SACRECTOMY ASSOCIATED WITH VERTEBRECTOMY: A NEW TECHNIQUE USING DOWEL GRAFTS FROM CADAVERS.
The purpose of this study was to demonstrate, in a case series, a new sacrectomy technique using an iliac crest dowel graft from a cadaver. Report of a case series with description of a new surgical technique. The technique uses four bars to support the posterior spine and a dowel graft in the iliac wings, with compression of the spine and pelvis above it, to support the anterior spine. Three cases were operated on, and in all of them, a vertebrectomy was used. In the first two cases, the technique was performed as a two-stage surgery. The first stage was performed via the anterior and peritoneal access routes, and the second stage via the posterior access route. In the third case, retroperitoneal access via the anterior route meant that the technique could be performed in one stage, resulting in an overall reduction in surgical time (1250 vs. 1750 vs. 990 minutes, respectively). The new technique enables fixation with biomechanical stability, which is essential to support the stress in the lumbosacral transition and promote earlier rehabilitation. Level of evidence IV, case series.


Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with chronic hepatitis B.
Reduction of necroinflammatory activity is a major goal of antiviral therapy of patients with chronic hepatitis B. Serum ALT does not detect all forms of cell death. To analyze dynamics of novel serum cell death markers for apoptosis and necrosis in association with virologic response to nucleos(t)ide (Nuc) analogue treatment. Quantification of the M30-apoptosis neoepitope and the cytokeratin-18 (M65-necrosis) serum levels before and during treatment of patients with chronic hepatitis B with Nuc (n = 26). Before treatment, M30-apoptotic activity was significantly correlated with M65-necrosis and fibrosis but not with serum ALT. During therapy with Nucs, cell death parameters M30-apoptosis, M65-necrosis, and ALT declined in association with virologic response. The most frequent cell death pattern was simultaneous decline of ALT and M30-apoptosis which occurred more frequently in patients with HBs-Antigen decline than in patients with HBs-Antigen increase during treatment (87.5% vs. 40.0%; p = 0.024). ALT decline in association with increase of M30 apoptosis was frequent in patients with HBs-Antigen increase during treatment (36.3%) but was not observed in patients with HBs-Antigen decline during treatment. Decline of cell death parameters in association with decline of HBV-DNA and HBs-Antigen indicates a reduction in overall cell death activity during Nuc treatment supporting the concept that response to Nuc therapy reduces necroinflammatory activity and progression of liver disease.


Biosorbent with superhydrophobicity and superoleophilicity for spilled oil removal.
The development of efficient and sustainable sorbents for emergent oil cleanup has attracted tremendous attention. In this study, the feasibility of enzymatic grafting of octadecylamine (ODA) on corn stalk pith (CSP) by laccase-TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) treatment for enhanced oil-water separation was investigated. The dynamic contact angle tests suggest that the modified CSP (LCSP) had higher hydrophobicity (WCA, 157.2˚) and lipophilicity (OCA, 0˚) than the CSP did. In addition, the introduction of ODA onto the surface of modified CSP was verified by a variety of characterization techniques including SEM, FT-IR, and XPS. Compared with the control, laccase-TEMPO treatment of CSP coupled with octadecylamine grafting greatly improved the oil sorption capacity from 13.24 g/g to 44.25 g/g, while substantially reduced the water sorption capacity from 15.52 g/g to 2.76 g/g. LCSP has fast kinetic (sorption equilibrium reached before 60 min) and high fits to the pseudo-second-order kinetic model. The results obtained in this study reveal the feasibility of using Laccase-TEMPO treatment to graft the ODA onto the surface of CSP, thereby enhancing the rate and capacity of oil separation from oily water. The method and sorbent developed in this study hold promise for green, simple and cost-effective oil cleanup during oil spillage emergency events.


