Enhancing Mechanical and Corrosion Properties of AISI 420 with Titanium-Nitride Reinforcement through High-Power-Density Selective Laser Melting Using Two-Stage Mixed TiN/AISI 420 Powder.
This study investigates the effect of laser volume energy density (VED) on the properties of AISI 420 stainless steel and TiN/AISI 420 composite manufactured by selective laser melting (SLM). The composite contained 1 wt.% TiN and the average diameters of AISI 420 and TiN powders were 45 µm and 1 µm, respectively. The powder for SLMing the TiN/AISI 420 composite was prepared using a novel two-stage mixing scheme. The morphology, mechanical, and corrosion properties of the specimens were analyzed, and their correlations with microstructures were investigated. The results showed that the surface roughness of both SLM samples decreases with increasing VED, while relative densities greater than 99% were achieved at VEDs higher than 160 J/mm3. The SLM AISI 420 specimen fabricated at a VED of 205 J/mm3 exhibited the highest density of 7.7 g/cm3, tensile strength (UTS) of 1270 MPa, and elongation of 3.86%. The SLM TiN/AISI 420 specimen at a VED of 285 J/mm3 had a density of 7.67 g/cm3, UTS of 1482 MPa, and elongation of 2.72%. The microstructure of the SLM TiN/AISI 420 composite displayed a ring-like micro-grain structure consisting of retained austenite on the grain boundary and martensite in the grain. The TiN particles strengthened the mechanical properties of the composite by accumulating along the grain boundary. The mean hardnesses of the SLM AISI 420 and TiN/AISI 420 specimens were 635 and 735 HV, respectively, which exceeded previously reported results. The SLM TiN/AISI 420 composite exhibited excellent corrosion resistance in both 3.5 wt.% NaCl and 6 wt.% FeCl3 solutions, with a resulting corrosion rate as low as 11 µm/year.


New gene evolution in the bonus-TIF1-γ/TRIM33 family impacted the architecture of the vertebrate dorsal-ventral patterning network.
Uncovering how a new gene acquires its function and understanding how the function of a new gene influences existing genetic networks are important topics in evolutionary biology. Here, we demonstrate nonconservation for the embryonic functions of Drosophila Bonus and its newest vertebrate relative TIF1-γ/TRIM33. We showed previously that TIF1-γ/TRIM33 functions as an ubiquitin ligase for the Smad4 signal transducer and antagonizes the Bone Morphogenetic Protein (BMP) signaling network underlying vertebrate dorsal-ventral axis formation. Here, we show that Bonus functions as an agonist of the Decapentaplegic (Dpp) signaling network underlying dorsal-ventral axis formation in flies. The absence of conservation for the roles of Bonus and TIF1-γ/TRIM33 reveals a shift in the dorsal-ventral patterning networks of flies and mice, systems that were previously considered wholly conserved. The shift occurred when the new gene TIF1-γ/TRIM33 replaced the function of the ubiquitin ligase Nedd4L in the lineage leading to vertebrates. Evidence of this replacement is our demonstration that Nedd4 performs the function of TIF1-γ/TRIM33 in flies during dorsal-ventral axis formation. The replacement allowed vertebrate Nedd4L to acquire novel functions as a ubiquitin ligase of vertebrate-specific Smad proteins. Overall our data reveal that the architecture of the Dpp/BMP dorsal-ventral patterning network continued to evolve in the vertebrate lineage, after separation from flies, via the incorporation of new genes.


Assessment and management of patients with obesity hypoventilation syndrome.
Obesity hypoventilation syndrome (OHS) is characterized by obesity, daytime hypercapnia, and sleep-disordered breathing in the absence of significant lung or respiratory muscle disease. Compared with eucapnic morbidly obese patients and eucapnic patients with sleep-disordered breathing, patients with OHS have increased health care expenses and are at higher risk of developing serious cardiovascular disease leading to early mortality. Despite the significant morbidity and mortality associated with this syndrome, diagnosis and institution of effective treatment occur late in the course of the syndrome. Given that the prevalence of extreme obesity has increased considerably, it is likely that clinicians will encounter patients with OHS in their clinical practice. Therefore maintaining a high index of suspicion can lead to early recognition and treatment reducing the high burden of morbidity and mortality and related health care expenditure associated with undiagnosed and untreated OHS. In this review we define the clinical characteristics of the syndrome and review the pathophysiology, morbidity, and mortality associated with it. Last, we discuss currently available treatment modalities.


Bandwidth-division in digitally enhanced optical frequency domain reflectometry.
We demonstrate for the first time the use of digital range-gating in OFDR to allow for orders of magnitude reduction in the required sampling rates. This allows for sensing over long lengths of fiber with fast sweeps of the optical source frequency, without requiring impractical sampling rates. The range-gating is achieved using digitally enhanced interferometry (DI), which isolates individual sections of OFDR signal bandwidth. The reductions in sampling rates permitted by the bandwidth-division are demonstrated both numerically and experimentally.


K-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian golden hamster.
K-ras oncogene mutation has been shown to be a frequent event in pancreatic ductal adenocarcinomas induced by the carcinogen N-nitroso-bis(2-oxopropyl)amine in the hamster. The present study examines the mutational status of the K-ras oncogene in lesions that precede the appearance of invasive ductal adenocarcinomas. Syrian golden hamsters (80-100 g) received 12 weekly doses of 15 mg/kg N-nitroso-bis(2-oxopropyl)amine and were serially sacrificed at 8, 12, 14, 16, or 24 weeks following the initiation of treatment. Ten microns-thick sections of formalin-fixed paraffin-embedded pancreas were examined for hyperplasia, papillary hyperplasia, carcinoma in situ, and invasive and metastatic ductal carcinoma. Marked lesions of interest were scraped from the slide, subjected to polymerase chain reaction-mediated amplification of the first exon of the K-ras gene, and probed by oligonucleotide-specific hybridization for mutations at codon either 12 or 13. Of 186 samples assayed, K-ras codon 12 mutations were detected in 26% of hyperplasias, 46% of papillary hyperplasias, 76% of carcinoma in situ, 80% of adenocarcinomas, and 43% of lymph node metastases. Codon 12 mutations were exclusively G to A changes at the second position. Codon 13 mutations were only detected in 9 of 168 samples. These results suggest that K-ras activation is an early event in N-nitroso-bis(2-oxopropyl)amine-induced pancreatic carcinogenesis in the hamster.


Carob pod water extracts as feedstock for succinic acid production by Actinobacillus succinogenes 130Z.
Carob pods are a by-product of locust bean gum industry containing more than 50% (w/w) sucrose, glucose and fructose. In this work, carob pod water extracts were used, for the first time, for succinic acid production by Actinobacillus succinogenes 130Z. Kinetic studies of glucose, fructose and sucrose consumption as individual carbon sources till 30g/L showed no inhibition on cell growth, sugar consumption and SA production rates. Sugar extraction from carob pods was optimized varying solid/liquid ratio and extraction time, maximizing sugar recovery while minimizing the extraction of polyphenols. Batch fermentations containing 10-15g/L total sugars resulted in a maximum specific SA production rate of 0.61Cmol/Cmol X.h, with a yield of 0.55Cmol SA/Cmol sugar and a volumetric productivity of 1.61g SA/L.h. Results demonstrate that carob pods can be a promising low cost feedstock for bio-based SA production.


TGF-β-induced CD4+Foxp3+ T cells attenuate acute graft-versus-host disease by suppressing expansion and killing of effector CD8+ cells.
The use of TGF-β-induced CD4(+)Foxp3(+) T cells (induced regulatory T cells [iTregs]) is an important prevention and treatment strategy in autoimmune diseases and other disorders. However, the potential use of iTregs as a treatment modality for acute graft-versus-host disease (aGVHD) has not been realized because they may be unstable and less suppressive in this disease. We restudied the ability of iTregs to prevent and treat aGVHD in two mouse models. Our results showed that, as long as an appropriate iTreg-generation protocol is used, these iTregs consistently displayed a potent ability to control aGVHD development and reduce mortality in the aGVHD animal models. iTreg infusion markedly suppressed the engraftment of donor CD8(+) cells and CD4(+) cells, the expression of granzyme A and B, the cytotoxic effect of donor CD8(+) cells, and the production of T cell cytokines in aGVHD. Therefore, we conclude that as long as the correct methods for generating iTregs are used, they can prevent and even treat aGVHD.


Disseminated trichosporonosis in a murine model of chronic granulomatous disease.
Over a period of ten months, five mice submitted to our service (the Pathology Section of the Veterinary Resources Program, Office of Research Services at the National Institutes of Health, Bethesda, Md.) were diagnosed with disseminated trichosporonosis. These mice had pyogranulomatous inflammation in multiple organs, including lung, liver, lymph nodes, salivary gland, and skin. Fungal elements in many of the lesions were identified, using special histochemical stains, and Trichosporon beigelii was obtained by use of culture of specimens at affected sites. This saprophytic fungus has caused disseminated disease in immunosuppressed humans. However, despite widespread use of immunosuppressed rodents in research, to the authors' knowledge, this organism had not previously been reported to cause spontaneous disseminated disease in laboratory mice. All affected mice had a genetically engineered defect in p47(phox), a critical component of the nicotinamide dinucleotide phosphate (NADPH) oxidase, the enzyme responsible for generating the phagocyte oxidative burst. These animals are used as a murine model of human chronic granulomatous disease. We discuss the lesions, differential diagnosis, identification of the organism, and the role of NADPH oxidase in protecting against disseminated trichosporonosis.


