Migration, transformation and nitrate source in the Lihu Underground River based on dual stable isotopes of δ15N-NO3- and δ18O-NO3.
Nitrate (NO3-) pollution is a common phenomenon in karst underground rivers, which are important water sources in karst landscapes. For drinking water safety and environmental protection, it is crucial to accurately identify NO3- sources and their migration and transformation processes in the Lihu Underground River. In this study, water samples of the Lihu Underground River in Guangxi were collected in May 2014, October 2014, January 2015, and July 2015, and water chemical and dual isotopic (δ15N-NO3- and δ18O-NO3-) approaches were used to evaluate the NO3- characteristics and sources in the Lihu Underground River. The concentration of NO3- in the Lihu Underground River ranged from 1.16 to 19.78 mg·L-1, with an average of 9.30 mg·L-1, which is more than 37% of the WHO standard (10 mg·L-1). The concentrations of NO3- in the wet season (May 2014 and July 2015) were slightly lower than those in the dry season (from October 2014 to January 2015) at most sampling sites due to dilution effects. The migration and transformation processes of NO3- were analyzed by comparing the measured and calculated concentrations of NO3- in the Lihu Underground River. In the dry season (from October 2014 to January 2015), the variation in NO3- concentration upstream and midstream of the Lihu Underground River was affected by exogenous input and nitrification. From midstream to the outlet of Xiaolongdong, it is affected by self-purification factors, including physical processes, chemical processes, and biological processes. In the wet season (May 2014 and July 2015), the dilution and mixing effects were the main factors controlling the variation in NO3- concentration in the Lihu Underground River. The contribution rates of potential NO3- sources (incl. atmospheric precipitation (AP), NO3- fertilizer (NF), NH4+ in fertilizer and rainfall (NFA), soil organic nitrogen (SON), and manure and sewage (M&S)) were quantitatively evaluated by using the IsoSource model. The results showed that in May 2014, the main sources of NO3- were M&S and NF, with contribution rates of 46% and 41%, respectively. In October 2014, NO3- sources were M&S with a contribution rate of 47%, followed by NFA with a contribution rate of 31%. In January 2015, NO3- sources in groundwater were M&S, with a contribution rate of 53%, followed by NFA (34%). In July 2015, the main NO3- sources were M&S and NF, whose contribution rates were 54% and 39%, respectively.


Space-time coupling by a soliton self-mode conversion technique in optical fibers.
Soliton self-mode conversion is a versatile technique that allows for both wavelength changes and mode transformations. This process can be controlled by adjusting the input power, with higher power resulting in a stronger nonlinear effect that facilitates soliton self-mode conversion. Our research has demonstrated that soliton self-mode conversion is a viable method for achieving spatiotemporal coupling. This technique can be applied in optical fibers to link two pulses, resulting in distinct spatial distributions that can be controlled by adjusting the initial time intervals.


The arterial blood supply of the pancreas: a review. IV. The anterior inferior and posterior pancreaticoduodenal aa., and minor sources of blood supply for the head of the pancreas. An anatomical review and radiologic study.
The present article is the fourth part of a comprehensive review of the arterial blood supply of the pancreas and completes the study of the arterial vascularization of the pancreatic head dealing with the anterior inferior and posterior inferior pancreaticoduodenal aa. and with some minor sources of blood supply not involving the classical system of the pancreaticoduodenal arches. The aim of this review is to summarise the anatomical studies, starting from Haller's reports, and to supply, as far as possible with original material, angiographic evidence for the classic anatomical concepts. For this purpose, 1015 selective angiographs (celiac trunk and its branches, superior mesenteric a.) were taken from the angiographic archives of the Institutes of Radiology of Siena, Rome (Catholic University), and Perugia. These demonstrated the anterior inferior pancreaticoduodenal a., present in most instances, as arising from the inferior pancreaticoduodenal a., from a common trunk with the posterior inferior pancreaticoduodenal a. and the 1st jejunal a., from the 1st jejunal a. or from the superior mesenteric a.; on the other hand, the posterior inferior pancreaticoduodenal a. was more variable, originating from the inferior pancreaticoduodenal a., from a common trunk with the anterior inferior pancreaticoduodenal a. and the 1st jejunal a., from the superior mesenteric a., from the dorsal pancreatic a., or from a right accessory hepatic a. coming from the superior mesenteric a. In addition, minor branches to the head of the pancreas arose from the gastroduodenal a., the dorsal pancreatic a., the common hepatic a. and the inferior right phrenic a. Other origins of the inferior pancreaticoduodenal aa. previously reported, but not angiographically detectable with certainty, as well as further minor sources of blood supply to the head of the pancreas, have been listed. The differing opinions regarding the incidence of the various ways the inferior pancreaticoduodenal aa. arise are discussed and an attempt is made to explain the variability of the vascular anatomy of the pancreatic head on embryologic grounds.


Impact of fascioliasis reinfection on Fasciola hepatica egg shedding: relationship with the immune-regulatory response.
Fascioliasis is a disease caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm. Control strategies in humans require the use of egg count techniques to calculate the appropriate treatment dose for colic risk prevention. The present study investigates how fascioliasis reinfection affects liver fluke egg shedding and its relationship with the immune-regulatory response. The experimental design reproduced the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 4 weeks (R4), 8 weeks (R8), 12 weeks (R12), and negative control rats. In a longitudinal study (0-20 weeks post-infection, p.i.), serical IgG1 levels and eggs per gram of faeces (epg) were analyzed. In a cross-sectional study, the expression of the genes associated with Th1 (Ifng, Il12a, Il12b, Nos2), Th2 (Il4, Arg1), Treg (Foxp3, Il10, Tgfb, Ebi3), and Th17 (Il17) in the spleen and thymus was analyzed. In R8 and R12, transiently higher averages of epg and epg/worm in reinfected groups vs PI group were detected at least in the weeks following reinfection. The kinetics of IgG1 levels shows that reinfected groups followed a pattern similar to the one in the PI group, but transiently higher averages of IgG1 levels in reinfected groups vs the PI group were detected in the weeks following reinfection. Epg correlated with IgG1 levels and also with systemic Il10 and thymic Ifng, and Il10 expression levels. These results suggest that epg depends on the Th1 and Treg phenotype and that the determination of the fluke burden by epg is likely to be an overestimation in cases of recent reinfection in low burden situations. A strategy to facilitate the implementation of epg count techniques and the subsequent decision on the appropriate treatment dose for each patient to prevent colic risk is required.


'Biofilm Clippers'- enzyme formulation for bovine mastitic biofilm therapy.
Mastitis is one of the most important diseases that are threatening modern dairy farms. Biofilms of mastitic teat canal have serious clinical implications because of colonized pathogens having the ability to construct an extracellular polymeric substance (EPS) with increased tolerance to antimicrobials leads to difficulty in eradicating the infection. In this study, we investigated the synergistic biofilm disruptive effect of a combination of carbohydrate hydrolases targeting extracellular polysaccharides of biofilm matrix and we termed it as 'Biofilm Clippers (BC)'. Our findings demonstrate that the BC formulation exhibits intense biofilm-disrupting activity against Staphylococcus aureus biofilms. The results of the study showed that BC enables activity equivalent to physiologically achievable concentrations in disrupting biofilms of S. aureus in vitro. The synergistic anti-biofilm activities of BC on S. aureus biofilms demonstrated that the biofilm matrix is predominant of complex polysaccharides. Further, the confocal microscopic analysis demonstrates that the BC formulation is highly effective compared to the single treatment of either of the enzymes in disrupting the biofilm. To the best of our knowledge, this is the first report on the synergistic anti-biofilm activity of a class of enzyme formulation against mastitic biofilm mass. Even though a small study showed a promising effect on mastitic teat canal, further extensive investigation on a large number of bovines for mastitis therapeutic potential of this BC-derived product is now warranted.


Liquid biopsy in the clinical management of bladder cancer: current status and future developments.
Introduction: The use of liquid biopsy on the blood from solid malignancies provides a convenient way of detecting actionable mutations, monitoring treatment response, detecting early recurrence and prognosticating outcomes. The aim of this review is to discuss the current status and future direction of serum biomarkers in the clinical management of urinary bladder cancer.Areas covered: This review provides an overview of blood liquid biopsy and bladder cancer using methods of circulating tumors cells, circulating RNA, serum metabolites and cell-free DNA. Recent clinical studies and advances in methodology are emphasized. We performed a literature search using PMC/PubMed with keywords including 'liquid biopsy', 'circulating tumor DNA', 'cell-free DNA', 'biomarkers', 'bladder cancer' 'precision medicine'. Additional articles were obtained from the cited references of key articles. An emphasis was placed on recent studies published since 2018.Expert opinion: Liquid biopsies represent a potential biomarker using cell-free DNA, metabolomic profiles of altered cellular metabolism, circulating cancer cells and RNA. Despite displaying tremendous clinical promise, the current status of the blood liquid biopsies has not reached fruition. However, future investigations should lead the evolution of liquid biomarker into clinical utility for the management of bladder cancer.


Comparing telehealth with office-based visits for common pediatric otolaryngology complaints.
The objective of this study was to evaluate the feasibility of telehealth visits and compare office-based visits for pediatric patients undergoing evaluation of recurrent acute otitis media or sleep-disordered breathing. A retrospective cohort study compared telehealth patients with matched controls seen in the office. The feasibility of a thorough patient evaluation in a single telehealth visit without a follow-up office visit was assessed. Both groups were also compared for completeness of physical exam, management, follow-up recommendations, and correlation of physical exam findings with intraoperative findings. 100 children [mean age (SD) = 20.7 (15.6) months] with a chief complaint of recurrent acute otitis media and 128 children [5.4 (3.2) years] with a chief complaint of sleep-disordered breathing were evaluated. Recommendations for surgery, additional studies, or routine follow-up were similar between telehealth and office-based groups. Physical exam feasibility was significantly different for the nasal cavity, oropharynx, and middle ear (P < .001). Patients who underwent office-based consultation were much more likely to have findings of middle ear fluid at the time of tympanostomy tube placement (79.3% vs 39.3%, P = .002). There was no significant difference between preoperative and intraoperative tonsil size discrepancies (P = .749). Telehealth can be used successfully for the evaluation of pediatric patients with sleep-disordered breathing; however, reliance on history alone may result in unnecessary tympanostomy tube placement in patients with recurrent acute otitis media. Physical examination of the oropharynx, nasal cavity, and middle ear via telehealth presents a unique challenge in pediatric otolaryngology.