Liquid crystal-on-organic field-effect transistor sensory devices for perceptive sensing of ultralow intensity gas flow touch.
We demonstrate liquid crystal-on-organic field-effect transistor (LC-on-OFET) sensory devices that can perceptively sense ultralow level gas flows. The LC-on-OFET devices were fabricated by mounting LC molecules (4-cyano-4'-pentylbiphenyl - 5CB) on the polymer channel layer of OFET. Results showed that the presence of LC molecules on the channel layer resulted in enhanced drain currents due to a strong dipole effect of LC molecules. Upon applying low intensity nitrogen gas flows, the drain current was sensitively increased depending on the intensity and time of nitrogen flows. The present LC-on-OFET devices could detect extremely low level nitrogen flows (0.7 sccm-11 μl/s), which could not be felt by human skins, thanks to a synergy effect between collective behavior of LC molecules and charge-sensitive channel layer of OFET. The similar sensation was also achieved using the LC-on-OFET devices with a polymer film skin, suggesting viable practical applications of the present LC-on-OFET sensory devices.


Environmental triggers for primary outbreaks of crown-of-thorns starfish on the Great Barrier Reef, Australia.
In this paper, we postulate a unique environmental triggering sequence for primary outbreaks of crown-of-thorns starfish (COTS, Acanthaster planci) on the central Great Barrier Reef (GBR, Australia). Notably, we extend the previous terrestrial runoff hypothesis, viz. nutrient-enriched terrestrial runoff → elevated phytoplankton 'bloom' concentrations → enhanced COTS larval survival, to include the additional importance of strong larvae retention around reefs or within reef groups (clusters) that share enhanced phytoplankton concentrations. For the central GBR, this scenario is shown to occur when El Niño-Southern Oscillation (ENSO) linked hydrodynamic conditions cause the 'regional' larval connectivity network to fragment into smaller 'local' reef clusters due to low ocean current velocities. As inter-annual variations in hydrodynamic circulation patterns are not amenable to direct management intervention, the ability to reduce the future frequency of COTS outbreaks on the central GBR is shown to be contingent on reducing terrestrial bioavailable nutrient loads ~20-40%.


Population-specific genetic variation at microRNA-629-binding site in the 3'-UTR of NBS1 gene in prostate cancer patients.
Prostate cancer is a genomically complex disease and recently emerging scientific evidence is adding new pieces of information into existing pool of knowledge of oncology. Prostate cancer cells tactfully rewire signaling cascades in presence or absence of androgen. We do not have finer proteome and genome based patient related information of our cancer patients. In the present laboratory research, we studied 3' UTR C/T and A/G polymorphism in NBS1 gene in 100 prostate cancer patients and 100 healthy individuals without any previous clinical history, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. For rs13312986 A>G genotypes, AA was 78% in patients and 80% in controls. AG was 21% in patients and 20% in controls. GG was 1% in patients and none was detected in control. Allelic frequencies for A was 0.885% in patients and 0.9% in controls. Allelic frequencies for G were 0.115% in patients and 0.1% in controls. For rs14448 T>C genotypes, TC was 23% in patients and 20% in controls. TT was 77% in patients and 80% in controls. CC was not detected either in patients or controls. T allele was 0.885% in patients and 0.9% in controls. C allele was 0.115% in patients and 0.1%-+ in controls. Future studies must converge on deeper and detailed mechanisms, as miRNA regulation of NBS1 is incompletely studied and exploration of these connections constitutes one of the most exciting areas in clinical oncology.


Inhibitory effects of long-chain alkyltrimethylammonium ions on aggregation of bovine platelets and the relation of their effects to Ca2+ mobilization.
The inhibitory effects of alkyltrimethylammonium ions on ADP- and thrombin-induced aggregation of bovine platelets were investigated. The ammonium cations inhibited the two aggregation reactions to similar extents. The relationship between their inhibitory effects on ADP-induced aggregation and their alkyl chain lengths from C8 to C18 was investigated. Results showed that the inhibitory effects of ammonium cations increased with increase of their alkyl chain lengths up to C16, and that the increase was linear with chain lengths of up to C14. This linear relation and slope of the linear regression line suggested that the inhibitory effects of the ammonium cations depended on their partitioning into the membrane. However, unlike long-chain unsaturated fatty acids, they did not affect the membrane fluidity of the platelets. Fluorescence analysis of fura-2 loaded platelets revealed that, in the concentration range where the alkyltrimethylammonium ions inhibited aggregation, they inhibited agonist-induced increase in cytosolic Ca2+ both in the presence and absence of extracellular Ca2+. These results suggest that inhibition of platelet aggregation by alkyltrimethylammonium ions is mainly due to their inhibition of increase in cytoplasmic Ca2+ by inhibition of both intracellular Ca2+ mobilization and Ca2+ uptake.


Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study.
Contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood-brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0.5 M at a dose of 0.1 mmol/kg bodyweight. Prospective, multicenter, double-blind, crossover trial in patients who underwent unenhanced MRI followed by enhanced imaging with gadobutrol or gadoteridol. Three blinded readers assessed the magnetic resonance images. The primary efficacy variables included number of lesions detected, degree of lesion contrast-enhancement, lesion border delineation, and lesion internal morphology. Of the 402 treated patients, 390 patients received study drugs. Lesion contrast-enhancement, lesion border delineation, and lesion internal morphology were superior for combined unenhanced/gadobutrol-enhanced imaging vs unenhanced imaging (P < 0.0001 for all). Compared with gadoteridol, gadobutrol was non-inferior for all primary variables and superior for lesion contrast-enhancement, as well as sensitivity and accuracy for detection of malignant disease. The percentage of patients with at least one drug-related adverse event was similar for gadobutrol (10.0%) and gadoteridol (9.7%). Gadobutrol is an effective and well-tolerated macrocyclic contrast agent for MRI of the CNS. Gadobutrol demonstrates greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity.


Noninvasive positron emission tomography imaging of cell death using a novel small-molecule probe, (18)F labeled bis(zinc(II)-dipicolylamine) complex.
The synthetic bis(zinc(II)-dipicolylamine) (DPAZn2) coordination complexes are known to have a high specific and selective affinity to target the exposed phosphatidylserine (PS) on the surface of dead and dying cells. An (18)F-labeled DPAZn2 complex (4-(18)F-Fluoro-benzoyl-bis(zinc(II)-dipicolylamine), (18)F-FB-DPAZn2) as positron emission tomography (PET) tracer was developed and evaluated for in vivo imaging of tumor treated with a chemical agent. The in vitro cell stain studies revealed that fluorescent DPAZn2 complexes (Dansyl-DPAZn2) stained the same cells (apoptotic and necrotic cells) as fluorescein isothiocyanate (FITC) labeled Annexin V (FITC-Annexin V). The radiosynthesis of (18)F-FB-DPAZn2 was achieved through the amidation the precursor bis(2,2'-dipicolylamine) derivative (DPA2) with the prosthetic group N-succinimidyl-4-[(18)F]-fluorobenzoate ((18)F-SFB) and chelation with zinc nitrate. In the biodistribution study, the fast clearance of (18)F-FB-DPAZn2 from blood and kidney was observed and high uptake in liver and intestine within 90 min postinjection was also found. For the PET imaging, significantly higher tumor uptake of (18)F-FB-DPAZn2 was observed in the adriamycin (ADM)-treated Hepa1-6 hepatocellular carcinoma-bearing mice than that in the untreated tumor-model mice, while a slightly decreased tumor uptake of (18)F-FDG was found in the ADM-treated tumor-bearing mice. The results indicate that (18)F-FB-DPAZn2 has the similar capability of apoptosis detection as FITC-Annexin V and seems to be a potential PET tracer for noninvasive evaluation and monitoring of anti-tumor chemotherapy. The high uptake of (18)F-FB-DPAZn2 in the abdomen needs to optimize the structure for improving its pharmacokinetics characteristics in the future work.


Peripheral T-cell non-Hodgkin's lymphoma.
T-cell non-Hodgkin's lymphoma (T-NHL) are uncommon malignancies accounting for 10% to 15% of all NHL. Geographic variation has been well documented, but the geographic variation may reflect exposure to specific pathogenic viruses, such as Epstein Barr Virus and Human T-cell leukemia virus-1 in Asian countries. The World Health Organization classification specifies 16 major subtypes of T-NHL. Each of the major subtype of peripheral T-NHL has unique characteristics and are addressed separately in this article.


Microbead-Induced Ocular Hypertension in a Rodent Model of Glaucoma.
Glaucoma is an irreversible blinding disease characterized by the loss of retinal ganglion cells. Development of therapeutics relies on suitable models and, given its complex nature, these are typically in vivo models. A widely used model, owing to its relative simplicity, is the microbead model. This model involves the injections of beads into the anterior chamber, which are suitably sized to block the aqueous outflow pathway, leading to an elevation in intraocular pressure and ultimately, retinal ganglion cell death. In this chapter, we describe in detail the materials and methods for modelling glaucoma using microbeads (both magnetic and nonmagnetic).