Effect of leuprorelin acetate on cell growth and prostate-specific antigen gene expression in human prostatic cancer cells.
We investigated modulation of cell growth and prostate-specific antigen (PSA) gene expression in prostatic cancer cells by the luteinizing hormone-releasing hormone analog (LH-RHa), leuprorelin acetate, alone or combined with other agents. The effect of the analog on proliferation of both androgen-sensitive and -insensitive prostate cancer cells, maintained in different culture conditions, was evaluated by cell counts at various intervals of time. Basal expression of PSA gene and its variations were determined by a reverse transcriptase-polymerase chain reaction assay. LH-RHa is ineffective in regulating cell growth, when used alone in both hormone-sensitive and -insensitive cell lines. Nevertheless, it counteracts the stimulatory action of androgens on proliferation of LNCaP cells, which respond to low concentrations of dihydrotestosterone. Moreover, LH-RHa has an inhibitory effect on the mitogenic action of epidermal growth factor (EGF) in androgen-unresponsive PC-3 cells. The analog reduces PSA gene expression in both hormone-sensitive and -insensitive cells. Interestingly, it counteracts the gene expression induced by androgens in LNCaP cells and by EGF in PC-3 cells. These data show that LH-RHa may behave like a negative growth factor, which directly regulates cell growth and PSA gene expression. Moreover, our findings support the idea that growth factors may interfere with the androgen signalling pathway.


An Unusual Cause of CPAP Intolerance.
Continuous positive airway pressure (CPAP) is a first-line treatment for obstructive sleep apnea (OSA). However, the adherence to CPAP can be difficult for patients due to several reasons. In this case report we describe a patient with severe OSA who initially was treated successfully with CPAP, but after a few months adherence problems developed because of macroglossia. This was caused by amyloidosis due to multiple myeloma. During treatment with chemotherapy and stem cell transplantation, the size of the patient's tongue decreased and he could successfully use his CPAP device again.


Fungal Planet description sheets: 281-319.
Novel species of fungi described in the present study include the following from South Africa: Alanphillipsia aloeicola from Aloe sp., Arxiella dolichandrae from Dolichandra unguiscati, Ganoderma austroafricanum from Jacaranda mimosifolia, Phacidiella podocarpi and Phaeosphaeria podocarpi from Podocarpus latifolius, Phyllosticta mimusopisicola from Mimusops zeyheri and Sphaerulina pelargonii from Pelargonium sp. Furthermore, Barssia maroccana is described from Cedrus atlantica (Morocco), Codinaea pini from Pinus patula (Uganda), Crucellisporiopsis marquesiae from Marquesia acuminata (Zambia), Dinemasporium ipomoeae from Ipomoea pes-caprae (Vietnam), Diaporthe phragmitis from Phragmites australis (China), Marasmius vladimirii from leaf litter (India), Melanconium hedericola from Hedera helix (Spain), Pluteus albotomentosus and Pluteus extremiorientalis from a mixed forest (Russia), Rachicladosporium eucalypti from Eucalyptus globulus (Ethiopia), Sistotrema epiphyllum from dead leaves of Fagus sylvatica in a forest (The Netherlands), Stagonospora chrysopyla from Scirpus microcarpus (USA) and Trichomerium dioscoreae from Dioscorea sp. (Japan). Novel species from Australia include: Corynespora endiandrae from Endiandra introrsa, Gonatophragmium triuniae from Triunia youngiana, Penicillium coccotrypicola from Archontophoenix cunninghamiana and Phytophthora moyootj from soil. Novelties from Iran include Neocamarosporium chichastianum from soil and Seimatosporium pistaciae from Pistacia vera. Xenosonderhenia eucalypti and Zasmidium eucalyptigenum are newly described from Eucalyptus urophylla in Indonesia. Diaporthe acaciarum and Roussoella acacia are newly described from Acacia tortilis in Tanzania. New species from Italy include Comoclathris spartii from Spartium junceum and Phoma tamaricicola from Tamarix gallica. Novel genera include (Ascomycetes): Acremoniopsis from forest soil and Collarina from water sediments (Spain), Phellinocrescentia from a Phellinus sp. (French Guiana), Neobambusicola from Strelitzia nicolai (South Africa), Neocladophialophora from Quercus robur (Germany), Neophysalospora from Corymbia henryi (Mozambique) and Xenophaeosphaeria from Grewia sp. (Tanzania). Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.


Alternative fates of newly formed PrPSc upon prion conversion on the plasma membrane.
Prion diseases are fatal neurodegenerative diseases characterised by the accumulation of misfolded prion protein (PrP(Sc)) in the brain. They are caused by the templated misfolding of normal cellular protein, PrP(C), by PrP(Sc). We have recently generated a unique cell system in which epitope-tagged PrP(C) competent to produce bona fide PrP(Sc) is expressed in neuroblastoma cells. Using this system we demonstrated that PrP(Sc) forms on the cell surface within minutes of prion exposure. Here, we describe the intracellular trafficking of newly formed PrP(Sc). After formation in GM1-enriched lipid microdomains at the plasma membrane, PrP(Sc) is rapidly internalised to early endosomes containing transferrin and cholera toxin B subunit. Following endocytosis, PrP(Sc) intracellular trafficking diverges: some is recycled to the plasma membrane via Rab11-labelled recycling endosomes; the remaining PrP(Sc) is subject to retromer-mediated retrograde transport to the Golgi. This pathway leads to lysosomal degradation, and we show that this is the dominant PrP(Sc) degradative mechanism in the early stages of prion infection.


[Photoinduced resonance phenomena in the human electroencephalogram as a function of frequency, intensity, and duration of stimulation].
The features of resonance phenomena in high-resolution EEG structure were analyzed for two intensities and three values of duration of exposure to 20 constant frequencies of intermittent photic stimulation in a range of 1-20 Hz with 1 Hz steps. It was shown that with a 6 s step duration, an irregular activation of multiple spectral EEG components for both light intensities occurs. With longer durations (12 and 18 s) of fixed-frequency stimulation, the EEG reactions are of resonance nature. Low-intensity flashes cause only the resonance activation of the intrinsic oscillator in the range of dominant alpha-EEG frequency. During a more intensive stimulation, the resonance EEG phenomena are observed for the whole range of stimulation frequencies. The interval of 6-12 s is supposed to be the relaxation period for a system of brain electrical activity generation. After this time, the low-intensity stimuli cause the adaptation of the system to light, whereas more intensive flashes cause more pronounced resonance EEG phenomena and physiological effects.


The relationship between sternum variation and mode of locomotion in birds.
The origin of powered avian flight was a locomotor innovation that expanded the ecological potential of maniraptoran dinosaurs, leading to remarkable variation in modern birds (Neornithes). The avian sternum is the anchor for the major flight muscles and, despite varying widely in morphology, has not been extensively studied from evolutionary or functional perspectives. We quantify sternal variation across a broad phylogenetic scope of birds using 3D geometric morphometrics methods. Using this comprehensive dataset, we apply phylogenetically informed regression approaches to test hypotheses of sternum size allometry and the correlation of sternal shape with both size and locomotory capabilities, including flightlessness and the highly varying flight and swimming styles of Neornithes. We find evidence for isometry of sternal size relative to body mass and document significant allometry of sternal shape alongside important correlations with locomotory capability, reflecting the effects of both body shape and musculoskeletal variation. Among these, we show that a large sternum with a deep or cranially projected sternal keel is necessary for powered flight in modern birds, that deeper sternal keels are correlated with slower but stronger flight, robust caudal sternal borders are associated with faster flapping styles, and that narrower sterna are associated with running abilities. Correlations between shape and locomotion are significant but show weak explanatory power, indicating that although sternal shape is broadly associated with locomotory ecology, other unexplored factors are also important. These results display the ecological importance of the avian sternum for flight and locomotion by providing a novel understanding of sternum form and function in Neornithes. Our study lays the groundwork for estimating the locomotory abilities of paravian dinosaurs, the ancestors to Neornithes, by highlighting the importance of this critical element for avian flight, and will be useful for future work on the origin of flight along the dinosaur-bird lineage.


Maxillary Anterior Segmental Distraction Osteogenesis to Correct Maxillary Deficiencies in a Patient With Cleft Lip and Palate.
This report describes a case of successful orthodontic treatment using maxillary anterior segmental distraction osteogenesis with an internal maxillary distractor and bilateral sagittal split ramus osteotomy in a girl with cleft lip and palate. A 16-year-old girl with unilateral cleft lip and palate exhibited midface retrusion because of growth inhibition of the maxillary complex and mandibular excess. After the presurgical orthodontic treatment, 6.0-mm advancement of the maxillary anterior segment and 4.0-mm set back of the mandible were performed. After a retention period, the patient's midface convexity was greatly improved and the velopharyngeal competence was preserved without relapse.


A Caenorhabditis elegans PUF protein family with distinct RNA binding specificity.
PUF proteins comprise a highly conserved family of sequence-specific RNA binding proteins that regulate target mRNAs via binding directly to their 3'UTRs. The Caenorhabditis elegans genome encodes several PUF proteins, which cluster into four groups based on sequence similarity; all share amino acids that interact with the RNA in the cocrystal of human Pumilio with RNA. Members of the FBF and the PUF-8/9 groups bind different but related RNA sequences. We focus here on the binding specificity of representatives of a third cluster, comprising PUF-5, -6, and -7. We performed in vivo selection experiments using the yeast three-hybrid system to identify RNA sequences that bind PUF-5 and PUF-6, and we confirmed binding to optimal sites in vitro. The consensus sequences derived from the screens are similar for PUF-5 and PUF-6 but differ from those of the FBF or PUF-8/-9 groups. Similarly, neither PUF-5 nor PUF-6 bind the recognition sites preferred by the other clusters. Mutagenesis studies confirmed the unique RNA specificity of PUF-5/-6. Using the PUF-5 consensus derived from our experiments, we searched a database of C. elegans 3'UTRs to identify potential targets of PUF-5, several of which indeed bind PUF-5. Therefore the consensus has predictive value and provides a route to finding genuine targets of these proteins.


