Superior Effects of Nebulized Epinephrine to Nebulized Albuterol and Phenylephrine in Burn and Smoke Inhalation-Induced Acute Lung Injury.
The severity of burn and smoke inhalation-induced acute lung injury (BSI-ALI) is associated with alveolar and interstitial edema, bronchospasm, and airway mucosal hyperemia. Previously, we have reported beneficial effects of epinephrine nebulization on BSI-ALI. However, the underlying mechanisms of salutary effects of nebulized epinephrine remain unclear. The present study compared the effects of epinephrine, phenylephrine, and albuterol on a model of BSI-ALI. We tested the hypothesis that both α1- and β2-agonist effects are required for ameliorating more efficiently the BSI-ALI. Forty percent of total body surface area, 3rd-degree cutaneous burn, and 48-breaths of cotton smoke inhalation were induced to 46 female Merino sheep. Postinjury, sheep were mechanically ventilated and cardiopulmonary hemodynamics were monitored for 48 h. Sheep were allocated into groups: control, n = 17; epinephrine, n = 11; phenylephrine, n = 6; and albuterol, n = 12. The drug nebulization began 1 h postinjury and was repeated every 4 h thereafter. In the results, epinephrine group significantly improved oxygenation compared to other groups, and significantly reduced pulmonary vascular permeability index, lung wet-to-dry weight ratio, and lung tissue growth factor-β1 level compared with albuterol and control groups. Epinephrine and phenylephrine groups significantly reduced trachea wet-to-dry weight ratio and lung vascular endothelial growth factor-A level compared with control group. Histopathologically, epinephrine group significantly reduced lung severity scores and preserved vascular endothelial-cadherin level in pulmonary arteries. In conclusion, the results of our studies suggest that nebulized epinephrine more effectively ameliorated the severity of BSI-ALI than albuterol or phenylephrine, possibly by its combined α1- and β2-agonist properties.


A growing toolbox of techniques for studying β-barrel outer membrane protein folding and biogenesis.
Great strides into understanding protein folding have been made since the seminal work of Anfinsen over 40 years ago, but progress in the study of membrane protein folding has lagged behind that of their water soluble counterparts. Researchers in these fields continue to turn to more advanced techniques such as NMR, mass spectrometry, molecular dynamics (MD) and single molecule methods to interrogate how proteins fold. Our understanding of β-barrel outer membrane protein (OMP) folding has benefited from these advances in the last decade. This class of proteins must traverse the periplasm and then insert into an asymmetric lipid membrane in the absence of a chemical energy source. In this review we discuss old, new and emerging techniques used to examine the process of OMP folding and biogenesis in vitro and describe some of the insights and new questions these techniques have revealed.


Anal sphincter repair: a report of 60 cases and review of the literature.
This is a retrospective review of 58 patients undergoing surgery for anal incontinence at the Cleveland Clinic. Forty-four patients had overlapping sphincter repairs, nine had postanal repairs, three had a combination of overlapping repair and postanal repair and two had Silastic slings. An associated loop colostomy or ileostomy was performed in 19 patients (33%). Satisfactory continence was attained in 86% of patients with direct sphincter injury (overlapping sphincter repairs) and this is comparable with the experience of others. These results with the postanal repair for patients with neurogenic incontinence were poor, however, as four of the nine were complete failures. Poor results were directly related to the age of the patient (P less than 0.0001) and the duration of incontinence (P less than 0.02). It was concluded that direct sphincter injury (obstetric, operative or traumatic) is effectively treated by an overlapping sphincter repair. Incontinence secondary to a degenerative neuropathy affecting the anal sphincter mechanism, however, whether it occurs in conjunction with a pre-existing sphincter injury or alone, is often not cured by surgery, that is, by postanal repair.


Direct comparisons of inhibitor sensitivities of reverse transcriptases from feline and human immunodeficiency viruses.
The sensitivities of reverse transcriptases (RTs) from feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV) were directly compared. The two enzymes had similar sensitivities to three analogs of dTTP, namely, 3'-azido-3'-deoxythymidine 5'-triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, and 2',3'-dideoxy-2',3'-didehydrothymidine 5'-triphosphate. Each of these analogs demonstrated competitive inhibition of both enzymes. Ki values for inhibition of FIV RT by these three inhibitors were 3.3, 6.7, and 1.8 nM, respectively; Ki values for inhibition of the HIV enzyme were 6.5, 5.9, and 8.3 nM, respectively. Ratios of the Ki for the inhibitor to the Km for the substrate were also determined for each inhibitor, and no differences between the two enzymes greater than threefold were observed. Inhibition constants for 3'-amino-3'-deoxythymidine 5'-triphosphate and 3'-fluoro-3'-deoxythymidine 5'-triphosphate were determined for FIV RT, and these were similar to published values for HIV RT. The activities of three dideoxynucleoside 5'-triphosphates against FIV RT were determined; ddGTP was slightly more potent than ddTTP, whereas both were much more effective than ddCTP. The activity of a noncompetitive inhibitor, phosphonoformate, was also examined with the FIV enzyme; it was much more active with poly(rA)-oligo(dT) as the template-primer than with poly(rC)-oligo(dG) or poly(rI)-oligo(dC).


Structure, organization, and expression of the lct gene for lacticin 481, a novel lantibiotic produced by Lactococcus lactis.
The structural gene for the lactococcal lantibiotic lacticin 481 (lct) has been identified and cloned using a degenerated 20-mer DNA oligonucleotide based on the amino-terminal 7 amino acid residues of the purified protein. The transcription of the lct gene was analyzed, and its promoter was mapped. DNA sequence analysis of the lct gene revealed an open reading frame encoding a peptide of 51 amino acids. Comparison of its deduced amino acid sequence with the amino-terminal sequence and the amino acid composition of lacticin 481 indicates that the 51-residue peptide is prelacticin 481, containing a 27-residue carboxyl-terminal propeptide and a 24-residue amino-terminal leader peptide which lacks the properties of a typical signal sequence and which is significantly different from the leaders of other lantibiotics. The predicted amino acid sequence of prolacticin 481 contains 3 cysteines, 2 serines, and 2 threonines which were not detectable in amino acid analyses of mature lacticin 481. Based on these results and on characterization by two-dimensional NMR techniques, a structural model is proposed in which 2 cysteine residues are involved in lanthionine and one in beta-methyllanthionine formation, and a 4th threonine residue is dehydrated. This model predicts a molecular mass for lacticin 481 of 2,901, which is in excellent agreement with that obtained from mass spectrometry.


Constitutive production of lymphokines by cloned murine B-cell lymphomas--CH12 B lymphoma produces interleukin-4.
B cells can be activated by T-independent antigens or mitogens such as lipopolysaccharide (LPS) which will induce proliferation and differentiation of the B cells into Ig-secreting cells, without the intervention of T cells. The precise mechanism of T-independent proliferation and differentiation of B cells is still unclear. It is possible however that antigen-stimulated B cells may produce some factors which play a role in T-independent B-cell responses. In addition, since it has now been established that B cells can function as antigen-presenting cells, it is possible that they too secrete a molecule which is involved in the activation of T cells, analogous to IL-1 production by antigen-presenting macrophages. A number of human B-cell lines, as well as human normal B cells activated appropriately, have been shown to produce various cytokines, and similar studies are now being undertaken in the mouse. In the present study, six cloned murine B-cell lymphomas of different origin were analyzed for the presence of mRNA encoding a number of lymphokines by hybridization of specific cDNA probes to poly-A RNA, followed by the sensitive S1 nuclease digestion technique. The lymphokines included (IL-) 1, 2, 3, 4, 5, and neuroleukin. Whereas none of the lines expressed detectable levels of IL-2, IL-3, or IL-5 mRNA, all the lines expressed high levels of neuroleukin mRNA. Three of the lymphomas (CH12, CH31, and NBL) expressed low levels of IL-1 mRNA. The most striking finding was that one lymphoma, CH12, constitutively expressed IL-4 mRNA. This mRNA appeared to be functional, as IL-4 activity measured by the HT-2 T cell proliferation assay could be detected in supernatants collected from CH12 cells. The growth-inducing activity of CH12 supernatant on HT-2 cells could be completely blocked by an anti-IL-4 monoclonal (11B11), but not by an anti-IL-2 antibody (S4B6), consistent with our observations that CH12 cells produce IL-4 but not IL-2. CH12 cells were also found to express high affinity receptors for IL-4. Proliferation of CH12 cells was not affected by the addition of exogenous IL-4. Addition of anti-IL-4 antibodies to CH12 cells in culture caused a slight but reproducible increase in their proliferation at low cell numbers, which is probably not highly significant. These findings open the possibilities that murine B lymphocytes are capable of lymphokine production or alternatively that aberrant lymphokine production underlies B-lymphocyte transformation.


Oral microbiota study of the patients after hospitalisation for COVID-19, considering selected dental indices and antibiotic therapy using the next generation sequencing method (NGS).
Poor oral hygiene and the increased incidence and severity of periodontitis may exacerbate SARS-CoV-2 infection. The aim was to evaluate the oral microbiota of 60 participants divided into groups: COVID-19 convalescents who received antibiotics during hospitalization (I), COVID-19 convalescents without antibiotic therapy (II) and healthy individuals (III). Dental examination was conducted, and oral health status was evaluated using selected dental indexes. Clinical samples (saliva, dorsal swabs, supragingival and subgingival plaque) were collected and used for metagenomic library to the next-generation sequencing (NGS) preparation. Each of the clinical materials in particular groups of patients showed a statistically significant and quantitatively different bacterial composition. Patients from group I showed significantly worse oral health, reflected by higher average values of dental indexes and also a higher percentage of Veillonella, Tannerella, Capnocytophaga and Selenomonas genera in comparison to other groups. Additionally, a statistically significant decrease in the amount of Akkermansia type in both groups with COVID-19 was observed for all materials. The primary factor affecting the composition of oral microbiota was not the SARS-CoV-2 infection itself, but the use of antibiotic therapy. The increased percentage of pro-inflammatory pathogens observed in COVID-19 patients underscores the importance of preventing periodontal disease and improving oral hygiene in the future.


