psychological Needs Theory, a sub-theory of Self-Determination Theory, relates academic engagement to three basic psychological needs (autonomy, competence and relatedness), whereas varying theories on loneliness highlight the complexities of engaging in a learning environment whilst feeling lonely. As university staff members have been struggling to keep students on task since the COVID-19 outbreak, the need arose for more knowledge about to what extent students have felt lonely, frustrated or satisfied in their need for relatedness and to what extent this affected their academic engagement. A convergent Mixed Methods research study was conducted among university students (N = 228) and an online questionnaire was administered to collect both quantitative and qualitative data. A series of multiple hierarchical regression analyses were performed, considering demographic characteristics, to analyze the quantitative data. Qualitative data was coded using a hybrid approach of deductive and inductive coding. Themes were generated that depicted in-depth issues of relatedness, loneliness, and academic engagement. Quantitative analysis demonstrated the importance for academic engagement of both (a) 'basic need satisfaction and frustration' of relatedness in life and in 'social study context', and (b) feeling (emotionally) lonely. The negative impact of frustration of relatedness seemed to be dominant but also overlapped with the effects of loneliness. The qualitative outcomes support and complement these quantitative results. The results showed that students' academic engagement suffered from the loss of a shared physical space and from uncertainty about university policies. For a minority of students, however, the relief from social obligations that came along with social distancing was a blessing in disguise.


Salicylic acid antagonism of EDS1-driven cell death is important for immune and oxidative stress responses in Arabidopsis.
Reactive oxygen species (ROS) have emerged as signals in the responses of plants to stress. Arabidopsis Enhanced Disease Susceptibility1 (EDS1) regulates defense and cell death against biotrophic pathogens and controls cell death propagation in response to chloroplast-derived ROS. Arabidopsis Nudix hydrolase7 (nudt7) mutants are sensitized to photo-oxidative stress and display EDS1-dependent enhanced resistance, salicylic acid (SA) accumulation and initiation of cell death. Here we explored the relationship between EDS1, EDS1-regulated SA and ROS by examining gene expression profiles, photo-oxidative stress and resistance phenotypes of nudt7 mutants in combination with eds1 and the SA-biosynthetic mutant, sid2. We establish that EDS1 controls steps downstream of chloroplast-derived O(2)(*-) that lead to SA-assisted H(2)O(2) accumulation as part of a mechanism limiting cell death. A combination of EDS1-regulated SA-antagonized and SA-promoted processes is necessary for resistance to host-adapted pathogens and for a balanced response to photo-oxidative stress. In contrast to SA, the apoplastic ROS-producing enzyme NADPH oxidase RbohD promotes initiation of cell death during photo-oxidative stress. Thus, chloroplastic O(2)(*-) signals are processed by EDS1 to produce counter-balancing activities of SA and RbohD in the control of cell death. Our data strengthen the idea that EDS1 responds to the status of O(2)(*-) or O(2)(*-)-generated molecules to coordinate cell death and defense outputs. This activity may enable the plant to respond flexibly to different biotic and abiotic stresses in the environment.


Design and Characterization of Model Systems that Promote and Disrupt Transparency of Vertebrate Crystallins In Vitro.
Positioned within the eye, the lens supports vision by transmitting and focusing light onto the retina. As an adaptive glassy material, the lens is constituted primarily by densely-packed, polydisperse crystallin proteins that organize to resist aggregation and crystallization at high volume fractions, yet the details of how crystallins coordinate with one another to template and maintain this transparent microstructure remain unclear. The role of individual crystallin subtypes (α, β, and γ) and paired subtype compositions, including how they experience and resist crowding-induced turbidity in solution, is explored using combinations of spectrophotometry, hard-sphere simulations, and surface pressure measurements. After assaying crystallin combinations, β-crystallins emerged as a principal component in all mixtures that enabled dense fluid-like packing and short-range order necessary for transparency. These findings helped inform the design of lens-like hydrogel systems, which are used to monitor and manipulate the loss of transparency under different crowding conditions. When taken together, the findings illustrate the design and characterization of adaptive materials made from lens proteins that can be used to better understand mechanisms regulating transparency.