A linkage study of the N-methyl-D-aspartate receptor subunit gene loci and schizophrenia in southern African Bantu-speaking families.
Both direct and indirect evidence implicate excitatory amino acid neurotransmission in the aetiology of schizophrenia. The data are particularly suggestive for N-methyl-D-aspartate (NMDA) neurotransmission. Four of the six genes coding for subunits of the neural NMDA receptor have been mapped. We have studied segregation and allele sharing of markers in these four regions in a sample of southern African Bantu-speaking families multiply affected with DSM-III-R schizophrenia. This population was chosen because anthropological and linguistic data suggest that it has diverged from a small initial population within the past 1000 years, making shared genetic aetiology more likely. We find positive LOD score maxima of 0.876 at a marker D9S1838 on chromosome 9q34.3 near the NMDAR1 central subunit gene, 0.758 at marker D17S784 on chromosome 17q25 near the NMDAR2C potentiating subunit gene, and 0.453 at marker D12S77 near the NMDAR2B gene on chromosome 12p12 when analysing affected samples only. Only the region of NMDAR2A, on chromosome 16p13, can be excluded in this population. There is evidence of increased allele sharing on chromosomes 9p34.3 and 17q25 using APM. Multipoint allele-sharing analysis using GENEHUNTER does not reject possible effects on chromosome 9q34.3, but does not support any involvement of chromosome 17q25. We propose that the NMDA receptor may be involved in the genetic predisposition to schizophrenia in this population through covariation in several of the subunits, which is consistent with the genetic models of the inheritance of the disease.


Retrospective review of the epidemiology of epilepsy in special schools for children with cerebral palsy, learning difficulties, and language and communication difficulties.
To determine in children the proportion and characteristics of epilepsy associated with cerebral palsy, learning difficulties and language and communication difficulties in a specific population of two special schools. Retrospective review of case notes for 142 children in two special schools (school A and school B) in Newcastle, UK MAIN FINDINGS: School A had more children with learning difficulties (X2=32.41, p<0.01) and active epilepsy (X2=3.03, p=0.08) than school B. There were more children with cerebral palsy (X2=9.56, p<0.01) and language and communication problems (X2=4.25, p=0.03) at school B compared to school A. Active epilepsy is significantly more common in children with cerebral palsy (X2=7.58, p=0.01). All children with cerebral palsy and learning difficulties had epilepsy (n=6). Although not statistically significant, those children who developed epilepsy within the first 24 hours of life were more likely to have cerebral palsy than those who developed epilepsy later in life (X2=3.10, p=0.08). Those children with cerebral palsy tended to have a lower birth weight (t=3.15, p<0.01) and a shorter gestation (t=3.17, p<0.01) than children without cerebral palsy. The data supports evidence from previous studies, demonstrating that epilepsy commonly accompanies cerebral palsy, thus complicating this difficult chronic condition. We show an association between both low birth weight and gestational age, and early age of onset of seizures, in children with cerebral palsy. This illustrates the importance, in these children, of past medical history from birth to determine risk factors for epilepsy later in life.


Characterization of memory load in an arithmetic task using non-linear analysis of EEG signals.
In this paper, we investigate non-linear analysis of electroencephalogram (EEG) signals to examine changes in working memory load during the performance of a cognitive task with varying difficulty levels. EEG signals were recorded during an arithmetic task while the induced load was varying in seven levels from very easy to extremely difficult. The EEG signals were analyzed using three different non-linear/dynamic measures; namely: correlation dimension, Hurst exponent and approximate entropy. Experimental results show that the values of the measures extracted from the delta frequency band of signals acquired from the frontal and occipital lobes of the brain vary in accordance with the task difficulty level induced. The values of the correlation dimension increased as the task difficulty increased, showing a rise in complexity of the EEG signals, while the values of the Hurst exponent and approximate entropy decreased as task difficulty increased, indicating more regularity and predictability in the signals.


Reexpression of the major protein kinase C substrate, SSeCKS, suppresses v-src-induced morphological transformation and tumorigenesis.
SSeCKS (pronounced essex) encodes a major protein kinase C substrate, the expression of which is down-regulated in src- and ras-transformed rodent fibroblasts but not in raf-transformed rodent fibroblasts (X. Lin et al., Mol. Cell. Biol., 15: 2754-2762, 1995). Using a panel of ras-transformed or revertant Rat-6 cells that exhibit selective parameters of transformation, we show that down-regulation of SSeCKS correlates with anchorage-independent growth. Cotransfection of NIH3T3 fibroblasts with an SSeCKS expression plasmid decreased 6-30-fold the ability of a v-src expressor plasmid to induce colonies in soft agar. To differentiate between possible tumor suppressive or growth-inhibitory effects of SSeCKS, we developed conditionally transformed cell lines (expressing ts72v-src) with tetracycline-regulated SSeCKS expression. SSeCKS suppressed the ability of v-src to induce increased cellular refractility, focus formation, soft agar colony formation, in vitro invasiveness in Matrigel, and growth in low serum (0.5%) but did not inhibit cell proliferation in high serum (10%) at the permissive (35 degrees C) temperature for src kinase activity. However, at the nonpermissive (39.5 degrees C) temperature, SSeCKS induced growth arrest. SSeCKS expression did not affect: (a) the protein level, in vivo or in vitro kinase activity of ts72src; (b) the activity of jun NH2-terminal kinase; and (c) the level of mitogen-activated protein kinase (extracellular signal-regulated kinase 2) protein. However, extracellular signal-regulated kinase 2 activity was induced 5-10-fold by SSeCKS in the presence of active src. SSeCKS reversed the ability of v-src to decrease the formation of vinculin-associated adhesion plaques, actin-based stress fibers, and filopodia structures. These data suggest a tumor suppressive role for SSeCKS via the control of cytoskeletal architecture and cell signaling.


Carers of older Australians: unmet support needs and carer well-being.
Primary carers play an important role in supporting the Australian Government's policy of 'ageing in place' or encouraging people to receive care in their own homes or communities rather than in institutions. Supporting carers in their role is therefore an important aspect of the policy's success. Despite numerous programs in place, this study finds that among carers of older Australians, a relatively high proportion (39%) cite unmet needs in their carer role, including a need for financial support, physical assistance, emotional support, improvement in carer health and more respite care. Concerningly, unmet support needs were shown to be strongly associated with markers of poor carer well-being, including an almost 2-fold increase in odds of poor carer satisfaction (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.24-2.51), a 4- to 5-fold increase in the odds of changes to physical and emotional well-being (OR 5.29, 95% CI 3.83-7.31), deterioration in financial situation (OR 4.60, 95% CI 3.26-6.48) and strained carer-recipient relationship (OR 3.79, 95% CI 2.39-6.01).


The prescription or proscription of exercise in colorectal cancer care.
Clinical guidelines recommend that oncologists prescribe exercise to their patients with colorectal cancer (CRC). However, 84% of oncologists do not prescribe exercise, citing concerns of safety and feasibility. Data are inadequate regarding the proportion of CRC survivors that could be safely prescribed with the dose of exercise recommended by the American College of Sports Medicine (ACSM), American Cancer Society (ACS), or National Comprehensive Cancer Network (NCCN) in an unsupervised setting. We reviewed published guidelines for exercise prescription among cancer survivors and extracted health factors that may necessitate referral to trained personnel (physical therapist or exercise professional) for an individualized exercise program or supervision of exercise as recommended by the ACSM/ACS/NCCN. We applied these health factors to a cohort of nonmetastatic CRC survivors 6 months after completing curative care. The primary outcome was the proportion of CRC survivors to whom oncologists could prescribe unsupervised exercise at the dose recommended by the ACSM/ACS/NCCN. Among 351 CRC survivors, 6 months after curative care, 21%-42% of patients could be prescribed with the dose of exercise recommended by the ACSM/ACS/NCCN. Estimates varied as a function of the inclusion or exclusion of several prevalent comorbid health conditions including hypertension, diabetes, arthritis, obesity, and hyperlipidemia. Our data are consistent with the clinical observation that a large proportion of CRC survivors may be unable to participate in unsupervised exercise 6 months after curative care. These data underscore the need for continued research to clarify the safety and feasibility of prescribing exercise to CRC survivors.


Gordonia desulfuricans sp. nov., a benzothiophene-desulphurizing actinomycete.
The taxonomic position of two actinomycetes isolated from soil was established using a polyphasic approach. The organisms, designated 213ET and 213F, were found to have chemical and morphological properties consistent with their assignment to the genus Gordonia. Nearly complete sequences of the 16S rDNA genes of the two strains were determined following the isolation and direct sequencing of the amplified genes. The tested strains were found to have identical 16S rDNA sequences and formed a phylogenetic line within the evolutionary radiation occupied by the genus Gordonia that was most closely related to Gordonia rubropertincta DSM 43197T. However, DNA-DNA relatedness data showed that strain 213ET and Gordonia rubropertincta DSM 43197T belonged to distinct genomic species. Strains 213ET and 213F also shared an identical phenotypic profile which distinguished them from representatives of validly described Gordonia species. The combined genotypic and phenotypic data show that strains 213ET and 213F merit recognition as a new species of Gordonia. The name proposed for the new species is Gordonia desulfuricans, for which the type strain is 213ET (= NCIMB 40816T).


[Resistant hypertension: a case report].
A 72-years-old man, having 230-210/110-90 mmHg with a 5-drugs antihypertensive regimen, was diagnosed with an aldosterone-producing adenoma. Blood pressure values remained elevated in spite of spironolactone therapy and surrenectomy, possibly because of renal insufficiency and vascular damage subsequent to long-term uncontrolled hypertension.


Computerized topographic brain mapping during carotid endarterectomy.
Computerized topographic brain mapping processes standard electroencephalographic data and displays it in a color map, thus simplifying interpretation. During a 2-year period, 65 carotid endarterectomies were performed with the use of brain mapping as the sole criterion for shunt replacement. Forty-three patients (66%) were found to have abnormal brain maps preoperatively. Ten patients (15%) developed ischemic changes after cross-clamping (all resolved after shunt placement). Postoperative brain maps were unchanged in 54 patients (83%) and improved in 7 patients (11%). A new, small focal abnormality was identified in 4 patients without shunts (6%), none of whom had a change in neurologic status. The overall major morbidity and mortality was 1.5%. Computerized brain mapping is a sensitive and readily interpretable means of monitoring cerebral perfusion during carotid surgery. We found the computerized electroencephalographic data to be a dependable criterion for selective shunting and for confirmation of shunt patency during carotid endarterectomy.