Physiology and ecology combine to determine host and vector importance for Ross River virus.
Identifying the key vector and host species that drive the transmission of zoonotic pathogens is notoriously difficult but critical for disease control. We present a nested approach for quantifying the importance of host and vectors that integrates species' physiological competence with their ecological traits. We apply this framework to a medically important arbovirus, Ross River virus (RRV), in Brisbane, Australia. We find that vertebrate hosts with high physiological competence are not the most important for community transmission; interactions between hosts and vectors largely underpin the importance of host species. For vectors, physiological competence is highly important. Our results identify primary and secondary vectors of RRV and suggest two potential transmission cycles in Brisbane: an enzootic cycle involving birds and an urban cycle involving humans. The framework accounts for uncertainty from each fitted statistical model in estimates of species' contributions to transmission and has has direct application to other zoonotic pathogens.


Prostate planning treatment volume margin calculation based on the ExacTrac X-Ray 6D image-guided system: margins for various clinical implementations.
To assess the prostate motion from day-to-day setup, as well as during irradiation time, to calculate planning target volume (PTV) margins. PTV margins differ depending on the clinical implementation of an image-guided system. Three cases were considered in this study: daily bony anatomy match, center of gravity of the implanted marker seeds calculated with a limited number of imaged days, and daily online correction based on implanted marker seeds. A cohort of 30 nonrandomized patients and 1,330 pairs of stereoscopic kV images have been used to determine the prostate movement. The commercial image guided positioning tool employed was ExacTrac X-Ray 6D (BrainLAB AG, Feldkirchen, Germany). Planning target volume margins such that a minimum of 95% of the prescribed dose covers the clinical target volume for 90% of the population are presented. PTV margins based on daily bony anatomy match, including intrafraction correction, would be 11.5, 13.5, and 4.5 mm in the anterior-posterior, superior-inferior, and right-left directions, respectively. This margin can be further reduced to 8.1, 8.6, and 4.8 mm (including intrafraction motion) if implanted marker seeds are used. Finally, daily on line correction based on marker seeds would result in the smallest of the studied margins: 4.7, 6.2, and 1.9 mm. Planning target volume margins are dependent on the local clinical use of the image-guided RT system available in any radiotherapy department.


Zhenhua Yan.
The greatest scientific advance of the next decade will be artificial intelligence … I advise my students to learn proactively and meet challenges courageously …" Find out more about Zhenhua Yan in his Introducing … Profile.


Species-specific chemosensory gene expression in the olfactory organs of the malaria vector Anopheles gambiae.
The malaria mosquito Anopheles gambiae has a high preference for human hosts, a characteristic that contributes greatly to its capacity for transmitting human malaria. A sibling species, An. quadriannulatus, has a quite different host preference and feeds mostly on bovids. For this reason it does not contribute to human malaria transmission. Host seeking in mosquitoes is modulated by the olfactory system, which is primarily housed in the antennae and maxillary palps. Therefore, the detection of differing host odors by sibling species may be reflected in the expression level of the olfactory genes involved. Accordingly, we compared the transcriptomes of the antennae and maxillary palps of An. gambiae and An. quadriannulatus. We identified seven relatively abundant olfactory receptors, nine ionotropic receptors and three odorant binding proteins that are substantially up-regulated in An. gambiae antennae. Interestingly, we find that the maxillary palps of An. gambiae contain a species-specific olfactory receptor, Or52, and five An. gambiae-specific gustatory receptors (AgGr48-52) that are relatively abundant. These five gustatory receptors are also expressed in An. gambiae antennae, although at lower level, indicating a likely role in olfaction, rather than gustation. We also document an approximately three-fold higher overall expression of olfaction genes in the maxillary palps of An. quadriannulatus, indicating an important role of this organ in the olfaction system of this species. Finally, the expression of the CO2 receptor genes is five to six-fold higher in the zoophilic An. quadriannulatus, implying a much higher sensitivity for detecting CO2. These results identify potential human host preference genes in the malaria vector An. gambiae. Interestingly, species-specific expression of several gustatory receptors in the olfactory organs indicate a role in olfaction rather than gustation. Additionally, a more expansive role for maxillary palps in olfaction is implicated than previously thought, albeit more so in the zoophilic An. quadriannulatus.


A genuine layer 4 in motor cortex with prototypical synaptic circuit connectivity.
The motor cortex (M1) is classically considered an agranular area, lacking a distinct layer 4 (L4). Here, we tested the idea that M1, despite lacking a cytoarchitecturally visible L4, nevertheless possesses its equivalent in the form of excitatory neurons with input-output circuits like those of the L4 neurons in sensory areas. Consistent with this idea, we found that neurons located in a thin laminar zone at the L3/5A border in the forelimb area of mouse M1 have multiple L4-like synaptic connections: excitatory input from thalamus, largely unidirectional excitatory outputs to L2/3 pyramidal neurons, and relatively weak long-range corticocortical inputs and outputs. M1-L4 neurons were electrophysiologically diverse but morphologically uniform, with pyramidal-type dendritic arbors and locally ramifying axons, including branches extending into L2/3. Our findings therefore identify pyramidal neurons in M1 with the expected prototypical circuit properties of excitatory L4 neurons, and question the traditional assumption that motor cortex lacks this layer.


Antireflux sleeve gastroplasty: description of a novel technique.
Laparoscopic sleeve gastrectomy for morbid obesity is associated with a high incidence of postoperative permanent heartburn as a result of gastroesophageal reflux. In order to avoid this complication, the authors developed a new technique, combining the creation of a very long and narrow vertical gastroplasty with an antireflux procedure. The new operation was performed in 3 patients with BMI 40, 46 and 50 (1 male, 2 females). All the procedures were conducted laparoscopically using 6 trocars. The greater curvature of the stomach was mobilized in the antral region. A primary hole in both walls of the stomach was made in the antrum 5-7 cm proximal to the pylorus. Starting from this hole, the stomach was stapled and divided along a 33-Fr bougie to the angle of His, creating a long (15-20 cm), narrow tube. The divided fundus was then passed behind the mobilized abdominal part of the esophagus and a 360 degrees wrap was made (as in a Nissen procedure). None of the 3 patients developed complications. Excess BMI loss at 5 to 7 months has been good. No signs of esophagitis have been revealed during postoperative upper GI endoscopy. This operation is technically simple. Preliminary early postoperative results regarding its antireflux and weight-loss effects are encouraging.


Cloning pigs: advances and applications.
Although mouse embryonic stem cells have been used widely for over a decade as an important tool for introducing precise genetic modification into the genome, demonstrating the great value of this technology in a range of biomedical applications, similar technology does not exist for domestic animals. However, the development of somatic cell nuclear transfer has bypassed the need for embryonic stem cells from livestock. The production of offspring from differentiated cell nuclei provides information and opportunities in a number of areas including cellular differentiation, early development and ageing. However, the primary significance of cloning is probably in the opportunities that this technology brings to genetic manipulation. Potential applications of gene targeting in livestock species are described with particular emphasis on the generation of pigs that can be used for xenotransplantation, and the production of improved models for human physiology and disease. The development of techniques for somatic cell nuclear transfer in pigs and the challenges associated with this technology are also reviewed.


Discourse over a contested technology on Twitter: A case study of hydraulic fracturing.
High-volume hydraulic fracturing, a drilling simulation technique commonly referred to as "fracking," is a contested technology. In this article, we explore discourse over hydraulic fracturing and the shale industry on the social media platform Twitter during a period of heightened public contention regarding the application of the technology. We study the relative prominence of negative messaging about shale development in relation to pro-shale messaging on Twitter across five hashtags (#fracking, #globalfrackdown, #natgas, #shale, and #shalegas). We analyze the top actors tweeting using the #fracking hashtag and receiving @mentions with the hashtag. Results show statistically significant differences in the sentiment about hydraulic fracturing and shale development across the five hashtags. In addition, results show that the discourse on the main contested hashtag #fracking is dominated by activists, both individual activists and organizations. The highest proportion of tweeters, those posting messages using the hashtag #fracking, were individual activists, while the highest proportion of @mention references went to activist organizations.


A narrative review of management of wounds in palliative care setting.
A chronic wound is one that is physiologically compromised as a result of a disturbance of the wound-healing cycle brought on by, among other parameters, poor angiogenesis, innervation, or cellular migration. Given the high frequency and incidence rates of different wound categories in clinical practice in the setting of chronically ill patients, wound management is becoming an increasingly important component and pillar of the overall care of patients with terminal illnesses. The purpose of this narrative review is to provide an overview and evaluation of the assessment methods and management of chronic wounds in the clinical practice of palliative care. Papers on the management of wounds in palliative care have been retrieved using PubMed to July 2023. The search terms used included "wounds", "ulcers", "palliative care", "palliative management", and "end of life". The review highlights the importance of early palliative care referral and total pain management in the management of wounds. Patients with wounds often report multiple symptoms, and pain is one of the most common and distressing among them. Despite the availability of multiple guidelines about treatment to relieve pain, almost half of all cancer patients still receive inappropriate care for pain. The review also discusses the etiology of pain and provides strategies for managing the painful wound once it has been identified. The greatest need today in the treatment of chronic wounds is consensus-based knowledge vetted by practical experience and backed up by scientific evidence, which is easily communicated and available to all wound care practitioners. High-quality research together with wound care practice that leads to the best outcomes might include pain reduction, exudate management, odor management, and/or other quality-of-life benefits to wound care. There is a need for specialized palliative care teams to manage expectations throughout the process while maintaining hope.


[Risk factors for intracerebral hemorrhage after intravenous thrombolysis in acute cerebral infarction].
To identify risk factors of intracerebral hemorrhage (ICH) after intravenous thrombolysis in acute cerebral infarction. Eighty-two patients with acute cerebral infarction were treated with intravenous urokinase within 12 hours from stroke onset. The data of clinic and laboratory were as readily available baseline factors and were analyzed to select potential contributors to ICH. ICH occurred in 15 patients (18.3%), including 6 hemorrhagic infarction (HI, 7.3%) and 9 Parenchyma hemorrhage (PH, 11.0%). Seven patients had symptomatic ICH, and 4 patients died. Patients with ICH had significantly lower European stroke scale (ESS) scores. Patients with ESS<60 scores, early ischemic changes (EIC) on cranial CT scans or artrial fibrillation had significantly higher risk of ICH. Risk factors associated with ICH are severity of neurological deficit, EIC and artrial fibrillation.