Multi-modal nonlinear optical and thermal imaging platform for label-free characterization of biological tissue.
The ability to characterize the combined structural, functional, and thermal properties of biophysically dynamic samples is needed to address critical questions related to tissue structure, physiological dynamics, and disease progression. Towards this, we have developed an imaging platform that enables multiple nonlinear imaging modalities to be combined with thermal imaging on a common sample. Here we demonstrate label-free multimodal imaging of live cells, excised tissues, and live rodent brain models. While potential applications of this technology are wide-ranging, we expect it to be especially useful in addressing biomedical research questions aimed at the biomolecular and biophysical properties of tissue and their physiology.


ARDS associated acute brain injury: from the lung to the brain.
A complex interrelation between lung and brain in patients with acute lung injury (ALI) has been established by experimental and clinical studies during the last decades. Although, acute brain injury represents one of the most common insufficiencies in patients with ALI and acute respiratory distress syndrome (ARDS), the underlying pathophysiology of the observed crosstalk remains poorly understood due to its complexity. Specifically, it involves numerous pathophysiological parameters such as hypoxemia, neurological adverse events of lung protective ventilation, hypotension, disruption of the BBB, and neuroinflammation in such a manner that the brain of ARDS patients-especially hippocampus-becomes very vulnerable to develop secondary lung-mediated acute brain injury. A protective ventilator strategy could reduce or even minimize further systemic release of inflammatory mediators and thus maintain brain homeostasis. On the other hand, mechanical ventilation with low tidal volumes may lead to self-inflicted lung injury, hypercapnia and subsequent cerebral vasodilatation, increased cerebral blood flow, and intracranial hypertension. Therefore, by describing the pathophysiology of ARDS-associated acute brain injury we aim to highlight and discuss the possible influence of mechanical ventilation on ALI-associated acute brain injury.


Conjugated oestrogen during the menstrual cycle measured by a direct radioimmunoassay with an antiserum prepared against oestradiol-17-glucosiduronate-[C-6]-BSA conjugate.
Early morning and 24 h urine samples and serum were collected daily throughout the menstrual cycle in women. Urinary oestradiol-17-glucosiduronate (E2-17-G) was measured with a direct radioimmunoassay whose antiserum had been prepared against E2-17-G-[C-6]-bovine serum albumin conjugate and was very specific. On the average, E2-17-G in early morning and 24 h urine samples showed a prominent peak one day before the peak of urinary LH. The time relationship between these urinary E2-17-G and serum E2 levels and peaks was also investigated.


Gibberellic acid induces non-Kranz anatomy with C4-like biochemical traits in the amphibious sedge Eleocharis vivipara.
Gibberellic acid induces photosynthetic tissues with non-Kranz anatomy and C4-like biochemical traits in terrestrial-form plants of Eleocharis vivipara. This suggests that the structural and biochemical traits are independently regulated. The amphibious leafless sedge, Eleocharis vivipara Link, develops culms (photosynthetic organs) with C4-like traits and Kranz anatomy under terrestrial conditions, and C3 traits and non-Kranz anatomy under submerged conditions. The conversion from C3 mode to C4-like mode in E. vivipara is reportedly mediated by abscisic acid. Here, we investigated the effects of gibberellic acid (GA) on the differentiation of anatomical and photosynthetic traits because GA is involved in heterophylly in aquatic plants. When 100 µM GA was sprayed on terrestrial plants, the newly developed culms had non-Kranz anatomy in the basal part and Kranz-like anatomy in the upper part. In the basal part, the mesophyll cells were well developed, whereas the Kranz (bundle sheath) cells were reduced and contained few chloroplasts and mitochondria. Stomatal frequency was lower in the basal part than in the upper part. Nevertheless, these tissues had abundant accumulation and high activities of C4 photosynthetic enzymes and had C4-like δ13C values, as seen in the culms of the terrestrial form. When submerged plants were grown under water containing GA-biosynthesis inhibitors (uniconazole or paclobutrazol), the new culms had Kranz anatomy. The culms developed under paclobutrazol had the C3 pattern of cellular accumulation of photosynthetic enzymes. These data suggest that GA induces production of photosynthetic tissues with non-Kranz anatomy in terrestrial plants of E. vivipara, without concomitant expression of C3 biochemical traits. The data also suggest that the differentiation of C4 structural and biochemical traits is regulated independently.


Electrochemical H2O2 biosensor based on horseradish peroxidase encapsulated protein nanoparticles with reduced graphene oxide-modified gold electrode.
In this study, an electrochemical biosensor composed of a horseradish peroxidase (HRP)-encapsulated protein nanoparticles (HEPNP) was fabricated for the sensitive and selective detection of H2O2. The HEPNP has a three-dimensional structure that can contain a large amount of HRP; therefore, HEPNP can amplify the electrochemical signals necessary for the detection of H2O2. Furthermore, reduced graphene oxide (rGO) was used to increase the efficiency of electron transfer from the HEPNP to an electrode, which could enhance the electrochemical signal. This biosensor showed a sensitive electrochemical performance for detection of H2O2 with signals in the range from 0.01-100 μM, and it could detect low concentrations up to 0.01 μM. Furthermore, this biosensor was operated against interferences from glucose, ascorbic acid, and uric acid. In addition, this fabricated H2O2 biosensor showed selective detection performance in human blood serum. Therefore, the proposed biosensor could promote the sensitive and selective detection of H2O2 in clinical applications.


Kindling of the dorsal and the ventral hippocampus: effects on learning performance in rats.
The hippocampus represents a heterogeneous structure which has been associated with different functions. It has been suggested that it plays an important role in both learning and memory and epileptogenesis. Thus, it is not surprising that seizure activity generated in the hippocampal formation interferes with memory storage. Little is known about the functional differentiation between the dorsal (DH) and ventral hippocampus (VH). To study this functional differentiation, we kindled Wistar rats either in the DH or in the VH by electrical stimulation. Afterwards, learning performance of these rats was tested in three different models, i.e., response to change (short-term memory), shuttle box (two-way active avoidance), and Y-chamber (brightness discrimination reaction). It was found that VH-kindled rats reached higher seizure scores than DH-kindled rats, but there was no difference in seizure duration. Kindling induced in the VH significantly impaired shuttle box learning, whereas DH-kindled rats showed a dramatically worsened acquisition in the brightness discrimination task. Different anatomical projections probably account, in part, for these differences.


Development of a microplate reader compatible microfluidic chip for ELISA.
We report a novel microfluidic device use for sandwich enzyme-linked immunoassay assay (ELISA). The related procedures including the introduction of reagents, dilution and distribution of samples, as well as immobilization of enzyme can be readily carried out on a poly (dimethylsiloxane) (PDMS) chip. Particularly, this microfluidic chip comprising of two distinct parallel units, and has an identical dimension as a conventional microtiter plate, which offers access to the directly quantitative detection by the microplate reader. Gradient-concentration reacting solutions at six different concentrations level generated by the microfluidic channel network are simultaneously transported to 24 reaction chambers to form enzymatic products. Alkaline phosphatase (ALP), 4-methylumbelliferyl phosphate (4-MUP) and KH(2)PO(4) are used as enzyme-substrate-inhibitor model, to demonstrate the utility of the developed microchip-based enzyme inhibitor assay. Various conditions such as the surface treatment of chip channels, fluids velocities, substrate concentration, and buffer pH are investigated. The present microfluidic device for ELISA holds several advantages, for instance frugal usage of samples and reagents, less of operating time, favorably integrated configuration, ease of manipulation, and could be explored to a variety of high throughput drug screening.


Alveolar surface tensions in excised rabbit lungs: effect of temperature.
In excised, perfused rabbit lungs the alveolar surface tension was measured in individual alveoli over the entire P-V loop at different temperatures (22 and 37 degrees C), using an improved microdroplet method. Additional in vitro experiments are reassuring that the microdroplets do not affect the properties of the alveolar surface film. The in situ measurements show that the alveolar surface tension and the surface tension to volume relation are essentially the same at 22 and 37 degrees C. A maximal surface tension of about 30 mN X m-1 was measured at TLC, and there is a substantial surface tension to volume hysteresis, which amounts to almost 10 mN X m-1 in the middle volume range of a complete pressure volume cycle of the lung. However, with respect to the absolute values of alveolar surface tension, and the shape and width of the hysteresis, these directly obtained results are different from previous findings.


Comparison of the efficacy of irsogladine maleate and famotidine for the healing of gastric ulcers after Helicobacter pylori eradication therapy: a randomized, controlled, prospective study.
Helicobacter pylori eradication therapy alone cannot heal gastric ulcers in Japanese patients. Irsogladine has previously been shown to accelerate the healing of gastric ulcers after H. pylori eradication therapy. And we previously reported that histamine H(2) receptor antagonists inhibit gastric ulcer relapse after H. pylori eradication therapy. We therefore compared the efficacy of irsogladine with famotidine as appropriate treatments for ulcers after eradication therapy. Gastric ulcer patients with H. pylori infection (n = 119) were randomized to treatment with irsogladine 4 mg/day (n = 60) or famotidine 40 mg/day (n = 59) following 1-week H. pylori eradication therapy. After treatment, assessments of gastric ulcer healing were performed. The ulcer healing rates in patients receiving irsogladine and famotidine were 85.2% (46/54) and 79.6% (43/54), respectively, and were not significantly different (p = 0.4484). In the famotidine group, the healing rate was significantly lower in patients who drink alcohol than in those who do not (60.0% vs. 91.2%; p = 0.0119). However, in the irsogladine group the healing rate did not differ between patients who drink alcohol and those who do not. Furthermore, the healing rate in smokers was significantly higher in the irsogladine group (88.0%) than in the famotidine group (59.1%) (p = 0.0233). Irsogladine and famotidine are both acceptable in treatment after H. pylori eradication therapy in gastric ulcer patients. Findings also suggest that irsogladine is more beneficial than famotidine in patients who drink alcohol and smoke.


The Self-Passivation Mechanism in Degradation of BiVO4 Photoanode.
BiVO4 is a promising photoanode material for solar-assisted water splitting in a photoelectrochemical cell but has a propensity to degrade. Investigations carried out here in 0.1 M Na2SO4 electrolyte showed that degradation is by dissolution of V in the electrolyte while Bi is retained on the anode probably in the form of solid Bi oxide (Bi2O3, Bi4O7). Accumulation of Bi oxide on the anode surface leads to passivation from further degradation. Thermodynamic modeling of possible degradation reactions has provided theoretical support to this mechanism. This self-passivation is accompanied by a decrease in photocurrent density, but it protects the anode against extensive photocorrosion and contributes to long-term stability. This is a more definitive understanding of degradation of BiVO4 during water splitting in a photoelectrochemical cell. This understanding is imperative for both fundamental and applied research.