Hepatic angiomyolipoma with special attention to radiologic imaging.
Angiomyolipoma is a unique mesenchymal neoplasm composed of blood vessels as well as smooth muscle and adipose cells. The liver is a less common site of origin, and hepatic angiomyolipoma is often an incidental finding on diagnostic imaging or is identified on evaluation of nonspecific symptoms. We experienced four patients who were diagnosed histologically with hepatic angiomyolipoma. The preoperative diagnoses were angiomyolipoma in two patients, hepatocellular carcinoma in one, and cavernous hemangioma in one. Three patients were treated with hepatectomy (one laparoscopic and two open approaches), and the diagnosis was completed by histological investigation of the resected specimen. The remaining one was diagnosed from tumor needle biopsy. Diffusion-weighted magnetic resonance imaging (MRI) with respiratory triggering using b values of 0 and 800 s/mm(2) was employed. An apparent diffusion coefficient map was generated from b values of 0 and 800 s/mm(2) for calculation of the apparent diffusion coefficient. The apparent diffusion coefficient values were calculated as 3.66, 1.21, 1.80, and 0.91 in patients 1 to 4, respectively. In MRI imaging, fat component was clearly demonstrated with chemical shift imaging in three patients. Early venous return was detected in three patients with computed tomography angiography. Fat component and early venous return are important for a correct diagnosis of hepatic angiomyolipoma. Unfortunately, apparent diffusion coefficient values in hepatic angiomyolipoma were overlapping with those in other benign and malignant tumors.


Effectiveness of Intra-Gastric Balloon as a Bridge to Definitive Surgery in the Super Obese.
British National guidelines (NICE) recommend bariatric surgery for patients with a body mass index (BMI) > 40 kg/m2, or BMI > 35 kg/m2 with any comorbidities of the metabolic syndrome. Intra-gastric balloons (IGB) can be used in super obese patients as a first step, before definitive surgery. Quantify weight loss 6 months after IGB placement, measure progression to definitive surgery and identify complications. Data collected retrospectively on 50 patients. Forty-six proposed for definitive bariatric surgery, four patients excluded. Analysis performed using SPSS v23.0. Median weight decreased from 165.5 to 155 kg (range 78 to 212, p < 0.01), BMI from 57.4 to 52.15 (range 32.9 to 70.5, p < 0.01), percentage excess weight loss (%EWL) was 12.9% (range - 3.3 to 64.66%, p < 0.01) and BMI reduction was 4.25 kg/m2 (range - 1.3 to 13.9, p < 0.01). Twenty-nine out of 46 patients (63%) progressed to definitive bariatric surgery. Ten out of 46 patients (21.7%) had complications requiring readmission. Seven of these patients required early balloon removal and six failed to progress to definitive surgery. Six patients had a second balloon placement, their actual weight loss was less successful, with some regaining weight. IGB is useful to aid weight loss prior to definitive bariatric surgery. Results from first balloon placement are encouraging and comparable with other studies "as reported by Genco et al. (Int J of Obes 30:129-133, 2006)." Readmission due to nausea, vomiting, dehydration and poor compliance may be associated with poor weight loss and failure to progress to definitive surgery. Second balloon placements were less successful. IGB as bridging therapy is a safe and useful adjunct. Sequential IGBs do not seem to provide additional benefit.


Genetic analysis of phosphomannomutase/phosphoglucomutase from Vibrio furnissii and characterization of its role in virulence.
The pmm gene from Vibrio furnissii, which encodes phosphomannomutase (PMM), was cloned and sequenced. The open reading frame consisted of 1,434 bp, encoding a polypeptide of 477 amino acids with a molecular mass of 53,325 Da. The predicted amino acid sequence of V. furnissii PMM showed high similarity with PMMs from other enteric bacteria, such as V. cholerae, Salmonella sp. and Escherichia coli. The PMM protein was overexpressed in E. coli as a His(6)-tagged recombinant protein. The estimated apparent K(m )and k(cat) values of the purified recombinant protein for mannose 1-phosphate were about 60 microM and 800 min(-1), respectively. To investigate the biochemical functions and the role of pmm in the virulence of V. furnissii, a pmm knock-out mutant was constructed by homologous recombination mutation. Under the various physical conditions, cell numbers of the wild-type and the mutant did not differ. Oral introduction of bacterial suspensions to a mouse model showed that the pmm-deficient mutant decreased in viability at the intestine. Microscopy of the isolated intestines from mice revealed significant damage after 3 days in intestinal mucosa infected with the wild-type as compared with the mutant. The pmm-deficient mutant caused a reduction of virulence in mice and the loss of O-antigen polysaccharide, and showed low resistance relative to the wild-type when incubated with normal human serum.