5,10-methylene tetrahydrofolate reductase C677T gene polymorphism, homocysteine concentration and the extent of premature coronary artery disease in southern Iran.
Elevated level of plasma homocysteine (Hcy) has been identified as an independent risk factor for coronary artery disease (CAD). Furthermore, numerous studies have documented the influences of a common polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) on homocysteine levels. However the relationship between this mutation and cardiovascular diseases (CVD) has remained as a controversial issue. The present study was undertaken to investigate the relationship between C677T polymorphism of MTHFR gene, plasma total Hcy levels and the number of affected vessels as a criterion for the extent of CAD. MTHFR genotypes and plasma homocysteine (HCY) concentrations were examined in 231 patients and 300 healthy subjects who underwent diagnostic coronary angiography. A multiple linear regression analysis was performed to identify the predictors of Hcy levels whereas logistic regression model was built to determine the association of Hcy quartiles with the risk of CAD adjusted for risk factors. The prevalence of MTHFR genotypes was similar between CAD patients and non-CAD individuals while the geometric mean of Hcy values was significantly higher in patient group (14.13 ± 4.11 μmol/l) than in control group (10.19 ± 3.52 μmol/l) (P < 0.001). Moreover, unlike the MTHFR polymorphism, Hcy concentration increased with increasing number of stenosed vessels and the CAD risk increased about 2 folds in the top two Hcy quartiles (≥ 17.03 and 13.20-17.02 μmol/l) compared with the lowest quartile (≤ 9.92 μmol/l) after controlling for conventional risk factors (P<0.001 for both). Our data suggest that hyperhomocysteinaemia (HHcy) is significantly associated to CAD risk increase as well as to the extent of coronary atherosclerosis.


Robust fabrication method for silicon nanowire field effect transistors for sensing applications.
This paper demonstrates a new method for the top-down production of silicon nanowire field effect transistors for sensing applications. A simple and robust method for the fabrication of these devices is described, using only conventional CMOS (Complementary Metal Oxide Semiconductor) processing techniques making it manufacturable on large scale in a broad range of production facilities. Moreover, the process is flexible in terms of the choice of the type of front oxide of the transistor, as it is applied in a separate, independent step from the application of the surrounding oxide. In case ultimate small dimensions are required that go beyond the wafer stepper resolution, the use of e-beam technology to produce even smaller structures can be easily integrated. Furthermore, the use of a passivation layer opens possibilities for adding selectivity via surface modification on silicon dioxide and silicon. After a detailed description of the process, the electrical characteristics of the devices are shown together with data on the device reliability, indicating that the process is easy to manufacture, has a large yield and results in sensor devices with electrical characteristics in the desired regime.


Case report: transverse colon volvulus in a patient with Clostridium difficile pseudomembranous colitis.
Sixty-eight cases of transverse colon volvulus have been reported in the literature. The authors report the first case of transverse colon volvulus in association with Clostridium difficile pseudomembranous colitis, with a review of the available literature. It is possible that the acute inflammation of the colonic mucosa, which occurred from the pseudomembranous colitis in this patient, contributed to the development of volvulus. Further studies are needed to explore the role of mucosal inflammation in the occurrence of volvulus.


Peginterferon alpha versus other antiviral regimes for Chinese HBeAg-positive chronic hepatitis B patients.
To conduct a meta-analysis to determine the efficacy of peginterferon alpha (PEG-IFN α) therapy versus IFN α, adefovir dipivoxil (ADV) and entecavir (ETV) for HBeAg-positive chronic hepatitis B patients in China. MEDLINE database and 3 main Chinese biomedical databases between 1966 and 2012 was retrieved. Two reviewers independently screened all reports to identify randomized controlled trials that evaluated PEG-IFN α therapy for the treatment of chronic hepatitis B in China. Fourteen trials met the eligibility criteria for this Meta analysis. PEG-IFN α therapy was more effective than IFN α therapy in achieving ALT normalization, serum HBV DNA clearance, HBeAg seroconversion, serum HBeAg clearance and fibrosis improvement in Chinese hepatitis B patients (P<0.05). PEG-IFN α was obviously superior to ETV in HBeAg seroconversion and serum HBeAg clearance (P<0.05), but the seroconversion rate was low. The combination therapy of PEG-IFN α and ADV was more effective than ADV monotherapy in ALT normalization, serum HBV DNA clearance and HBeAg seroconversion (P<0.05). PEG-IFN α showed no priority to other treatment regimes in HBsAg clearance. Treatment with PEG-IFN α is safe and effective, and can be prescribed as firstline treatment options for chronic hepatitis B patients in China. Data are too limited to exclude a substantial benefit or harm of PEG-IFN α combination therapy for CHB patients in China.


Characterization of a Novel cis-3-Hydroxy-l-Proline Dehydratase and a trans-3-Hydroxy-l-Proline Dehydratase from Bacteria.
Hydroxyprolines, such as trans-4-hydroxy-l-proline (T4LHyp), trans-3-hydroxy-l-proline (T3LHyp), and cis-3-hydroxy-l-proline (C3LHyp), are present in some proteins including collagen, plant cell wall, and several peptide antibiotics. In bacteria, genes involved in the degradation of hydroxyproline are often clustered on the genome (l-Hyp gene cluster). We recently reported that an aconitase X (AcnX)-like hypI gene from an l-Hyp gene cluster functions as a monomeric C3LHyp dehydratase (AcnXType I). However, the physiological role of C3LHyp dehydratase remained unclear. We here demonstrate that Azospirillum brasilense NBRC 102289, an aerobic nitrogen-fixing bacterium, robustly grows using not only T4LHyp and T3LHyp but also C3LHyp as the sole carbon source. The small and large subunits of the hypI gene (hypIS and hypIL, respectively) from A. brasilense NBRC 102289 are located separately from the l-Hyp gene cluster and encode a C3LHyp dehydratase with a novel heterodimeric structure (AcnXType IIa). A strain disrupted in the hypIS gene did not grow on C3LHyp, suggesting its involvement in C3LHyp metabolism. Furthermore, C3LHyp induced transcription of not only the hypI genes but also the hypK gene encoding Δ1-pyrroline-2-carboxylate reductase, which is involved in T3LHyp, d-proline, and d-lysine metabolism. On the other hand, the l-Hyp gene cluster of some other bacteria contained not only the AcnXType IIa gene but also two putative proline racemase-like genes (hypA1 and hypA2). Despite having the same active sites (a pair of Cys/Cys) as hydroxyproline 2-epimerase, which is involved in the metabolism of T4LHyp, the dominant reaction by HypA2 was clearly the dehydration of T3LHyp, a novel type of T3LHyp dehydratase that differed from the known enzyme (Cys/Thr).IMPORTANCE More than 50 years after the discovery of trans-4-hydroxy-l-proline (generally called l-hydroxyproline) degradation in aerobic bacteria, its genetic and molecular information has only recently been elucidated. l-Hydroxyproline metabolic genes are often clustered on bacterial genomes. These loci frequently contain a hypothetical gene(s), whose novel enzyme functions are related to the metabolism of trans-3-hydroxyl-proline and/or cis-3-hydroxyl-proline, a relatively rare l-hydroxyproline in nature. Several l-hydroxyproline metabolic enzymes show no sequential similarities, suggesting their emergence by convergent evolution. Furthermore, transcriptional regulation by trans-4-hydroxy-l-proline, trans-3-hydroxy-l-proline, and/or cis-3-hydroxy-l-proline significantly differs between bacteria. The results of the present study show that several l-hydroxyprolines are available for bacteria as carbon and energy sources and may contribute to the discovery of potential metabolic pathways of another hydroxyproline(s).


Focal dermal hypoplasia: updates.
Focal dermal hypoplasia (FDH), or Goltz-Gorlin syndrome, is a rare syndrome and may result in multisystem disorders. Several reviews of FDH have been published. However, the last comprehensive review of this disorder appeared more than 20 years ago. To date, a number of new clinical manifestations have been reported and considerable knowledge has accumulated regarding etiology and pathogenetic mechanisms. The purpose of this review is to gather these more recent data and to provide organized and reliable information. So we reviewed 159 cases of FDH that had been reported from 1990 to 2012, summarized the new discoveries, and suggested a potential standard for the diagnosis of FDH. We also reported on a Chinese girl with FDH, who was clinically and histologically in accord with FDH, as an example.


Changes in diet and physical activity following BRCA1/2 testing.
The present study prospectively examined change in diet and physical activity behaviors in 115 women undergoing BRCA1/2 gene testing (46 mutation positive, 46 uninformative and 23 definitive negative). Participants completed measures of diet and physical activity at three time points: prior to genetic testing and 1-and 6-months after receipt of genetic test results. Repeated measures analyses examined between-and within-group differences among participants who received BRCA1/2 positive, uninformative, or definitive negative results. There were no within-group differences across time points or between-group differences at any time point for diet or physical activity. Most participants, overall and within each group, did not meet recommended guidelines for fruit and vegetable and dietary fat consumption. These findings suggest that women do not make spontaneous changes in diet and physical activity following the genetic testing and counseling process. A brief intervention may be necessary for patients who are interested in making changes in modifiable risk factors to complement more definitive risk-reduction strategies.


DNA structure constraint is probably a fundamental factor inducing CpG deficiency in bacteria.
It has been speculated that CpG dinucleotide deficiency in genomes is a consequence of DNA methylation. However, this hypothesis does not adequately explain CpG deficiency in bacteria. The hypothesis based on DNA structure constraint as an alternative explanation was therefore examined. By comparing real bacterial genomes and Markov artificial genomes in the second order, we found that the core structure of a restricted pattern, the TTCGAA pattern, was under represented in low GC content bacterial genomes regardless of CpG dinucleotide level. This is in contrast to the AACGTT pattern, indicating that the counterselection is context-dependent. Further study discovered nine underrepresented patterns that were supposed to be capable of inducing DNA structure constraint. In summary, most of them are in TTCGNA and TTCGAN patterns in both DNA strands. An explanation is also proposed for the strong correlation between GC content and CpG deficiency. The result of random sequence simulation showed that the occurrences of these patterns were correlated with GC content, as well as the percentage of CpG dinucleotides being trapped in these patterns. Finally, we suggest that the degree of counter-selection against these restricted patterns could be influenced by global GC content of a genome.