What a Rat Race: A Case Study of Rat Bite Fever in an Emergency Department.
Rat bite fever is an acute illness caused by bacteria from rodents. In the United States, rat bite fever is considered rare; however, actual incidence is unknown because of lack of mandatory disease reporting requirements. Risk of development of rat bite fever after being bitten by a rat is approximately 10%. Early treatment is imperative as death is a potential complication. The following case study demonstrates the gravity of the syndrome.


Neurons in the hypothalamic paraventricular nucleus mediate the serotonergic stimulation of renin secretion.
The aim of the present study was to resolve which hypothalamic nucleus is necessary for the serotonergic control of renin secretion. RU 24969 is considered a serotonin (5-HT1A/5-HT1B) agonist, while p-chloroamphetamine is a 5-HT releaser. Both drugs reliably elevate plasma levels of renin when injected peripherally. Previous studies suggest that serotonergic neurons, projecting to the hypothalamus, mediate the effect of p-chloroamphetamine on renin secretion. Discrete cell-selective lesions were made with ibotenic acid in three hypothalamic sites: the paraventricular, the dorsomedial or the ventromedial nuclei. Two weeks after surgery rats were injected with RU 24969 (5 mg/kg, i.p.) or p-chloroamphetamine (8 mg/kg, i.p.). The renin response to both RU 24969 and p-chloroamphetamine was significantly reduced in rats with histologically verified paraventricular lesions compared to vehicle treated controls. In contrast, the renin response to p-chloroamphetamine remained unchanged in rats with either dorsomedial or ventromedial hypothalamic lesions. Thus, these results are consistent with the hypothesis that 5-HT receptors located on cell bodies in the paraventricular nucleus mediate the renin response to a serotonin agonist and releaser. Furthermore, they confirm previous studies that suggest that 5-HT neurons regulate renin secretion through central receptors.


Hypothermic effect of harmala alkaloid in rats: involvement of serotonergic mechanism.
The effect of total alkaloid extracted from Peganum harmala seeds collected in Egypt on body temperature was studied in rats. Intraperitoneal administration of the Peganum harmala extract produced significant and dose-dependent hypothermia. Similarly, harmine and harmaline, major constituents of the harmala alkaloid, lowered the body temperature. Pretreatment with p-chlorophenylalanine (100 mg/kg/day for 3 days), a 5-HT synthesis inhibitor, significantly attenuated the hypothermic effect of the total alkaloid and harmine, while it tended to block the hypothermic action of harmaline. Methysergide (2 mg/kg), a 5-HT antagonist, significantly attenuated the hypothermia induced by harmala alkaloids. Pindolol (0.05-2 mg/kg), a 5-HT1A receptor and beta-adrenoceptor antagonist, partly blocked the hypothermic effect of the harmala alkaloids in a dose-dependent manner, whereas propranolol (10 mg/kg), a beta-adrenoceptor antagonist, failed to alter it, suggesting that beta-adrenoceptor is not involved in the hypothermia caused by the alkaloids. Pretreatment with a dopamine receptor antagonist haloperidol (5 mg/kg, s.c. and 2 mg/kg, i.p. 24 and 2 h before the experiment, respectively) significantly attenuated the hypothermic effect of harmala alkaloids. Moreover, in haloperidol pretreated rats, methysergide (2 mg/kg, i.p.) and pindolol (0.05 and 2 mg/kg) completely attenuated the hypothermic effect of the alkaloids. These data suggest that harmala alkaloids produce hypothermic effect mainly through endogenous 5-HT stimulation of 5-HT1A receptor.


Translation, ribosome biogenesis, and oxidative damage caused by chlorpyrifos exposure to common carp (Cyprinus carpio L.) liver: application of combined RNA-seq with sRNA-seq in risk evaluation of environmental toxicant chlorpyrifos.
Pesticide chlorpyrifos (CPF) is a widespread environmental pollutant gaining attention as it is highly injurious to aquatic life. Although the toxicity of CPF is well characterized, but the mechanism of toxic response especially, the hepatotoxicity remained unclear. In this study, we performed integrated analysis, including micro-RNA (miRNA) and small RNA (sRNA) to analyze CPF exposure responding genes and enrichment pathways. A total of 23,742 expressed genes were detected and out of these expression levels of 1746 were changed significantly. Majority of them participated in protein biosynthesis, nucleotide binding, and oxidation-reduction activities. In extensive analysis of micro-RNA (miRNA) expression profiles by comparing CPF treated carp with control, we identified 214 novel miRNAs with CPM > 5 in at least one sample. The miRNAs have the same change in direction compared with overlapped mRNA pairs in upregulated genes, suggesting potential positive correlation. As a whole, we detected many differently expressed genes (DEGs) and miRNAs, which may be used as the biomarkers for the detection of CPF pollution in water and aquatic product safety. However, their functions are required to be deeply analyzed, especially more samples or time pointed data are needed to illustrate their concrete mechanism.


Label electrochemical immunosensor for prostate-specific antigen based on graphene and silver hybridized mesoporous silica.
Prostate-specific antigen (PSA), as the specificity of prostate cancer markers, has been widely used in prostate cancer diagnosis and screening. In this study, we fabricated an electrochemical immunosensor for PSA detection using the amino-functionalized graphene sheet-ferrocenecarboxaldehyde composite materials (NH2-GS@FCA) and silver hybridized mesoporous silica nanoparticles (Ag@NH2-MCM48). Under optimal conditions, the fabricated immunosensor showed a wide linear range with PSA concentration (0.01-10.0ng·ml(-1)). Low detection limit (2pg·ml(-1)) proved the high sensitivity. In addition, the immunosensor possessed good stability and reproducibility. Moreover, the application to PSA analysis in serum samples yielded satisfactory results.


Comparisons of microRNA expression profiles in vitreous humor between eyes with macular hole and eyes with proliferative diabetic retinopathy.
MicroRNAs (miRNAs) are small noncoding RNAs which regulate the activities of target mRNAs. We compared the expression profiles of the miRNAs in the vitreous of eyes with macular hole (MH) to that in eyes with proliferative diabetic retinopathy (PDR). Vitreous and whole blood samples were collected from four patients with MH and from four patients with PDR. We assayed for 168 miRNAs in the vitreous and serum samples by the microRNA PCR Panel method. The mean number of miRNAs expressed in the vitreous was 63 (55-69) in eyes with MH and 86 (65-117) in eyes with PDR. The mean number of miRNAs expressed in the serum was 162 (159-167) in the MH patients and 142 (115-160) in the PDR patients. Twenty-six miRNAs were expressed in the vitreous of both MH and PDR eyes. Although there was no significant difference in the levels of 20 of the 26 (73 %) miRNAs expressed in both MH and PDR eyes, six of 26 miRNAs (24 %) (hsa-miR-15a, hsa-miR320a, hsa-miR-320b, hsa-miR-93, hsa-miR-29a, and hsa-miR-423-5p) were expressed significantly more highly in PDR eyes. In addition, the mean fold changes of three miRNAs, hsa-miR-23a, hsa-miR-320a, and hsa-miR-320b, in the vitreous to serum were significantly higher in the PDR group than in the MH group. The expression of several miRNAs related to angiogenesis and fibrosis was expressed significantly higher in the vitreous of eyes with PDR. Further studies are needed to understand the role played by the miRNAs in the biological function of the eye.


Increased nuchal translucency at 10-14 weeks of gestation as a marker for major cardiac defects.
Screening for fetal cardiac defects is traditionally based on the ultrasonographic examination of the four-chamber view of the fetal heart at mid-gestation, which has been shown to identify 26% of major cardiac defects. Pathological studies in fetuses with increased nuchal translucency at 10-14 weeks of gestation, a sonographic marker for chromosomal abnormalities, have shown an association between increased nuchal translucency and congenital abnormalities of the heart. This study reports the prevalence of cardiac defects in 1427 chromosomally normal fetuses with increased nuchal translucency thickness, and examines the potential value of this sonographic marker in screening for major cardiac defects. The diagnosis of cardiac defects was made either by postmortem examination in terminations of pregnancy and intrauterine or neonatal deaths or by clinical examination and appropriate investigations in live births. The prevalence of major cardiac defects was 17 per 1000 (24 of 1427 fetuses) and increased with translucency thickness from 5.4 per 1000 for translucency of 2.5-3.4 mm to 233 per 1000 for translucency of > or = 5.5 mm. These findings suggest that measurement of nuchal translucency thickness at 10-14 weeks may prove to be a useful method of screening for abnormalities of the heart and great arteries in addition to its role in screening for chromosomal defects.


[Synchronization of electromyographic and cinematographic recordings. Applications to vertebrate biomechanics].
Synchronizing each frame of the cinema of a moving animal with the corresponding EMG of some muscles permits a precise interpretation of the variations of the electric potentials in that muscle with each phase of the movement. e.g. in the rabbit, three bundles of the masseter muscle function independently during the mastication; in the pigeon, electric potentials appear in both ilio-tibialis and biceps femoris muscles some frames before the actual raising of the leg, when the animal on its perch becomes out of balance.


Elucidation of the viral disassembly switch of tobacco mosaic virus.
Stable capsid structures of viruses protect viral RNA while they also require controlled disassembly for releasing the viral genome in the host cell. A detailed understanding of viral disassembly processes and the involved structural switches is still lacking. This process has been extensively studied using tobacco mosaic virus (TMV), and carboxylate interactions are assumed to play a critical part in this process. Here, we present two cryo-EM structures of the helical TMV assembly at 2.0 and 1.9 Å resolution in conditions of high Ca2+ concentration at low pH and in water. Based on our atomic models, we identify the conformational details of the disassembly switch mechanism: In high Ca2+ /acidic pH environment, the virion is stabilized between neighboring subunits through carboxyl groups E95 and E97 in close proximity to a Ca2+ binding site that is shared between two subunits. Upon increase in pH and lower Ca2+ levels, mutual repulsion of the E95/E97 pair and Ca2+ removal destabilize the network of interactions between adjacent subunits at lower radius and release the switch for viral disassembly.


