Nitric oxide-derived nitrate anion contributes to endotoxic shock and multiple organ injury/dysfunction.
Because nitrate represents the major end-product of nitric oxide in vivo and can affect enzyme activity, cell electrophysiological functions, and cell membrane integrity, we hypothesized that overaccumulated nitric oxide-derived nitrate anion in tissues or organs in vivo may contribute to endotoxic shock and multiple organ injury/dysfunction during endotoxemia. Prospective, experimental animal study. Laboratory at a university hospital. Sprague-Dawley rats. Rats were injected intraperitoneally with 5, 10, or 20 mg/kg lipopolysaccharide or saline and were studied in groups at 0, 6, 12, and 24 hrs. Significant differences were seen between nitrate concentrations in the heart, lung, kidney, liver, brain, aorta, diaphragm, spleen, thymus, testis or ovary, hind limb muscle, intestine, adipose tissue, bone, bladder, urine and plasma, which imply a nitrate gradient between intracellular and extracellular compartments. Lipopolysaccharide significantly increased nitrate concentration at 12 hrs in most tissues and organs, except in the brain, adipose tissue, and muscle. It increased more in plasma than in tissues. The lipopolysaccharide dose-dependent nitrate concentration was observed only in the aorta and lungs. The nitrate concentration change was paralleled by the systemic inflammatory response syndrome, as indicated by alterations of myeloperoxidase activity and by impaired histologic and cellular membrane integrity in tissues and organs. Mean arterial pressure was negatively correlated with nitrate concentration modifications in the aorta during 24 hrs of endotoxemia. These results collectively indicate that overaccumulated nitric oxide-derived nitrate anion in tissues or organs in vivo contributes to endotoxic shock and multiple organ injury/dysfunction during endotoxemia.


An analysis of the predictive value of the HIV Ag/Ab screening assay within the performance characteristics of the DiaSorin LIAISON XL for the detection of blood-borne viruses.
Correct identification of blood borne viral infections, such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is crucial in detection and follow up of infection in patients. We evaluated the diagnostic performance of the DiaSorin LIAISON XL (LIAISON XL) for screening of HBV, HCV and HIV infection. In addition, we investigated the variability of the signal-to-cuttoff ratio (S/CO) of the LIAISON XL HIV Ag/Ab assay and it's predictive value in subsequent confirmation of HIV-1 infection. We analyzed 16,497 blood samples on which HBV, HCV and HIV screening was performed. We defined A) archived samples previously tested with an arbitrary result in the Abbott ARCHITECT i2000SR system; B) prospectively collected samples which were simultaneously tested on the LIAISON XL and ARCHITECT i2000SR; C) prospectively collected serum samples for HIV testing which were tested solely on the LIAISON XL. The agreements of HBV-, HCV-, and HIV markers between the two compared systems are remarkably high. Among the samples which were prospectively tested for HIV Ab/Ag on the LIASON XL, 229 (1.6%) were reactive of which 141 (61.6%) could be confirmed. Increasing the signal-to-cutoff value to 4 could increase the positive predictive value (PPV) to 88.1% without decreasing sensitivity. The LIAISON XL system proved to be an excellent system for diagnosing HBV, HCV, and HIV. Our data for the first time showed that increasing the HIV S/CO ratio was safe and increased the PPV for confirmed HIV infection in the tested population.


Microsatellite instability and loss of heterozygosity in primary breast tumours.
Allelic imbalance or loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour suppressor genes. We looked for evidence of microsatellite instability (MI) and LOH on chromosome 7q, 10q, 11p and 17q using seven polymorphic microsatellite markers. In 42 paired breast cancer-peripheral blood DNA samples we identified 24 tumours (57%) exhibiting genetic alterations. Twenty-one specimens exhibited LOH (50%), while 11 specimens exhibited MI (26%) in at least one microsatellite marker. The most frequent incidence of LOH was found for the marker THRA1 (8/33, 24%) indicating that thra I gene becomes a strong candidate tumour suppressor gene, whereas of MI it was D10S109 (3/26, 12%). These MI and LOH data were analysed using a range of clinicopathological parameters. Tumours displaying MI with no evidence of LOH and tumours exhibiting MI and LOH belonging to stage II or III were found, however none were at stage I. These data suggest that MI may be an early event in mammary tumorigenesis whereas LOH occurs at a late stage. A significant association between the absence of oestrogen receptors (p < 0.01) and the absence of both oestrogen and progesterone receptors (p < 0.001) at 17q21 were observed, indicating a possible relationship between specific genetic changes at this region and hormonal deregulation in the progression of breast cancer.


Effect of casein infusion in the rumen, duodenum or both sites on factors affecting forage intake and performance of dairy cows fed red clover-grass silage.
Four lactating dairy cows were used in a balanced 4 x 4 Latin square design to examine the effects of casein infusion in the rumen, duodenum, or both on the intake of red clover-grass silage, chewing behavior, diet digestion, microbial protein synthesis, rumen fermentation, digestion, and passage kinetics, milk production, and milk composition. Duodenal infusion increased eating time, silage intake, rumen neutral detergent fiber pool, yields of milk, protein, and lactose, and concentration of milk protein, and tended to decrease that of milk fat. Ruminal infusion tended to decrease eating time, and increased significantly microbial protein synthesis, rumen ammonia-N concentration, molar proportions of isovalerate and valerate, digestion rate of digestible neutral detergent fiber, passage rate of indigestible neutral detergent fiber, and milk urea content, and decreased rumen neutral detergent fiber pool. Silage intake, and yields of milk, protein, and lactose were highest when casein was simultaneously infused in both sites.


Luteinizing Hormone To Follicle Stimulating Hormone Ratio In Patients With Polycystic Ovary Syndrome.
Polycystic ovary syndrome is the most commonly occurring endocrinopathy in females of reproductive age group. It is characterized by a wide range of signs and symptoms resulting from hormonal derangements leading to reduced fertility. This was a crosssectional (comparative) study. We took 40 cases of polycystic ovary syndrome and 40 controls of infertility without polycystic ovary syndrome depending on the presence of clinical features and ultrasound scans. Blood samples were collected and assayed for luteinizing hormone and follicle stimulating hormone. Data was analyzed with SPSS-19. Luteinizing hormone to follicle stimulating hormone ratio was raised in 3 out of 35 patients (8%) in cases and in 2 out of 39 patients (5%) in controls. There was no statistically significant difference in the luteinizing hormone levels and the follicle stimulating hormone levels and the luteinizing hormone to follicle stimulating hormone ratio of the two groups as indicated by a p-value> 0.05. Luteinizing hormone to follicle stimulating hormone ratio was not found to be raised in majority of the polycystic ovary syndrome patients included in this study.


Extracting depth information of 3-dimensional structures from a single-view X-ray Fourier-transform hologram.
We demonstrate how information about the three-dimensional structure of an object can be extracted from a single Fourier-transform X-ray hologram. In contrast to lens-based 3D imaging approaches that provide depth information of a specimen utilizing several images from different angles or via adjusting the focus to different depths, our method capitalizes on the use of the holographically encoded phase and amplitude information of the object's wavefield. It enables single-shot measurements of 3D objects at coherent X-ray sources. As the ratio of longitudinal resolution over transverse resolution scales proportional to the diameter of the reference beam aperture over the X-ray wavelength, we expect the approach to be particularly useful in the extreme ultraviolet and soft-X-ray regime.


Educational therapy for the failing and frustrated student offender.
Methods of treatment are described for meeting the needs of the failing and frustrated student offender. Attention is given to both the public school and juvenile justice setting for the following areas of treatment: classroom management systems, curriculum and instructional adjustment, counseling and support services, and alternative educational programming.


Feeding methods for the preterm infant.
As more very immature preterm infants survive, provision of enteral feedings has become a major focus of concern. Although many aspects of gastrointestinal function are immature in the preterm infant, the ability of the preterm neonate to process and absorb enteral nutrients appears to be adequate enough to sustain nutritional needs. Few prospective randomized trials have compared the efficacy of different feeding methods. However, some studies have compared differing routes of feeding, rates of feeding, and volume of feeding. The ability to successfully digest enteral feedings may be inhibited or enhanced by pharmacological agents. The need to modify a feeding strategy can be monitored by tracking several measurements prospectively. Finally, there is a need to assess ongoing dietary needs of preterm infants for discharge planning.


Poly[(μ(3)-benzene-1,3,5-tricarboxyl-ato-κO:O:O)(μ(2)-2-methyl-imidazolato-κN:N')tris-(2-methyl-imidazole-κN)dizinc(II)].
Hydro-thermal reaction involving zinc nitrate hexa-hydrate, tris-odium benzene-1,3,5-tricarboxyl-ate (Na(3)BTC) and 2-methyl-imidazole (2-MeImH) yielded the title compound, [Zn(2)(C(9)H(3)O(6))(C(4)H(5)N(2))(C(4)H(6)N(2))(3)]. In this mixed-ligand metal-organic compound, Zn(2+) ions are coordinated by N atoms from 2-MeImH mol-ecules and (2-MeIm)(-) ions, as well as by O atoms from (BTC)(3-) ions. This results in two different distorted tetra-hedra, viz. ZnN(3)O and ZnN(2)O(2). These tetra-hedra are inter-connected via (BTC)(3-) ions and N:N'-bridging (2-MeIm)(-) ions, thus forming a layered structure in the bc plane. Hydrogen bonds between the O atoms of carboxyl-ate ions and NH groups of 2-MeImH ligands link the layers into a three-dimensional structure.