Improving anticoagulation of patients with an implantable left ventricular assist device.
Patients supported with implantable left ventricular assist devices (LVAD) have a significant risk of bleeding and thromboembolic complications. All patients require anticoagulation with warfarin, aiming for a target international normalised ratio (INR) of 2.5 and most patients also receive antiplatelet therapy. We found marked variation in the frequency of INR measurements and proportion of time outside the therapeutic INR range in our LVAD-supported patients. As part of a quality improvement initiative, home INR monitoring and a networked electronic database for recording INR results and treatment decisions were introduced. These changes were associated with increased frequency of INR measurement. We anticipate that changes introduced in this quality improvement project will reduce the likelihood of adverse events during long-term LVAD support.


Response of the difference-of-Gaussians model to circular drifting-grating patches.
Forty years ago R.W. Rodieck introduced the Difference-of-Gaussians (DOG) model, and this model has been widely used by the visual neuroscience community to quantitatively account for spatial response properties of cells in the retina and lateral geniculate nucleus following visual stimulation. Circular patches of drifting gratings are now regularly used as visual stimuli when probing the early visual system, but for this stimulus type the mathematical evaluation of the DOG-model response is significantly more complicated than for moving bars, full-field drifting gratings, or circular flashing spots. Here we derive mathematical formulas for the DOG-model response to centered circular patch gratings. The response is found to be given as the difference between two summed series, where each term in the series involves the confluent hypergeometric function. This function is available in commonly used mathematical software, and the results should thus be readily applicable. Example results illustrate how a strong surround suppression in area-summation curves for iso-luminant circular spots may be reversed into a surround enhancement for circular patch gratings. They also show that the spatial-frequency response changes from band-pass to low-pass when going from the full-field grating situation to the situation where the patch covers only the receptive-field center.


Does the use of statins improve outcomes in coronary artery bypass graft surgery?
Statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) are one of the most frequently prescribed medications throughout the world with beneficial effects that extend beyond their lipid-lowering activity. It has been suggested that statins may offer a simple and cost-effective strategy to reduce some of the complications that occur in association with coronary artery bypass graft (CABG) surgery. Limited existing randomized trial evidence in the setting of cardiac surgery suggests that statins may reduce the incidence of postoperative atrial fibrillation. However, any effect of statins on other outcomes is less clear. The clinical significance of specific statin agent and dose, acute statin withdrawal and the potential benefits associated with statin reloading remain important yet currently unresolved issues. Despite limited high-quality evidence, class I recommendations have been made that all patients undergoing coronary artery bypass graft surgery should receive statin therapy unless contraindicated.


Mechanism of paraquat-stimulated lipid peroxidation in mouse brain and pulmonary microsomes.
Paraquat-stimulated NADPH-dependent lipid peroxidation in mouse brain and pulmonary microsomes was inhibited by superoxide dismutase and singlet oxygen quenchers, but not by catalase or hydroxyl radical scavengers. MnCl2, which might form a salt with unsaturated lipid, inhibited the lipid peroxidation in brain microsomes, but not that in pulmonary microsomes. These findings suggest that activated oxygen species, especially superoxide and singlet oxygen, may play a major role in the stimulation of microsomal lipid peroxidation by paraquat in both brain and lung, and that the nature of the lipids exposed to peroxidative attack may be different in microsomes of the two organs.


Anoctamin 5 promotes osteosarcoma development by increasing degradation of Nel-like proteins 1 and 2.
Anoctamin 5 (ANO5) is a member of the Anoctamin (ANO) family of calcium-activated chloride channels. Although ANO5 expression is upregulated in various cancers, its role in osteosarcoma remains largely unknown. In this study, bioinformatics analysis, western blot, and immunohistochemical staining revealed that ANO5 was upregulated in osteosarcoma cell lines and osteosarcoma tissues, and ANO5 expression was positively associated with tumor size, tumor grade, and metastasis. Functional experiments demonstrated that inhibition of ANO5 decreased, while ANO5 overexpression increased, osteosarcoma cell proliferation and mobility in vitro. Immunoprecipitation, western blot, and confocal microscopy experiments showed that ANO5 bound to and promoted the degradation of Nel-like proteins 1 (NELL1) and 2 (NELL2). Moreover, a subcutaneous tumor transplantation model revealed that ANO5 knockdown reduced osteosarcoma cell proliferation and increased NELL1 and NELL2 expression in vivo. Finally, rescue experiments showed that knockdown of NELL1 or NELL2 reversed the inhibitory effects of ANO5 knockdown on osteosarcoma cell proliferation and migration. These results demonstrated that upregulation of ANO5 promoted osteosarcoma development by decreasing the stability of the NELL1 and NELL2 proteins and that ANO5 may be an effective target for the treatment of osteosarcoma.


Extubation in the Operating Room After Coronary Artery Bypass Graft Surgery Reduces Hospital Stay.
The aim of this analysis was to compare the effect of extubating in the operating room (OR) versus and the intensive care unit (ICU) among patients undergoing coronary artery bypass grafting (CABG). A retrospective cohort analysis. Ten cardiac referral hospitals in Latin America; participants of the São Paulo Registry of Cardiovascular Surgery II (REPLICCAR II). The database included a total of 4,015 patients who underwent primary and isolated CABG surgery and were ≥18 years old, of whom 205 patients were extubated in the OR. The analysis was made after a propensity score matching (PSM) adjustment in the population sample of patients extubated in the OR and ICU by the following variables: sex, age, body mass index, smoking, type of surgery, chronic obstructive pulmonary disease, preoperative atrial fibrillation, cardiopulmonary bypass time, preoperative creatinine, and preoperative left ventricular ejection fraction. This study focused on the analysis of the ICU and hospital length of stay, need for reintubation, morbidity, and mortality. After PSM, 402 patients were analyzed. Both groups had similar baseline characteristics, such as age (p = 0.132), sex (p = 1.00), and estimated risk of prolonged ventilation (>24 hours, p = 0.168); however, the median ventilation time was significantly shorter in the group extubated in the OR compared to the ICU group (5.67 hours v 17.55 hours, p < 0.001). The group of patients extubated in the ICU had a longer postoperative stay (7.54 ± 3.40 days v 6.41 ± 2.91 days, p < 0.001) and longer total hospitalization time (11.49 ± 5.70 days v 10.36 ± 5.72, p = 0.013) compared to those extubated in the OR. The authors did not observe a significant difference in the need for reintubation, morbidity, or mortality rates among the evaluated groups. In the REPLICCAR II database, extubation performed in the OR was associated with a reduced length of postoperative and total hospital stays compared to extubation in the ICU.


Ammonium removal from aqueous solutions by clinoptilolite: determination of isotherm and thermodynamic parameters and comparison of kinetics by the double exponential model and conventional kinetic models.
The adsorption isotherm, the adsorption kinetics, and the thermodynamic parameters of ammonium removal from aqueous solution by using clinoptilolite in aqueous solution was investigated in this study. Experimental data obtained from batch equilibrium tests have been analyzed by four two-parameter (Freundlich, Langmuir, Tempkin and Dubinin-Radushkevich (D-R)) and four three-parameter (Redlich-Peterson (R-P), Sips, Toth and Khan) isotherm models. D-R and R-P isotherms were the models that best fitted to experimental data over the other two- and three-parameter models applied. The adsorption energy (E) from the D-R isotherm was found to be approximately 7 kJ/mol for the ammonium-clinoptilolite system, thereby indicating that ammonium is adsorbed on clinoptilolite by physisorption. Kinetic parameters were determined by analyzing the nth-order kinetic model, the modified second-order model and the double exponential model, and each model resulted in a coefficient of determination (R(2)) of above 0.989 with an average relative error lower than 5%. A Double Exponential Model (DEM) showed that the adsorption process develops in two stages as rapid and slow phase. Changes in standard free energy (∆G°), enthalpy (∆H°) and entropy (∆S°) of ammonium-clinoptilolite system were estimated by using the thermodynamic equilibrium coefficients.


APDB: a database on air pollutant characterization and similarity prediction.
The World Health Organization estimates that 9 out of 10 people worldwide breathe air containing high levels of pollutants. Long-term and chronic exposure to high concentrations of air pollutants is associated with deleterious effects on vital organs, including increased inflammation in the lungs, oxidative stress in the heart and disruption of the blood-brain barrier. For this reason, in an effort to find an association between exposure to pollutants and the toxicological effects observable on human health, an online resource collecting and characterizing in detail pollutant molecules could be helpful to investigate their properties and mechanisms of action. We developed a database, APDB, collecting air-pollutant-related data from different online resources, in particular, molecules from the US Environmental Protection Agency, their associated targets and bioassays found in the PubChem chemical repository and their computed molecular descriptors and quantum mechanics properties. A web interface allows (i) to browse data by category, (ii) to navigate the database by querying molecules and targets and (iii) to visualize and download molecule and target structures as well as computed descriptors and similarities. The desired data can be freely exported in textual/tabular format and the whole database in SQL format. Database URL http://apdb.di.univr.it.


[Long-Term Capecitabine Therapy Was Successful for Locally Advanced Breast Cancer Patient - Report of a Case].
For the treatment of locally advanced breast cancer, chemotherapy involving anthracycline and/or taxane-containg regimens is generally performed. However, some patients have difficult reasons for administering these intravenous chemotherapeutic agents. We experienced a case of locally advanced breast cancer patient who received long-term capecitabine therapy. This therapy was effective for this patient. A 72 year-old woman presented with a lump in her right breast. The tumor had been increasing for 15 years. The tumor had spread from the right breast to the axilla and the lateral chest, accompanied with ulceration. A core needle biopsy was performed and the pathological diagnosis was papillotubular carcinoma. We checked up her body, and there was no distant metastasis. We diagnosed the clinical stage as T4cN3aM0, stage III C. She was concerned about the side effect of depilation and did not wish the standard chemotherapy. We chose capecitabine therapy. She continued capecitabine therapy and endocrine therapy. The tumor and tumor markers were decreased. The tumor size has not increased and metastatic lesions have not appeared for 5 years and a half.