Effect of lithium on superoxide production and intracellular free calcium mobilization in elastin peptide (kappa-elastin) and FMLP stimulated human PMNS. Effect of age.
The effect of lithium pretreatment on superoxide anion production and intracellular free calcium levels was investigated in polymorphonuclear leukocytes (PMN) from middle-aged and old individuals after stimulation by elastin peptides or FMLP. K-elastin (KE) significantly stimulated the production of superoxide anion by PMNs from middle-aged subjects, while this stimulation decreased with age and was absent in PMNs of elderly arteriosclerotic patients. Li pretreatment slightly increased this stimulating effect of KE in PMNs from middle-aged subjects and elderly arteriosclerotic patients, while slightly decreased in healthy elderly subjects. Moreover, Li was able to increase superoxide anion production even in the absence of KE, but this effect decreased also in PMNs of healthy and arteriosclerotic elderly patients. FMLP significantly increased superoxide anion production in all age-groups, but this effect was further amplified by Li only in PMNs of middle-aged subjects. In aged individuals Li pretreatment slightly decreased the effect of FMLP and had no effect in arteriosclerotic patients. Ca-mobilization induced by KE was inhibited by Li pretreatement in each age group. This inhibition by Li was much weaker in FMLP-stimulated PMNs. Li pretreatment did however modify the shape of the Ca-transient curves in FMLP stimulated leukocytes suggesting a qualitative modification of ion channel regulation. No such shape change of Ca-transient curves was observed after KE stimulation of Li pretreated PMNs. It appears that the regulation of these two receptors is differently affected by Li treatment.


Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleus and Dispensable for Efficient Mitotic Exit.
Cdc14 phosphatase is a key regulator of exit from mitosis, acting primarily through antagonism of cyclin-dependent kinase, and is also thought to be important for meiosis. Cdc14 is released from its sequestration site in the nucleolus in two stages, first by the non-essential Cdc Fourteen Early Anaphase Release (FEAR) pathway and later by the essential Mitotic Exit Network (MEN), which drives efficient export of Cdc14 to the cytoplasm. We find that Cdc14 is confined to the nucleus during early mitotic anaphase release, and during its meiosis I release. Proteins whose degradation is directed by Cdc14 as a requirement for mitotic exit (e.g. the B-type cyclin, Clb2), remain stable during mitotic FEAR, a result consistent with Cdc14 being restricted to the nucleus and not participating directly in mitotic exit. Cdc14 released by the FEAR pathway has been proposed to have a wide variety of activities, all of which are thought to promote passage through anaphase. Proposed functions of FEAR include stabilization of anaphase spindles, resolution of the rDNA to allow its segregation, and priming of the MEN so that mitotic exit can occur promptly and efficiently. We tested the model for FEAR functions using the FEAR-deficient mutation net1-6cdk. Our cytological observations indicate that, contrary to the current model, FEAR is fully dispensable for timely progression through a series of anaphase landmarks and mitotic exit, although it is required for timely rDNA segregation. The net1-6cdk mutation suppresses temperature-sensitive mutations in MEN genes, suggesting that rather than activating mitotic exit, FEAR either inhibits the MEN or has no direct effect upon it. One interpretation of this result is that FEAR delays MEN activation to ensure that rDNA segregation occurs before mitotic exit. Our findings clarify the distinction between FEAR and MEN-dependent Cdc14 activities and will help guide emerging quantitative models of this cell cycle transition.


Cancer-associated fibroblasts in neoadjuvant setting for solid cancers.
Therapeutic approaches for cancer have become increasingly diverse in recent times. A comprehensive understanding of the tumor microenvironment (TME) holds great potential for enhancing the precision of tumor therapies. Neoadjuvant therapy offers the possibility of alleviating patient symptoms and improving overall quality of life. Additionally, it may facilitate the reduction of inoperable tumors and prevent potential preoperative micrometastases. Within the TME, cancer-associated fibroblasts (CAFs) play a prominent role as they generate various elements that contribute to tumor progression. Particularly, extracellular matrix (ECM) produced by CAFs prevents immune cell infiltration into the TME, hampers drug penetration, and diminishes therapeutic efficacy. Therefore, this review provides a summary of the heterogeneity and interactions of CAFs within the TME, with a specific focus on the influence of neoadjuvant therapy on the microenvironment, particularly CAFs. Finally, we propose several potential and promising therapeutic strategies targeting CAFs, which may efficiently eliminate CAFs to decrease stroma density and impair their functions.


Human erythrocyte clathrin and clathrin-uncoating protein.
Clathrin, a Mr = 72,000 clathrin-associated protein, and myosin were purified in milligram quantities from the same erythrocyte hemolysate fraction. Erythrocyte clathrin closely resembled brain clathrin in several respects: (a) both are triskelions as visualized by electron microscopy with arms 40 nm in length with globular ends and a flexible hinge region in the middle of each arm, and these triskelions assemble into polyhedral "cages" at appropriate pH and ionic strength; (b) both molecules contain heavy chains of Mr = 170,000 that are indistinguishable by two-dimensional maps of 125I-labeled peptides; and (c) both molecules contain light chains of Mr approximately 40,000 in a 1:1 molar ratio with the heavy chain. Erythrocyte clathrin is not identical to brain clathrin since antibody raised against the erythrocyte protein reacts better with erythrocyte clathrin than with brain clathrin and since brain clathrin contains two light chains resolved on sodium dodecyl sulfate gels while the light chain of erythrocyte clathrin migrates as a single band. The erythrocyte Mr = 72,000 clathrin-associated protein is closely related to a protein in brain that mediates ATP-dependent disassembly of clathrin from coated vesicles and binds tightly to clathrin triskelions (Schlossman, D. M., Schmid, S. L., Braell, W. A., and Rothman, J. E. (1984) J. Cell Biol. 99, 723-733). The erythrocyte and brain proteins have identical Mr on sodium dodecyl sulfate gels and identical maps of 125I-labeled peptides, share antigenic sites, and bind tightly to ATP immobilized on agarose. Clathrin and the uncoating protein are not restricted to reticulocytes since equivalent amounts of these proteins are present in whole erythrocyte populations and reticulocyte-depleted erythrocytes. Clathrin is present at 6,000 triskelions/cells, while the uncoating protein is in substantial excess at 250,000 copies/cell.


Extrahepatic Diseases and NAFLD: The Triangular Relationship between NAFLD, Type 2-Diabetes and Dysbiosis.
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases from simple steatosis with hepatic lipid accumulation to end-stage liver disease with decompensated cirrhosis, liver failure and hepatocellular carcinoma. Recent data from the USA showed that in 2013, NAFLD was the second most frequent indication for liver transplantation behind hepatitis C. Since there are now effective treatments for hepatitis C and there is currently no licensed treatment for NAFLD, it has been predicted that over the next 10-15 years, NAFLD will replace hepatitis C as the most frequent indication for liver transplantation. Besides, increasing the risk of hepatocellular carcinoma and end-stage liver disease, it has recently become clear that NAFLD also increases risk of extrahepatic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, cardiac diseases and chronic kidney disease, to name but a few. Of each of these extrahepatic diseases, the evidence to date suggests that NAFLD is a strong risk factor for T2DM. When NAFLD occurs in combination with obesity and insulin resistance (as it frequently does), there is a marked increase in risk of incident T2DM with possible synergism occurring between liver fat accumulation, insulin resistance and obesity to further increase risk of development of T2DM. Thus, there is a reciprocal relationship between NAFLD as a risk factor for T2DM, and T2DM as a risk factor for liver disease progression in NAFLD. Moreover, recent evidence now points to the importance of perturbation of the intestinal microbiota (dysbiosis) in both T2DM and NAFLD. Consequently, there is a triangular relationship between dysbiosis and T2DM and NAFLD. This review will focus on T2DM as a key extrahepatic complication of NAFLD and will describe and discuss the triangular relationship between dysbiosis and T2DM and NAFLD and the factors and potential mechanisms underpinning this relationship.


On the use of computational models for the quantitative assessment of surgery in congenital heart disease.
The surgical repair of congenital heart disease often involves significant modifications to the circulatory tree. Resections, reconstructions, graft insertions and the deployment of implants and biomedical devices have an impact on local and systemic haemodynamics, which may be difficult to foresee or to assess quantitatively by clinical investigation alone. Mathematical models can be employed to visualise, estimate or predict events and physical quantities that are difficult to observe or measure, and can be successfully applied to the study of the pre- and post-operative physiology of cardiovascular malformations. This paper analyses the potentialities of computation fluid dynamics in this respect, outlining the method, its requirements and its limitations. Examples are given of lumped parameter models, axi-symmetric models, three-dimensional models, fluid-structure interaction simulations and multiscale computing applied to total cavo-pulmonary connection, aortic coarctation and aortic arch reconstruction.


Different encoding of reward location in dorsal and intermediate hippocampus.
Hippocampal place cells fire at specific locations in the environment. They form a cognitive map that encodes spatial relations in the environment, including reward locations.1 As part of this encoding, dorsal CA1 (dCA1) place cells accumulate at reward.2-5 The encoding of learned reward location could vary between the dorsal and intermediate hippocampus, which differ in gene expression and cortical and subcortical connectivity.6 While the dorsal hippocampus is critical for spatial navigation, the involvement of intermediate CA1 (iCA1) in spatial navigation might depend on task complexity7 and learning phase.8-10 The intermediate-to-ventral hippocampus regulates reward-seeking,11-15 but little is known about the involvement in reward-directed navigation. Here, we compared the encoding of learned reward locations in dCA1 and iCA1 during spatial navigation. We used calcium imaging with a head-mounted microscope to track the activity of CA1 cells over multiple days during which mice learned different reward locations. In dCA1, the fraction of active place cells increased in anticipation of reward, but the pool of active cells changed with the reward location. In iCA1, the same cells anticipated multiple reward locations. Our results support a model in which the dCA1 cognitive map incorporates a changing population of cells that encodes reward proximity through increased population activity, while iCA1 provides a reward-predictive code through a dedicated subpopulation. Both of these location-invariant codes persisted over time, and together they provide a dual hippocampal reward location code, assisting goal-directed navigation.16,17.