Comparative analysis of four malaria diagnostic tools and implications for malaria treatment in southwestern Nigeria.
One of the problems encountered in malaria control and elimination is inaccurate diagnosis, resulting from the degree of sensitivity of the different malaria diagnostic tools. Even though microscopy remains the gold standard for malaria diagnosis, more sensitive and robust diagnostic tools such as polymerase chain reactions (PCR) are used in research settings to monitor interventions and track sub-microscopic infections due to some of the drawbacks of microscopy. Since diagnosis is a critical determinant for rational malaria treatment, it is imperative that accurate diagnosis must be assured for an effective treatment plan. Therefore, this study compared two routinely used point of care malaria diagnostic tools with two molecular tools and discussed their implication for malaria treatment. In this study, 436 individuals with suspected malaria were sampled and systematically tested using four methods, namely rapid diagnostic test (henceforth referred to as malaria RDT- mRDT), microscopy, nested PCR (nPCR), and quantitative PCR (qPCR). Test sensitivities and specificities were compared, and their level of concordance was determined. With nPCR as the gold standard, a false positivity rate of 42.2%, 8.9%, and 57.8% was obtained for mRDT, microscopy, and qPCR. Similarly, false negativity rates of 12.5%, 62.5%, and 0.8% were obtained for each of the methods mentioned above, respectively. Of all the tools assessed, qPCR gave the highest sensitivity (99.2%) and moderate specificity (42.2%), followed by the mRDT kit used (87.5%). With the detection of a high false positivity rate based on mRDT and a substantial proportion of sub-microscopic carriers in this study area by nested/quantitative PCR, we recommend that these molecular tools should be in specialized laboratories within the region to (i) track and treat sub-microscopic carriers to prevent their contribution to malaria transmission; (ii) provide reliable epidemiological data using high throughput testing tools for evaluating malaria interventions.


A phase II clinical trial of neoadjuvant ketoconazole and docetaxel chemotherapy before radical prostatectomy in high risk patients.
Patients with high risk prostate cancer (prostate specific antigen greater than 20 ng/ml, Gleason score greater than 7, or clinical stage T2b or greater) have been shown to have a 30% to 40% biochemical recurrence rate after definitive local therapy. Looking for improvement on these outcomes, we conducted a phase II clinical trial examining the combination of ketoconazole and docetaxel in the neoadjuvant setting before radical prostatectomy. A total of 22 patients with clinically localized, high risk prostate cancer were enrolled in the study. For 12 weeks they were treated with neoadjuvant docetaxel and ketoconazole, with dosing based on phase I data. Patients were monitored for tolerance of therapy and dosing adjustments were made for significant toxicities. Radical prostatectomy with extended lymph node dissection was subsequently performed and patients were followed postoperatively for biochemical recurrence. At a median followup of 18 months 8 patients remained biochemically free of recurrence after surgery alone. An additional 6 patients received salvage therapy and had an undetectable prostate specific antigen. Of the 22 patients 16 experienced National Cancer Institute grade 3 or 4 toxicity at some point during the therapy. However, 16 patients completed all 4 cycles of chemotherapy. Neoadjuvant ketoconazole combined with docetaxel has appreciable but acceptable toxicity with 73% of the patients completing all 4 courses of therapy. Of those who underwent radical prostatectomy 36% remained continuously biochemically free of recurrence at a median followup of 18 months.


Hidden motions and motion-induced invisibility: Dynamics-based spectral editing in solid-state NMR.
Solid-state nuclear magnetic resonance (ssNMR) spectroscopy enables the structural characterization of a diverse array of biological assemblies that include amyloid fibrils, non-amyloid aggregates, membrane-associated proteins and viral capsids. Such biological samples feature functionally relevant molecular dynamics, which often affect different parts of the sample in different ways. Solid-state NMR experiments' sensitivity to dynamics represents a double-edged sword. On the one hand, it offers a chance to measure dynamics in great detail. On the other hand, certain types of motion lead to signal loss and experimental inefficiencies that at first glance interfere with the application of ssNMR to overly dynamic proteins. Dynamics-based spectral editing (DYSE) ssNMR methods leverage motion-dependent signal losses to simplify spectra and enable the study of sub-structures with particular motional properties.


A study of the induction of gene conversion in yeast by sodium bisulphite under radical reaction conditions.
Sodium bisulphite (NaHSO3) at low concentrations is known to undergo radical reactions in the presence of Mn2+ ions, generating sulphite anion radicals (SO-3.). The kinetics of pH variation in aqueous solutions of NaHSO3 in the presence of 0.1 mM-MnSO4 suggests that the anion radicals are generated rapidly at low bisulphite concentration (10 mM) and quenched at a higher concentration (100 mM). The ability of NaHSO3 to induce gene conversion in the diploid yeast Saccharomyces cerevisiae BZ34 under conditions suitable for radical reactions has been investigated. The results show that NaHSO3 does not induce gene conversion under these conditions.


Dilatation of lymphatic vessels increases liver stiffness on transient elastography irrespective of fibrosis.
Liver stiffness measured using transient elastography (TE) is affected by tissue viscosity. The role of intrahepatic lymphatic fluid in liver stiffness is unclear. The present study aimed to investigate the effects of lymphatic vessel dilatation on liver stiffness. Patients with chronic liver disease (n = 116) were enrolled from June 2018 to March 2020. All specimens were acquired by laparoscopic liver biopsy. Biopsy samples were stained with D2-40 for lymphatic vessel quantification based on a five-point scale for each specimen. Independent associations of liver stiffness measured by TE, strain elasticity (liver fibrosis index), and controlled attenuation parameter with fibrosis, lymphatic vessels, alanine aminotransferase, bilirubin, and steatosis were evaluated. Fibrosis, splenic stiffness measurement, and splenic volume were significantly correlated with the area of lymphatic vessels. Fibrosis, lymphatic vessels, and alanine aminotransferase were independent factors significantly associated with liver stiffness measurement (LSM; standardized coefficient [β] = 0.375, P < 0.001; β = 0.342, P < 0.001; and β = 0.359, P < 0.001, respectively). Fibrosis was the only independent factor significantly associated with liver fibrosis index (β = 0.360, P < 0.001), whereas the fat deposit area was the only independent factor significantly associated with controlled attenuation parameter (β = 0.455, P < 0.001). The areas under the receiver operating characteristic curves for diagnosing controlled ascites based on LSM, liver fibrosis index, splenic stiffness measurement, collagen proportionate area, and area of lymphatic vessels were 0.94, 0.66, 0.76, 0.64, and 0.79, respectively. Lymphatic vessel dilatation can affect liver stiffness measured using TE. Liver stiffness measurement is a predictive factor for ascites.


The MBD4 Glu346Lys polymorphism is associated with the risk of cervical cancer in a Chinese population.
Methyl-CpG binding domain 4 (MBD4) protein functions as a DNA repair enzyme and plays an important role in maintaining genome integrity and carcinogenesis. The polymorphisms in the MBD4 gene may be associated with differences in DNA repair capacity and thereby influence an individual's susceptibility to cervical cancer. To verify this hypothesis, we examined the potential association between the MBD4 Glu346Lys polymorphism (rs140693, G>A) and the risk of cervical cancer in a Chinese population. We genotyped the MBD4 Glu346Lys polymorphism in 146 cervical cancer cases and 320 healthy female subjects using polymerase chain reaction-based restriction fragment length polymorphism method. Unconditional logistic regression analysis was used to estimate the association between the genotypes and the risk of cervical cancer. We observed a significantly decreased risk of cervical cancer associated with the heterozygous Lys/Glu genotype (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.36-0.99; P = 0.046) and the homozygous Glu/Glu genotype (OR, 0.52; 95% CI, 0.30-0.89; P = 0.018), compared with the Lys/Lys homozygotes. Moreover, the reduced cervical cancer risk was more predominant among younger subjects or human papillomavirus-positive individuals carrying Glu/Glu genotypes (OR, 0.33; 95% CI, 0.14-0.78, P = 0.011; and OR, 0.27; 95% CI, 0.09-0.75, P = 0.013, respectively). The MBD4 codon 346 polymorphism may play a role in cervical cancer susceptibility in the Chinese population. Further larger case-control and functional studies are needed to validate these findings.


A systematic approach to public health - Novel application of the human factors analysis and classification system to public health and COVID-19.
In this article, we argue for a novel adaptation of the Human Factors Analysis and Classification System (HFACS) to proactive incidence prevention in the public health and in particular, during and in response to COVID-19. HFACS is a framework of causal categories of human errors typically applied for systematic retrospective incident analysis in high-risk domains. By leveraging this approach proactively, appropriate, and targeted measures can be quickly identified and established to mitigate potential errors at different levels within the public health system (from tertiary and secondary healthcare workers to primary public health officials, regulators, and policymakers).


HIV-Associated Neurocognitive Impairment Knowledge and Current Practices: A Survey of Frontline Healthcare Workers in South Africa.
Neurocognitive impairment (NCI) associated with the human immunodeficiency virus (HIV) remains prevalent amongst people living with HIV. Testing for HIV-associated NCI in routine clinical care is limited in South Africa and reasons for this are unclear. We conducted an online survey amongst healthcare workers (HCW) to assess HIV-associated NCI knowledge and current practices. The final sample included four hundred surveys (n=400). Chi-square analyses were used to explore HCW knowledge of HIV-associated NCI and screening tools. One-way ANOVA was used to compare mean responses between HCW categories. We observed low awareness of HIV-associated NCI terminology and screening tools. HCW seldom suspected NCI among patients and screening practices were uncommon. Referrals for further NCI investigations were never requested. HCW expressed a desire to receive further training to identify HIV associated NCI. The current study highlights the context of HIV-associated NCI knowledge and practices among front-line HIV HCW in resource-limited settings.


Melt migration in basalt columns driven by crystallization-induced pressure gradients.
The structure of columnar-jointed lava flows and intrusions has fascinated people for centuries and numerous hypotheses on the mechanisms of formation of columnar jointing have been proposed. In cross-section, weakly developed semicircular internal structures are a near ubiquitous feature of basalt columns. Here we propose a melt-migration model, driven by crystallization and a coeval specific volume decrease inside cooling and solidifying columns, which can explain the observed macroscopic features in columnar-jointed basalts. We study basalts from Hrepphólar (Iceland), combining macroscopic observations, detailed petrography, thermodynamic and rheological modelling of crystallization sequences, and Anisotropy of Magnetic Susceptibility (AMS) of late crystallizing phases (that is, titanomagnetite). These are all consistent with our proposed model, which also suggests that melt-migration features are more likely to develop in certain evolved basaltic lava flows (with early saturation of titanomagnetite), and that the redistribution of melt within individual columns can modify cooling processes.