Comparison of three methods for determination of glucose.
Study refers comparison of three methods for glucose determination - precision (repeatability, reproducibility), traceability to SRM 965a NIST, comparability in blood-pools and in patients' samples: Electrochemical determination on Super GL (DiaSys, Germany) in hemolyzate - GL method, spectrophotometric determination using hexokinase (Glucose System Reagent 800, Olympus) - HKL method - and using glucose dehydrogenase (Glucose Gluc-DH, EcolineS+, DiaSys, Germany) - GDL method - in hemolyzate. For showing differences between the concentration of glucose in hemolyzed blood and corresponding plasma, spectrophotometric determination using hexokinase in plasma was used (Glucose System Reagent 800, Olympus) - HKP method. Coefficients of variation characterizing precision under repeatability and reproducibility conditions are not higher than 3.0% for the GL method, 6.3% for the GDL method and 15.8% for the HKL method with low sensitivity. For glucose concentration less than 8 mmol/l, HKL tends to give lower results than GDL, and GL tends to give higher results than GDL. For glucose concentration about 2 mmol/l, the results of glucose in plasma - HKP method - tend to be significantly lower (by more than ten percent) than in corresponding total (hemolyzed) blood. HKL method can be reasonably used in a high number of parallel determinations. For glucose 8 mmol/l and lower, comparability of results given by HKL, GDL and GL methods gradually worsens, while for glucose between 8 and 34 mmol/l results of the three mentioned methods are well comparable.


A versatile platform for graphene nanoribbon synthesis, electronic decoupling, and spin polarized measurements.
The on-surface synthesis of nano-graphenes has led the charge in prototyping structures with perspectives beyond silicon-based technology. Following reports of open-shell systems in graphene-nanoribbons (GNRs), a flurry of research activity was directed at investigating their magnetic properties with a keen eye for spintronic applications. Although the synthesis of nano-graphenes is usually carried out on Au(111), the substrate is difficult to use for electronic decoupling and spin-polarized measurements. Using a binary alloy Cu3Au(111), we show possibilities for gold-like on-surface synthesis compatible with spin polarization and electronic decoupling known from copper. We prepare copper oxide layers, demonstrate the synthesis of GNRs, and grow thermally stable magnetic Co islands. We functionalize the tip of a scanning tunneling microscope with carbon-monoxide, nickelocene, or attach Co clusters for high-resolution imaging, magnetic sensing, or spin-polarized measurements. This versatile platform will be a valuable tool in the advanced study of magnetic nano-graphenes.


[Enhancement of quality by employing qualification-oriented staff and team-oriented cooperation].
Taking three practical examples from a university hospital the present article describes how quality can be improved by linking deployment of qualification-oriented staff with team-oriented cooperation, especially with regard to the professional groups of physicians and nurses. In the first example, a cross-professional work group defined tasks which--in a legally acceptable manner--allow selected activities to be transferred from physicians to nurses, improving the work processes of all persons concerned. Work and duty profiles, training and modified work processes were created and implemented according to the PDCA circle-based process. The first evaluation took place after nine months using interviews, questionnaires (patients, physicians, and nurses) as well as CIRS. In the second example, emphasis was placed on offers of supplementary services for private patients resulting in a lightening of the workload on the nursing staff. These supplementary services are intended to enhance the wellbeing of the patients. Special external-service staff provide high standard hotel services. These services consistently receive high ratings from the patients. The methods used for introduction and evaluation are analogous to those used in the first example. The third example is concerned with the extension of nursing care and patient empowerment beyond the boundaries of ward and hospital. The guidelines were the implementation of the national expert standard for discharge management according to the DNQP. The methods of introduction were analogous to those used in example 1. For the evaluation interviews were conducted with all participating groups. In all examples actual quantitative measures (key ratios) are not yet available; however, the data collected from the interviews and questionnaires of all the participants are promising.


Absence of conclusive evidence for the safety and efficacy of gonadotropin-releasing hormone analogue treatment in protecting against chemotherapy-induced gonadal injury.
Every year, an increasing number of women with malignant and nonmalignant diseases is successfully treated with cytotoxic chemotherapy and/or radiotherapy. Many of these patients suffer from infertility and gonadal failure as a result of these treatments. At present, these patients may resort to assisted-reproduction techniques to protect their future childbearing potential before the implementation of cytotoxic therapy. While embryo cryopreservation is an established technology, oocyte and ovarian tissue freezing techniques are still investigational. Nevertheless both of these techniques have resulted in live births. Apart from assisted-reproduction techniques, it has been extensively debated whether administration of gonadotropin-releasing hormone (GnRH) analogues in conjunction with chemotherapy can protect ovarian reserve against cytotoxic insult. In this manuscript, we debate the rationale for the effectiveness of GnRH analogue coadministration in preservation of fertility by reviewing the literature, and provide preliminary data to support our views.


Aspirin resistance frequency in healthy males.
Aspirin has been shown to have variable antiplatelet activity in individuals. Previous studies have estimated that 5% to 45% of the population do not achieve an adequate antiplatelet effect from aspirin and still suffer ischemic events despite therapy. In this study, we aimed to evaluate aspirin resistance in healthy males. We prospectively enrolled 175 healthy males who were ≥19 years old and taking 100 mg of aspirin daily ≥7 consec¬utive days before study entry. Demographic information and laboratory data were collected. Aspirin resistance was detected by optical platelet aggregometry, a widely accepted method using adenosine diphosphate (ADP) and arachidonic acid (AA). 28% of the participants were aspirin-resistant, 62% were aspirin-semi-responders and 10% were aspirin-sensitive. The aspirin-resistant individuals were older than the semi-responders (p<0.01), and had higher erythrocyte sedimentation rate than the semi-responders (p<0.01) and sensitive individuals (p<0.05). Our study demonstrates aspirin resistance to be particularly important given its high frequency in our study population. The biological effects of aspirin, which is widely used as an antithrombotic drug, are not similar in all individuals.


Distinguishing hepatic metastases from hemangiomas: qualitative and quantitative diagnostic performance through dual echo respiratory-triggered fast spin echo magnetic resonance imaging.
To determine the relative value of qualitative (reader opinion) and quantitative (values derived from dual echo T2 fast spin echo [FSE]) measures in distinguishing hepatic metastases from hemangiomas. Forty-nine patients with hemangiomas and 23 with metastases were studied with dual echo respiratory-triggered FSE and dynamic 2-dimensional spoiled gradient echo (GRE) imaging. Lesion T2 was estimated from signal intensity ratios on the first and second echoes. Two experienced radiologists independently evaluated groups of images based on 5 separate qualitative measures: first echo FSE, second echo FSE, first and second echo FSE, dynamic GRE, and all images together. The mean calculated T2s were 226 +/- 74 milliseconds for hemangiomas and 105 +/- 22 milliseconds for metastases (P < 0.001). A T2 cutoff of 130 milliseconds distinguished metastases from hemangiomas with a sensitivity of 94%, specificity of 91%, and accuracy of nearly 94%. There was no significant difference between the best quantitative measure and the best qualitative measure for either reader. Liver lesion T2 relaxation times calculated from dual echo FSE images provide information useful in discriminating metastases from hemangiomas, as does reader opinion.


The toxicity of brominated sesame oil and brominated soybean oil in miniature swine.
Miniature swine were fed brominated sesame oil at dietary levels of 0, 5, 25, 50 or 500 mg/kg of body weight for 17 weeks and brominated soybean oil at levels of 0, 5, 50 or 500 mg/kg of body weight for 28 weeks. Growth rate and food intake were decreased only at the high dose level in the brominated sesame oil study. In both studies, signs of lethargy and ataxia occurred in pigs fed the highest dose, and were probably due to a dose-related increase in serum bromine concentrations. Marked elevations in lactic dehydrogenase (LDH), serum glutamic-oxalacetic transaminase (SGOT) and serum glutamicpyruvic transaminase (SGPT) values were seen at the highest dose level with both substances and these enzyme activities were increased at the 50 mg/kg dose level in the brominated sesame oil study. Histopathologic lesions were confined to animals given the highest dose level of either oil. Marked fatty degeneration of the hepatic plate cells and renal tubular epithelial cells were seen in both studies. In the brominated sesame oil study, neutral fat was moderately increased in the myocardium of the pigs fed 500 mg/kg. However, marked diffuse accumulation of LDH, marked diffuse fatty degeneration and focal degeneration, and/or necrosis of individual or small groups of cardiac muscle fibers were seen in the group fed brominated soybean oil at 500 mg/kg. A moderate to marked testicular atrophy was also observed in this group. A dose-related accumulation of total and hexane-soluble bromine was observed in all tissues examined in both studies; the highest concentrations occurred in adipose tissue of the pigs given the highest dose level. Kidneys, livers, hearts and thyroids of these groups also contained large amounts of bromine. In pigs given the 50 mg/kg dose level, total and hexane-soluble bromine concentrations were higher in the brominated sesame oil study than in the longer brominated soybean oil study and may be responsible for the elevations in LDH, SGPT and SGOT activities in this group.


Altered functional properties of the renal glomerulus in autologous immune complex nephritis: an ultrastructural tracer study.
The altered functional properties of the glomerular capillary wall in a model of autologous immune complex disease (Heymann's nephritis) was studied by electron microscopy using intravenously injected protein tracers of varying molecular weight. There was an increase in the permeability of the glomerular basement membrane (GBM) itself to large molecules; this change was focal and was found in those areas where the GBM contained immune complex deposits. Both ferritin and catalase, tracers normally restricted from passing the glomerular filter, were present in the urinary space within minutes of injection. No evidence was obtained for increased glomerular epithelial transport in this disease. Foot process swelling and "close" junction formation was moderate, even in animals with marked degrees of proteinuria. Indirect evidence, therefore, makes an alteration in the slit pore complex likely. In addition, there was immediate and selective concentration of all tracers within deposits, though ferritin was partially excluded from some deposits. This phenomenon may be of significance in the perpetuation of the disease.