Secretagogue-stimulated pancreatic secretion is differentially regulated by constitutive NOS isoforms in mice.
Nitric oxide (NO) and NO synthase (NOS) play controversial roles in pancreatic secretion. NOS inhibition reduces CCK-stimulated in vivo pancreatic secretion, but it is unclear which NOS isoform is responsible, because NOS inhibitors lack specificity and three NOS isoforms exist: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). Mice having individual NOS gene deletions were used to clarify the NOS species and cellular interactions influencing pancreatic secretion. In vivo secretion was performed in anesthetized mice by collecting extraduodenal pancreatic duct juice and measuring protein output. Nonselective NOS blockade was induced with N(omega)-nitro-L-arginine (L-NNA; 10 mg/kg). In vivo pancreatic secretion was maximal at 160 pmol.kg(-1).h(-1) CCK octapeptide (CCK-8) and was reduced by NOS blockade (45%) and eNOS deletion (44%). Secretion was unaffected by iNOS deletion but was increased by nNOS deletion (91%). To determine whether the influence of NOS on secretion involved nonacinar events, in vitro CCK-8-stimulated secretion of amylase from isolated acini was studied and found to be unaltered by NOS blockade and eNOS deletion. Influence of NOS on in vivo secretion was further examined with carbachol. Protein secretion, which was maximal at 100 nmol.kg(-1).h(-1) carbachol, was reduced by NOS blockade and eNOS deletion but unaffected by nNOS deletion. NOS blockade by L-NNA had no effect on carbachol-stimulated amylase secretion in vitro. Thus constitutive NOS isoforms can exert opposite effects on in vivo pancreatic secretion. eNOS likely plays a dominant role, because eNOS deletion mimics NOS blockade by inhibiting CCK-8 and carbachol-stimulated secretion, whereas nNOS deletion augments CCK-8 but not carbachol-stimulated secretion.


Synaptic and nonsynaptic ictogenesis occurs at different temperatures in submerged and interface rat brain slices.
To investigate the temperature sensitivity of low-Ca2+-induced nonsynaptic and low-Mg2+-induced synaptic ictogenesis under submerged and interface conditions, we compared changes of extracellular field potential and extracellular potassium concentration at room temperature (23 +/- 1 degrees C; mean +/- SD) and at 35 +/- 1 degrees C in hippocampal-entorhinal cortex slices. The induction of spontaneous epileptiform activity under interface conditions occurred at 35 +/- 1 degrees C in both models. In contrast, under submerged conditions, spontaneous epileptiform activity in low-Mg2+ artificial cerebrospinal fluid (ACSF) was observed at 35 +/- 1 degrees C, whereas epileptiform discharges induced by low-Ca2+ ACSF occurred only at room temperature. To investigate the different temperature effects under submerged and interface conditions, measurements of extra- and intracellular pH and extracellular space volume were performed. Lowering the temperature from 35 +/- 1 degrees C to room temperature effected a reduction in extracellular pH under submerged and interface conditions. Under submerged conditions, temperature changes had no significant influence on the intracellular pH in presence of either normal or low-Mg2+ ACSF. In contrast, application of low-Ca2+ ACSF effected a significant increase in intracellular pH at room temperature but not at 35 +/- 1 degrees C under submerged conditions. Therefore increasing intracellular pH by lowering the temperature in low-Ca2+ ACSF may push slices to spontaneous epileptiform activity by opening gap junctions. Finally, extracellular space volume significantly decreased by switching from submerged to interface conditions. The reduced extracellular space volume under interface conditions may lead to an enlarged ephaptic transmission and therefore promotes low-Mg2+- and low-Ca2+-induced spontaneous epileptiform activity. The results of the study indicate that gas-liquid interface and total-liquid submerged slice states impart distinct physiological parameters on brain tissue.


FSH and TSH binding to their respective receptors: similarities, differences and implication for glycoprotein hormone specificity.
The crystal structures of the leucine-rich repeat domain (LRD) of the FSH receptor (FSHR) in complex with FSH and the TSH receptor (TSHR) LRD in complex with the thyroid-stimulating autoantibody (M22) provide opportunities to assess the molecular basis of the specificity of glycoprotein hormone-receptor binding. A comparative model of the TSH-TSHR complex was built using the two solved crystal structures and verified using studies on receptor affinity and activation. Analysis of the FSH-FSHR and TSH-TSHR complexes allowed identification of receptor residues that may be important in hormone-binding specificity. These residues are in leucine-rich repeats at the two ends of the FSHR and the TSHR LRD structures but not in their central repeats. Interactions in the interfaces are consistent with a higher FSH-binding affinity for the FSHR compared with the binding affinity of TSH for the TSHR. The higher binding affinity of porcine (p)TSH and bovine (b)TSH for human (h)TSHR compared with hTSH appears not to be dependent on interactions with the TSHR LRD as none of the residues that differ among hTSH, pTSH or bTSH interact with the LRD. This suggests that TSHs are likely to interact with other parts of the receptors in addition to the LRD with these non-LRD interactions being responsible for affinity differences. Analysis of interactions in the FSH-FSHR and TSH-TSHR complexes suggests that the alpha-chains of both hormones tend to be involved in the receptor activation process while the beta-chains are more involved in defining binding specificity.


An abnormal activated partial thromboplastin time clotting waveform is associated with high mortality and a procoagulant state.
We studied the associations of a biphasic waveform identified in 61 consecutive patients by activated partial thromboplastin times performed with an MDA 180 coagulation analyzer (bioMérieux Inc., Durham, NC, USA). The patients were encountered in a wide range of locations, including medical and surgical services, emergency and outpatient departments, and intensive care unit. The patients encountered also had a variety of clinical diagnoses. Of the patients, 42.6% were dead on follow-up evaluation at 3 months, and 67.2% had a clinical condition known to predispose to the development of disseminated intravascular coagulation (DIC). Sepsis was the most frequent associated condition and was present in 54% of the patients. Only 6 patients had overt DIC according to a standardized scoring system. However, D-dimer was elevated in 90% of patients, and antithrombin III and protein C levels decreased in 75.4% and 63.9%, respectively. The platelet count was decreased in 26%. Our results indicated that a biphasic waveform is associated with high mortality in general hospital patients and is frequently associated with sepsis. This waveform appears to be associated with a consumptive procoagulant state, which may represent early or nonovert DIC.


Shared neural underpinnings of multisensory integration and trial-by-trial perceptual recalibration in humans.
Perception adapts to mismatching multisensory information, both when different cues appear simultaneously and when they appear sequentially. While both multisensory integration and adaptive trial-by-trial recalibration are central for behavior, it remains unknown whether they are mechanistically linked and arise from a common neural substrate. To relate the neural underpinnings of sensory integration and recalibration, we measured whole-brain magnetoencephalography while human participants performed an audio-visual ventriloquist task. Using single-trial multivariate analysis, we localized the perceptually-relevant encoding of multisensory information within and between trials. While we found neural signatures of multisensory integration within temporal and parietal regions, only medial superior parietal activity encoded past and current sensory information and mediated the perceptual recalibration within and between trials. These results highlight a common neural substrate of sensory integration and perceptual recalibration, and reveal a role of medial parietal regions in linking present and previous multisensory evidence to guide adaptive behavior.


Depressed-type submucosal colon cancer: report of a case.
The article presents one of very few Korean reports on the detection of depressed early colorectal cancers, which have been cited by some Japanese doctors as another pathway for the development of colon cancers. Depressed-type early colorectal cancers have mainly been reported in Japan, and recently a few have also been reported in Western countries. Depressed early colorectal cancers are still rarely detected in Korea, where most colorectal surgeons, endoscopists, and radiologists refer to Western guidelines. Recently, the authors experienced a typical 12-mm depressed-type early colon cancer in the ascending colon of a 55-year-old Korean male patient. It was detected by a colonoscopic examination. The lesion was flexible on insufflation and deflation with air and was considered an early colon cancer. Because of the large size, a surgical resection was performed. The final pathologic result was a minimally invasive submucosal cancer without lymph node metastasis. This Korean case is one of very few reported abroad, so we think that it might make an important contribution to research on depressed-type early colorectal cancer.


Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts.
Rats have a natural tendency to spend more time exploring novel objects than familiar objects, and this preference can be used as an index of object recognition. Rats also show an exploratory preference for objects in locations where they have not previously encountered objects (an index of place memory) and for familiar objects in contexts different from those in which the objects were originally encountered (an index of context memory). In this experiment, rats with cytotoxic lesions of the hippocampal formation were tested on all three versions of the novelty-preference paradigm, with a 5-min retention interval between the familiarization and test phases. Rats with sham lesions displayed a novelty preference on all three trial types, whereas the rats with hippocampal lesions displayed a novelty preference on Object trials but did not discriminate between the objects on Place trials or Context trials. The findings indicate that hippocampal damage impairs memory for contextual or spatial aspects of an experience, whereas memory for objects that were part of the same experience are left relatively intact.


Stochastic process leading to wave equations in dimensions higher than one.
Stochastic processes are proposed whose master equations coincide with classical wave, telegraph, and Klein-Gordon equations. Similar to predecessors based on the Goldstein-Kac telegraph process, the model describes the motion of particles with constant speed and transitions between discreet allowed velocity directions. A new ingredient is that transitions into a given velocity state depend on spatial derivatives of other states populations, rather than on populations themselves. This feature requires the sacrifice of the single-particle character of the model, but allows to imitate the Huygens' principle and to recover wave equations in arbitrary dimensions.


[Clinical characteristics of patients infected with Chlamydia pneumoniae in Beijing from 2015 to 2019].
Objective: To aralyze the clinical characteristics of Chlamydia pneumoniae infection in Beijing. Methods: Based on Beijing Respiratory Pathogen Surveillance System, acute respiratory infection patients were recruited from 35 different types of sentinel hospitals in Beijing. Their epidemiological and clinical data were systematically collected and clinical specimens were also obtained. Nuclear acid testing was performed for 30 types of respiratory pathogens (including Chlamydia pneumoniae). The identified patients of Chlamydia pneumoniae infection were divided into two groups, the acute upper respiratory tract infection (AURI) group and pneumoniae group. The differences in clinical characteristics, laboratory examination and prognosis were compared by using independent sample t test, Mann-Whitney U test, χ2 test or Fisher's exact probability test. Results: A total of 119 patients of Chlamydia pneumoniae infection were included, including 12 patients in the AURI group and 107 patients in pneumoniae group. Chlamydia pneumoniae infection mainly occurred in people aged from 5 to 44 years, accounting for 81.5% (97/119). The three most common clinical symptoms were cough (92.4%, 110/119), fever (88.8%, 95/107), and sputum production (76.5%, 91/119). White blood cell counts increased in 39.3% (46/117) of patients. Neutrophile granulocyte proportion increased in 39.7% (46/116) of patients. Platelet count increased in 36.9% (41/111) of patients. An increase of the creatine kinase MB isoenzyme (CKMB) was observed in 12 pneumonia patients (24.5%, 12/49). Radiological examination showed that 90.6% (87/105) of patients in the pneumoniae group had pulmonary parenchymal changes; the lesion occurred most commonly in the lower right lung lobe (34.3%, 36/105) and the lower left lung lobe (27.6%, 29/105). Although 73.8% (79/107) of patients in the pneumoniae group were hospitalized, no case received intensive care unit or mechanical ventilation. As to outcomes, one patient developed respiratory failure and 6 patients suffered myocardial injury. No death was observed in this study. The median days of hospitalization and course of illness for pneumonia patients M(P25,P75) were 10.0 (7.0, 13.0) days and 18.0 (13.5, 22.0) days, respectively. Conclusion: Generally, Chlamydia pneumoniae infections in Beijing from 2015 to 2019 were mild, and the main clinical manifestations were cough, fever and sputum. However, most patients in the pneumoniae group caused by Chlamydia pneumoniae still required hospitalization but with a better outcome.