Etanercept Reduces Neuron Injury and Neuroinflammation via Inactivating c-Jun N-terminal Kinase and Nuclear Factor-κB Pathways in Alzheimer's Disease: An In Vitro and In Vivo Investigation.
Inflammation contributes to amyloid beta (Aβ) aggregation and neuron loss in Alzheimer's disease (AD). Meanwhile, tumor necrosis factor-α (TNF-α) inhibitors present strong effect on suppressing inflammation. Thus, this study aimed to investigated the effect and molecular mechanism of etanercept (ETN) (a commonly used TNF-α inhibitor) on neuron injury and neuroinflammation in AD. AD cellular model was constructed by co-culture of primary embryonic neuron cells and microglial cells, followed by Aβ treatment. Subsequently, ETN was used to treat AD cellular model. Besides, APPswe/PS1M146V/tauP301L transgenic (AD) mice were respectively treated with saline or ETN by intravenous injection once per 3 days for 10 times. In vitro data revealed that cell viability and neurite outgrowth were increased, but apoptosis and levels of pro-inflammatory cytokines (including TNF-α, interleukin-1β, Interleukin-6 and C-C motif chemokine ligand 2 (CCL2)) were decreased by ETN treatment in AD cellular model. In vivo experiments found that ETN treatment improved spatial, long-term memory (reflected by Morrison water maze) and working memory (reflected by Y maze) in AD mice. Besides, ETN treatment reduced neuron injury (reflected by Hematoxylin-Eosin (HE) and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assays) and levels of pro-inflammatory cytokines (including TNF-α, interleukin-1β, Interleukin-6 and CCL2) in AD mice. Moreover, ETN repressed the activation of c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) pathways in AD both in vitro and in vivo. In conclusion, ETN exerts neuroprotective function via inactivating JNK and NF-κB pathways in AD, indicating the potential of ETN for improving AD management.


Altered sleep quality is associated with Crohn's disease activity: an actimetry study.
Sleep is involved in the regulation of inflammation, healing, and digestion. The pathophysiology of Crohn's disease (CD) is unclear, and the role of sleep disturbances has recently been suggested. The present study investigated a putative association between sleep disturbances and CD activity. We conducted a prospective observational monocenter translational study, recruiting major CD patients from 2013 to 2015. Disease activity was assessed by the Harvey-Bradshaw index and the CD activity index. Objective sleep quantity and quality were measured by wrist actigraphy over a period of 7 days. The primary objective was to look for an association between wrist actigraphy parameters and CD activity. Thirty-four CD patients, including 14 with active disease and 20 in remission, were included. Sleep efficiency measured by wrist actigraphy was lower in patients with active CD compared to patients in remission. Wake after sleep onset time best predicted CD activity with an AUROC of 0.83. Patients with active CD were more frequently characterized as "poor sleepers" and frequently suffered from excessive daytime sleepiness. Sleep efficiency is lower in patients with active CD than in those in remission. Further studies aimed at better characterizing CD patients' sleep are warranted.


Oral hairy leukoplakia in a child using a corticosteroid nasal spray.
We report a case of atypical oral hairy leukoplakia (OHL) in a 9-year-old immunocompetent girl treated with fluticasone propionate nasal spray for allergic rhinitis. The OHL in childhood is uncommon and should be included in a differential diagnosis of white lesions in the oral mucosa.


New methodical approaches for the investigation of weathered epoxy resins used for corrosion protection of steel constructions.
Epoxy resin coatings applied to steel constructions for corrosion protection purposes are often exposed to UV-irradiation and weathering during the construction process. Chemical alteration of the hardened coating might lead to i) the release of potentially harmful substances into the environment and ii) delamination of the polyurethane top layer. However, chemical processes and mechanisms occurring on the surfaces of exposed epoxy resin coatings are not fully understood yet. Herein, we present an innovative approach combining time-of-flight secondary ion mass spectrometry (ToF-SIMS) with inductively coupled plasma mass spectrometry (ICP-MS) and liquid chromatography mass spectrometry (LC-MS) enabling the elucidation of underlying chemical processes and the identification of released organic and inorganic photolytic products. IR-spectroscopy and experiments targeting the acidity/pH-value changes on top of weathered surfaces complement our investigations. It was confirmed that UV-A irradiation leads to photooxidative degradation of the epoxy resin and that inorganic photolytic products are exposed on the weathered surfaces. Polar moieties (hydroxyls, carbonyls, carboxyls, amines) and released metalloids form a hydrophilic surface layer, which hinders adhesion and eventually prevents profound chemical linkage of the polyurethane top layer. Thus, an early delamination of the top layer might occur very likely.


Enhanced tumor killing by Apo2L/TRAIL and CPT-11 co-treatment is associated with p21 cleavage and differential regulation of Apo2L/TRAIL ligand and its receptors.
Apo2L/TRAIL exhibits enhanced apoptotic activity in tumor xenograft models when used in combination with the topoisomerase 1 inhibitor CPT-11. To investigate the cellular mechanisms involved in this increased tumor-killing activity, a series of in vitro experiments were conducted using the human colon carcinoma cell line (HCT116). Apo2L/TRAIL induced a transient upregulation of DR5 mRNA, while CPT-11 increased both death and decoy receptor expression. Upregulation of decoy receptors by CPT-11 was partially inhibited by co-administration of Apo2L/TRAIL. CPT-11 treatment resulted in accumulation of cells at G(2)M-phase and correlated with a substantial increase in the protein levels of the cyclin-dependent kinase inhibitor p21. However, cells co-treated with CPT-11 and Apo2L/TRAIL, or pretreated with CPT-11 for up to 24 h followed by 2 h Apo2L/TRAIL, resulted in a caspase-dependent degradation of p21, reversal of G(2)-M phase arrest with a concomitant increase in apoptosis. The sequential treatment produced the greatest induction of DR5 and DR4, caspase-3-like cleavage/activation and p21 degradation, as well as increased apoptosis. These data indicate that the up-regulation of Apo2L/TRAIL ligand and its death receptors as well as cleavage of p21 protein in the Apo2L/TRAIL plus CPT-11 treatment contributes to the positive cooperation between these agents in enhancing tumor cell apoptosis.


Effect of renin angiotensin blockers on angiotensin converting enzyme 2 level in cardiovascular patients.
Renin-angiotensin-aldosterone system (RAAS) is hypothesized to be in the center of COVID pathophysiology as the angiotensin converting enzyme 2 (ACE2) represents the main entrance of the virus, thus there is a need to address the effect of chronic use of RAAS blockers, as in case of treatment of cardiovascular diseases, on the expression of ACE2. Accordingly, this study aimed to clarify the effect of ACE inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on ACE2 and to assess the correlation between ACE2 and several anthropometric and clinic-pathological factors. A total of 40 healthy controls and 60 Egyptian patients suffering from chronic cardiovascular diseases were enrolled in this study. Patients were divided into 40 patients treated with ACEIs and 20 patients treated with ARBs. Serum ACE2 levels were assessed by ELISA. Assessment of serum ACE2 level in different groups showed a significant difference between ACEIs and healthy groups and ACEIs and ARBs group, while there was no difference between ARBs and healthy. Multivariate analysis using ACE2 level as constant and age, female sex, ACEIs use and myocardial infarction (MI) showed that there was a significant effect of female sex and ACEIs use on ACE2 level with no effect of age, MI and diabetes. ACE2 levels varied between ACEIs and ARBs. It tends to be lower in ACEIs group and there is a strong positive association between ACE2 level and the female sex. This needs to be considered in Future studies to further understand the relationship between gender, sex hormones and ACE2 level. Retrospectively registered ClinicalTrials.gov ID: NCT05418361 (June 2022).


[Retrospective analysis of mortality due to neoplasms of the larynx in Jelenia Góra district (1982-1989)].
The authors presents a retrospective analysis of mortality from laryngeal cancer in the population of Jelenia Góra in the years 1982-1989. The analysis was based on the death register books and cards.


Plasmon-Accelerated Generation of Singlet Oxygen on an Au/MoS2 Nanohybrid for Enhanced Photodynamic Killing of Bacterial Pathogens/Cancerous Cells.
Benefiting from its strong cytotoxic features, singlet oxygen (1O2) has garnered considerable research attention in photodynamic therapy (PDT) and thus, plenty of inorganic PDT agents have been recently developed. However, inorganic PDT agents consisting of metal/semiconductor hybrids are surprisingly rare, bearing very low 1O2 quantum yield, and their in vivo PDT applications remain elusive. Herein, we provide an unprecedented report that the Au/MoS2 hybrid under plasmon resonant excitation can sensitize 1O2 generation with a quantum yield of about 0.22, which is much higher than that of the reported hybrid-based photosensitizers (PSs). This significant enhancement in 1O2 quantum yield is attributed to the hot-electron injection from plasmonic AuNPs to MoS2 NSs due to the matched energy levels. Electron paramagnetic resonance (EPR) spectroscopy with spin trapping and spin labeling verifies the plasmonic generation of hot charge carriers and reactive oxygen species such as superoxide and 1O2. This plasmonic PDT agent shows a remarkable photodynamic bacterial inactivation in vitro and anti-cancer therapeutic ability both in vitro and in vivo, which is solely attributed to high 1O2 generation rather than the plasmonic photothermal effect. Hence, plasmonic Au/MoS2 with enhanced 1O2 quantum yield and appreciable in vivo cancer plasmonic PDT performance holds great promise as an inorganic PS to treat near-surface tumors. As a first demonstration of how metal localized surface plasmon resonance could enhance 1O2 generation, the present study opens up promising opportunities for enhancing 1O2 quantum yield of hybrid-based PSs, leading to achieving a high therapeutic index in plasmon PDT.


Innovations in modeling influenza virus infections in the laboratory.
Respiratory viruses represent one of the most substantial infectious disease burdens to the human population today, and in particular, seasonal and pandemic influenza viruses pose a persistent threat to public health worldwide. In recent years, advances in techniques used in experimental research have provided the means to better understand the mechanisms of pathogenesis and transmission of respiratory viruses, and thus more accurately model these infections in the laboratory. Here, we briefly review the model systems used to study influenza virus infections, and focus particularly on recent advances that have increased our knowledge of these formidable respiratory pathogens.


Human botfly infestation presenting as peri-auricular mass.
To report a new cause of peri-auricular mass in children: cutaneous myiasis-botfly infestation. Case report. The human botfly (Dermatobia hominis) is found in the tropics of Central and South America. However, cases of infestation are uncommon in the United States. We present the case of a 5-year-old girl with cutaneous myiasis in order to expand the differential diagnosis for a peri-auricular mass in children. In our report, the parasite was initially identified as sparganum, but was later reclassified by the center for disease control and prevention (CDC) as a botfly larva. Parasitic infection should be considered with a newly noted head and neck mass, and cutaneous myiasis should be included in the differential diagnosis. Cutaneous myiasis has not been previously reported in the literature describing the peri-auricular region as the site of occurrence. Furthermore, when an unusual parasite is extracted from a lesion, it should be confirmed by an authority such as CDC for definitive diagnosis, so appropriate plan of care and follow up can be instituted.