[Novel inhibitors against the bacterial signal peptidase I].
New antibiotics with novel modes of action and structures are urgently needed to combat the emergence of multidrug-resistant bacteria. Bacterial signal peptidase I (SPase I) is an indispensable enzyme responsible for cleaving the signal peptide of preprotein to release the matured proteins. Increasing evidence suggests that SPase I plays a crucial role in bacterial pathogenesis by regulating the excretion of a variety of virulent factors, maturation of quorum sensing factor and the intrinsic resistance against beta-lactams. Recently, breakthrough has been achieved in the understanding of three-dimensional structure of SPase I as well as the mechanism of enzyme-inhibitors interaction. Three families of inhibitors are identified, i.e. signal peptide derivatives, beta-lactams and arylomycins. In this article, we summarize the recent advance in the study of structure, activity and structure-activity relationship of SPase I inhibitors.


Pump side scattering in ultrapowerful backward Raman amplifiers.
Extremely large laser power might be obtained by compressing laser pulses through backward Raman amplification (BRA) in plasmas. Premature Raman backscattering of a laser pump by plasma noise might be suppressed by an appropriate detuning of the Raman resonance, even as the desired amplification of the seed persists with a high efficiency. In this paper we analyze side scattering of laser pumps by plasma noise in backward Raman amplifiers. Though its growth rate is smaller than that of backscattering, the side scattering can nevertheless be dangerous, because of a longer path of side-scattered pulses in plasmas and because of an angular dependence of the Raman resonance detuning. We show that side scattering of laser pumps by plasma noise in BRA might be suppressed to a tolerable level at all angles by an appropriate combination of two detuning mechanisms associated with plasma density gradient and pump chirp.


A comparison of the interactions of galactosyltransferase with a glycoprotein substrate (Ovalbumin) and with alpha-lactalbumin.
Sedimentation velocity ultracentrifugation and other procedures have been used to investigate macromolecular interactions of bovine colostrum galactosyltransferase with a glycoprotein substrate (ovalbumin) and with the lactose synthase regulatory protein, alpha-lactalbumin. The determination of equilibrium binding constants for these interactions and the effects of ligands and combinations of ligands on the equilibria have clarified several aspects of the mechanism of galactosyltransferase and its regulation by alpha-lactalbumin. 1. The attachment of Mn2+ at the tight binding site on galactosyltransferase (site I, Kd 2.3 muM) is an essential prerequisite for interactions with ovalbumin and with alpha-lactalbumin. 2. The attachment of Mn2+ or Ca2+ at the weaker metal binding site (site II, Kd 1 to 2 mM) does not significantly affect the interaction of galactosyltransferase with either protein. This is consistent with the hypothesis derived from kinetic studies that site II is functionally connected with the binding of UDP-derivatives. 3. While the binding of ovalbumin to galactosyltransferase in the presence of Mn2+ alone can be observed by ultracentrifugation, this interaction is too weak to cause binding of galactosyltransferase to ovalbumin-Sepharose. Binding to ovalbumin-Sepharose could only be detected by affinity chromatography in the presence of both Mn2+ (10 mM) and UDP (0.3 MM). Sedimentation studies showed that the association of galactosyltransferase with ovalbumin is pressure-dependent, and that the presence of UDP in the complex increases the equilibrium association constant by a factor of 46. The enzyme Mn2+-UDP-ovalbumin complex has unusual hydrodynamic properties. 4. The presence of saturating concentrations of UDP-galactose potentiates the binding of alpha-lactalbumin at high concentrations of Mn2+, as shown by a 25-fold increase in the association constant. Competitive inhibition by alpha-lactalbumin, with respect to ovalbumin that is observed by steady state kinetics, is attributed to the mutally exclusive binding of the proteins with an enzyme complex containing Mn2+ and UDP-galactose. 5. Monsaccharides (N-acetylglucosamine and glucose) strongly enhance the binding of alpha-lactalbumin to enzyme complexes containing Mn2+, in the presence or absence of UDP-glucose. The binding of alpha-lactalbumin and monosaccharide to form enzyme complexes containing both is random, and evaluation of the four associated equilibrium constants shows that the binding is strongly synergistic. 6. Although the significance of some of the many equilibria studied cannot be ascertained, it appears than an element of randomness may be present in reactions catalyzed by galactosyltransferase...


Tibiotalocalcaneal Arthrodesis Using Hybrid Plate-Nail Constructs: A Novel Technique for Treatment of Unstable Ankle and Hindfoot Deformities.
Tibiotalocalcaneal (TTC) arthrodesis is a treatment option for several pathologies of the ankle and hindfoot, including acute trauma, posttraumatic arthritis, and Charcot neuroarthropathy. Traditional fixation options for TTC arthrodesis include intramedullary hindfoot nailing or internal fixation with plates and/or screws. In certain patients, either due to poor bone quality, impaired sensation, or concern for noncompliance, more robust fixation may be desired. In such patients, we have used a hybrid plate-nail construct with promising results. This article and the accompanying video demonstrate our technique for TTC arthrodesis using a plate-nail construct and review treatment decisions involved with management of these complex cases.


The Influence of Selected Insecticides on the Oxidative Response of Atta sexdens (Myrmicinae, Attini) Workers.
Reactive oxygen species (ROS) are generated as products of normal cellular metabolic activities; however, the use of pesticides to control leafcutter ants leads to unbalanced ROS production. We evaluated the effects of two insecticides (fipronil, sulfluramid) and metallic insecticide complex (magnesium complex [Mg(hesp)2(phen)] (1)) on the superoxide dismutase (SOD), glutathione (GSH) and the overall antioxidant capacity using two different methodologies: total radical-trapping potential (TRAP) and oxygen radical absorbance capacity (ORAC). Media workers of Atta sexdens (C. Linnaeus) were exposed to the insecticides for 24 h, 48 h, 72 h and 96 h before their fat bodies were dissected for analysis. The results showed that although the sulfluramid may cause the production of ROS, its slow action in the organism does not lead to oxidative stress. There is a rise in oxidative stress in workers of leafcutter ants treated with fipronil because SOD significantly increased when compared to the control group. On the other hand, Mg1-complex suppressed both GSH and SOD, indicating that the immune system may be affected by Mg1-complex, which has a delayed activity ideal for its use in chemical pest control. Both TRAP and ORAC evaluated total antioxidant capacities; however, ORAC proved to be a more sensitive method. In conclusion, the Mg1-complex is a new compound that should be further investigated as a potential replacement for fipronil and sulfluramid in pest control.


Removal of a large bizarre uterine leiomyoma by operative hysteroscopy. Case report and review of the literature.
Atypical leiomyomas are relatively uncommon in the general practice of gynaecology. We present a case of a large uterine bizarre leiomyoma removed by operative hysteroscopy and review of the literature. The patient, a 49-year-old, gravida 3, para 3, perimenopausal Greek woman presented to our Department because of dysmenorrhea and abnormal vaginal bleeding. She underwent hysteroscopy in which a large submucosal leiomyoma was detected and entirely removed in one session. The histopathology revealed bizarre uterine leiomyoma. There is no evidence to indicate that hysterectomy is necessary, if the diagnosis of atypical leiomyoma has been firmly established.


Recording sympathetic nerve activity in conscious humans and other mammals: guidelines and the road to standardization.
Over the past several decades, studies of the sympathetic nervous system in humans, sheep, rabbits, rats, and mice have substantially increased mechanistic understanding of cardiovascular function and dysfunction. Recently, interest in sympathetic neural mechanisms contributing to blood pressure control has grown, in part because of the development of devices or surgical procedures that treat hypertension by manipulating sympathetic outflow. Studies in animal models have provided important insights into physiological and pathophysiological mechanisms that are not accessible in human studies. Across species and among laboratories, various approaches have been developed to record, quantify, analyze, and interpret sympathetic nerve activity (SNA). In general, SNA demonstrates "bursting" behavior, where groups of action potentials are synchronized and linked to the cardiac cycle via the arterial baroreflex. In humans, it is common to quantify SNA as bursts per minute or bursts per 100 heart beats. This type of quantification can be done in other species but is only commonly reported in sheep, which have heart rates similar to humans. In rabbits, rats, and mice, SNA is often recorded relative to a maximal level elicited in the laboratory to control for differences in electrode position among animals or on different study days. SNA in humans can also be presented as total activity, where normalization to the largest burst is a common approach. The goal of the present paper is to put together a summary of "best practices" in several of the most common experimental models and to discuss opportunities and challenges relative to the optimal measurement of SNA across species.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-measuring-sympathetic-nerve-activity/.


Design and Implementation of an Automated Illuminating, Culturing, and Sampling System for Microbial Optogenetic Applications.
Optogenetic systems utilize genetically-encoded proteins that change conformation in response to specific wavelengths of light to alter cellular processes. There is a need for culturing and measuring systems that incorporate programmed illumination and stimulation of optogenetic systems. We present a protocol for building and using a continuous culturing apparatus to illuminate microbial cells with programmed doses of light, and automatically acquire and analyze images of cells in the effluent. The operation of this apparatus as a chemostat allows the growth rate and the cellular environment to be tightly controlled. The effluent of the continuous cell culture is regularly sampled and the cells are imaged by multi-channel microscopy. The culturing, sampling, imaging, and image analysis are fully automated so that dynamic responses in the fluorescence intensity and cellular morphology of cells sampled from the culture effluent are measured over multiple days without user input. We demonstrate the utility of this culturing apparatus by dynamically inducing protein production in a strain of Saccharomyces cerevisiae engineered with an optogenetic system that activates transcription.