Increased sensitivity for detection of human cytomegalovirus in urine by removal of inhibitors for the polymerase chain reaction.
The presence of inhibitors in urine interferes with the enzymatic reaction of the polymerase chain reaction (PCR) for detection of human cytomegalovirus (HCMV). To remove inhibitors, HCMV virions in urine were precipitated with polyethylene glycol, or DNA was extracted from urine by the use of glass powder and subjected to PCR followed by Southern blot hybridization with alkaline phosphatase-linked oligonucleotide probes. These simple, rapid methods increased significantly the sensitivity of PCR for detection of HCMV in urine.


Climate change and waterborne diarrhoea in northern India: impacts and adaptation strategies.
Although several studies show the vulnerability of human health to climate change, a clear comprehensive quantification of the increased health risks attributable to climate change is lacking. Even more complicated are assessments of adaptation measures for this sector. We discuss the impact of climate change on diarrhoea as a representative of a waterborne infectious disease affecting human health in the Ganges basin of northern India. A conceptual framework is presented for climate exposure response relationships based on studies from different countries, as empirical studies and appropriate epidemiological data sets for India are lacking. Four climate variables are included: temperature, increased/extreme precipitation, decreased precipitation/droughts and relative humidity. Applying the conceptual framework to the latest regional climate projections for northern India shows increases between present and future (2040s), varying spatially from no change to an increase of 21% in diarrhoea incidences, with 13.1% increase on average for the Ganges basin. We discuss three types of measures against diarrhoeal disease: reactive actions, preventive actions and national policy options. Preventive actions have the potential to counterbalance this expected increase. However, given the limited progress in reducing incidences over the past decade consorted actions and effective implementation and integration of existing policies are needed.


Lead levels in retail samples of Spanish infant formulae and their contribution to dietary intake of infants.
Lead concentrations in 82 different types of infant formulae (cow's milk and soy based) marked in Spain were analysed by acid-microwave decomposition and anodic stripping voltammetry. Dietary lead intake from infant formula and tap water used for powder formula reconstitution were estimated in comparison with the provisional tolerable weekly intake (PTWI). Additionally, the influence of physical state (powder and ready-to-use formulae), the type of container used and the impact of the industrial process from different manufacturers on lead levels were evaluated. According to the results, lead exposure from drinking water was negligible with respect to formulae investigated; where soya formulae contributed the highest intake (58-73% PTWI), non-adapted starter and specialized formulae gave an moderate intake (31-42 and 26-37% PTWI, respectively), and, finally, pre-term, adapted starter and follow-up formulae provided the lowest lead intake (22-25, 22-26 and 16-22% PTWI, respectively). Based on the current state of knowledge about lead toxicity, manufacturers are called to make an additional effort in order to keep a maximum lead level at 20 microg l-1 for all infant formulae, although it is recommendable that these formulations supply the upper limit (5 microg l-1) of 'normal' human milk.


Iron regulatory factor--the conductor of cellular iron regulation.
All cells have to adjust uptake, utilization and storage of iron according to the availability and their requirement for this essential metal. Progress in recent years has led to the elucidation of the molecular control mechanisms that co-ordinate the uptake, utilization and storage of iron in mammalian cells and has highlighted the role of a newly-identified regulatory protein, the iron regulatory factor (IRF). IRF is a cytoplasmic protein that senses the intracellular iron level and responds by adjusting its function. When the iron level is low, it binds to so-called 'iron responsive elements' (IREs) contained in the mRNAs encoding proteins involved in iron metabolism and erythroid haem synthesis. When levels of cellular iron rise, IRF converts into the enzyme aconitase and looses its ability to bind to IREs. We discuss both functions of this Janus face protein and describe how its function is controlled by the status of an iron sulphur cluster in the IRF protein. We also speculate about how an IRF-mediated regulation may relate to certain medical disorders.