Synapsin III gene silencing redeems alpha-synuclein transgenic mice from Parkinson's disease-like phenotype.
Fibrillary aggregated α-synuclein (α-syn) deposition in Lewy bodies (LB) characterizes Parkinson's disease (PD) and is believed to trigger dopaminergic synaptic failure and a retrograde terminal-to-cell body neuronal degeneration. We described that the neuronal phosphoprotein synapsin III (Syn III) cooperates with α-syn to regulate dopamine (DA) release and can be found in the insoluble α-syn fibrils composing LB. Moreover, we showed that α-syn aggregates deposition, and the associated onset of synaptic deficits and neuronal degeneration occurring following adeno-associated viral vectors-mediated overexpression of human α-syn in the nigrostriatal system are hindered in Syn III knock out mice. This supports that Syn III facilitates α-syn aggregation. Here, in an interventional experimental design, we found that by inducing the gene silencing of Syn III in human α-syn transgenic mice at PD-like stage with advanced α-syn aggregation and overt striatal synaptic failure, we could lower α-syn aggregates and striatal fibers loss. In parallel, we observed recovery from synaptic vesicles clumping, DA release failure, and motor functions impairment. This supports that Syn III consolidates α-syn aggregates, while its downregulation enables their reduction and redeems the PD-like phenotype. Strategies targeting Syn III could thus constitute a therapeutic option for PD.


Enhanced GABA release in cerebral cortical slices derived from rats with thioacetamide-induced hepatic encephalopathy.
The release of newly loaded [3H]GABA was studied in slices of different brain regions derived from rats in which acute hepatic encephalopathy (HE) was induced with a hepatotoxin thioacetamide. HE increased both spontaneous and high (50 mM) ammonium chloride-evoked GABA release in cerebral cortical slices by 38% and 50%, respectively. No effects of HE were noted in cerebellar or striatal slices. An increased release of GABA in the cerebral cortex may contribute to the endogenous benzodiazepine-mediated enhancement of GABAergic tone, which is thought to be partly responsible for the pathophysiological mechanism of HE.


Feasibility of a blended therapy approach in the treatment of patients with inflammatory myopathies.
Inflammatory myopathies (IMs) are a group of rare conditions characterized by proximal and often symmetrical muscle weakness and reduced muscle endurance. The recommended medical treatment is based on corticosteroids in combination with immunosuppressants. This anti-inflammatory therapy serves to inhibit and prevent inflammation but does not influence impaired muscle strength. Exercise, particularly progressive resistance training, plays therefore an important role in IMs management. Blended therapy, a combination of face-to-face treatment and telerehabilitation, may be a powerful therapy option in improving exercise program adherence in these patients. The feasibility of a 12-week interactive tablet-based home exercise program combined with face-to-face therapy sessions - a 'blended therapy' approach - was evaluated using a quasi-experimental one-group pre-post comparison design. Primary outcomes were recruitment, attrition and adherence rates, plus measures of acceptance (Technology Acceptance Model Questionnaire (TAM)) and satisfaction (satisfaction questionnaire). Secondary outcomes comprised potential effects of the intervention on muscle strength and function, activity limitation, disability and health-related quality of life. Thirteen of the included 14 participants completed the study without any related adverse events. Mean adherence to exercise program was 84% (range: 25-100%) and participants indicated high acceptance of the intervention with mean TAM scores between 6.1 and 6.5 points. Overall satisfaction with the therapy sessions, the home program, and the technology was good. Approximately half the participants wished for longer training periods and more training sessions per week. There were inconsistent effects on muscle strength, muscle function, activity limitation, disability, and health-related quality of life. Blended therapy combining the use of an interactive tablet-based resistance training program with face-to-face therapy sessions is feasible and safe and participants` acceptance with this approach was high. Furthermore, results were obtained that might be useful in selecting appropriate assessments and sample sizes in future trials. NCT03713151 .


[Establishment of a rat model of flutamide-induced cryptorchidism with remaining gonocytes].
To observe the effects of flutamide (Flu) on the development of testicular germocytes in SD rats, and to establish a rat model for further researches on the maldevelopment of cryptorchidism gonocytes (Go). Pregnant SD rats were subcutaneously injected with Flu from gestational day (GD) 12 to 21 to establish a model of cryptorchidism. The testes of the newborns were harvested on postnatal day (PD) 1, 10, 20 and 80 for observation of their morphological and histological changes by HE staining and detection of the expression of neural cell adhesion molecules (NCAM) by immunohistochemistry and RT-PCR. Flu induced 43.9% (29/66) of cryptorchidism in the exposed rats. Significant differences were found in the testicular weight and organ coefficient between the Flu and the control groups on PD 20 and 80. Gos remained in the center of seminiferous tubules of the Flu-induced testis on PD 10, and in the center of seminiferous tubules in the cryptorchids' testicular tissues on PD 20 and 80. Immunohistochemistry showed the expression of NCAM on the membrane of the remaining Gos, and RT-PCR revealed significantly up-regulated expression of NCAM mRNA in the Flu-induced testes on PD 10 and 20 as compared with the controls (P < 0.05). A rat model of Flu-induced cryptorchidism with remaining Gos was successfully established, which could be used to study the mechanism and management of the maldevelopment of cryptorchidism gonocytes.


A new method providing complementary explanation of the blood-enriching function and mechanism of unprocessed Angelica sinensis and its four kinds of processed products based on tissue-integrated metabolomics and confirmatory analysis.
Angelica sinensis (AS) is a common Traditional Chinese Medicine used for tonifying blood in China. Unprocessed AS and its four kinds of processed products (ASs) are used to treat blood deficiency syndrome in the country. The different blood-tonifying mechanisms of ASs remain unclear. In this work, a novel method integrating metabolomics and hematological and biochemical parameters was established to provide a complementary explanation of blood supplementation mechanism of ASs. Our results revealed that different ASs exhibited various blood supplementation effect, and that AS parched with alcohol demonstrated the best blood supplementation effect. Eight metabolites from liver tissue and 12 metabolites from spleen tissue were considered to be potential biomarkers. These biomarkers were involved in four metabolic pathways. Correlation analysis results showed that l-aspartic acid and l-alanine (spleen tissue), linoleic acid, and l-cystathionine (liver tissue) exhibited a high positive or negative correlation with the aforesaid biochemical indicators. The blood-supplementation effect mechanism of ASs were related to four metabolic pathways. l-Aspartic acid and l-alanine (spleen tissue), linoleic acid, and l-cystathionine (liver tissue) were the four key metabolites associated with the blood supplementation effect of ASs. This study gives a complementary explanation of the blood supplementation effect and mechanism of action of ASs.


The feasibility of enzyme hydrolysate gross energy for formulating duck feeds.
Two experiments were designed to investigate the feasibility of enzyme hydrolysate gross energy (EHGE) for formulating duck feeds. In experiment 1, six mixed diets and 6 experimental diets (compound feeds) with 20% CP were formulated, and their EHGE, AME, and TME were determined so as to analyze the correlation between EHGE and AME, TME. In experiment 2, six experimental diets with different EHGE levels were further arranged to determine the EHGE requirement for Pekin ducks from hatch to 21 D of age. A total of 384 freshly hatched ducklings was randomly divided into 6 experimental treatments, each treatment containing 8 replicates with 8 ducks per replicate. The results showed that there were a linear correlation between EHGE and AME (r = 0.998, P < 0.01), TME (r = 0.997, P < 0.01) for 6 mixed diets, and the regression models were AME = 0.996 × EHGE-1.062 (R2 = 0.996, P < 0.01), TME = 0.997 × EHGE+0.304 (R2 = 0.995, P < 0.01). For the 6 experimental diets, EHGE was also positively correlated with AME (r = 0.983, P < 0.01), TME (r = 0.984, P < 0.01), and the regression models were AME = 1.2054 × EHGE-3.180 (R2 = 0.967, P < 0.01), TME = 1.2054 × EHGE-1.783 (R2 = 0.967, P < 0.01). According to the broken-line model and optimal BW, the EHGE requirement for ducks from hatch to 21 D of age was 2,937 kcal/kg (calculated value), 3,182 kcal/kg (determined value). In conclusion, EHGE could be used to predict the AME and TME values for mixed diets and compound feeds based on established regression models, and the simulated digestion method in vitro has the potential for effective energy evaluation and formulation for duck feeds.


Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and l-DOPA reversible motor deficits.
The dopamine transporter is a key protein responsible for regulating dopamine homeostasis. Its function is to transport dopamine from the extracellular space into the presynaptic neuron. Studies have suggested that accumulation of dopamine in the cytosol can trigger oxidative stress and neurotoxicity. Previously, ectopic expression of the dopamine transporter was shown to cause damage in non-dopaminergic neurons due to their inability to handle cytosolic dopamine. However, it is unknown whether increasing dopamine transporter activity will be detrimental to dopamine neurons that are inherently capable of storing and degrading dopamine. To address this issue, we characterized transgenic mice that over-express the dopamine transporter selectively in dopamine neurons. We report that dopamine transporter over-expressing (DAT-tg) mice display spontaneous loss of midbrain dopamine neurons that is accompanied by increases in oxidative stress markers, 5-S-cysteinyl-dopamine and 5-S-cysteinyl-DOPAC. In addition, metabolite-to-dopamine ratios are increased and VMAT2 protein expression is decreased in the striatum of these animals. Furthermore, DAT-tg mice also show fine motor deficits on challenging beam traversal that are reversed with l-DOPA treatment. Collectively, our findings demonstrate that even in neurons that routinely handle dopamine, increased uptake of this neurotransmitter through the dopamine transporter results in oxidative damage, neuronal loss and l-DOPA reversible motor deficits. In addition, DAT over-expressing animals are highly sensitive to MPTP-induced neurotoxicity. The effects of increased dopamine uptake in these transgenic mice could shed light on the unique vulnerability of dopamine neurons in Parkinson's disease.