Higher Intra-Dialysis Serum Phosphorus Reduction Ratio as a Predictor of Mortality in Patients on Long-Term Hemodialysis.
BACKGROUND Rapid shifting between extracellular and intracellular phosphorus can occur during dialysis sessions, which can cause aberrant intracellular signaling in long-term hemodialysis (LTHD) patients. However, the effect of these intra-dialysis fluctuations of phosphorus on clinical outcomes has not been examined. Therefore, we investigated the relationship between intradialysis serum phosphorus reduction ratio (IDSPRR) and mortality in LTHD patients. MATERIAL AND METHODS This was a retrospective, observational cohort study to assess the predictive power of IDSPRR (>0.63 vs. ≤0.63) on mortality in a total of 805 LTHD patients. All these fatal events were analyzed using the Cox proportional hazards regression model. RESULTS After multivariable analysis, baseline IDSPRR higher than 0.63 was significantly predictive of all-cause mortality (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.10-2.26), but not for cardiovascular (CV) mortality (HR: 1.41; 95% CI: 0.91-2.18). However, when time-varied IDSPRRs were applied, a value greater than 0.63 was not only significantly predictive of all-cause mortality (HR: 1.74, 95% CI: 1.16-2.63), but also CV mortality (HR: 2.04, 95% CI: 1.23-3.40). CONCLUSIONS High IDSPRR (>0.63) is independently associated with increased all-cause and CV mortality, which shows the negative effect of rapid intracellular phosphorus-shifting on LTHD patients.


Two linked blood pressure quantitative trait loci on chromosome 10 defined by dahl rat congenic strains.
Aquantitative trait locus (QTL) for blood pressure was previously detected on rat chromosome 10 (RNO10) by linkage analysis and confirmed by the construction of congenic strains that encompass large regions of RNO10. In the present study, the rat RNO10 blood pressure QTL was dissected by the further construction of congenic substrains. The original congenic region was shown to contain 2 blood pressure QTLs (QTL 1 and QTL 2) approximately 24 cM apart. These were localized to a <2.6-cM region between markers D10Rat27 and D10Rat24 for QTL 1 and to a <3.2-cM region between D10Rat12 and D10Mco70 for QTL 2. Comparative mapping suggests that the rat RNO10 QTL 2 could be localized very close to a blood pressure QTL described by sib-pair analysis on human chromosome 17, but this is not definitively established because of multiple and complex chromosomal rearrangements between rodents and humans.


The duration of measuring partial AUCs for the assessment of bioequivalence.
To determine favourable sampling conditions for assessing bioequivalence by the comparison of partial AUCs in the early phase of concentration-time profiles. Two-period crossover trials were simulated. They assumed a wide range of the ratios of absorption rate constants of the test (T) and reference (R) formulations (kaT/kaR). Averages and standard deviations of the corresponding ratios of simulated partial AUCs (AUCpT/AUCpR) were determined together with the statistical power of assessing bioequivalence, i.e., the percentage of simulated trials in which bioequivalence was declared. The power for stating bioequivalence was high when AUCp was recorded until the earlier rather than the later of two peaks in each subject. Similarly, power was comparatively high when AUCp was measured until the time of the reference peak instead of multiples of this time. Power was high also when AUCp was determined until the fixed true, population mean time of the reference formulation instead of multiples of this time. The pattern for the kinetic sensitivity parallelled that found for the power, while the standard deviations changed generally in the opposite direction. The effectiveness (power) of evaluating bioequivalence in the early phase of concentration-time profiles by partial AUCs generally decreases when the duration for measuring the metric is extended. Among the investigated designs, determination of partial AUCs until the earlier of two peaks in each subject is the most powerful.


Hepatic palmitate metabolism in fasting Zucker rats: effect of lactate on partitioning.
Hepatocytes were isolated from 48-h fasted lean and obese Zucker rats and incubated with [1-14C] palmitate. The partitioning of fatty acids to oxidation and esterification products and the effect of lactate or glucose on this partitioning were studied. With palmitate as the only substrate, the cells from the lean rats oxidized 80% of the palmitate that was metabolized compared with only 35% oxidation in the cells from the obese rats. Thus fatty acid esterification remained the predominate pathway of palmitate metabolism in the hepatocytes from fasting obese rats. The addition of lactate to the cells from the lean rats decreased oxidation and increased esterification to levels similar to those in the obese rat hepatocytes. Glucose had similar effects on esterification in lean rat hepatocytes but was less potent than lactate. The cells from the obese rats were insensitive to the addition of lactate or glucose. These studies indicate that the inability of hepatocytes from obese rats to induce ketogenesis from exogenous fatty acids after a 48-h fast and their insensitivity to added lactate or glucose may be related to the availability of endogenous energy sources in the obese liver that can be oxidized and thus inhibit ketogenesis and support fatty acid esterification.


Thrombospondins 1 and 2 are necessary for synaptic plasticity and functional recovery after stroke.
Thrombospondins 1 and 2 (TSP-1/2) belong to a family of extracellular glycoproteins with angiostatic and synaptogenic properties. Although TSP-1/2 have been postulated to drive the resolution of postischemic angiogenesis, their role in synaptic and functional recovery is unknown. We investigated whether TSP-1/2 are necessary for synaptic and motor recovery after stroke. Focal ischemia was induced in 8- to 12-week-old wild-type (WT) and TSP-1/2 knockout (KO) mice by unilateral occlusion of the distal middle cerebral artery and the common carotid artery (CCA). Thrombospondins 1 and 2 increased after stroke, with both TSP-1 and TSP-2 colocalizing mostly to astrocytes. Wild-type and TSP-1/2 KO mice were compared in angiogenesis, synaptic density, axonal sprouting, infarct size, and functional recovery at different time points after stroke. Using the tongue protrusion test of motor function, we observed that TSP-1/2 KO mice exhibited significant deficit in their ability to recover function (P<0.05) compared with WT mice. No differences were found in infarct size and blood vessel density between the two groups after stroke. However, TSP-1/2 KO mice exhibited significant synaptic density and axonal sprouting deficits. Deficiency of TSP-1/2 leads to impaired recovery after stroke mainly due to the role of these proteins in synapse formation and axonal outgrowth.


Climate change, health, and vulnerability in Canadian northern Aboriginal communities.
Canada has recognized that Aboriginal and northern communities in the country face unique challenges and that there is a need to expand the assessment of vulnerabilities to climate change to include these communities. Evidence suggests that Canada's North is already experiencing significant changes in its climate--changes that are having negative impacts on the lives of Aboriginal people living in these regions. Research on climate change and health impacts in northern Canada thus far has brought together Aboriginal community members, government representatives, and researchers and is charting new territory. In this article we review experiences from two projects that have taken a community-based dialogue approach to identifying and assessing the effects of and vulnerability to climate change and the impact on the health in two Inuit regions of the Canadian Arctic. The results of the two case projects that we present argue for a multi-stakeholder, participatory framework for assessment that supports the necessary analysis, understanding, and enhancement of capabilities of local areas to respond and adapt to the health impacts at the local level.


A low proportion of BRCA2 mutations in Finnish breast cancer families.
One hundred breast cancer families were identified at the Helsinki University Central Hospital in Finland and were screened for germ-line mutations in the coding regions and splice boundaries of the BRCA2 gene. Eight families (8%) were found to carry five different mutations, all of which are predicted to prematurely truncate the protein product. These BRCA2 families have early-onset breast cancer (mean and median age = 49 years), with four of the eight families including ovarian cancer but with no families including male breast cancer. A wide spectrum of other cancers also is seen in these families. Three mutations were identified in more than one family, and haplotype analysis in the families suggested a common founder for each recurrent mutation. One recurrent mutation, 999del5, previously has been noted as a common mutation in Iceland. The relationship between the Icelandic 999del5 mutation and the Finnish 999del5 mutation was explored by comparison of families from both countries. A common haplotype covering a minimal region intragenic to the BRCA2 gene was shared between the Icelandic and the Finnish mutation carriers.


Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.
Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.


Multiplexed DNA detection with a composite molecular beacon based on guanine-quenching.
We developed a multiplexed DNA detection method with a composite molecular beacon (MB) probe based on guanine-quenching by synchronous fluorescence analysis. It is demonstrated by two types of tumor-suppressor genes namely exon segments of p16 (T1) and p53 (T2) genes. The composite MB probe includes two loops and two stems, and two fluorophores of 6-carboxyfluorescein group (FAM) and tetramethyl-6-carboxyrhodamine (TAMRA) are connected to the two ends of molecular beacon. Every stem portion of MB include four continuous nucleotides with guanine (G) base as quencher, every loop portion is a probe sequence that is complementary to a corresponding target sequence. In the absence of target DNA, the composite MBs are in the stem-closed form, the fluorescence of FAM and TAMRA are quenched by G bases. At this time, the fluorescence signals of FAM and TAMRA are all very low. In the presence of target DNA, the MBs hybridize with the target DNA and form double-strands, FAM and TAMRA are separated from G bases, and the fluorescence of FAM and TAMRA recovers simultaneously. Thus, the simultaneous detection of two targets of DNA can be realized by measuring fluorescence signals of FAM and TAMRA, respectively. Under the optimum conditions, the fluorescence intensities of FAM and TAMRA all exhibit good linear dependence on their target DNA concentration in the range from 5 × 10(-11) to 5.5 × 10(-9) M. The detection limit of T1 is 4 × 10(-11) M (3σ), and that of T2 is 3 × 10(-11) M. This composite MB can be applied to detect the real sample, and can be applied to detect two aleatoric sequences of DNA. Compared with previously reported methods of detecting multiplexed target DNA with MBs, the proposed method has some advantages including easy synthesis of composite MB probes, low detection cost and shorter analytical time.


Comparison of distance-based and model-based ordinations.
Distance-based ordinations have played a critical role in community ecology for more than half a century, but are still under active development. These methods employ a matrix of pairwise distances or dissimilarities between sample units, and map sample units from the high-dimensional distance or dissimilarity space to a low-dimensional representation for analysis. Distance- or dissimilarity-based methods employ continuum or gradient ecological theory and a variety of statistical models to achieve the mapping. Recently, ecologists have developed model-based ordinations based on latent vectors and individual species response models. These methods employ the individualistic perspective of Gleason as the ecological model, and Bayesian or maximum-likelihood methods to estimate the parameters for the low dimensional space represented by the latent vectors. In this research I compared two distance-based methods (NMDS and t-SNE) with two model-based methods (BORAL and REO) on five data sets to determine which methods are superior for (1) extracting meaningful ecological drivers of variability in community composition, and (2) estimating sample unit locations in ordination space that maximize the goodness-of-fit of individual species response models to the estimated sample unit locations. Environmental variables and species were fitted to the ordinations by generalized additive models (GAMs) with Gaussian, negative binomial, or Poisson distribution models as appropriate. Across the five data sets, 22 models of environmental variability and 449 models of species distributions were calculated for each of the ordination methods. To minimize the effects of stochasticity the entire analysis was replicated three times and results averaged across the replicates. Results were evaluated by deviance explained and AIC for environmental variables and species distributions, averaged by ordination method for each data set, and ranked from best to worst. For the four assessments distance-based methods ranked 1 and 2 in three cases, and 1 and 3 in one case, significantly out performing the model-based methods. t-SNE was the top-performing method, out performing NMDS especially on the more complex data sets. In general the gradient-based theoretical basis and data sufficiency of distance-based methods allowed distance-based methods to outperform model-based methods in every assessment.