Surgical modifications in bladder neck reconstruction and vesicourethral anastomosis during radical retropubic prostatectomy to reduce bladder neck contractures.
We describe surgical modifications in radical retropubic prostatectomy (RRP) which have significantly reduced the incidence of bladder neck contractures (BNC). Between March 1994-July 2005, 977 men underwent a RRP by a single surgeon. Group I comprised 548 patients operated upon July 1994-December 1999, without the modifications described below. Group II comprised 429 men operated upon January 2000-December 2004, with the following surgical modifications: 1) reconstruction of the bladder neck (BN) to a diameter of 28 French; 2) placement of the posterior (6 o'clock) vesicourethral suture on mild traction before placing this suture into the bladder, allowing inspection and, if necessary, replacement of any of the previously placed sutures; 3) bladder displacement when tying the vesicourethral sutures which allows the sutures to be tied under direct vision and prevents incorporation of extraneous tissue. Data were retrospectively analyzed. Demographic data were comparable between groups. In group I, 31/548 (5.7%) developed a BNC compared to 1/429 (0.2%) in Group II, p < 0.001. Urinary continence (no pads/maximum of one light pad for security in 24 hours) at 12 months in the 32 patients who developed a BNC was worse when compared to patients who did not develop a BNC (58% versus 80%, p = 0.003). After excluding the patients who developed a BNC, continence rates were comparable between both groups. The positive margin rate at the BN was not adversely affected by these modifications. Simple, easily applied modifications to the management of the BN and vesicourethral anastomosis can substantially reduce the incidence of BNC.


Characterization of Fragile X Mental Retardation Protein granules formation and dynamics in Drosophila.
FMRP is an evolutionarily conserved protein that is highly expressed in neurons and its deficiency causes fragile X mental retardation syndrome. FMRP controls the translation of target mRNAs in part by promoting their dynamic transport in neuronal RNA granules. We have previously shown that high expression of mammalian FMRP induces formation of granules termed FMRP granules. These RNA granules are reminiscent of neuronal granules, of stress granules, as well as of the recently described in vitro-assembled granules. In contrast with mammalian FMRP, which has two paralog proteins, Drosophila FMRP (dFMRP) is encoded by a single gene that has no paralog. Using this genetically simple organism, we investigated formation and dynamics of FMRP granules. We found that increased expression of dFMRP in Drosophila cells induces the formation of dynamic dFMRP RNA granules. Mutagenesis studies identified the N-terminal protein-protein domain of dFMRP as a key determinant for FMRP granules formation. The RGG RNA binding motif of dFMRP is dispensable for dFMRP granules formation since its deletion does not prevent formation of those granules. Deletion of the RGG motif reduced, however, dFMRP trafficking between FMRP granules and the cytosol. Similarly, deletion of a large part of the KH RNA binding motif of dFMRP had no effect on formation of dFMRP-granules, but diminished the shuttling activity of dFMRP. Our results thus suggest that the mechanisms controlling formation of RNA granules and those promoting their dynamics are uncoupled. This study opens new avenues to further elucidate the molecular mechanisms controlling FMRP trafficking with its associated mRNAs in and out of RNA granules.


GABAergic and glutamatergic effects on nigrostriatal and mesolimbic dopamine release in the rat.
In this review, a series of experiments is presented, in which γ-amino butyric acid (GABA)ergic and glutamatergic effects on dopamine function in the rat nigrostriatal and mesolimbic system was systematically assessed after pharmacological challenge with GABAA receptor (R) and and N-methyl d-aspartate (NMDA)R agonists and antagonists. In these studies, [123I]iodobenzamide binding to the D2/3R was mesured in nucleus accumbens (NAC), caudateputamen (CP), substantia nigra/ventral tegmental area (SN/VTA), frontal (FC), motor (MC) and parietal cortex (PC) as well as anterior (aHIPP) and posterior hippocampus (pHIPP) with small animal SPECT in baseline and after injection of either the GABAAR agonist muscimol (1 mg/kg), the GABAAR antagonist bicuculline (1 mg/kg), the NMDAR agonist d-cycloserine (20 mg/kg) or the NMDAR antagonist amantadine (40 mg/kg). Muscimol reduced D2/3R binding in NAC, CP, SN/VTA, THAL and pHIPP, while, after amantadine, decreases were confined to NAC, CP and THAL. In contrast, d-cycloserine elevated D2/3R binding in NAC, SN/VTA, THAL, frontal cortex, motor cortex, PC, aHIPP and pHIPP, while, after bicuculline, increases were confined to CP and THAL. Taken together, similar actions on regional dopamine levels were exterted by the GABAAR agonist and the NMDAR antagonist on the one side and by the GABAAR antagonist and the NMDAR agonist on the other, with agonistic action, however, affecting more brain regions. Thereby, network analysis suggests different roles of GABAARs and NMDARs in the mediation of nigrostriatal, nigrothalamocortical and mesolimbocortical dopamine function.


The dimensions of the human dentogingival junction.
This study examined the naturally occurring dimensions of the dentogingival junction in 10 adult human cadaver jaws. The connective tissue attachment, epithelial attachment, loss of attachment, and sulcus depth were measured histomorphometrically for 171 tooth surfaces. Mean measurements were 1.34 +/- 0.84 mm for sulcus depth; 1.14 +/- 0.49 mm for epithelial attachment; 0.77 +/- 0.32 mm for connective tissue attachment; and 2.92 +/- 1.69 mm for loss of attachment. These dimensions, as measured in this study, support the concept that the connective tissue attachment is a variable width within a more narrow distribution and range than the epithelial attachment, sulcus depth, or loss of attachment. The level of the loss of attachment was not predictive of the connective tissue attachment length.


Conversion of fused hips to low friction arthroplasty.
Fifty-four hips converted to low friction arthroplasty between 1965 and 1975 have been reviewed one to eleven years after operation. In many cases malposition had led to degenerative changes in the opposite hip, the lumbar spine or the knee, often with severe loss of function due to pain. It was found that total replacement could give useful relief of pain and improved function, though the range of movement obtained was not as good as in primary replacement. An outstanding feature was the correction of inequality of leg length. In general, the results were much better in cases of ankylosis acquired in adult life than in cases of spontaneous fusion after sepsis in childhood. The most important complication was a single case of sciatic palsy.


Comparison Between Transimpedance Matrix (TIM) Measurement and X-ray Fluoroscopy for Intraoperative Electrode Array Tip Fold-Over Detection.
The aim of this study was to compare Transimpedance Matrix (TIM-) measurement and X-ray fluoroscopy for the intraoperative detection of electrode array tip fold-over in cochlear implant recipients. Retrospective agreement study. Tertiary referral hospital. Forty-two patients (47 ears) consecutively implanted with the Slim Modiolar Electrode. Five raters, with different levels of clinical experience, individually retrospectively evaluated the TIM-heatmaps and X-ray fluoroscopy images of all patients included in this study for electrode array tip fold-over. Agreement between raters' individual evaluation and the diagnosis given during clinical intraoperative evaluation for both modalities, as well as the inter-method agreement between TIM-measurement and fluoroscopy, and the inter-rater agreement for both modalities. A tip fold-over was found in three of the forty-seven implantations (6.4%) included in this study. The average agreement between raters' evaluation and the intraoperative evaluation was 88% (Cohens κ = 0.378) for fluoroscopy and 99% (Cohens κ = 0.915) for TIM-measurement. Two raters misdiagnosed at least one tip fold-over as being correctly positioned when evaluating the fluoroscopy images (1/3 and 3/3, respectively). Each of the raters correctly detected all three tip fold-overs using the TIM-heatmaps. The inter-rater agreement for fluoroscopy was classified as "fair" (Fleiss' κ = 0.286), while the inter-rater agreement for TIM-measurement was classified as "near-perfect" (Fleiss' κ = 0.850). TIM-measurement has a high potential to replace X-ray fluoroscopy for intraoperatively detecting electrode array tip fold-over in cochlear implantation, especially in patients implanted with flexible, precurved arrays.


Experimental and Computational Modeling of the Effects of Voice Therapy Using Tubes.
Purpose Phonations into a tube with the distal end either in the air or submerged in water are used for voice therapy. This study explores the effective mechanisms of these therapy methods. Method The study applied a physical model complemented by calculations from a computational model, and the results were compared to those that have been reported for humans. The effects of tube phonation on vocal tract resonances and oral pressure variation were studied. The relationships of transglottic pressure variation in time Ptrans ( t) versus glottal area variation in time GA( t) were constructed. Results The physical model revealed that, for the phonation on [u:] vowel through a glass resonance tube ending in the air, the 1st formant frequency ( F1 ) decreased by 67%, from 315 Hz to 105 Hz, thus slightly above the fundamental frequency ( F0 ) that was set to 90-94 Hz . For phonation through the tube into water, F1 decreased by 91%-92%, reaching 26-28 Hz, and the water bubbling frequency Fb ≅ 19-24 Hz was just below F1 . The relationships of Ptrans ( t) versus GA( t) clearly differentiate vowel phonation from both therapy methods, and show a physical background for voice therapy with tubes. It is shown that comparable results have been measured in humans during tube therapy. For the tube in air, F1 descends closer to F0 , whereas for the tube in water, the frequency Fb occurs close to the acoustic-mechanical resonance of the human vocal tract. Conclusion In both therapy methods, part of the airflow energy required for phonation is substituted by the acoustic energy utilizing the 1st acoustic resonance. Thus, less flow energy is needed for vocal fold vibration, which results in improved vocal efficiency. The effect can be stronger in water resistance therapy if the frequency Fb approaches the acoustic-mechanical resonance of the vocal tract, while simultaneously F0 is voluntarily changed close to F1.