Effect of sumatriptan, a selective 5-HT1-like receptor agonist, on pial vessel diameter in anaesthetised cats.
The action of sumatriptan, a selective 5-HT1-like receptor agonist that is effective for the acute treatment of migraine, was compared on pial vessel diameter following perivascular or intravenous administration to anaesthetised cats. Sumatriptan (0.01-10 microM), when microinjected perivascularly, caused a decrease in pial artery diameter (maximum change of -19 +/- 9%; mean +/- SD) but had no effect on the diameter of pial veins. Sumatriptan (1 microM)-induced pial artery vasoconstriction was unaffected by coadministration of ketanserin (1 microM) or ondansetron (1 microM) but was significantly (p less than 0.01) attenuated by methiothepin (1 microM). Intravenous infusion of a clinically effective dose of sumatriptan (64 micrograms/kg/10 min) caused selective carotid vasoconstriction (22 +/- 6% increase in carotid vascular resistance with little or no change in blood pressure or heart rate) and no change in pial artery diameter, although sumatriptan (1 microM) administered perivascularly in these animals before and after the infusion caused pial artery vasoconstriction. These results demonstrate that perivascularly administered sumatriptan causes pial artery vasoconstriction via activation of 5-HT1-like receptors. However, intravenously administered sumatriptan does not cause pial artery vasoconstriction, which suggests that sumatriptan does not readily penetrate the cerebrovascular intima.


Negative cone biopsies after colposcopy and their prediction.
A retrospective study of 899 cone biopsies revealed significantly more cones containing no dysplastic epithelium in patients who had a prior colposcopic assessment compared with those who had not been so assessed. A case-control study of 48 'negative' cones, 47 cones containing intraepithelial neoplasia (CIN), 44 microcarcinoma containing cones and 27 occult Ib containing cones has allowed five variables to be identified which can predict the presence of dysplastic or neoplastic tissue in the cone specimen. These variables include a colposcopic suspicion of invasion; a positive or worse pre-cone smear; two severely dyskaryotic smears within a 12-month observation period, previous abnormal histology and previous treatment for CIN. Using these criteria, 44% of 'negative' cones could be avoided without overlooking any cases of microcarcinoma or occult carcinoma.


Impaired long-term T cell immunity to Epstein-Barr virus in patients with nasopharyngeal carcinoma.
The long-term T cell immunity to Epstein-Barr virus (EBV) is considered to play an important role in suppressing proliferation of EBV-infected B cells and outgrowth of EBV-associated tumors. It can be manifested and quantified by the EBV-induced focus regression assay. In the present study, we examined the strength of T cell immunity to EBV in patients with nasopharyngeal carcinoma (NPC) and other cancers originating from the head and neck region. In contrast to patients with other types of cancers, including EBV-negative NPC, patients with EBV-positive NPC were found to have a profound impairment in the long-term T cell immunity to EBV.


Ileosigmoid knotting: A case report of unique cause of acute abdomen in a Nepalese patient.
Ileosigmoid knotting is a surgical emergency. Common in Asian males, it is presented with signs and symptoms of diffuse peritonitis. Aggressive resuscitation with intravenous fluids and antibiotics followed by workup enable the patient hemodynamically stable. Explorative laparotomy followed by colo-colic anastomosis and double barrel ileostomy is curative. A 32-year-old-male from Nepal with a chief complain of diffuse abdominal pain for a day and signs of peritonitis presented to Emergency room. After assessing and stabilizing the patient, explorative laparotomy was performed. Ileal and sigmoid resection followed by colo-colic anastomosis and double barrel ileostomy was done. On regular follow-up, he is in his usual state of health. The incidence of ileosigmoid knotting is reported to be about 1.6 cases per year. It is often misdiagnosed as non-specific intestinal obstruction which confers poor prognostic value to the patient. It should be identified promptly and intervened timely. Ileosigmoid knotting is a rare but dangerous differential of acute abdomen not to be missed. Early assessment and quick decision making is the key to provide excellent prognosis to the patient in need, provided adequate surgical skills are demonstrated.