Arthroscopic Treatment of Labral Tears of the Hip in Adolescents: Patterns of Clinical Presentation, Intra-articular Derangements, Radiological Associations and Minimum 2-Year Outcomes.
To report on patterns of clinical presentation, intra-articular derangements, radiological associations, and minimum 2-year outcomes after hip arthroscopy (HA) in patients 18 years or younger. This study was a retrospective case series on patients 18 years or younger who had undergone HA for labral tears that had failed nonoperative management from April 2008 to April 2013 with a minimum 2-year follow-up. Exclusion criteria were previous hip conditions or surgery. The following were recorded: demographic, examination, radiological and intraoperative findings, intraoperative procedures performed, patient-reported outcomes (PROs), and patient satisfaction. The PROs reported included the modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Sport-Specific Subscale, Hip Outcome Score-Activities of Daily Living, and Visual Analogue Score for pain. One hundred and two patients satisfied the inclusion criteria, of whom 90 (88.2%, 77 females and 13 males) had minimum 2-year follow-up. Females had increased external rotation in flexion (58.9° vs 50.0°, P = .041). Sixty-eight females had a Beighton's score of >4 compared to 6 males (P < .001). There was no distinct pattern within the group or between genders for radiological markers of acetabular coverage, depth, or version and femoral cam size. Mean femoral anteversion for females was 15.7° and for males 11.3°. Females had significantly smaller labral tears (1.73 hours vs 2.34 hours on the acetabular clock face, P = .028). Females were more likely to require a capsular plication and iliopsoas fractional lengthening (88.3% vs 46.2%, and 77.9% vs 38.5%, respectively). There was a significant improvement in all PRO measures in both males and females (P < .01), but females had lower preoperative and postoperative scores. Mean preoperative and postoperative PROs for males and females were as follows: modified Harris Hip Score 71.0/94.3 and 63.4/88.8, Hip Outcome Score-Activities of Daily Living 78.1/93.4 and 64.0/91.8, Hip Outcome Score-Sport-Specific Subscale 51.7/91.0 and 45.7/78.6, Non-Arthritic Hip Score 78.1/94.5 and 63.1/89.2, and visual analog score 4.77/1.85 and 6.29/2.21. The mean patient satisfaction score was 8.29 out of 10. Five patients (5.56%) required a revision procedure. HA is associated with improved outcomes and pain and high satisfaction scores at minimum 2-year follow-up in adolescent population. The pattern of labral injury is different in males and females and dictates the arthroscopic approach. Females are likely to require a capsular plication and iliopsoas release to address soft-tissue laxity and impingement. Level IV, therapeutic case series.


Bacterial infections of the lower genital tract in fertile and infertile women from the southeastern Poland.
The objective of the study was to investigate the detection rates of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis, Escherichia coli, Streptococcus agalactiae and Enterococcus faecalis, showing no clinical signs of an ongoing, acute inflammatory state of the vagina and/or the cenrvix, in fertile and infertile women. The study encompassed 161 women, including 101 women treated for infertility and 60 fertile women who had already given birth to healthy children. The material for the presence of C. trachomatis, N. gonorrhoeae, M. genitalium, M. hominis and U. urealyticum was collected from the cervical canal and analyzed by PCR. Furthermore, BD ProbeTec ET system was used to detect C. trachomatis infection. Vaginal swabs were collected for classification of bacterial vaginosis and aerobic vaginitis and assessed according to the Nugent score, as well as by traditional culture methods. U. urealyticum was identified in 9% of the infertile women and in 8% of controls. Presence of M. hominis was demonstrated only in the former (4%) and C. trachomatis only in latter (3%). N. gonorrhoeae and M. genitalium were not found in any of the examined women. The frequency of aerobic vaginitis in both groups was estimated at 12%. There were 7% bacterial vaginosis cases in the study group, and none in the control group (p=0.0096). Despite having no symptoms of an ongoing acute inflammation of the reproductive tract, many women may experience permanent or periodic shifts of equilibrium of the vaginal and/or cervical microflora. BV develops more frequently in infertile patients when compared to the fertile women.


Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial.
Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs -2.1; P<0.001) and the number of Headache Days per month (-8.8 vs -4.0; P=0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (-4.6 vs -1.2; P=0.01) and the n-6 in HUFA score (-21.0 vs -4.0%; P<0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P<0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P<0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population.


Atomic interaction networks in the core of protein domains and their native folds.
Vastly divergent sequences populate a majority of protein folds. In the quest to identify features that are conserved within protein domains belonging to the same fold, we set out to examine the entire protein universe on a fold-by-fold basis. We report that the atomic interaction network in the solvent-unexposed core of protein domains are fold-conserved, extraordinary sequence divergence notwithstanding. Further, we find that this feature, termed protein core atomic interaction network (or PCAIN) is significantly distinguishable across different folds, thus appearing to be "signature" of a domain's native fold. As part of this study, we computed the PCAINs for 8698 representative protein domains from families across the 1018 known protein folds to construct our seed database and an automated framework was developed for PCAIN-based characterization of the protein fold universe. A test set of randomly selected domains that are not in the seed database was classified with over 97% accuracy, independent of sequence divergence. As an application of this novel fold signature, a PCAIN-based scoring scheme was developed for comparative (homology-based) structure prediction, with 1-2 angstroms (mean 1.61A) C(alpha) RMSD generally observed between computed structures and reference crystal structures. Our results are consistent across the full spectrum of test domains including those from recent CASP experiments and most notably in the 'twilight' and 'midnight' zones wherein <30% and <10% target-template sequence identity prevails (mean twilight RMSD of 1.69A). We further demonstrate the utility of the PCAIN protocol to derive biological insight into protein structure-function relationships, by modeling the structure of the YopM effector novel E3 ligase (NEL) domain from plague-causative bacterium Yersinia Pestis and discussing its implications for host adaptive and innate immune modulation by the pathogen. Considering the several high-throughput, sequence-identity-independent applications demonstrated in this work, we suggest that the PCAIN is a fundamental fold feature that could be a valuable addition to the arsenal of protein modeling and analysis tools.


Efficient secretion of the model antigen M6-gp41E in Lactobacillus plantarum NCIMB 8826.
Four Lactobacillus strains (Lb. plantarum NCIMB 8826, Lb. paracasei LbTGS1.4, Lb. casei ATCC 393 and Lb. fermentum KLD) were tested for their ability to produce and secrete heterologous proteins. These strains were first screened with an alpha-amylase reporter under the control of a set of expression or expression/secretion signals from various lactic acid bacteria. With most of the constructions tested, the level of extracellular production was highest in Lb. plantarum NCIMB 8826, and lowest in Lb. paracasei LbTGS1.4. These two strains were next assayed using a model antigen consisting of the N-terminal part of the M6 protein from Streptococcus pyogenes fused to the linear epitope ELDKWAS from human immunodeficiency virus gp41 protein. Secretion of this heterologous protein was inefficient in Lb. paracasei LbTGS1.4, which accumulated a large intracellular pool of the unprocessed precursor, whereas Lb. plantarum NCIMB 8826 was able to secrete the antigen to a level as high as 10 mg l-1.


Inter Maxillary Fixation Versus Open Reduction for the Treatment of Mandibular Condyle Fractures: A Comparative Evaluation.
The treatment for fractured mandibular condyles aims at restoring the masticatory ability, occlusion, symmetry, and function as the bit were before the trauma. The treatment of the mandibular condylar fracture can be done based on the two protocols. The present clinical trial was conducted to collate aftertreatment upshot of closed treatment and open surgical treatment for mandibular condyle fractures. Forty-two patients were divided into two groups (n = 12) which were treated with either the closed reduction using intermaxillary fixation or open reduction and internal fixation. The following clinical parameters were assessed at 1st and 3rd day and at 1, 3, and 6 weeks: lateral excursion and protrusion, occlusion; interincisal opening, mandibular ramus height, deviation/deflection during jaw opening, and pain assessment using visual analog score. The collected data were subjected to statistical evaluation. Interincisal opening was found to be 8.125 ± 0.3467 mm and 6.016 ± 0.1528 mm, respectively, for Group I and Group II which was statistically significant (P < 0.00001). At the 3 months and 6th week postoperatively, it was increased in the surgical groups to 17.433 ± 0.3822 mm and 19.175 ± 0.3696 mm, respectively. The present trial suggests surgical open reduction and internal fixation treatment of the mandibular condylar fracture is better than the nonsurgical closed reduction in terms of interincisal opening, lateral excursion, and protrusive mandibular movement range.


Inverted and Programmable Poynting Effects in Metamaterials.
The Poynting effect generically manifests itself as the extension of the material in the direction perpendicular to an applied shear deformation (torsion) and is a material parameter hard to design. Unlike isotropic solids, in designed structures, peculiar couplings between shear and normal deformations can be achieved and exploited for practical applications. Here, a metamaterial is engineered that can be programmed to contract or extend under torsion and undergo nonlinear twist under compression. First, it is shown that the system exhibits a novel type of inverted Poynting effect, where axial compression induces a nonlinear torsion. Then the Poynting modulus of the structure is programmed from initial negative values to zero and positive values via a pre-compression applied prior to torsion. The work opens avenues for programming nonlinear elastic moduli of materials and tuning the couplings between shear and normal responses by rational design. Obtaining inverted and programmable Poynting effects in metamaterials inspires diverse applications from designing machine materials, soft robots, and actuators to engineering biological tissues, implants, and prosthetic devices functioning under compression and torsion.


Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. We searched the Cochrane Airways Group Specialised Register and reference lists of articles on eight separate occasions, the most recent being in September 2008. Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. One review author extracted data. We contacted study authors and drug companies for missing information. Twenty-eight trials involving 7042 participants were included. Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.04 per month, 95% confidence interval -0.05 to -0.03). Using a weighted annualised rate of exacerbations in the control patients of 2.4 per year, this is a 21% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval (CI) -0.77 to -0.35). One recent study has shown that the benefit may apply only to patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the mucolytic group (odds ratio (OR) 1.93 (95% CI 1.71 to 2.17)). There is no strong evidence of improvement in lung function and treatment is not associated with any increase in adverse effects. Patients on mucolytics may be less likely to be hospitalised during the study period. In participants with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. Mucolytics should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.


Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats.
To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Dams were killed on the 20th day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects: the fetal resorption amounted to approximately 60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severity of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.