Exceptional Multiple Foreign-Body Ingestion by a Patient with Schizophrenia.
Swallowing foreign body in adult is uncommon. This mostly occurs accidentally or in psychologically unsound patient. A 32-years-old male patient with abdominal pain admitted in surgery department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh with a history of swallowing various objects. After endoscopic confirmation and psychological evaluation he underwent laparotomy and 29 different objects were removed from his stomach by Gastrotomy. He was psychiatrically evaluated after recovery from operation and was found to be suffering from Schizophrenia with cannabis use. The aim of reporting this case can raise awareness at the patients complains should be taken seriously to prevent morbidity and even mortality.


miR-382 functions as a tumor suppressor against esophageal squamous cell carcinoma.
To explore the effect of miR-382 on esophageal squamous cell carcinoma (ESCC) in vitro and its possible molecular mechanism. Eca109 cells derived from human ESCC and Het-1A cells derived from human normal esophageal epithelium were used. Lentivirus-mediated miR-382 was overexpressed in Eca109 cells. The effect of miR-382 on cell proliferation was evaluated by MTT and colony formation assay. For cell cycle analysis, cells were fixed and stained for 30 min with propidium iodide (PI) staining buffer containing 10 mg/mL PI and 100 mg/mL RNase A, and analyzed by BD FACSCalibur™ flow cytometer. For cell apoptosis assay, cells were stained with an Annexin V-FITC/PI Apoptosis Detection Kit according to the manufacturer's instructions and analyzed by a dual-laser flow cytometer. Cell invasion and migration abilities were determined through use of transwell chambers, non-coated or pre-coated with matrigel. Levels of proteins related to cell growth and migration were examined by western blotting. Endogenous miR-382 was down-regulated in Eca109 cells compared with Het-1A. Introduction of miR-382 not only significantly inhibited proliferation and colony formation, but also arrested cell cycle at the G2/M phase, as well as promoted apoptosis and autophagy in Eca109 cells. Migration, invasion and epithelial-mesenchymal transition of Eca109 cells were suppressed by overexpressing miR-382. Western blotting results showed that miR-382 inhibited the phosphorylation of mTOR and 4E-BP1. miR-382 functions as a tumor suppressor against ESCC development and metastasis, and could be considered as a potential drug source for the treatment of ESCC patients.


Lymphatic absorption of docosahexaenoic acid given as monoglyceride, diglyceride, triglyceride, and ethyl ester in rats.
Lymphatic absorption of docosahexaenoic acids (DHA) given as monoglyceride (MG), consisting of 1(or 3)-species (9 1.4%), 2-species (4.2%) and diglyceride (DG) consisting of 1,3-species (70.8%), 1(or 3),2-species (28.6%), were investigated in comparison with that of triglyceride (TG) and ethyl ester (EE). Rats were infused with a lipid emulsion containing 200 mg of DHA-MG, DG, TG, or EE via a gastric cannula. Lymph was collected through the thoracic lymph duct at 2 h intervals for 10 h and at a single collection from 10 to 30 h. Physiological saline containing glucose was infused (2 mL/h) throughout the lymph collection. The overall recovery of DHA at 30 h after its infusion was significantly higher in the rank order DHA-MG>DG>TG=EE. Moreover, time-dependent changes in recovery rates from 2 to 10 h of DHA given as MG were significantly higher than those of the corresponding DG, TG, and EE. These results indicate that DHA-MG and DG are absorbed and transported more effectively than TG and EE forms under restricted water supply, even if they mainly consist of 1(or 3)-species. Lymph lipids were mainly transported as TG, and a large amount of DHA was incorporated into a TG fraction in all fat types examined. Furthermore, the intramolecular distribution of DHA in lymph TG was similar in all groups. docosahexaenoic acid, monoglyceride, diglyceride triglyceride, ethyl ester


Somatostatin analogs in pregnant patients with neuroendocrine tumor.
Somatostatine analogs (SSAs) are currently indicated in the treatment of acromegaly and neuroendocrine tumors (NETs). Actually, pregnancy in patients with acromegaly and NETs does not represent an exceptional event because reproductive behavior has changed in the last decades and patients with NETs show more frequently long-term survival. The safety profile of SSAs during pregnancy is still controversial. Concerning acromegaly, based on case reports and series, SSAs administration during pregnancy seems to be relatively well tolerated. Concerning patients with NETs, up to date only one patient with NET receiving SSA during pregnancy has been reported in literature. We report two cases of gastroenteropancreatic-NET patients receiving SSA lanreotide for the entire course of their pregnancy, with favorable outcomes for both mothers and babies. Our experience supports the possibility to continue safely SSA lanreotide during pregnancy in patients with NET.


A randomised controlled trial on the efficacy of advance care planning on the quality of end-of-life care and communication in patients with COPD: the research protocol.
Recent research shows that advance care planning (ACP) for patients with chronic obstructive pulmonary disease (COPD) is uncommon and poorly carried out. The aim of the present study was to explore whether and to what extent structured ACP by a trained nurse, in collaboration with the chest physician, can improve outcomes in Dutch patients with COPD and their family. A multicentre cluster randomised controlled trial in patients with COPD who are recently discharged after an exacerbation has been designed. Patients will be recruited from three Dutch hospitals and will be assigned to an intervention or control group, depending on the randomisation of their chest physician. Patients will be assessed at baseline and after 6 and 12 months. The intervention group will receive a structured ACP session by a trained nurse. The primary outcomes are quality of communication about end-of-life care, symptoms of anxiety and depression, quality of end-of-life care and quality of dying. Secondary outcomes include concordance between patient's preferences for end-of-life care and received end-of-life care, and psychological distress in bereaved family members of deceased patients. Intervention and control groups will be compared using univariate analyses and clustered regression analysis. Ethical approval was received from the Medical Ethical Committee of the Catharina Hospital Eindhoven, the Netherlands (NL42437.060.12). The current project provides recommendations for guidelines on palliative care in COPD and supports implementation of ACP in the regular clinical care. NTR3940.


Additional chemotherapy and salvage surgery for poor response to chemoradiotherapy in rectal cancers.
A proportion of locally advanced rectal cancer patients who receive neoadjuvant chemoradiotherapy (NACRT) are still unresectable. This study was undertaken to assess the outcomes of giving additional chemotherapy to rectal cancer patients with unresectable disease after NACRT. Patients with poor response to NACRT where mesorectal fascia was still involved on MRI and R0 resection was doubtful, received additional four cycles of chemotherapy with either CAPOX or FOLFIRINOX regimen, and the response was reevaluated with MRI and reassessed for surgical resection. Between June 2012 and December 2014, 50 patients received additional chemotherapy with CAPOX regime (19%, 38%) or FOLFIRINOX (31%, 62%) after CRT. Median number of chemotherapy cycles received was four (range 2-8 cycles). Overall 34 (68%) patients underwent exploration and 31 (62%) underwent R0 resection. The median time to surgery following chemoradiation was 5 months (range 3-18 months). Complete pathological response was seen in seven (22%) patients. Patients with poor response to NACRT may be further downstaged using additional chemotherapy so as to achieve R0 resection in 62% of cases.


Non-expression of HLA-A*2901102 N is caused by a nucleotide exchange in the mRNA splicing site at the beginning of intron 4.
We describe the identification of the novel human leukocyte antigen (HLA) blank allele A*2901102 N which was detected in an individual of mixed race. The serological HLA class I typing was A1; B7,44 whereas PCR-SSP indicated the presence of an additional A*29 allele. The pedigree analysis demonstrated that the new blank allele segregated with the haplotype A*29null B*07, inherited from the individual's Vietnamese father. A single G-->Tau transversion was detected at position 1 of intron 4, which is a highly conserved nucleotide position in vertebrate splice donor sites. Accordingly, it is very likely that this nucleotide exchange inhibits the splicing of intron 4, resulting in a premature stop codon further downstream. Despite this alteration, transcription into mRNA was demonstrated.


Biomarkers in the diagnosis of aspiration syndromes.
Recognizing and managing the different types of aspiration events remain a challenging task due to the lack of distinguishing clinical or laboratory characteristics. Numerous biomarkers in serum, sputum and bronchoalveolar lavage have been studied, and their role in the recognition of aspiration remains controversial at this time. Recent animal investigations using an array of biomarkers based on distinct pathogenic features of each aspiration event have produced promising results; however, they have not been validated in humans. Newer markers are being introduced as diagnostic and prognostic tools in conditions such as community-acquired pneumonia and sepsis, but they have not been examined in aspiration. The present review summarizes the different biomarkers that have been studied in aspiration and those who might have a potential clinical use in the future.


Pancreatic microcirculatory changes in experimental pancreatitis of graded severity in the rat.
A technique with two complementary methods, intravital microscopy (IVM) and diffuse reflectance spectroscopy (DRS), was developed to analyze pancreatic tissue perfusion. After initial in vivo and in vitro validation of the techniques, we studied pancreatic microcirculation in models of mild, moderate, and severe pancreatitis. Anesthetized Sprague-Dawley rats were randomly allocated to the three models or to serve as controls. Stable systemic hemodynamic parameters were maintained with normal saline solution infusion. Exocrine capillary perfusion was assessed by IVM; hemoglobin oxygenation and hemoglobin content were measured by DRS. Capillary perfusion in mild pancreatitis initially increased significantly at 30 minutes to 155% +/- 38% of baseline values but returned to baseline within 3 hours. Hemoglobin content and oxygen saturation remained stable. In moderate and severe pancreatitis capillary perfusion significantly decreased versus the control group to 12% +/- 6% and 6% (range, 0% to 14%) of baseline values, respectively, at 6 hours. Oxygen saturation decreased significantly in moderate pancreatitis from 48.5% +/- 2.3% to 41.6% +/- 3.5% (p < 0.05) and in severe pancreatitis from 47.2% +/- 1.5% to 38.9% +/- 0.5% (p < 0.05), whereas hemoglobin content did not change. We conclude that (1) IVM and DRS provide both unique and complementary data on tissue perfusion of the pancreas, (2) that moderate and severe experimental pancreatitis are accompanied by progressive tissue ischemia, and (3) that significant stasis (decreased perfusion) and decreased oxygen saturation occur whereas generalized vasoconstriction (decreased hemoglobin levels) was not found. In contrast, mild experimental pancreatitis was accompanied by initial hyperperfusion and normal oxygen delivery was maintained.