On the identification of group II introns in nucleotide sequence data.
Four different consensus sequences (GTI, group II identifiers) have been derived from domains V of known group II introns and are used as query input sequences for sensitive database screenings with the FASTA and LFASTA programs. The set of four GTI sequences can identify all domains V of the 96 known group II introns in the completely sequenced chloroplast genomes of Marchantia polymorpha, Epifagus virginiana, Oryza sativa, Nicotiana tabacum and the completely sequenced mitochondrial genomes of Saccharomyces cerevisiae, Podospora anserina, Schizosaccharomyces pombe and Marchantia polymorpha. Seven moderately high-scoring hits can easily be rejected as false-positives since they do not fulfil secondary structure requirements. Large FASTA outputs obtained after screening the entire nucleotide sequence database are evaluated in a second step by a program (D5SCAN) that allows the assignment of variable selection criteria for potential domain V secondary structures. Database searches with these routines yield evidence for several group II intron sequences previously unrecognized. These include novel intron structures in the cyanobacterium Synechocystis and in the mitochondrial genomes of Marchantia, soybean, pea, broad bean, sugar beet and a heterobasidiomycete. Potential intron remnants are found contributing to the secondary structure of rRNAs in several trypanosome species. At a given sensitivity of 95% positively identified true domains V, the search routine produces one false positive hit per 10,000 kb.


Role of the natural killer T lymphocytes in Th2 responses during allergic asthma and helminth parasitic diseases.
The recent discovery that T cells recognize endogenous and foreign lipid and glycolipid molecules presented by CD1 proteins has brought a major contribution in the understanding of innate and adaptive immune response to certain harmless antigens and infectious pathogens. Among (glyco)lipid-reactive T cells, CD1d-restricted natural killer (NK) T cells represent a population of innate/memory lymphocytes that, upon stimulation, rapidly release important amounts of immunoregulatory cytokines that in turn can shape the acquired immune response in a Th1 or a Th2 direction. Here we review the general features of these cells as well as their diverse influence in various disease models. A particular emphasis will be placed on the role of NK T cells in the promotion of asthma, a typical Th2-related inflammatory disease. Moreover, recent studies suggest that NK T cells could also be important in the modulation of the host immune response during helminthic infections, generally associated with dominated Th2 responses. Our current understanding of the role and of the mode of NK T cell activation during the initial immunological events that lead to the promotion of Th2 responses will be discussed.


Fluorescence enhancement in an over-etched gold zero-mode waveguide.
The fluorescence enhancement in an over-etched gold zero-mode waveguide (ZMW) was investigated through both numerical simulation and experiments. Using Cy3 and Cy5 as the fluorescent probes, the simulation showed that the undercut not only enhances the fluorescence signals of both fluorophores, but also greatly improves the radial uniformity of the excitation fields in the ZMW. Furthermore, using a focused-ion-beam tool, we fabricated Au-ZMW arrays with different radius and undercut. The fluorescence enhancement per molecule and the effective excitation volume of the Au-ZMW were then measured as functions of its radial size and over-etching depth by using fluorescence correlation spectroscopy. It was found that the undercut can significantly enhance the fluorescence signal per molecule in the ZMW, but it also slightly increased the excitation volume. Decreasing the radial size of the ZMW can efficiently reduce the excitation volume and also further enhance the fluorescence per molecule. These results together indicate that combining the undercut and reduction of radius of the ZMW can serve as a simple and effective way to essentially improve the performance of an Au-ZMW for single molecule fluorescence detection.


Green synthesis of titanium dioxide nanoparticles with volatile oil of Eugenia caryophyllata for enhanced antimicrobial activities.
Different chemo-physical methods are used to synthesise titanium oxide nanoparticles (TiO2 NPs), which are often expensive, unfriendly to the environment, toxic, not biocompatible, with a small yield. To resolve these problems, the researchers use green procedures to synthesise TiO2-NPs by plant extracts of Capsicum annum L. and Allium cepa (onion) and characterise using atomic force microscopy, scanning electron microscopy, transmission electronic microscopy, X-ray diffraction, ultraviolet (UV)-visible (Vis) spectra and Fourier transform infrared spectroscopy. The results indicate that most NPs synthesised by the first and second procedures of onion had an average diameter of 95.7 and 89.1 nm, while NPs synthesised by C. annum had an average diameter of 103.60 and 90.07 nm, respectively. In UV-Vis spectra, strong absorption was below 470 nm, and energy gap was 3.3 eV in each of the first procedure of A. cepa and the second procedure of C. annum compared with 270 nm, 6.3 eV for each of the second procedure of A. cepa and the first procedure of C. annum. The antimicrobial activities of NPs were evaluated and an attempt was made to enhance these activities by Eugenia caryophyllata plant's oil in combination therapies. There were synergistic effects between NPs and plant's oil.


Purification and Injection of Retroviral Vectors.
Retroviral vectors are powerful tools for genetic manipulation. This protocol discusses the production, purification, and use of replication-deficient retroviral vectors based on Moloney murine leukemia virus and lentivirus. It also describes the injection of a retroviral vector into the dentate gyrus of young adult mice to fluorescently label live murine brain tissue.


Anatomic donor surgeries increase self-efficacy in physical therapy education: Use of live versus recorded viewing.
Anatomy serves as a foundational course in physical therapy education, but, due to its early placement in the curriculum, may have limited clinical application at that point of a student's education. Thus, augmenting a standard dissection course with surgical procedures can enhance the clinical relevance and knowledge of the anatomical structures involved in those surgeries. Doctor of Physical Therapy students viewed a variety of cadaveric orthopedic and cardiothoracic surgeries performed by a surgeon. Students unable to participate live viewed the recorded surgeries. Participants completed a 10-point Likert scale survey, developed by the researchers, pre- and post-viewing, on self-efficacy of knowledge, patient intervention and communication. Data analysis revealed improved self-efficacy of knowledge of the anatomy and the surgical procedures, confidence in treating patients undergoing those surgeries, and confidence communicating with surgeons, regardless of whether students viewed the surgeries live or recorded. Students participating in this experience expressed a clear value enhancement on their education. Programs should feel confident that this type of experience in the curriculum, whether live or recorded, will have a positive effect on student self-efficacy as related to the relationships and pertinence of anatomical structures involved in the surgeries, the surgical procedures, treating patients having undergone those surgeries, and interprofessional communication.


Node-Loss Detection Methods for CZ Silicon Single Crystal Based on Multimodal Data Fusion.
Monocrystalline silicon is an important raw material in the semiconductor and photovoltaic industries. In the Czochralski (CZ) method of growing monocrystalline silicon, various factors may cause node loss and lead to the failure of crystal growth. Currently, there is no efficient method to detect the node loss of monocrystalline silicon at industrial sites. Therefore, this paper proposed a monocrystalline silicon node-loss detection method based on multimodal data fusion. The aim was to explore a new data-driven approach for the study of monocrystalline silicon growth. This article first collected the diameter, temperature, and pulling speed signals as well as two-dimensional images of the meniscus. Later, the continuous wavelet transform was used to preprocess the one-dimensional signals. Finally, convolutional neural networks and attention mechanisms were used to analyze and recognize the features of multimodal data. In the article, a convolutional neural network based on an improved channel attention mechanism (ICAM-CNN) for one-dimensional signal fusion as well as a multimodal fusion network (MMFN) for multimodal data fusion was proposed, which could automatically detect node loss in the CZ silicon single-crystal growth process. The experimental results showed that the proposed methods effectively detected node-loss defects in the growth process of monocrystalline silicon with high accuracy, robustness, and real-time performance. The methods could provide effective technical support to improve efficiency and quality control in the CZ silicon single-crystal growth process.


Arterial Stiffness: Recommendations and Standardization.
The use of arterial stiffness measurements in longitudinal cohorts of normal populations, hypertensive patients, diabetic patients, healthy elderly, and patients on hemodialysis have confirmed the value of this important measure of arterial health, and established its complementary role to measures of blood pressure. Its contribution to understanding cardiovascular and mortality risk beyond blood pressure measurements has moved measures of arterial stiffness into the ranks of factors such as elevated cholesterol, diabetes, and left ventricular hypertrophy in considering cardiovascular risk. The recent international collaboration's publication of reference ranges for normal people and those with hypertension, along with the American Heart Association's recent scientific statement on standardizing arterial stiffness measurements are important aspects to consider in future studies employing these valuable methods, particularly as interventions that not only lower blood pressure but improve arterial function are tested in the clinical arena.


A monoclonal antibody against dolphin lymphocytes (6E9) which recognizes bovine MHC class II antigens.
A monoclonal antibody, 6E9 established from mice injected with dolphin peripheral blood lymphocytes (PBLs) was characterized. In addition to its reactivity against 89.4% of dolphin PBLs, 6E9 reacted with 33.1% of bovine PBLs of which 22% were CD5+, 11.1% were CD5-. 6E9 recognized a 34 kD protein on the surface of dolphin and bovine PBLs. Analysis of the protein's N-terminal amino acid sequence indicated that 6E9 recognizes bovine major histocompatibility complex (MHC) class II antigens. These results suggested that 6E9 recognized MHC class II antigens on bovine PBLs. As we have already produced an anti-dolphin MHC class I monoclonal antibody, analysis of immune system using these monoclonal antibodies will advance our understanding of the evolution of the mammalian immune system.