Diversity studies of Salmonella incidents in some domestic livestock and their potential relevance as indicators of niche width.
This study attempts to determine whether or not livestock are becoming more susceptible to epidemics of salmonella infections by the analysis of published data on the annual number of reported infections in various animals. The number of incidents reported each year may be subject to a variety of biases due to temporal and geographical differences in reporting practices. This study analysed these reports by the calculation of diversity indices which are not subject to some of these potential biases. The relationship between the ecological concept of niche width and the diversity of species or types occupying that niche is discussed. The diversity of salmonella types reported in fowl has shown a highly significant decline over the 13-year period 1976-88. It is suggested that this declining diversity may be related to the declining niche width of the biotope available to this pathogen. Although speculative, this reduction in niche width could be related to a declining genetic diversity in the host animals or to an increasing intensification of animal husbandry.


Multilocus sequence typing of a global collection of Pasteurella multocida isolates from cattle and other host species demonstrates niche association.
Pasteurella multocida causes disease in many host species throughout the world. In bovids, it contributes to bovine respiratory disease (BRD) and causes haemorrhagic septicaemia (HS). Previous studies have suggested that BRD-associated P. multocida isolates are of limited diversity. A multilocus sequence typing (MLST) scheme for P. multocida was used to determine whether the low levels of diversity reported are due to the limited discriminatory power of the typing method used, restricted sample selection or true niche association. Bovine respiratory isolates of P. multocida (n = 133) from the UK, the USA and France, collected between 1984 and 2008 from both healthy and clinically affected animals, were typed using MLST. Isolates of P. multocida from cases of HS, isolates from other host species and data from the MLST database were used as comparison. Bovine respiratory isolates were found to be clonal (I(S)(A) 0.45) with 105/128 belonging to clonal complex 13 (CC13). HS isolates were not related to bovine respiratory isolates. Of the host species studied, the majority had their own unique sequence types (STs), with few STs being shared across host species, although there was some cross over between porcine and bovine respiratory isolates. Avian, ovine and porcine isolates showed greater levels of diversity compared to cattle respiratory isolates, despite more limited geographic origins. The homogeneity of STs of bovine respiratory P. multocida observed, and the differences between these and P. multocida subpopulations from bovine non-respiratory isolates and non-bovine hosts may indicate niche association.


DNA methylation as a therapeutic target in hematologic disorders: recent results in older patients with myelodysplasia and acute myeloid leukemia.
DNA methylation provides a major epigenetic code (besides histone modification) of the lineage- and development-specific genes (such as regulators of differentiation in the hematopoietic lineages) that control expression of normal cells. However, DNA methylation is also involved in malignancies because aberrant methylating gene activity occurs during leukemic transformation. Thus, genes such as tumor suppressor genes, growth-regulatory genes, and adhesion molecules are often silenced in various hematopoietic malignancies by epigenetic inactivation via DNA hypermethylation. This inactivation is frequently seen not only in transformed cell lines but also in primary leukemia cells. Because this defect is amenable to reversion by pharmacologic means, agents that inhibit DNA methylation have been developed to specifically target this hypermethylation defect in leukemia and preleukemia cases. The most clinically advanced agents, the azanucleosides 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine), were discovered more than 25 years ago, when their methylation-inhibitory activities, even at low concentrations, became apparent. Although both of these agents, like cytarabine, had been clinically used until then at high doses, the redevelopment of these agents for low-dose schedules has revealed very interesting clinical activities for treating myelodysplasia (MDS) and acute myeloid leukemia (AML). Because these diseases occur mostly in patients over 60 years of age, low-dose schedules with these compounds provide a very promising approach in such patient groups by virtue of their low nonhematologic toxicity profiles. In the present review, we describe the development of treatments that target DNA hypermethylation in MDS and AML, and clinical results are presented. In addition, pharmacologic DNA demethylation may be viewed as a platform for biological modification of malignant cells to become sensitized (or resensitized) to secondary signals, such as differentiating signals (retinoids, vitamin D3) and hormonal signals (eg, estrogen receptor in breast cancer cells, androgen receptor in prostate cancer cells). Finally, an in vitro synergism between the reactivating potency of demethylating agents and inhibitors of histone deacetylation has been tested in several pilot studies of AML and MDS treatment. Finally, gene reactivation by either group of compounds results in therapeutically meaningful reactivation of fetal hemoglobin in patients with severe hemoglobinopathies, extending the therapeutic range of derepressive epigenetic agents to nonmalignant hematopoietic disorders.


Divergent selection on, but no genetic conflict over, female and male timing and rate of reproduction in a human population.
The sexes often have different phenotypic optima for important life-history traits, and because of a largely shared genome this can lead to a conflict over trait expression. In mammals, the obligate costs of reproduction are higher for females, making reproductive timing and rate especially liable to conflict between the sexes. While studies from wild vertebrates support such sexual conflict, it remains unexplored in humans. We used a pedigreed human population from preindustrial Finland to estimate sexual conflict over age at first and last reproduction, reproductive lifespan and reproductive rate. We found that the phenotypic selection gradients differed between the sexes. We next established significant heritabilities in both sexes for all traits. All traits, except reproductive rate, showed strongly positive intersexual genetic correlations and were strongly genetically correlated with fitness in both sexes. Moreover, the genetic correlations with fitness were almost identical in men and women. For reproductive rate, the intersexual correlation and the correlation with fitness were weaker but again similar between the sexes. Thus, in this population, an apparent sexual conflict at the phenotypic level did not reflect an underlying genetic conflict over the studied reproductive traits. These findings emphasize the need for incorporating genetic perspectives into studies of human life-history evolution.


Characterisation of antioxidants in photosynthetic and non-photosynthetic leaf tissues of variegated Pelargonium zonale plants.
Hydrogen peroxide is an important signalling molecule, involved in regulation of numerous metabolic processes in plants. The most important sources of H2 O2 in photosynthetically active cells are chloroplasts and peroxisomes. Here we employed variegated Pelargonium zonale to characterise and compare enzymatic and non-enzymatic components of the antioxidative system in autotrophic and heterotrophic leaf tissues at (sub)cellular level under optimal growth conditions. The results revealed that both leaf tissues had specific strategies to regulate H2 O2 levels. In photosynthetic cells, the redox regulatory system was based on ascorbate, and on the activities of thylakoid-bound ascorbate peroxidase (tAPX) and catalase. In this leaf tissue, ascorbate was predominantly localised in the nucleus, peroxisomes, plastids and mitochondria. On the other hand, non-photosynthetic cells contained higher glutathione content, mostly located in mitochondria. The enzymatic antioxidative system in non-photosynthetic cells relied on the ascorbate-glutathione cycle and both Mn and Cu/Zn superoxide dismutase. Interestingly, higher content of ascorbate and glutathione, and higher activities of APX in the cytosol of non-photosynthetic leaf cells compared to the photosynthetic ones, suggest the importance of this compartment in H2 O2 regulation. Together, these results imply different regulation of processes linked with H2 O2 signalling at subcellular level. Thus, we propose green-white variegated leaves as an excellent system for examination of redox signal transduction and redox communication between two cell types, autotrophic and heterotrophic, within the same organ.


Base composition at mtDNA boundaries suggests a DNA triple helix model for human mitochondrial DNA large-scale rearrangements.
Different mechanisms have been proposed to account for mitochondrial DNA (mtDNA) instability based on the presence of short homologous sequences (direct repeats, DR) at the potential boundaries of mtDNA rearrangements. Among them, slippage-mispairing of the replication complex during the asymmetric replication cycle of the mammalian mitochondrial DNA has been proposed to account for the preferential localization of deletions. This mechanism involves a transfer of the replication complex from the first neo-synthesized heavy (H) strand of the DR1, to the DR2, thus bypassing the intervening sequence and producing a deleted molecule. Nevertheless, the nature of the bonds between the DNA strands remains unknown as the forward sequence of DR2, beyond the replication complex, stays double-stranded. Here, we have analyzed the base composition of the DR at the boundaries of mtDNA deletions and duplications and found a skewed pyrimidine content of about 75% in the light-strand DNA template. This suggests the possible building of a DNA triple helix between the G-rich neo-synthesized DR1 and the base-paired homologous G.C-rich DR2. In vitro experiments with the purified human DNA polymerase gamma subunits enabled us to show that the third DNA strand may be used as a primer for DNA replication, using a template with the direct repeat forming a hairpin, with which the primer could initiate DNA replication. These data suggest a novel molecular basis for mitochondrial DNA rearrangements through the distributive nature of the DNA polymerase gamma, at the level of the direct repeats. A general model accounting for large-scale mitochondrial DNA deletion and duplication is proposed. These experiments extend to a DNA polymerase from an eucaryote source the use of a DNA triple helix strand as a primer, like other DNA polymerases from phage and bacterial origins.


Use of Oxygen Pulse in Predicting Doppler-Derived Maximal Stroke Volume in Adolescents.
Clinical exercise physiologists and physicians administering stress tests in the young have used oxygen pulse as a surrogate measure of stroke volume. It is important to recognize 1) the accuracy of O₂ pulse in predicting maximal stroke volume during exercise, and 2) the normal pattern of O₂ pulse during a progressive exercise test. This study examined both of these issues in a cohort of 44 healthy adolescent males and females (ages 14-16 years) who performed routine progressive cycle exercise to exhaustion. Gas exchange variables were measured by standard open circuit techniques. Stroke volume at rest and during exercise was assessed by the Doppler ultrasound method. At peak exercise O₂ pulse correlated closely with stroke volume (r = .73) with a SEE of 12.6 ml·beat⁻¹. Values of maximal O₂ pulse in nonathletic boys and girls were 13.3 ± 2.5 and 11.0 ± 1.7 ml·beat⁻¹, respectively. After the initial workload, a steady rise was observed in O₂ pulse, entirely reflecting an increasing arterial venous oxygen difference, with a slope of approximately 4 ml/beat per 100 watts work load. The findings support the use of O₂ pulse as a valid predictor of stroke volume during exercise in youth with a moderately high level of accuracy.