Validation of the French version of the MSA health-related Quality of Life scale (MSA-QoL).
Multiple system atrophy (MSA) has considerable impact on health-related quality of life. The MSA health-related Quality of Life scale (MSA-QoL) is a patient-reported questionnaire, which has been recently designed to evaluate the quality of life in MSA. The objective of the present study was to validate the French version of the MSA-QoL questionnaire. One hundred and thirty-six consecutive MSA patients were included in the study. Four patients with more than 10% missing responses were excluded from the final analysis. Data quality, scaling assumptions, acceptability, reliability and validity were assessed similar to the original validation of the English version. Missing responses were low, item and subscale scores were evenly distributed and floor and ceiling effects were negligible. Item-total correlations were higher than the recommended greater than 0.30 and internal consistency was high for all subscales. Test-retest reliability was good for all subscales. Validity was supported by moderate interscale correlations between the subscales and the predicted correlations with other scales assessing motor disability, activities of daily living, quality of life and mood. The French version of the MSA-QoL displays robust psychometric properties similar to the English version. The French version of MSA-QoL seems suitable for assessing quality of life in French speaking MSA patients.


In vivo evaluation of three-dimensional of volumetric changes using a CAD/CAM chair-side system: Technical procedure.
An intraoral digital scanner in combination with specialized three-dimensional surface analysis software monitors volumetric changes to soft tissues or dental restorations. This technology can evaluate the success of a specific technique or medium- or long-term clinical outcomes in both clinical and research situations. This article describes how this technology was used to provide immediate chair-side data analysis without the help of specialized laboratory support. Key words:Intraoral scanner, CAD-CAM, best fit-method, surface tessellation language.


Down regulation of adhesion protein E-cadherin in Epstein-Barr virus infected nasopharyngeal carcinomas.
Nasopharyngeal carcinoma (NPC) is a unique tumour due to its aetiology, incidence pattern and its consistent association with Epstein-Barr virus (EBV). EBV encodes many viral proteins, which targets crucial cell cycle regulatory proteins. Cadherins are a family of transmembrane glycoproteins, which mediates Ca2+-dependent intercellular adhesion. Epithelial (E)-cadherin is an important member of this family, which is expressed predominantly on the surface of epithelial cells. E-cadherin acts as an invasion/metastasis-suppressor gene, hence knowledge of the molecular mechanism that controls its expression or function is of primary importance in understanding the process of tumor invasion. Loss of E-cadherin function has been shown to potentiate tumor cell invasion and interestingly, a large number of invasive tumors do not involve mutation of E-cadherin, but rather down regulation of expression. Hence in this study, an attempt was made to evaluate the protein level expression pattern of E-cadherin in relation to viral involvement and to correlate it with other clinico-pathological parameters. We observed a significant down regulation of E-cadherin in NPC and its histological subsets, when compared to the controls (p<0.001). Expression of E-cadherin ranged from mild to moderate and none of the NPC showed intense expression. E-cadherin expression showed a significant down-regulation in NPC lesions with EBV infection (r=-0.436, p<0.001). The down regulation of E-cadherin observed in NPC is in line with the previous reports in E-cadherin expression in various cancers. The total lack of E-cadherin expression in neoplastic cells might be due to hypermethylation of E-cadherin promoter or its down regulation by cellular transcription repressor. Our study also shows a significant down regulation of E-cadherin in the presence of EBV, which also might involve the cellular DNA methylation machinery.


[Investigation on the usage and prescription of adrenaline self-injector against anaphylaxis].
In Japan Adrenaline self injector (ASJ) became available for patients with anaphylaxis including children in 2005. Countermeasure against anaphylaxis in Japan is far behind international standards, and understanding of anaphylaxis and its treatment by doctors is thought to be unsatisfactory level. This investigation was carried out using questionnaire towards 1,196 doctors who had contributed nationwide survey of food allergy monitoring in 2005. The investigation was done on January in 2006. The questionnaire consisted of possession of registration as ASJ prescription doctor, prescription experience, indication of ASJ prescription, and timing for patients to use ASJ. Seven hundred and seven replies were obtained out of 1,196 doctors, and 443 doctors (62.7%) were reported to be registered as an ASJ prescription doctors. Among 443 registered doctors, 209 doctors had experienced to prescribe ASJ. Only 88 percent of doctors accepted the cases with repeated anaphylaxis as criteria for absolute prescription of ASJ, and 41.6 percent of doctors accepted cases with history of anaphylaxis as the criteria. Timing by doctors to inject adrenaline was reported to be cases with circulatory symptom (93.7%), airway mucosa symptom (79.4%), and with respiratory symptom (56.6%), Japanese doctors seem to have unsatisfactory level of knowledge of anaphylaxis . It is important for Japanese doctors to receive appropriate education on anaphylaxis and ASJ.


Molecular Imaging of the Cannabinoid System in Idiopathic Parkinson's Disease.
The endocannabinoid system is a modulator of neurotransmitter release and is involved in several physiological functions. Hence, it has been increasingly studied as a potential pharmacologic target of Parkinson's disease. Several preclinical and clinical studies evidenced a substantial rearrangement of the endocannabinoid system in the basal ganglia circuit following dopamine depletion. The endocannabinoid system has been additionally implicated in the regulation of neuroinflammation and neuroprotection through the activation of CB2 receptors, suggesting a potential target for disease modifying therapies in Parkinson's disease. In this chapter, current pharmacological and physiological knowledge on the role of the endocannabinoid system will be reviewed, focusing on preclinical studies animal models and clinical studies in patients with idiopathic Parkinson's disease. The main strategies for imaging the brain cannabinoid system will be summarized to finally focus on in vivo imaging of patients with Parkinson's disease.


Late nonfatal and fatal cardiac events after infrainguinal bypass for femoropopliteal occlusive disease during a thirty-one-year period.
In patients with peripheral vascular disease the complications of associated coronary artery disease have always been a leading cause of morbidity and mortality. Therefore we evaluated the risk for late cardiac morbidity and mortality in 376 consecutive patients after infrainguinal bypass. Follow-up was complete for 373 patients (99.3%) with a mean follow-up period of 5.9 years. After operation all but four patients were treated with lifelong warfarin (Coumadin therapy.) During follow-up 129 patients (34.3%) had 183 late cardiac events. Of these patients, 79 (61.2%) died of late cardiac events and 13 (10.0%) required either coronary angioplasty or bypass. The risk of late cardiac events was 34% at 5 years and increased to 56% at 15 years. Multivariate analysis demonstrated that age, cardiac disease, and impaired renal function at the time of operation were associated with an increased risk of cardiac events during follow-up. Independent predictors of cardiac death were age, cardiac disease, hypertension, diabetes, and impaired renal function. Morbidity and mortality was particularly high in patients with critical ischemia. The subset of patients with claudication had a life expectancy that appeared to be similar to that of a matched sample of the normal population. Our findings clearly demonstrate that some patients undergoing infrainguinal bypass are at high risk for late cardiac events of which many are fatal, whereas others may have an almost normal life expectancy. Most important, the occurrence of cardiac events may be predicted by simple and readily obtainable clinical variables at the time of the initial infrainguinal bypass procedure. Because these events were related to late cardiac death, this may be the key for angiographic evaluation and possible prevention of cardiac death.


Sociocultural Factors Associated With Abuse of Mentally Impaired Persons in Imo State, Nigeria.
This study examined sociocultural factors associated with abuse of mentally impaired persons (MIP) in Imo state, Nigeria. A cross-sectional survey of 1,147 persons aged 10 years and above who had at least one MIP in their household was conducted. Six in-depth interviews and 21 focus group discussion (FGD) sessions with 160 study participants comprising adult male and female members of the communities, respectively, were conducted. The study established that a multitude of cultural and social factors shape the attitude of individuals toward mental impairment and MIPs. It was found that cultural perceptions of the cause of mental impairment as supernatural and evil forces were widespread within the study communities. Among those surveyed, 74.6% were aware that MIPs are victims of abuse. Perpetrators identified were mostly relatives and persons close to MIPs. The findings provide useful insights into gaps in conventional understanding of mental impairment and abuse of MIPs in Imo State.


Prevention of postoperative pneumothorax in patients undergoing cardiac surgery.
Postoperative pneumothorax is a potentially fatal complication occurring in approximately 1.4% of patients after cardiac surgical procedures. Prevention of this complication could save lives, morbidity, and money in this large patient population. This study was undertaken to evaluate the effectiveness of a very simple technique to prevent this complication. One thousand three hundred and ninety-seven consecutive adult patients undergoing cardiac surgical procedures performed by the author were evaluated. In each patient a 3-cm opening in the mediastinal pleura of any unopened hemithorax was performed to allow communication of the pleural space with the mediastinum. When a hemithorax had been opened for internal mammary harvesting, the usual pleural drain was inserted. A standard, straight mediastinal tube was then placed in routine fashion without any additional tube placement or unusual positioning. The essence of the approach was the establishment of communication of both pleural spaces with the mediastinum in such a way that any air exiting the lung would be able to evacuate through the mediastinal tube. One patient with obstructive lung disease developed a loculated basilar pneumothorax that was treated with chest tube placement. Two patients required maintenance of mediastinal tube drainage for persistent air leak for 7 and 9 days, respectively. No other patients required chest tube placement for pneumothorax. No patient experienced any complication that could be attributed to the small opening in the pleural space. The technique herein described is a safe and effective method for prevention of postoperative pneumothorax. It adds nothing to the cost of the surgical procedure. The author would recommend that this technique be adopted as a surgical routine.


Predictive role of impulsivity, anxiety, and depression in the efficacy of intermittent theta burst transcranial magnetic stimulation modalities for treating methamphetamine use disorder: A randomized clinical trial.
Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.