CALPUFF and AERMOD model validation study in the near field: Martins Creek revisited.
This paper describes a near-field validation study involving the steady-state, U.S. Environmental Protection Agency (EPA) guideline model AERMOD and the nonsteady-state puff model CALPUFF. Relative model performance is compared with field measurements collected near Martins Creek, PA-a rural, hilly area along the Pennsylvania-New Jersey border. The principal emission sources in the study were two coal-fired power plants with tall stacks and buoyant plumes. Over 1 yr of sulfur dioxide measurements were collected at eight monitors located at or above the two power plants' stack tops. Concurrent meteorological data were available at two sites. Both sites collected data 10 m above the ground. One of the sites also collected sonic detection and ranging measurements up to 420 m above ground. The ability of the two models to predict monitored sulfur dioxide concentrations was assessed in a four-part model validation. Each part of the validation applied different criteria and statistics to provide a comprehensive evaluation of model performance. Because of their importance in regulatory applications, an emphasis was placed on statistics that demonstrate the model's ability to reproduce the upper end of the concentration distribution. On the basis of the combined results of the four-part validation (i.e., weight of evidence), the performance of CALPUFF was judged to be superior to that of AERMOD.


Coordinated regulation of symbiotic adaptation by NodD proteins and NolA in the type I peanut bradyrhizobial strain Bradyrhizobium zhanjiangense CCBAU51778.
Type I peanut bradyrhizobial strains can establish efficient symbiosis in contrast to symbiotic incompatibility induced by type II strains with mung bean. The notable distinction in the two kinds of key symbiosis-related regulators nolA and nodD close to the nodABCSUIJ operon region between these two types of peanut bradyrhizobia was found. Therefore, we determined whether NolA and NodD proteins regulate the symbiotic adaptations of type I strains to different hosts. We found that NodD1-NolA synergistically regulated the symbiosis between the type I strain Bradyrhizobium zhanjiangense CCBAU51778 and mung bean, and NodD1-NodD2 jointly regulated nodulation ability. In contrast, NodD1-NolA coordinately regulated nodulation ability in the CCBAU51778-peanut symbiosis. Meanwhile, NodD1 and NolA collectively contributes to competitive nodule colonization of CCBAU51778 on both hosts. The Fucosylated Nod factors and intact type 3 secretion system (T3SS), rather than extra nodD2 and full-length nolA, were critical for effective symbiosis with mung bean. Unexpectedly, T3SS-related genes were activated by NodD2 but not NodD1. Compared to NodD1 and NodD2, NolA predominantly inhibits exopolysaccharide production by promoting exoR expression. Importantly, this is the first report that NolA regulates rhizobial T3SS-related genes. The coordinated regulation and integration of different gene networks to fine-tune the expression of symbiosis-related genes and other accessory genes by NodD1-NolA might be required for CCBAU51778 to efficiently nodulate peanut. This study shed new light on our understanding of the regulatory roles of NolA and NodD proteins in symbiotic adaptation, highlighting the sophisticated gene networks dominated by NodD1-NolA.


Differential mutagenicity of N-methyl-N-nitrosocarbamate insectides in Escherichia coli strains having different DNA repair capacities.
Four isogenic strains of Escherichia coli with the same auxotrophic marker (arg Fam--namely wild-type, uvrA-, polA- and recA-) were used for testing the lethalities and mutagenicities of 1-naphthyl N-methyl-N-nitrosocarbamate (nitroso-NAC), 3-methylphenyl N-methyl-N-nitrosocarbamate (nitroso-MTMC), and 3,4-dimethylphenyl N-methyl-N-nitrosocarbamate (nitroso-MPMC). The strains recA- and polA- showed a similarly higher sensitivity to killing than wild-type and uvrA- after treatments with each of the three chemicals, whereas the strains wild-type, uvrA-, and polA- were equally mutable by these compounds at equal doses. The strain recA- was hardly mutable by nitroso-NAC, but significant levels of Arg+ mutations were observed after treatments with nitroso-MTMC and nitroso-MPMC. These and previous results suggest that both nitroso-MTMC and nitroso-MPMC are similar in their mutagenicity pattern to N-methyl-N'-nitro-N-nitrosoguanidine whereas nitroso-NAC is similar to methyl methanesulfonate or X-rays, and that the major damage to DNA of the three agents is not excisable by the uvrA+-dependent excision repair, probably methylation in DNA.


Establishment of monoclonal antibodies reactive with epithelial and myoepithelial cells in the breast.
Monoclonal antibodies which are considered to be able to differentiate epithelial and myoepithelial cells in the breast have been developed. Human mammary carcinoma cell line (HBC-4W) was used for immunization. Monoclonal antibodies-B4B2F10 (epi-1), E9E8B7 (myo-1)-with IgM was examined using tissues from diseased breast by avidin-biotin-peroxidase assay. Epi-1 antibody reacted with epithelial cells while myo-1 antibody reacted with myoepithelial cells in the mammary glands, respectively. The reaction was markedly visible, in particular, in fibroadenoma, mastopathy, and papilloma, which showed clear two-cell-type structures. In the infiltrating ductal carcinoma, epi-1 antibody reacted with carcinoma cells, while myo-1 antibody reacted with stromal cells rather than carcinoma cells suggesting that infiltrating ductal carcinoma was mainly of epithelial origin. In the infiltrating lobular carcinoma, however, myo-1 as well as epi-1 antibodies reacted with carcinoma cells. It is suggested that infiltrating lobular carcinoma was of a mixture of epithelial and myoepithelial cell origin.


Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation (Marshall-PLAN): Prospective, single-center study.
Beyond pulmonary vein isolation (PVI), the optimal ablation strategy for persistent atrial fibrillation (AF) remains poorly defined. The purpose of this study was to examine a novel comprehensive ablation strategy (Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation [Marshall-PLAN]) strictly based on anatomical considerations. Left atrial (LA) sites were sequentially targeted as follows: (1) coronary sinus and vein of Marshall (CS-VOM) musculature; (2) PVI; and (3) anatomical isthmuses (mitral, roof, and cavotricuspid isthmus [CTI]). The primary endpoint was 12-month freedom from AF/atrial tachycardia (AT). Seventy-five consecutive patients were included (age 61 ± 9 years; 10 women; AF duration 9 ± 11 months; mean LA volume 197 ± 43 mL). VOM ethanol infusion was completed in 69 patients (92%). The full Marshall-PLAN lesion set (VOM, PVI, mitral, roof, and CTI with block) was successfully completed in 68 patients (91%). At 12 months, 54 of 75 patients (72%) were free from AF/AT after a single procedure (no antiarrhythmic drugs) in the overall cohort. In the subset of patients with a complete Marshall-PLAN lesion set (n = 68), the single procedure success rate was 79%. After 1 or 2 procedures, 67 of 75 patients (89%) remained free from AF/AT (no antiarrhythmic drugs). After 1 or 2 procedures, VOM ethanol infusion was complete in 72 of 75 patients (96%). A novel ablation strategy that systematically targets anatomical atrial structures (VOM ethanol infusion, PVI, and prespecified linear lesions) is feasible, safe, and associated with a high rate of freedom from arrhythmia recurrence at 12 months in patients with persistent AF.


[Oxidoreductase activity of peat soils as an indicator of the degree of biochemical transformation of drained and forested bogs in west Siberia].
Multivariate analysis unambiguously demonstrated the differentiation of oxidoreductase activity (catalase, peroxidase, and dehydrogenase) in peat soils after a 20-25-year period of bog drainage and afforestation. The enzyme activity depended on the drainage depth. A statistical model has been developed to predict the degree of humification of peat organic matter from peroxidase activity and moisture of drained soils. Soil peroxidase activity can be an important indicator of the degree of biochemical transformation of drained and forested bogs.


Metallic Inverse Opals: An Electrochemiluminescence enhanced Substrate for Sensitive Bioanalysis.
Here, we proposed a novel local surface plasmon resonance (LSPR) enhanced ECL strategy based on the metallic inverse opals and Ru(bpy)32+-doped silica nanoparticles (RuSi NPs). Gold inverse opals (GIOs), as a plasmonic array, could interact with the ECL of RuSi NPs and excite the electromagnetic (EM) field at the gold surface. The triggered EM field could enhance the ECL emission of RuSi NPs. We compared the electrochemical and ECL performances of RuSi NPs modified on the gold electrodes with different surface morphologies and found that the ECL emission of RuSi NPs patterned at the inner surface of GIOs exhibited the highest intensity. The finite-difference time-domain (FDTD) simulations indicated that the EM field was related to the surface morphology of the metallic nanostructure, and the highest EM field was observed at the inner surface of the GIOs. Because of the superior ECL performances, the inner surfaces of GIOs were developed for nucleic acid detection with a detection limit of 3.3 fM (S/N = 3), which shows great promise for bioanalysis.


PTK-pathways and TGF-beta signaling pathways in schistosomes.
Schistosome parasites have co-evolved an intricate relationship with their human and snail hosts as well as a novel interplay between the adult male and female parasites. Drug-induced suppression of female schistosome sexual maturation is an auspicious strategy to combat schistosomiasis since the eggs are the causative agent. Studies on signaling in schistosomes opens a new era for investigation of host-parasite and male-female interactions. We review the role of the TGF-beta signaling pathway in parasite development, host-parasite interactions and male-female interactions. This review also summarizes recent studies suggesting tyrosine kinases as important factors for the regulation of female gonad development. In this context, cytoplasmatic tyrosine kinases of the Src class seem to play especially dominant roles. Moreover, experimental data and theoretical concepts are provided supporting a crosstalk between tyrosine kinase and TGF-beta signaling in the production of vitellocytes. Finally, we take advantage of the schistosome genome project to propose a model for the regulation of vitelline-cell production and differentiation.


Induction of donor-specific tolerance by adenovirus-mediated CD40Ig gene therapy in rat liver transplantation.
Blockade of CD40-CD40 ligand (CD154) costimulatory pathway with anti-CD154 antibody (Ab) prolongs allograft survival in experimental organ transplantations; however, repeated agent administration is needed to provide an adequate immunosuppression. Seeking for simple and effective approach to interfere this signaling, we applied adenovirus-mediated gene therapy by encoding CD40Ig gene (AdCD40Ig). Liver graft from ACI (RT1av1) rat was transplanted orthotopically into LEW (RT1l) rat, and AdCD40Ig was given to animals via the penile vein immediately after grafting (n=6). A single treatment with AdCD40Ig at 1x10(9) plaque forming units induced specific expression of CD40Ig gene on allograft liver, produced substantial amount of the protein in the sera, and allowed indefinite graft survival. Whereas, LEW recipients given no treatment or control adenovirus vector (AdLacZ) promptly rejected ACI liver. In addition, AdCD40Ig-treated, long-term survivors accepted skin graft from the donor strain but not the third party graft. Histopathology revealed that liver structure of the long-term surviving animals was completely preserved in normal with no infiltration of mononuclear cells. Blockade of CD40-CD154 pathway by CD40Ig gene therapy is a potent alloantigen-specific immunosuppressive strategy to induce permanent acceptance of liver allograft and would be a new therapeutic candidate in a clinical liver transplantation.