Differences in the clinical and radiological presentation of intrathoracic tuberculosis in the presence or absence of HIV infection.
To describe the differences in the clinical and radiological presentation of tuberculosis in the presence or absence of HIV infection. A sample of 231 consecutive adults with active pulmonary tuberculosis admitted to a tuberculosis hospital were studied, assessing HIV infection, AIDS, and associated factors, as well as re-evaluating chest X-rays. There were 113 HIV-positive patients (49%) Comparing the 113 HIV-positive patients (49%) to the 118 HIV-negative patients (51%), the former presented a higher frequency of atypical pulmonary tuberculosis (pulmonary lesions accompanied by intrathoracic lymph node enlargement), hematogenous tuberculosis, and pulmonary tuberculosis accompanied by superficial lymph node enlargement, as well as presenting less pulmonary cavitation. The same was found when HIV-positive patients with AIDS were compared to those without AIDS. There were no differences between the HIV-positive patients without AIDS and the HIV-negative patients. Median CD4 counts were lower in HIV-positive patients with intrathoracic lymph node enlargement and pulmonary lesions than in the HIV-positive patients with pulmonary lesions only (47 vs. 266 cells/mm3; p < 0.0001), in HIV-positive patients with AIDS than in those without AIDS (136 vs. 398 cells/mm3; p < 0.0001) and in patients with atypical pulmonary tuberculosis than in those with other forms of tuberculosis (31 vs. 258 cells/mm3; p < 0.01). Atypical forms and disseminated disease predominate among patients with advanced immunosuppression. In regions where TB prevalence is high, the presence of atypical pulmonary tuberculosis or pulmonary tuberculosis accompanied by superficial lymph node enlargement should be considered an AIDS-defining condition.


Analysing the predictive capacity and dose-response of wellness in load monitoring.
This study aimed to identify the predictive capacity of wellness questionnaires on measures of training load using machine learning methods. The distributions of, and dose-response between, wellness and other load measures were also examined, offering insights into response patterns. Data (n= 14,109) were collated from an athlete management systems platform (Catapult Sports, Melbourne, Australia) and were split across three sports (cricket, rugby league and football) with data analysis conducted in R (Version 3.4.3). Wellness (sleep quality, readiness to train, general muscular soreness, fatigue, stress, mood, recovery rating and motivation) as the dependent variable, and sRPE, sRPE-TL and markers of external load (total distance and m.min-1) as independent variables were included for analysis. Classification and regression tree models showed high cross-validated error rates across all sports (i.e., > 0.89) and low model accuracy (i.e., < 5% of variance explained by each model) with similar results demonstrated using random forest models. These results suggest wellness items have limited predictive capacity in relation to internal and external load measures. This result was consistent despite varying statistical approaches (regression, classification and random forest models) and transformation of wellness scores. These findings indicate practitioners should exercise caution when interpreting and applying wellness responses.


Structure of a human gastrin gene.
A gastrin gene was isolated from a genomic library of human DNA. The human gastrin gene is about 4100 base pairs long and contains two intervening sequences. Thus, a 3500-base-pair intervening sequence is located 5 base pairs proximal to the ATG initiator codon, while a 129-base-pair intervening sequence separates the region coding for the principal hormonal form of gastrin, the heptadecapeptide, from the region coding for the major amino-terminal portion of the gastrin precursor. The 5' flanking region of the gene contains the conserved sequences, T-A-T-A-A and G-A-C-T-C-A-T-A-T, in positions similar to those of other eukaryotic genes.


Cardiac 18F-dopamine positron emission tomography predicts the type of phenoconversion of pure autonomic failure.
Pure autonomic failure (PAF) is a rare disease characterized by neurogenic orthostatic hypotension (nOH), no known secondary cause, and lack of a neurodegenerative movement or cognitive disorder. Clinically diagnosed PAF can evolve ("phenoconvert") to a central Lewy body disease [LBD, e.g., Parkinson's disease (PD) or dementia with Lewy bodies (DLB)] or to the non-LBD synucleinopathy multiple system atrophy (MSA). Since cardiac 18F-dopamine-derived radioactivity usually is low in LBDs and usually is normal in MSA, we hypothesized that patients with PAF with low cardiac 18F-dopamine-derived radioactivity would be more likely to phenoconvert to a central LBD than to MSA. We reviewed data from all the patients seen at the National Institutes of Health Clinical Center from 1994 to 2023 with a clinical diagnosis of PAF and data about 18F-dopamine positron emission tomography (PET). Nineteen patients (15 with low 18F-dopamine-derived radioactivity, 4 with normal radioactivity) met the above criteria and had follow-up data. Nine (47%) phenoconverted to a central synucleinopathy over a mean of 6.6 years (range 1.5-18.8 years). All 6 patients with low cardiac 18F-dopamine-derived radioactivity who phenoconverted during follow-up developed a central LBD, whereas none of 4 patients with consistently normal 18F-dopamine PET phenoconverted to a central LBD (p = 0.0048), 3 evolving to probable MSA and 1 upon autopsy having neither a LBD nor MSA. Cardiac 18F-dopamine PET can predict the type of phenoconversion of PAF. This capability could refine eligibility criteria for entry into disease-modification trials aimed at preventing evolution of PAF to symptomatic central LBDs.


Isolation of active polyribosomes from the cytoplasm, mitochondria and chloroplasts of Euglena gracilis.
1. A procedure is described for the isolation of intact polyribosomes from the cytoplasm, chloroplasts and mitochondria of Euglena gracilis. 2. All three polyribosomal preparations incorporated labelled amino acids in a system in vitro. The cytoplasmic system was inhibited by chcloheximide but not by chloramphenicol. Both the chloroplast and the mitochondrial systems, however, were inhibited by chloramphenicol but not by cycloheximide. It is shown that mitochondrial polyribosomes, like the polyribosomes from cytoplasm and chloroplasts, can participate directly in protein synthesis without supplementary mRNA being added to the synthesizing system, as in previously reported instances. 3. Sedimentation coefficients were measured for the ribosomes, ribosomal subunits, and rRNA of the cytoplasm, chloroplasts and mitochondria. 4. The G+C content was 55% for cytoplasmic rRNA, 50% for chloroplast rRNA, and 29% for mitochondrial rRNA. 5. The cytoplasmic ribosomal subunits contained a ribonuclease activity that was inhibited by heparin.


PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays.
Immune checkpoint blockade (ICB) drugs are a novel, effective treatment for advanced urothelial carcinoma. Worldwide, several different ICB drugs are approved, each developed and clinically validated with a specific PD-L1 compound diagnostic assay. As a result, PD-L1 testing workflows in routine practice are complex: requiring multiple assays across two platforms, with each assay having a different method of interpretation. Our service tested 1,401 urothelial carcinoma cases for PD-L1 expression, using both the 22C3 PharmDx assay (required prior to Pembrolizumab therapy) and SP142 assay (required prior to Atezolizumab therapy). Of the 1,401 cases tested, 621 cases (44%) were tested with both the 22C3 PharmDx and SP142 assays, 492 cases (35%) with 22C3 PharmDx only, and 288 cases (21%) with SP142 only. Each assay was used and interpreted according to the manufacturer's guidelines. The rate of positivity we observed was 26% with the 22C3 assay and 31% with the SP142 assay, similar to the pre-licensing studies for both drugs. The discrepancy observed between the assays was 11%, which reinforces the requirement for utilisation of the correct assay for each agent, and limits potential cross-utility of assays. This aspect must be considered when setting up a PD-L1 testing strategy in laboratories where both Pembrolizumab and Atezolizumab are available for the treatment of urothelial carcinoma but also has broader implications for testing of other cancers where multiple ICB drugs and their respective assays are approved.


Out of the bottleneck: the Diversity Outcross and Collaborative Cross mouse populations in behavioral genetics research.
The historical origins of classical laboratory mouse strains have led to a relatively limited range of genetic and phenotypic variation, particularly for the study of behavior. Many recent efforts have resulted in improved diversity and precision of mouse genetic resources for behavioral research, including the Collaborative Cross and Diversity Outcross population. These two populations, derived from an eight way cross of common and wild-derived strains, have high precision and allelic diversity. Behavioral variation in the population is expanded, both qualitatively and quantitatively. Variation that had once been canalized among the various inbred lines has been made amenable to genetic dissection. The genetic attributes of these complementary populations, along with advances in genetic and genomic technologies, makes a systems genetic analyses of behavior more readily tractable, enabling discovery of a greater range of neurobiological phenomena underlying behavioral variation.


[Proton stereotaxic therapy of cerebral arteriovenous aneurysms].
Stereotaxic proton beam therapy using narrow beams (5-10 mm at 50% of isodose) at the energy of 100 MeV in single irradiation and the delivery of absorbed doses, the maximum dosage being 40-80 Gy, was provided to 99 patients with arteriovenous brain aneurysms. An analysis of the therapeutic results based on angiography data was performed in 50 patients with arteriovenous malformations with the volume up to 10 cm3. A positive effect was obtained in 31 of 50 patients.


Feasibility of T-cell receptor gamma (TCRgamma) gene rearrangement on formalin-fixed, paraffin-embedded tissues by PCR assays.
T- and B-lymphocytes are involved in recognition of foreign antigen by the specificity of their surface T-cell receptor and immunoglobulin, generated by gene rearrangement. Each T- and B-lymphocyte carries unique rearranged TCR or immunoglobulin gene, which has been applied to detect clonal from non-clonal T- and B-cell proliferation. Paraffin-embedded biopsy tissues of 85 T-, 24 B-cell non-Hodgkin's lymphomas (NHL) of various subtypes, and seven reactive lymphoid hyperplasia were retrieved from the archives for determining the feasibility of TCRgamma gene rearrangement analysis by PCR assays in our laboratory. DNA was extracted by Proteinase K digestion. The analyses were performed by five PCR assays, and analysed on polyacrylamide gel. Clonal TCRgamma gene rearrangement was demonstrated in 69/85 (81.2%) of the cases. Selective rearrangement of specific Vgamma segment was observed, especially in peripheral T-cell lymphoma-unspecified and nasal NK/T-cell lymphoma. Clonal TCRgamma rearranged band was also demonstrated in 4/24 (16.7%) and 2/7 (28.6%) of B-NHL and reactive lymphoid tissues respectively. PCR assays were able to demonstrate clonal TCRgamma gene rearrangement in a high proportion of T-NHL. However, the PCR results should be interpreted carefully. A neoplasm should only be considered as T-cell type if it does not express any B-cell marker because TCRgamma is not lineage specific as shown by the presence of clonal TCRgamma gene rearrangement in B-NHL. Hence, the results for TCR gene rearrangement should always be interpreted in conjunction with histology and immunophenotyping.