Have adults lost their sense of play? An observational study of the social dynamics of physical (in)activity in German and Hawaiian leisure settings.
Physical inactivity is one of the biggest health problems nowadays. Recent research shows that socio-cultural barriers to physical activity are mostly related to modern lifestyles. However, there is a lack of research on how social and group dynamics influence engagement in physical activity. Furthermore, there are few cross-cultural studies that have compared the social dynamics of (in)activity in different cultural settings. This paper therefore aims to analyse how social group dynamics influence physical activity and inactivity in informal social environments and whether physical activity is influenced by the socio-cultural settings. The paper presents the qualitative data collected within a covert participant observation study. Data was collected by keeping observational notes in order to record typical, regular patterns regarding physical (in)activity related behaviour of groups at an artificial open air swimming pool in Germany and a natural pond in Hawai'i. The data collection period was eight and a half months. Data was interpreted based on constant comparative analysis in order to identify most generative patterns in the field notes. Group structures appear to play a significant role regarding the activity of the group members. In this study, we identified four key factors that influence group based physical activity: 1) Physical activity seems to be a group disturbing behaviour particularly in larger groups of adults; 2) Physical activity appears to be more functional and less joyful in adults than in children; 3) Group activity is influenced by (in)activity anchors, including 'domestication' of a group's site, obesity, and controlling parents. 4) Physical activity is to a certain extent socially contagious, particularly with regard to playful activities. Successful promotion of physical activity should target the social structures of inactive individuals' groups. In this regard, one of the main problems is that fun and wellbeing, as very important targets of public health strategies for the adult population, appear not to be compatible with physical activity. Developing strategies to reframe physical activity rather as 'fun' and less as functional may be one way to engage inactive individuals in physical activity in leisure settings.


Ambulatory Management of Worsening Heart Failure: Current Strategies and Future Directions.
Heart failure (HF) is a highly prevalent and morbid disease in the USA. The chronic, progressive course of HF is defined by periodic exacerbations of symptoms, described as 'worsening heart failure' (WHF). Previously, episodes of WHF have required hospitalization for intravenous diuretics; however, recent innovations in care delivery models for patients with HF have allowed a transition from the acute care setting to the ambulatory setting. The development of remote monitoring strategies, including device-based algorithms and implantable haemodynamic monitoring systems, has facilitated more advanced surveillance of patients, aiming to prevent the clinical deterioration that leads to hospitalization. Additionally, the establishment of multidisciplinary HF clinics has provided the setting and resources for the outpatient treatment of WHF, specifically the administration of intravenous diuretics. Here we review the current state of ambulatory HF management, including mechanisms for patient monitoring and treatment, and outline future opportunities for outpatient management of this patient population.


Prions in dermatology.
Prion diseases are uncommon fatal neurodegenerative disorders that have gained scientific importance as a result of the emergence of new forms of these diseases in both animals and humans. Prions appear to be composed principally or entirely of abnormal isoforms of a host-encoded glycoprotein. There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy ("mad cow disease") has affected humans. Recent studies have demonstrated that prions can adhere easily to metal surfaces, and normal sterilization procedures are not likely to completely inactivate them. Iatrogenic transmission of prion diseases, such as Creutzfeldt-Jakob disease, was recognized after corneal transplantations, dura mater grafts, neurosurgical procedures, and the use of human hormones (growth hormone and gonadotropin). Although bovine collagen has long been recognized as a safe and biocompatible material, dermatologists should be aware of the theoretical potential for prion transmission when materials from bovine origin and products obtained from cultured cells fed with fetal or newborn calf serum are used.


[Successful percutaneous drainage of epidural abscess with a 4Fr sheath and pig-tail catheter].
A 61-year-old woman was transfered to our emergency center because of epidural abcess with neurological deficits. Magnetic resonance imaging (MRI) revealed high intensity (T 2 WI) abscess in the epidural space from 5 th cervical to 3 rd thoracic spine level. Surgical drainage was interfered with her poor general conditions. Instead of surgical approach, we inserted a 4 Fr pig-tail catheter into the epidural space with a loss of resistance method, then made a continuous drainage of the abscess. Her neurological state improved after the procedure. Diminished epidural abscess was found on the MRI after the drainage. We demonstrated successfully treated epidural abscess by percutaneous drainage with a 4 Fr short sheath and pig-tail catheter.


In Operando Quantification of Three-Dimensional Water Distribution in Nanoporous Carbon-Based Layers in Polymer Electrolyte Membrane Fuel Cells.
Understanding the function of nanoporous materials employed in polymer electrolyte membrane fuel cells (PEMFCs) is crucial to improve their performance, durability, and cost efficiency. Up to now, the water distribution in the nm-sized pore structures was hardly accessible during operation of the cells. Here we demonstrate that phase contrast synchrotron X-ray tomography allows for an in operando quantification of the three-dimensional water distribution within the nm-sized pores of carbon-based microporous layers (MPLs). For this purpose, a fuel cell design optimized for tomographic phase contrast measurements was realized. Water in the pores of the entire MPL was detected and quantified. We found an inhomogeneous distribution of the local water saturation and a sharp boundary between mostly filled MPL and almost empty areas. We attribute the latter observation to the two-phase boundary created because condensation takes place predominantly on one side of the boundary. Furthermore, high water saturation in large areas hints at gas diffusion or transport along preferred three-dimensional paths through the material, therefore bypassing most of the MPL volume. Our approach may contribute significantly to future investigations of nanoporous fuel cell materials under realistic operating conditions.


Indirect blood pressure measurement at the common femoral artery.
In the present study the technique and the reliability of indirect blood pressure measurement at the common femoral level was described. The blood pressure was measured by using a long cuff, which encircled the hips at the level of the groin, and determining the flow signals by Doppler technique applied at the ankle. In order to transmit the cuff pressure to the artery, a slender bag with air, which was a blood pressure cuff used in children, was placed over the common femoral artery under the cuff. A 14 cm. wide cuff-bladder was usually used, but in obese subjects with the size of hips more than 90 cm, a 16 cm. wide cuff-bladder was applied. In patients with collateral vessels around the groin due to the iliac disease, the blood pressure could be measured by placing the Doppler flat probe over the common femoral artery or the collateral vessel. In observation of 24 subjects, a close correlation was obtained between the femoral cuff pressures and common femoral intra-arterial pressures. Furthermore, blood pressure values at the common femoral level measured indirectly showed similar reproducibility as those at the ankle and toe levels.


Cervicothoracic Manual Therapy Plus Exercise Therapy Versus Exercise Therapy Alone in the Management of Individuals With Shoulder Pain: A Multicenter Randomized Controlled Trial.
Study Design Multicenter randomized controlled trial. Background Cervicothoracic manual therapy has been shown to improve pain and disability in individuals with shoulder pain, but the incremental effects of manual therapy in addition to exercise therapy have not been investigated in a randomized controlled trial. Objectives To compare the effects of cervicothoracic manual therapy and exercise therapy to those of exercise therapy alone in individuals with shoulder pain. Methods Individuals (n = 140) with shoulder pain were randomly assigned to receive 2 sessions of cervicothoracic range-of-motion exercises plus 6 sessions of exercise therapy, or 2 sessions of high-dose cervicothoracic manual therapy and range-of-motion exercises plus 6 sessions of exercise therapy (manual therapy plus exercise). Pain and disability were assessed at baseline, 1 week, 4 weeks, and 6 months. The primary aim (treatment group by time) was examined using linear mixed-model analyses and the repeated measure of time for the Shoulder Pain and Disability Index (SPADI), the numeric pain-rating scale, and the shortened version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH). Patient-perceived success was assessed and analyzed using the global rating of change (GROC) and the Patient Acceptable Symptom State (PASS), using chi-square tests of independence. Results There were no significant 2-way interactions of group by time or main effects by group for pain or disability. Both groups improved significantly on the SPADI, numeric pain-rating scale, and QuickDASH. Secondary outcomes of success on the GROC and PASS significantly favored the manual therapy-plus-exercise group at 4 weeks (P = .03 and P<.01, respectively) and on the GROC at 6 months (P = .04). Conclusion Adding 2 sessions of high-dose cervicothoracic manual therapy to an exercise program did not improve pain or disability in patients with shoulder pain, but did improve patient-perceived success at 4 weeks and 6 months and acceptability of symptoms at 4 weeks. More research is needed on the use of cervicothoracic manual therapy for treating shoulder pain. Level of Evidence Therapy, level 1b. Prospectively registered March 30, 2012 at www.ClinicalTrials.gov (NCT01571674). J Orthop Sports Phys Ther 2016;46(8):617-628. doi:10.2519/jospt.2016.6319.


Temperature related seasonal changes in Golgi complex of brain, heart and intestine of a teleost.
Impact of temperature related seasonal changes in density of Golgi complex were studied in brain, heart and intestine of the freshwater catfish, Clarias batrachus (Linnaeus). The density of Golgi complex was more in these organs of the fish acclimatized to a lower temperature (20 degrees C) than that to a higher temperature (29 degrees C). This suggests that lower temperature induces secretory activity in cells to cope up with the changes in surrounding environment. It could be a kind of histophysiological adaptation in poikilothermic animal.


Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities.
Monoamine oxidase A (MAOA) harbours a polymorphic upstream variable-number tandem repeat (u-VNTR). The MAOA-L allele of the u-VNTR leads to decreased gene expression levels in vitro and has been found to increase the risk of conduct disorder in males with childhood adversities. Early-life adversities have been associated with hypermethylation of the glucocorticoid receptor (NR3C1). In this study, we first performed a genetic association analysis of the MAOA u-VNTR using individuals with depression (n = 392) and controls (n = 1276). Next, DNA methylation analyses of MAOA and NR3C1 were performed using saliva samples of depressed and control subgroups. Adult MAOA-L females with childhood adversities were found to have a higher risk of developing depression (p = 0.006) and overall MAOA methylation levels were decreased in depressed females compared to controls (mean depressed, 42% vs. mean controls, 44%; p = 0.04). One specific childhood adversity [early parental death (EPD)] was associated with hypermethylation of NR3C1 close to an NGFI-A binding site (mean EPD, 19% vs. mean non-EPD, 14%; p = 0.005). Regression analysis indicated that this association may be mediated by the MAOA-L allele (adjusted R² = 0.24, ANOVA: F = 23.48, p < 0.001). Conclusively: (1) depression in females may result from a gene × childhood-adversity interaction and/or a dysregulated epigenetic programming of MAOA; (2) childhood-adversity subtypes may differentially impact DNA methylation at NR3C1; (3) baseline MAOA-genotypic variations may affect the extent of NR3C1 methylation.