Src suppressed C kinase substrate regulates the lipopolysaccharide-induced TNF-alpha biosynthesis in rat astrocytes.
The protein kinase C (PKC) is known to be a critical component in the signaling cascades that lead to astrocyte-activation. To further understand the mechanism of PKC signaling in astrocyte-activation, we investigated the effect of SSeCKS, a PKC substrate, on LPS-induced cytokine expression in astrocytes by RT-PCR and enzyme-linked immunosorbent assay. Exposure of the cells to LPS induced rapid translocation of SSeCKS to the perinuclear sides, ERK activation and pronounced TNF-alpha production, which can be inhibited by the PKC inhibitor Gö6983. By using siRNA knockdown of SSeCKS expression, LPS-induced signaling events were partly inhibited, including ERK activation, inducible TNF-alpha biosynthesis and secretion. These results suggest that SSeCKS is involved in the LPS-induced TNF-alpha expression in astrocytes mediated by PKC.


Internationally trained pharmacists' perception of their communication proficiency and their views on the impact on patient safety.
According to Great Britain (GB)'s pharmacy regulator's standards of conduct, ethics and performance, pharmacists have a responsibility to ensure that they have sufficient linguistic skills to communicate and perform their job safely. Yet, very little is known about internationally trained pharmacists' (ITPs) linguistic proficiency. The purpose of this study was to investigate ITPs' perceptions of their communication proficiency and the resultant impact on patient safety. Eight focus groups were conducted between May and July 2010, with 31 European Economic Area (EEA) and 11 non-EEA pharmacists who, at the time of the study, practiced in community pharmacy (n = 29) or hospital (n = 13), in London, Manchester, Liverpool and Glasgow. The framework method was used to analyze qualitative data, and the Model of Communicative Proficiency (MCP) served as a framework to handle and explain the data obtained. ITPs experienced communication difficulties through new dialects, use of idioms and colloquial language in their workplace. The differences between the "BBC English" they learned formally and the "Street English" used in GB also led to difficulties. Culture was also recognized as an important aspect of communication. ITPs in this study were adamant that communication difficulty did not compromise patient safety. Communicative deficiency of ITPs arose primarily from two sources: linguistic competence and socio-cultural competence. These deficiencies could have negative implications for patient safety. The findings of this study should be taken into account when designing adaptation programs for ITPs.


Finger-Powered Electro-Digital-Microfluidics.
Portable microfluidic devices are promising for point-of-care (POC) diagnosis and bio- and environmental surveillance in resource-constrained or non-laboratory environments. Lateral-flow devices, some built off paper or strings, have been widely developed but the fixed layouts of their underlying wicking/microchannel structures limit their flexibility and present challenges in implementing multistep reactions. Digital microfluidics can circumvent these difficulties by addressing discrete droplets individually. Existing approaches to digital microfluidics, however, often require bulky power supplies/batteries and high voltage circuits. We present a scheme to drive digital microfluidic devices by converting mechanical energy of human fingers to electrical energy using an array of piezoelectric elements. We describe the integration our scheme into two promising digital microfluidics platforms: one based on the electro-wetting-on-dielectric (EWOD) phenomenon and the other on the electrophoretic control of droplet (EPD). Basic operations of droplet manipulations, such as droplet transport, merging and splitting, are demonstrated using the finger-powered digital-microfluidics.


Planned complex suicide by penetrating captive-bolt gunshot and hanging: case study and review of the literature.
Captive-bolt guns or slaughterer's guns are devices widely used in meat industry and private farmer households for slaughtering animal stocks. They consist of a simple cylindrical metal tube (barrel) with a metal bolt placed in their centre (around 9-15cm long and 1-1.5cm wide). The bolt is actuated by a trigger pull and is propelled forward by compressed air or by the discharge of a blank powder gun cartridge. Violent deaths inflicted by captive-bolt guns are rarely encountered in forensic practice and are predominantly suicidal events. We report an unusual complex suicide by hanging and self-shooting with a slaughterer's gun in a 21-year-old boy. The victim after putting a ceiling fixed rope around his neck shot himself in the head (occipital region) with a Kerner captive-bolt gun. He used two mirrors (a cosmetic mirror and a man-sized one) in order to properly visualize his back and to target the occipital region of his head. Radiological data (computed tomography with three dimensional reconstruction) and autopsy findings are discussed according to the clinical and forensic literature. A brief review on planned complex suicides is also given.


Immune therapy in respiratory disease.
Pharmacologic manipulation of pulmonary immunity plays an important role in primary and adjunct therapy for equine respiratory disease. Frequent exposure to respiratory viral pathogens, strenuous exercise, long distance transport, and inhalation of harmful substances destroy various aspects of the pulmonary defense system and predispose performance horses to development of infectious and noninfectious respiratory disease. Pulmonary immunity may be bolstered by nonspecific immunostimulants to combat primary or secondary immunodeficiency. State of the art technology improves active and passive-specific immunity for prevention of common infectious respiratory diseases in horses. Immuno-suppressive therapy can attenuate hyperreactive pulmonary immune responses in horses with allergic airway disease.


Glutathione transferase catalyzed conjugation of benzo[a]pyrene 7,8-diol 9,10-epoxide with glutathione in human skin.
Glutathione transferase (GST) activity towards racemic as well as the resolved enantiomers of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene (anti-BPDE) and 1-chloro-2,4-dinitrobenzene (CDNB) was measured in post-microsomal supernatants (PMS) obtained from eight human skin samples. All preparations showed significant activity towards anti-BPDE and an almost exclusive preference for the more tumourigenic (+)-enantiomer. The specific activity towards (+)-anti-BPDE varied about five-fold between different PMS (range 147-781 pmol/min per mg protein) whereas the variation in specific activities towards CDNB was about two-fold (range 30-71 nmol/min per mg protein). The activities obtained with PMS at saturating concentrations of racemic anti-BPDE were about half of the activity towards the (+)-enantiomer indicating that (-)-anti-BPDE competitively inhibits conjugation of the (+)-form. No correlation was evident between the activities towards (+)-anti-BPDE and CDNB implying that different classes of GST isoenzymes participated in the two different reactions. Immunoblot analysis revealed the presence of Class Alpha and Pi isoenzymes whereas Class Mu isoenzymes seemed to be absent in the human skin samples analyzed. Quantitatively, the Class Pi isoenzyme(s) predominated in all skin samples and the amount of enzyme was about 1-3 micrograms GST Pi/mg PMS protein. The almost exclusive conjugation of (+)-anti-BPDE by PMS and previous results with GST Pi enzymes from human placenta suggested that this type of enzymes catalysed the conjugation reaction. The five-fold variation in specific activity towards (+)-anti-BPDE observed among the different PMS may be explained by individual differences in GST Pi content or by the presence of endogenous modifiers of GST activity towards the diol-epoxide.


Immunoscreening of λgt11 Expression Libraries Using an Avidin-Biotin Detection System.
Although the avidin-biotin detection system has been used for immunochemical staining of tissues for some time, its use for amplification in immunoassays was not described until 1979 (1). The biological basis for the system is the very tight binding of four molecules of biotin to one of avidin. This has an amplification ability that can be used to increase the sensitivity of detection of antibodies or other biotin-labeled molecules. Using antibodies raised to a purified peptide and an efficient expression system, such as λgtll (2), the clone(s) containing the cDNA for that peptide can usually be identified by detection of expressed antigens.


Recent advances in de novo protein design: Principles, methods, and applications.
The computational de novo protein design is increasingly applied to address a number of key challenges in biomedicine and biological engineering. Successes in expanding applications are driven by advances in design principles and methods over several decades. Here, we review recent innovations in major aspects of the de novo protein design and include how these advances were informed by principles of protein architecture and interactions derived from the wealth of structures in the Protein Data Bank. We describe developments in de novo generation of designable backbone structures, optimization of sequences, design scoring functions, and the design of the function. The advances not only highlight design goals reachable now but also point to the challenges and opportunities for the future of the field.


Note: ferrule-top atomic force microscope. II. Imaging in tapping mode and at low temperature.
In a recent paper [D.Chavan et al., Rev. Sci. Instrum. 81, 123702 (2010)] we have demonstrated that ferrule-top cantilevers, obtained by carving the end of a ferruled fiber, can be used for contact mode atomic force microscopy in ambient conditions. Here we show that those probes can provide tapping mode images at both room and cryogenic temperatures (12 K).


The Antibiotic Resistome and Its Association with Bacterial Communities in Raw Camel Milk from Altay Xinjiang.
Raw camel milk is generally contaminated with varied microbiota, including antibiotic-resistant bacteria (ARB), that can act as a potential pathway for the spread of antibiotic resistance genes (ARGs). In this study, high-throughput quantitative PCR and 16S rRNA gene-based Illumine sequencing data were used to establish a comprehensive understanding of the antibiotic resistome and its relationship with the bacterial community in Bactrian camel milk from Xinjiang. A total of 136 ARGs and up to 1.33 × 108 total ARG copies per gram were identified, which predominantly encode resistance to β-lactamas and multidrugs. The ARGs' profiles were mainly explained by interactions between the bacteria community and physicochemical indicators (77.9%). Network analysis suggested that most ARGs exhibited co-occurrence with Corynebacterium, Leuconostoc and MGEs. Overall, raw camel milk serves as a reservoir for ARGs, which may aggravate the spread of ARGs through vertical and horizontal gene transfer in the food chain.


Effect of polymeric network structure on drug release from cross-linked poly(vinyl alcohol) micromatrices.
Three types of poly(vinyl alcohol) were cross-linked by glutaraldehyde to form water-swellable materials possessing a three-dimensional, molecular network. Proxyphylline and theophylline were incorporated into the polymer networks during the cross-linking reaction. The firm hydrogels formed were dried and reduced to a particle size of 400-630 microns. The molecular structure of the gels was characterized by equilibrium swelling measurements which allowed the determination of the average distance between two cross-links and, hence, the macromolecular mesh size. The sulfate and glutaraldehyde residues contained in the purified and nonpurified cross-linked polymers were analyzed, and methods for their elimination and inactivation were developed. Drug release from the highly cross-linked gels could be controlled over more than 12 hr, as the diffusion process in these very dense macromolecular networks is rather slow. The extent of branching and entanglement of the polymeric chains appeared to have an important effect. In addition, the release rate was influenced greatly by the amount and, to a lesser extent, by the type of drug in the network.