Vulnerability of xylem vessels to cavitation in sugar maple. Scaling from individual vessels to whole branches.
The relation between xylem vessel age and vulnerability to cavitation of sugar maple (Acer saccharum Marsh.) was quantified by measuring the pressure required to force air across bordered pit membranes separating individual xylem vessels. We found that the bordered pit membranes of vessels located in current year xylem could withstand greater applied gas pressures (3.8 MPa) compared with bordered pit membranes in vessels located in older annular rings (2.0 MPa). A longitudinal transect along 6-year-old branches indicated that the pressure required to push gas across bordered pit membranes of current year xylem did not vary with distance from the growing tip. To understand the contribution of age-related changes in vulnerability to the overall resistance to cavitation, we combined data on the pressure thresholds of individual xylem vessels with measurements of the relative flow rate through each annual ring. The annual ring of the current year contributed only 16% of the total flow measured on 10-cm-long segments cut from 6-year-old branches, but it contributed more than 70% of the total flow when measured through 6-year-old branches to the point of leaf attachment. The vulnerability curve calculated using relative flow rates measured on branch segments were similar to vulnerability curves measured on 6-year-old branches (pressure that reduces hydraulic conductance by 50% = 1.6-2.4 MPa), whereas the vulnerability curve calculated using relative flow rates measured on 6-year-old branches were similar to ones measured on the extension growth of the current year (pressure that reduces hydraulic conductance by 50% = 3.8 MPa). These data suggest that, in sugar maple, the xylem of the current year can withstand larger xylem tensions than older wood and dominates water delivery to leaves.


Disconnection analysis of CA3 and DG in mediating encoding but not retrieval in a spatial maze learning task.
The dentate gyrus (DG) subregion of the hippocampus has been shown to be involved in encoding but not retrieval in a spatial maze task (modified Hebb-Williams maze). The first experiment in this study examined whether a lesion to the CA3 would contribute to a similar encoding deficit. A DG group was included in order to replicate previous results. Relative to controls, animals receiving CA3 lesions were impaired in encoding, not retrieval, on the modified Hebb-Williams maze--similar to a group that received DG lesions. This suggests the possibility that CA3 and DG are working together to mediate encoding processes. The second experiment in this study was designed to test the interaction between CA3 and DG using a disconnection paradigm. Animals with contralateral lesions (CA3 lesioned in one hemisphere, DG lesioned in the other hemisphere) showed a significant disruption effect on encoding, but not retrieval, when compared with animals with ipsilateral lesions (CA3 and DG lesioned in the same hemisphere, leaving the other hemisphere intact). This suggests an interaction between CA3 and DG in supporting encoding but not retrieval processes in a spatial maze learning task.


A-D-A Type Nonfullerene Acceptors Synthesized by Core Segmentation and Isomerization for Realizing Organic Solar Cells with Low Nonradiative Energy Loss.
Reducing non-radiative recombination energy loss (ΔEnonrad ) in organic solar cells (OSCs) has been considered an effective method to improve device efficiency. In this study, the backbone of PTBTT-4F/4Cl is divided into D1-D2-D3 segments and reconstructed. The isomerized TPBTT-4F/4Cl obtains stronger intramolecular charge transfer (ICT), thus leading to elevated highest occupied molecular orbital (HOMO) energy level and reduced bandgap (Eg ). According to ELoss = Eg- qVOC , the reduced Eg and enhanced open circuit voltage (VOC ) result in lower ELoss , indicating that ELoss has been effectively suppressed in the TPBTT-4F/4Cl based devices. Furthermore, compared to PTBTT derivatives, the isomeric TPBTT derivatives exhibit more planar molecular structure and closer intermolecular stacking, thus affording higher crystallinity of the neat films. Therefore, the reduced energy disorder and corresponding lower Urbach energy (Eu ) of the TPBTT-4F/4Cl blend films lead to low ELoss and high charge-carrier mobility of the devices. As a result, benefitting from synergetic control of molecular stacking and energetic offsets, a maximum power conversion efficiency (PCE) of 15.72% is realized from TPBTT-4F based devices, along with a reduced ΔEnonrad of 0.276 eV. This work demonstrates a rational method of suppressing VOC loss and improving the device performance through molecular design engineering by core segmentation and isomerization.


Confronted With Death: Factors Affecting End of Life Decisions in the Intensive Care Unit.
To determine how often care is limited at the end of life and the factors that are associated with this decision, we reviewed the medical records of all patients that passed away in the intensive care units (ICU) of Aga Khan University. We found that a majority of patients had Do-Not-Resuscitate orders in place at the time of death. Our analysis yielded 6 variables that were associated with the decision to limit care. These are patient age, sex, duration of mechanical ventilation, Glasgow Coma Scale (GCS) ≤8 at any point during ICU stay, GCS ≤8 in the first 24 hours following ICU admission, and mean arterial pressure <65 mm of Hg while on vasopressors in the first 24 hours following ICU admission. These variables require further study and should be carefully considered during end of life discussions to allow for optimal management at the end of life.


Serengeti ungulates: feeding selectivity influences the effectiveness of plant defense guilds.
Association of Themeda triandra, a palatable grass species, with less palatable plants protected it from grazing by two comparatively unselective herbivores, wildebeest and African buffalo. Grazing on T. triandra by two more selective herbivores, Thomson's gazelle and zebra, was not related to the relative abundance of less palatable plants. The differential effectiveness of plant defense guilds against different ungulates may contribute to the high species diversity of the East African grazer fauna.


Dynamics of Clostridium genus and hard-cheese spoiling Clostridium species in anaerobic digesters treating agricultural biomass.
Biogas plants are a widespread renewable energy technology. However, the use of digestate for agronomic purposes has often been a matter of concern. It is controversial whether biogas plants might harbor some pathogenic clostridial species, which represent a biological risk. Moreover, the inhabitance of Clostridium hard-cheese spoiling species in anaerobic digesters can be problematic for hard-cheese manufacturing industries, due to the issue of cheese blowing defects. This study investigated the effect of mesophilic anaerobic digestion processes on the Clostridium consortia distribution over time. Specifically, three lab-scale CSTRs treating agricultural biomass were characterized by considering both the whole microbial community and the cultivable clostridial spores. It is assessed an overall reduction of the Clostridium genus during the anaerobic digestion process. Moreover, it was evidenced a slight, but steady decrease of the cultivable clostridial spores, mainly represented by two pathogenic species, C. perfringens and C. bifermentans, and one hard-cheese spoiling species, C. butyricum. Thus, it is revealed an overall reduction of the clostridial population abundance after the mesophilic anaerobic digestion treatment of agricultural biomass.


Primary cerebellar glioblastoma multiforme.
Primary glioblastoma multiforme of cerebellar hemispheres in adults is a rare condition. Most of them result from dedifferentiation of astrocytoma to glioblastoma. We present two cases of unusual de novo cerebellar glioblastomas, one of which is the giant-cell variant. We review their clinical behaviour with conventional MR imaging features and discuss the key findings that can lead to the correct diagnosis in sight of new MR imaging technologies.


Giant oral tumor in a child with malnutrition and sickle cell trait: Anesthetic challenges.
Pediatric oral tumors have always been challenging for the even most skilled anesthesiologists. The conventional method of awake intubation is not realistic in this age group. The management is to chart out a plan to intubate the child post induction. We describe successful management of a case of giant of ossifying fibroma in a child with sickle cell trait where non-conventional innovate approach helped us to secure the airway pre-operatively and avoid possible medical complications.


Endovascular management of iliac aneurysmal disease with hypogastric artery preservation.
Common iliac artery aneurysms (CIAAs) pose a challenge in endovascular aneurysm repair. Aneurysm repair of CIAA traditionally requires embolization of the ipsilateral hypogastric artery (HA). Symptoms of buttock claudication and more feared complications of pelvic ischemia make HA preservation an appealing addition to aneurysm repair. In this review, we discuss various methods of CIAA repair with devices specifically designed for aneurysm repair and other custom techniques of HA preservation.


Timing is Everything: Stochastic Optogenetic Stimulation Reduces Adaptation in Retinal Ganglion Cells.
Optogenetics gives us unprecedented power to investigate brain connectivity. The ability to activate neural circuits with single cell resolution and its ease of application has provided a wealth of knowledge in brain function. More recently, optogenetics has shown tremendous utility in prosthetics applications, including vision restoration for patients with retinitis pigmentosa. One of the disadvantages of optogenetics, however, is its poor temporal bandwidth, i.e. the cell's inability to fire at a rate that matches the optical stimulation rate at high frequencies (>30 Hz). This research proposes a new strategy to overcome the temporal limits of optogenetic stimulation. Using whole-cell current clamp recordings in mouse retinal ganglion cells expressing channelrhodopsin-2 (H134R variant), we observed that randomizing inter-pulse intervals can significantly increase a retinal ganglion cell's temporal response to high frequency stimulation.Clinical Relevance- A significant disadvantage of optogenetic stimulation is its poor temporal dynamics which prohibit its widespread use in retinal prosthetics. We have shown that randomizing the interval between stimulation pulses reduces adaptation in retinal ganglion cells. This stimulation strategy may contribute to new levels of functional restoration in therapeutics which incorporate optogenetics.


Hox gene evolution in nematodes: novelty conserved.
The conserved homeobox (Hox) gene cluster is neither conserved nor clustered in the nematode Caenorhabditis elegans. Instead, C. elegans has a reduced and dispersed gene complement that is the result the loss of Hox genes in stages throughout its evolutionary history. The roles of Hox genes in patterning the nematode body axis are also divergent, although there are tantalising remnants of ancient regulatory systems. Hox patterning also differs greatly between C. elegans and a second 'model' nematode, Pristionchus pacificus. The pattern of Hox gene evolution may be indicative of the move to deterministic developmental modes in nematodes.