Vitamin D supplementation increases the attractiveness of males' scent for female Iberian rock lizards.
Evolutionary theory proposes that signals used in sexual selection can only be stable if they are honest and condition dependent. However, despite the fact that chemical signals are used by many animals, empirical research has mainly focused on visual and acoustic signals. Vitamin D is an essential nutrient for lizards, but in some lizards its precursor (cholesta-5,7-dien-3-ol=provitamin D) is found in femoral gland secretions, which males use for scent marking and intraspecific communication. By allocating provitamin D to secretions, males might need to divert vitamin D from metabolism. This might be costly and condition dependent. We tested whether diet quality affected chemical signals of male Iberian rock lizards (Lacerta monticola) and its consequences for sexual selection. After experimental supplementation of dietary vitamin D, males increased the proportion of provitamin D in femoral secretions. Further experiments showed that females detected these changes in males' signals by chemosensory cues, and discriminated provitamin D, and changes in its concentration, from similar steroids (i.e. cholesterol) found in secretions. Moreover, females preferred areas scent marked by males with more provitamin D in their secretions. This mechanism would confer honesty to chemical signals of male lizards, and, thus, females may rely on it to select high-quality males. We suggest that the allocation of vitamins and other essential nutrients to either visual (e.g. carotenoids) or chemical ornaments might be the common basis of honest sexual displays in many animals.


Novel neural modulators.
The discovery that nitric oxide (NO) is produced by neurons and regulates synaptic activity has challenged the definition of a neurotransmitter. NO is not stored in synaptic vesicles and does not act at conventional receptors on the surface of adjacent neurons. The toxic gases carbon monoxide (CO) and hydrogen sulfide (H2S) are also produced by neurons and modulate synaptic activity. D-serine synthesis and release by astrocytes as an endogenous ligand for the "glycine" site of N-methyl D-aspartate (NMDA) receptors defy the concept that a neurotransmitter must be synthesized by neurons. We review the properties of these "atypical" neural modulators.


Electronic transport through ruthenium-based redox-active molecules in metal-molecule-metal nanogap junctions.
Electronic transport through ruthenium-based redox-active organometallic molecules is measured by self-assembling diruthenium(III) tetra(2-anilinopyridinate)-di(4-thiolphenylethynyl) (trans-Ru2(ap)4(C'CC6H4S-)2 (A) and trans- Ru2(ap)4((C'CC6H4)2S-)2 (B) molecules in nanogap molecular junctions. Voltage sweeps at a high scan rate show low bias current peaks (at +/-0.35 +/- 0.05 V for A and +/-0.27 +/- 0.05 V for B), which change to plateaus in slow bias scans and a second conductance peak at approximately +/-1.05 +/- 0.15 V. The peaks/plateaus are not observed in the return bias sweeps, possibly due to charge storage in the molecules. The energy states for the molecular orbitals of these molecules as estimated from the conductance peaks are in close agreement with the respective energy values from voltammetric measurements in solution.


[Production of ligninase by co-fermentation of Coprinus comatus and Trichoderma reesei].
In order to enhance the utilization efficiency, reduce the environmental pollution of traditional chemical treatment and the agriculture waste incineration; we studied the ligninase production by Coprinus comatus, Aspergillus niger and Trichoderma reesei through the plate screening. The results showed that C. comatus mixed culture with T. reesei have a good compatibility and higher yields of Laccase. On the basis of this pre-experiment, we studied the optimal conditions of mixed culture for enzyme production. Under the optimal conditions: the inoculation proportion of C. comatus and T. reesei (5:2), the interval of time (12 h), the temperature 260C, the shake rotation speed 150 r/min, fermented for 3 days, the Laccase activity reached 3267.1 U/mL, increased by 106% contrasted with single culture of C. commatus.


FTY720 prevents renal T-cell infiltration after ischemia/reperfusion injury.
Ischemia/reperfusion (I/R) injury, a common early feature in renal transplantation, results from both free radical species generation and local inflammatory responses that attract different types of cells. The interaction with infiltrating leukocytes could promote damage and death of resident renal cells contributing to worsening of renal function. It has been shown that depletion of host T cells protects against kidney damage after I/R injury, although the mechanism is not fully understood. FTY720, a synthetic analog of a natural product extracted from Isaria sincclairii has shown modulatory properties in experimental models of autoimmune disease, transplantation, and I/R injury. FTY720 alters lymphocyte responses to chemokine homing signals, thereby decreasing the number of lymphocytes in inflammatory sites. We evaluated renal function in mice at 3, 5, and 7 days after I/R injury in the presence or absence of FTY720 treatment. FTY720 treatment promoted earlier recovery of renal function associated with a lower number of renal-infiltrating lymphocytes. These findings confirm previous results showing a protective effect of FTY720 in I/R injury models.


[Comparative evaluation of effects of p-tyrosol and Rhodiola rosea extract on bone marrow cells in vivo].
The effects of p-tyrosol and Rhodiola rosea extract on the hemopoietic system were compared on a model of subacute lead intoxication. No significant differences between the activity of two preparations were revealed by the study of plasma membrane blebbing, apoptosis, and necrosis processes in bone marrow. At the same time, p-tyrosol exhibited a more pronounced effect upon lipid peroxidation and offered significant protection against lead intoxication.


Do women know that prenatal testing detects fetuses with Down syndrome?
This questionnaire-based study in Victoria, Australia, examined the responses of pregnant women, aged 37 years and over, to a question about what they expected prenatal testing (screening and/or diagnosis) for birth defects to tell them about their pregnancy. Content analysis showed that, of the 432 tested women, 61.3% mentioned Down syndrome, chromosomal abnormalities or trisomies. Women undergoing both screening and diagnosis were more likely than those having one or other test to mention Down syndrome (adjusted OR = 1.6, P = 0.06), having adjusted for age, marital status, education, residence and parity. Similarly, those from an English-speaking background were more likely to mention Down syndrome, etc. compared to women from a non-English-speaking background (adjusted OR = 3.5, P < 0.001). Down syndrome, a fundamental piece of information about prenatal tests, was not mentioned in nearly 40% of women's responses. This suggests that pregnant women need clearer information about prenatal testing, including the conditions that might be detected.


Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients.
Stromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis. Stromal remodeling is characterized by collagen fiber restructuring and realignment in stromal and tumoral areas. The patients in our study were diagnosed with triple-negative breast cancer in Singapore General Hospital from 2003 to 2015. We designed novel image processing and quantification pipelines to profile collagen structures using numerical imaging parameters. Our solution differentiated the collagen into two distinct modes: aggregated thick collagen (ATC) and dispersed thin collagen (DTC). Extracted parameters were significantly associated with bigger tumor size and DCIS association. Of numerical parameters, ATC collagen fiber density (CFD) and DTC collagen fiber length (CFL) were of significant prognostic value for disease-free survival and overall survival for the TNBC patient cohort. Using these two parameters, we built a predictive model to stratify the patients into four groups. Our study provides a novel insight for the quantitation of collagen in the tumor microenvironment and will help predict clinical outcomes for TNBC patients. The identified collagen parameters, ATC CFD and DTC CFL, represent a new direction for clinical prognosis and precision medicine. We also compared our result with benign samples and DICS samples to get novel insight about the TNBC heterogeneity. The improved understanding of collagen compartment of TNBC may provide insights into novel targets for better patient stratification and treatment.


Graphene-coated nanowires with a drop-shaped cross section for 10 nm confinement and 1 mm propagation.
Strong confinement and long-range propagation of electromagnetic energy are longed for when designing efficient miniaturized photonic devices. Here, a graphene-coated nanowire with a drop-shaped cross section is proposed for guiding graphene surface plasmon polaritons to demonstrate an extremely long propagation length (1 mm) with ultra-strong mode confinement (10 nm), which results from the distinctive mode field distribution caused by both the top and bottom arcs of the waveguide. The combination of nanoconcentration and long-range propagation makes the waveguide very useful in nanophotonics, bio-photonics, and highly integrated photonic circuits.


Modulation of MAPK/NF-κB Pathway and NLRP3 Inflammasome by Secondary Metabolites from Red Algae: A Mechanistic Study.
The pharmacological properties of seaweeds are diverse. No studies have been conducted on the protective effect of Galaxaura oblongata (GOE) against lippopolysaccharide (LPS)-induced inflammation in the brain. This study is divided into three phases, the first of which is the initial phase. In vitro study includes antioxidant, radical scavenging, and anti-inflammatory activities, including cyclooxygenase-1 (COX1), COX2, NO, acetylcholine inhibition, sphingosine kinase 1, tumor necrosis factor α (TNF-α), and interleukin-6, as well as antioxidant and radical-scavenging activities, including 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid. Using LPS-induced acute inflammation, the second phase was conducted in vivo. Antioxidant and anti-inflammatory assays were performed to investigate the protective role of GOE. In addition to the phytochemical analysis, the bioactive content of GOE was also investigated. In vitro results demonstrated the potential of GOE as an antioxidant, anti-inflammatory, and neuroprotective agent. A study using LPS as an induced lung injury and neuroinflammation model confirmed the in vitro results. The GOE significantly reduced inflammatory, oxidative, and neurodegenerative biomarkers based on histopathological and immuno-histochemistry results. Based on computational drug design, four target proteins were approved: nuclear factor κB, mitogen-activated protein kinases, TNF-α, and NLRP3. Using polyphenolic compounds in GOE as ligands demonstrated good alignment and affinity against the three proteins. Finally, the current study offers a new approach to developing drug leads considering GOE's protective and curative roles.


Lectin-based affinity capture for MALDI-MS analysis of bacteria.
Immobilized lectins have now been incorporated into affinity surfaces that can be used to isolate broad classes of samples for mass spectrometric analysis. A carbohydrate and a bacterial species that displays the carbohydrate binding motif were isolated and concentrated out of solutions containing salt, urea, buffers, and other contaminants that are deleterious to MALDI mass spectrometry. Concanavalin A was immobilized to a gold foil via a self-assembled monolayer. Samples in phosphate buffer or urine were applied to the capture surface and allowed to interact. The capture surface was then washed to remove salts and other unbound components and subjected to matrix-assisted laser desorption/ionization on a time-of-flight mass spectrometer. The lectin-derivatized surface allowed samples to be concentrated and readily characterized at relatively low levels.