Mapping Transcription Regulatory Networks with ChIP-seq and RNA-seq.
Bacterial genomes encode numerous transcription factors, DNA-binding proteins that regulate transcription initiation. Identifying the regulatory targets of transcription factors is a major challenge of systems biology. Here I describe the use of two genome-scale approaches, ChIP-seq and RNA-seq, that are used to map transcription factor regulons. ChIP-seq maps the association of transcription factors with DNA, and RNA-seq determines changes in RNA levels associated with transcription factor perturbation. I discuss the strengths and weaknesses of these and related approaches, and I describe how ChIP-seq and RNA-seq can be combined to map individual transcription factor regulons and entire regulatory networks.


[Corneal endothelium variants in the area of corneal changes].
Contact specular microscopy of the corneal endothelium and subsequent image analysis permit investigations of corneal endothelium reactions after circumscribed corneal damage. The extent and development of an endothelial process can thus be estimated.


Investigation of Brain Functional Networks in Children Suffering from Attention Deficit Hyperactivity Disorder.
ADHD defects the recognition of facial emotions. This study assesses the neurophysiological differences between children with ADHD and matched healthy controls during a face emotional recognition task. The study also explores how brain connectivity is affected by ADHD. Electroencephalogram (EEG) signals were recorded from 64 scalp electrodes. Event-related phase coherence (ERPCOH) method was applied to pre-processed signals, and functional connectivity between any pair of electrodes was computed in different frequency bands. A logistic regression (LR) classifier with elastic net regularization (ENR) was trained to classify ADHD and HC participants using the functional connectivity of frequency bands as a potential biomarker. Subsequently, the brain network is constructed using graph-theoretic techniques, and graph indices such as clustering coefficient (C) and shortest path length (L) were calculated. Significant intra-hemispheric and the inter-hemispheric discrepancy between ADHD and healthy control (HC) groups in the beta band was observed. The graph features indicate that the clustering coefficient is significantly higher in the ADHD group than that in the HC group. At the same time, the shortest path length is significantly lower in the beta band. ADHD's brain networks have a problem in transferring information among various neural regions, which can cause a deficiency in the processing of facial emotions. The beta band seems better to reflect the differences between ADHD and HC. The observed functional connectivity and graph differences could also be helpful in ADHD investigations.


Psychiatric nursing education: doing the impossible?
Historically, psychiatric nursing has struggled to attract sufficient numbers of graduates of comprehensive nursing programs. Limited available research suggests that psychiatric-nursing education can produce more positive attitudes towards psychiatric-nursing practice and the care of the mentally ill. This article describes the results of a research project undertaken in Victoria, Australia, to extend existing knowledge by determining the impact of education in augmenting interest in psychiatric nursing as a future career option. The results of this quasi-experimental study suggest education can significantly increase the popularity of psychiatric nursing as a profession.


Protection against COVID-19 hospitalisation conferred by primary-series vaccination with AZD1222 in non-boosted individuals: first vaccine effectiveness results of the European COVIDRIVE study and meta-regression analysis.
Vaccine effectiveness (VE) studies with long-term follow-up are needed to understand durability of protection against severe COVID-19 outcomes conferred by primary-series vaccination in individuals not receiving boosters. COVIDRIVE is a European public-private partnership evaluating brand-specific vaccine effectiveness (VE). We report a prespecified interim analysis of primary-series AZD1222 (ChAdOx1 nCoV-19) VE. Seven Study Contributors in Europe collected data on individuals aged ≥18 years who were hospitalised with severe acute respiratory infection (June 1st, 2021-September 5th, 2022) and eligible for COVID-19 vaccination prior to hospitalisation. In this test-negative case-control study, individuals were defined as test-positive cases or test-negative controls (SARS-CoV-2 RT-PCR) and were either fully vaccinated (two AZD1222 doses, 4-12 weeks apart, completed ≥14 days prior to symptom onset; no booster doses) or unvaccinated (no COVID-19 vaccine prior to hospitalisation). The primary objective was to estimate AZD1222 VE against COVID-19 hospitalisation. A literature review and meta-regression were conducted to contextualise findings on durability of protection. 761 individuals were included during the 15-month analysis period. Overall AZD1222 VE estimate was 72.8% (95% CI, 53.4-84.1). VE was 93.8% (48.6-99.3) in participants who received second AZD1222 doses ≤8 weeks prior to hospitalisation, with spline-based VE estimates demonstrating protection (VE ≥ 50%) 30 weeks post-second dose. Meta-regression analysis (data from seven publications) showed consistent results, with ≥80% protection against COVID-19 hospitalisation through ∼43 weeks post-second dose, with some degree of waning. Primary-series AZD1222 vaccination confers protection against COVID-19 hospitalisation with enduring levels of VE through ≥6 months. AstraZeneca.