Endoscope-assisted three-wire technique for extensive nasal septum resection in horses.
To describe a 3-wire method with endoscopic guidance for extensive nasal septum resection. Retrospective study. Thirteen horses with nasal septum diseases. In anesthetized horses in left lateral recumbency, endoscopic guidance was used to place obstetrical wires for the ventral and caudal incisions in the nasal septum and a trephine opening was used to place the dorsal wire. The rostral aspect of the septum was incised with a scalpel, followed by incisions with the preplaced wires, and the nasal passages were packed with gauze. Horses were recovered with a temporary tracheotomy. Conversion to intraoral placement of wires was required in two horses, one to correct entangled wires and the other because hemorrhage obscured the endoscopic view. Exercise tolerance was improved postoperatively, abnormal respiratory noise was decreased or eliminated by surgery in all horses, and all owners were satisfied. One Thoroughbred racehorse performed with modest success. Modification of the 3-wire method was effective and safe for extensive nasal septum removal. Technical complications of the procedure include entangling of wires and intraoperative hemorrhage. Endoscopic guidance can be used to place obstetrical wires for nasal septum resection in small horses and precludes use of a large tracheotomy for anesthetic delivery. Reasons for athletic failures were difficult to establish retrospectively, although assessment of postoperative noise at speed might be more relevant to recovery of athletic potential than assessment at slower gaits.


Removal of target odorous molecules on to activated carbon cloths.
Activated carbon materials are adsorbents whose physico-chemical properties are interesting for the treatment of odorous compounds like hydrogen sulfide. Indeed, their structural parameters (pore structure) and surface chemistry (presence of heteroatoms such as oxygen, hydrogen, nitrogen, sulfur, phosphorus) play an important role in H2S removal. The cloth texture of these adsorbents (activated carbon cloths) is particularly adapted for dealing with high flows, often found in the treatment of odor emissions. Thus, this paper first presents the influence of these parameters through adsorption isothermal curves performed on several materials. Secondly, tests in a dynamic system are described. They highlight the low critical thickness of the fabric compared to granular activated carbon.


Cancer cachexia: understanding the molecular basis.
Cancer cachexia is a devastating, multifactorial and often irreversible syndrome that affects around 50-80% of cancer patients, depending on the tumour type, and that leads to substantial weight loss, primarily from loss of skeletal muscle and body fat. Since cachexia may account for up to 20% of cancer deaths, understanding the underlying molecular mechanisms is essential. The occurrence of cachexia in cancer patients is dependent on the patient response to tumour progression, including the activation of the inflammatory response and energetic inefficiency involving the mitochondria. Interestingly, crosstalk between different cell types ultimately seems to result in muscle wasting. Some of the recent progress in understanding the molecular mechanisms of cachexia may lead to new therapeutic approaches.


Linear interpolation algorithm for low dose risk assessment of toxic substances.
In order to detect potential toxic effects of substances, relatively high doses generally are administered to relatively small numbers of laboratory animals. It is impossible to estimate low levels of disease incidence with precision at low environmental dose levels even with large numbers of laboratory animals. However, upper limits on risk can be obtained for convex dose response curves by linear interpolation between the lowest experimental dose level and zero. A simple mathematical algorithm is provided for low dose risk assessment from dose response data and the performance of this procedure is evaluated for a variety of toxicological data, including but not limited to carcinogenesis. The low dose confidence limits resulting from linear interpolation are similar to those obtained from the Armitage-Doll multistage model.


Epidemiology of severe Streptococcus pyogenes disease in Europe.
The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe.


Bipolar Disorder Among Patients Diagnosed With Frontotemporal Dementia.
Previous studies have documented manic and hypomanic symptoms in behavioral variant frontotemporal dementia (bvFTD), suggesting a relationship between bipolar disorder and bvFTD. The investigators conducted a literature review as well as a review of the psychiatric histories of 137 patients with bvFTD, and patients with a prior diagnosis of bipolar disorder were identified. The clinical characteristics of patients' bipolar disorder diagnosis, family history, features of bvFTD, and results from fluorodeoxyglucose positron emission tomography (FDG-PET), as well as autopsy findings, were evaluated. Among the 137 patients, 14 (10.2%) had a psychiatric diagnosis of bipolar disorder, eight of whom met criteria for bipolar disorder (type I, N=6; type II, N=2) 6-12 years preceding onset of classic symptoms of progressive bvFTD. Seven of the eight patients with bipolar disorder had a family history of mood disorders, four had bitemporal predominant hypometabolism on FDG-PET, and two had a tauopathy involving temporal lobes on autopsy. Three additional patients with late-onset bipolar I disorder proved to have a nonprogressive disorder mimicking bvFTD. The remaining three patients with bvFTD had prior psychiatric symptoms that did not meet criteria for a diagnosis of bipolar disorder. The literature review and the findings for one patient further suggested a shared genetic mutation in some patients. Manic or hypomanic episodes years before other symptoms of bvFTD may be a prodrome of this dementia, possibly indicating anterior temporal involvement in bvFTD. Other patients with late-onset bipolar disorder exhibit the nonprogressive frontotemporal dementia phenocopy syndrome. Finally, a few patients with bvFTD have a genetic predisposition for both disorders.