Respiratory Syncytial Virus Attachment Glycoprotein Contribution to Infection Depends on the Specific Fusion Protein.
Human respiratory syncytial virus (RSV) is an important pathogen causing acute lower respiratory tract disease in children. The RSV attachment glycoprotein (G) is not required for infection, as G-null RSV replicates efficiently in several cell lines. Our laboratory previously reported that the viral fusion (F) protein is a determinant of strain-dependent pathogenesis. Here, we hypothesized that virus dependence on G is determined by the strain specificity of F. We generated recombinant viruses expressing G and F, or null for G, from the laboratory A2 strain (Katushka RSV-A2GA2F [kRSV-A2GA2F] and kRSV-GstopA2F) or the clinical isolate A2001/2-20 (kRSV-2-20G2-20F and kRSV-Gstop2-20F). We quantified the virus cell binding, entry kinetics, infectivity, and growth kinetics of these four recombinant viruses in vitro. RSV expressing the 2-20 G protein exhibited the greatest binding activity. Compared to the parental viruses expressing G and F, removal of 2-20 G had more deleterious effects on binding, entry, infectivity, and growth than removal of A2 G. Overall, RSV expressing 2-20 F had a high dependence on G for binding, entry, and infection. RSV is the leading cause of childhood acute respiratory disease requiring hospitalization. As with other paramyxoviruses, two major RSV surface viral glycoproteins, the G attachment protein and the F fusion protein, mediate virus binding and subsequent membrane fusion, respectively. Previous work on the RSV A2 prototypical strain demonstrated that the G protein is functionally dispensable for in vitro replication. This is in contrast to other paramyxoviruses that require attachment protein function as a prerequisite for fusion. We reevaluated this requirement for RSV using G and F proteins from clinical isolate 2-20. Compared to the laboratory A2 strain, the G protein from 2-20 had greater contributions to virus binding, entry, infectivity, and in vitro growth kinetics. Thus, the clinical isolate 2-20 F protein function depended more on its G protein, suggesting that RSV has a higher dependence on G than previously thought.


First Report of Diplodia intermedia Causing Canker and Dieback Diseases on Apple Trees in Canada.
A dieback of apple trees (Malus domestica (Suckow) Borkh.) associated with cankers was observed in commercial orchards in southwestern Ontario, Canada, in 2019. Fifteen 2 to 10-year-old symptomatic trees were collected from three orchards exhibiting up to 37% disease incidence. Small sections of diseased wood (1 cm long) were surface sterilized with 70% ethanol for 30 sec and 1% NaClO for 20 min, rinsed thrice in sterile water, placed on 2% PDA (Difco) amended with kanamycin (50 mg liter-1), and incubated at 22°C for 5 days in the dark (Ilyukhin et al. 2023). Fungal colonies that were consistently isolated were hyphal-tipped, transferred to individual PDA plates and incubated at 22°C for 7 days in the dark. Purified isolates with same characteristics were classed into morphotypes. One morphotype was initially white and turned dark olivaceous with dense aerial mycelium. Pycnidia were produced on pine needles on PDA (Fig. S2) after incubation at 22°C for 17 days in the dark. Conidia were brown, aseptate, ovoid, and measured 27.9 to 31.3 μm x 12.1 to 14.2 μm (mean ± S.D. of 15 conidia = 29.9 ± 0.9 μm × 13.2 ± 0.6 μm), the typical morphology of a Diplodia sp. (Phillips et al. 2012). Genomic DNA was extracted from a 7-day-old culture of a representative isolate M45-28, using the Plant/Fungi DNA Isolation Kit (Norgen Biotech, Canada). The internal transcribed spacer (ITS), translation elongation factor 1-α (EF1-α) and β-tubulin gene regions were amplified and sequenced with primers ITS1/ITS4, EF1-728F/EF1-986R and Bt2a/Bt2b and deposited in GenBank with accession numbers MZ970605, MZ995430 and MZ995431, respectively. Based on the sequence, the fungus was identified as Diplodia intermedia A.J.L. Phillips et al. and matched isolates from different hosts and countries (ITS: 100%, MG220378; EF1-α: 100%, MG220385; β-tubulin: 99.24%, MT592502). The maximum likelihood-based phylogenetic analysis of ITS, EF1-α and β-tubulin concatenated sequences was performed using IQ-Tree 188.8.131.52 (Minh et al. 2020). M45-28 was clustered with high bootstrap support values with D. intermedia isolates from the Westerdijk Fungal Biodiversity Institute collection, including the ex-holotype (CBS 124462) (Fig. S1). A living culture of M45-28 was deposited in the Canadian Collection of Fungal Cultures (DAOMC 252253). Pathogenicity assay was conducted by inoculating mycelial plugs from a 7-day-old culture of M45-28 into wounds made on the trunk of 5 eight-month-old potted healthy 'Royal Gala' apple seedlings. Five control seedlings were inoculated with sterile plugs. Canker symptoms appeared 15 days after inoculation, spread around, up and down the main stem from the inoculation point, and by 7 weeks the upper portion of the seedling was dead (Fig. S2). Diplodia intermedia was re-isolated from all inoculated seedlings and species identity was confirmed by sequencing as described above, fulfilling Koch's postulates. Control seedlings remained symptomless and the fungus was not isolated from the wood. Diplodia intermedia was reported to cause cankers on apple in Uruguay (Delgado-Cerrone et al. 2016), wild apple (Malus sylvestris) in Portugal (Phillips et al. 2012), grapevines in France (Comont et al. 2016) and forest trees in Iran (Kazemzadeh Chakusary et al. 2019). To the best of our knowledge, this is the first report of D. intermedia causing canker and dieback diseases on apple trees in Canada. Further studies are required to better understand the epidemiology involved in the dynamic spread of the disease in order to recommend an adequate phytosanitary program for its control.


Sparse CNT networks with implanted AgAu nanoparticles: A novel memristor with short-term memory bordering between diffusive and bipolar switching.
With this work we introduce a novel memristor in a lateral geometry whose resistive switching behaviour unifies the capabilities of bipolar switching with decelerated diffusive switching showing a biologically plausible short-term memory. A new fabrication route is presented for achieving lateral nano-scaled distances by depositing a sparse network of carbon nanotubes (CNTs) via spin-coating of a custom-made CNT dispersion. Electrochemical metallization-type (ECM) resistive switching is obtained by implanting AgAu nanoparticles with a Haberland-type gas aggregation cluster source into the nanogaps between the CNTs and shows a hybrid behaviour of both diffusive and bipolar switching. The resistance state resets to a high resistive state (HRS) either if the voltage is removed with a retention time in the second- to sub-minute scale (diffusive) or by applying a reverse voltage (bipolar). Furthermore, the retention time is positively correlated to the duration of the Set voltage pulse. The potential for low-voltage operation makes this approach a promising candidate for short-term memory applications in neuromorphic circuits. In addition, the lateral fabrication approach opens the pathway towards integrating sensor-functionality and offers a general starting point for the scalable fabrication of nanoscaled devices.


Isolation and structure of the fibril protein, a major component of the internal ribbon for Spiroplasma swimming.
Spiroplasma, which are known pathogens and commensals of arthropods and plants, are helical-shaped bacteria that lack a peptidoglycan layer. Spiroplasma swim by alternating between left- and right-handed helicity. Of note, this system is not related to flagellar motility, which is widespread in bacteria. A helical ribbon running along the inner side of the helical cell should be responsible for cell helicity and comprises the bacterial actin homolog, MreB, and a protein specific to Spiroplasma, fibril. Here, we isolated the ribbon and its major component, fibril filament, for electron microscopy (EM) analysis. Single-particle analysis of the fibril filaments using the negative-staining EM revealed a three-dimensional chain structure composed of rings with a size of 11 nm wide and 6 nm long, connected by a backbone cylinder with an 8.7 nm interval with a twist along the filament axis. This structure was verified through EM tomography of quick-freeze deep-etch replica sample, with a focus on its handedness. The handedness and pitch of the helix for the isolated ribbon and fibril filament agreed with those of the cell in the resting state. Structures corresponding to the alternative state were not identified. These results suggest that the helical cell structure is supported by fibril filaments; however, the helical switch is caused by the force generated by the MreB proteins. The isolation and structural outline of the fibril filaments provide crucial information for an in-depth clarification of the unique swimming mechanism of Spiroplasma.


Retinal vascular changes after treatment with hyperbaric oxygen.
A healthy 44-year-old man, who accompanied patients with multiple sclerosis as an attendant into a pressure chamber for hyperbaric oxygen treatment at 203 kPa (2 atm) absolute pressure, used a spare 100% oxygen mask himself for one hour on two occasions, and later noticed a field defect in his left eye. The vasoconstrictive, and consequent possible ischaemic, effects of hyperbaric oxygen are discussed, and the sensitivity of the retinal vasculature to hyperbaric oxygen is emphasized.


Usefulness of magnetic resonance imaging dobutamine stress in asymptomatic and minimally symptomatic patients with decreased cardiac reserve from congenital heart disease (complete and corrected transposition of the great arteries and subpulmonic obstruction).
We explored the effect of dobutamine stress and its possible clinical implications in different groups of asymptomatic patients with chronic right ventricular (RV) pressure overload due to congenital heart disease. Forty-seven asymptomatic and minimally symptomatic patients with chronic RV pressure overload were studied: 24 patients with systemic right ventricles (16 surgically corrected transposition of the great arteries (TGA) (Mustard or Senning), 8 congenitally corrected TGA), 23 patients with chronic pressure overloaded subpulmonic right ventricles, and 11 age- and sex-matched healthy volunteers. Magnetic resonance imaging (MRI) was performed both at baseline and during dobutamine stress to determine RV volumes and ejection fraction. At baseline, RV ejection fraction in patients with surgically corrected TGA was significantly lower than in controls (58 +/- 10% vs 70 +/- 8%, p = 0.02). During dobutamine stress, RV ejection fraction increased significantly in controls and patient groups except for patients with pressure overloaded subpulmonic right ventricles. RV stroke volume increased in controls (21 +/- 21%, p = 0.008); RV stroke volume remained unchanged in patients with congenitally corrected TGA and surgically corrected TGA (2 +/- 17%, p = NS; -8 +/- 29%, p = NS). A significant RV stroke volume decrease was observed in patients with subpulmonic right ventricles (-15 +/- 16%, p = 0.0002). The changes in RV stroke volume were accompanied by a significant decrease in RV end-diastolic volume (-13 +/- 14%, p = 0.001) in patients with subpulmonic right ventricles and in patients with surgically corrected TGA (-23 +/- 16%, p = 0.0001). In controls and in patients with congenitally corrected TGA there was no change in RV end-diastolic volume (3 +/- 15%, p = NS; -5 +/- 11%, p = NS). There is a clear heterogeneity in response to MRI dobutamine stress between different groups of patients with chronic RV pressure overload. Our data suggest impaired filling in surgically corrected TGA and decreased contractility in patients with chronic pressure overloaded subpulmonic right ventricles. Dobutamine stress MRI may facilitate follow-up of RV (dys)function in patients with chronic RV pressure overload due to congenital heart disease.