CoCoView - A codon conservation viewer via sequence logos.
Sequence logos are a simple way to display a set of aligned sequences, and they are useful to identify conserved patterns. Since their introduction, several tools have been developed for generating these representations at the single residue level (amino acids or nucleotides). We have developed a tool to build sequence logos of protein-coding sequences at the codon level, allowing more accurate analysis of coding-sequences as they represent synonymous and non-synonymous changes instead of showing only changes that imply on amino acid substitutions. We built CoCoView on top of the Logomaker Python API. It creates codon sequence logos from a multiple sequence alignment of protein-coding sequences. Some properties of the data and the generated logos can be controlled by the end-users, such as data redundancy, plot type and alphabet color. • Split aligned sequences into codon positions; • For each position compute codon frequency and information content; • Use the computed information to plot the graphic.


Flagella from F18+Escherichia coli play a role in adhesion to pig epithelial cell lines.
F18 fimbriae and toxins produced by F18 fimbriae-carrying Escherichia coli (E. coli) strains are known virulence factors responsible for post-weaning diarrhea (PWD) and edema disease (ED). In this study, we showed that fliC isogenic mutants constructed in two reference wild-type F18 fimbriae (F18+) E. coli were markedly impaired in adherence in vitro cell models (p < 0.05). Flagella purified from F18+E. coli could directly bind to cultured piglet epithelial cells and block adherence of F18+E. coli to cells when pre-incubated. In addition, the F18+E. coli fliC deletion mutants up-regulated the expression of type I fimbriae produced by F18+E. coli strains. These results demonstrated that expression of flagella is essential for the adherence of F18+E. coli in vitro.


Optimized gamma radiation produces physiological and morphological changes that improve seed yield in wheat.
To study the effect of gamma radiation on various morphological and agronomic characters of bread wheat (Triticum aestivum L.), seeds were subjected to different gamma radiation doses; and selected M5 and M6 generation lines were evaluated. The optimum doses to induce desirable changes in bread wheat were 100-200 Gy. Seed loss decreased while grain yield, yield components, fertile florets number, biological yield, plant height, harvest index and flag leaf area increased in all mutant lines. Shear strength increased in many lines. Selected mutant lines also showed reduced seed shattering that can greatly reduce seed loss at harvest. Some new phenotypic characters such as the appearance of bristles on the glume, important for drought tolerance, two spikelets at each rachis and more fertile florets at each spikelet. These can greatly increase yield, as seen in some mutant lines. Also, some physiological characteristics including photosynthetic rate, stomatal conductance, water use efficiency, and chlorophyll content improved in some mutant lines. About 95.8% of the total variation in grain yield was explained by three selected variables: flag leaf area, number of seeds per spike, and spike number per plant. Grain yield increased more than 45% in some mutant lines the highest ever reported using this approach to the genetic improvement of wheat. Wheat grain yield has increased 2.2 times in the last 50 years, which indicates that if mutagens are optimally used and the selection is carefully performed as described herein, it is possible to improve important economic traits, in a much shorter time. The online version contains supplementary material available at 10.1007/s12298-022-01225-0.


High-speed ion-exclusion chromatography of dissolved carbon dioxide on a small weakly acidic cation-exchange resin column with ion-exchange enhancement columns of conductivity detection.
The high-speed ion-exclusion chromatographic determination of dissolved carbon dioxide, i.e., carbonic acid, hydrogencarbonate or carbonate, with conductivity detection was obtained using a small column packed with a weakly acidic cation-exchange resin in the H+-form (40 mm long x 4.6 mm i.d., 3 microm-particle and 0.1 meq./ml-capacity). Two different ion-exchange resin columns, which were a strongly acidic cation-exchange resin in the K+-form and a strongly basic anion-exchange resin in the OH- -form, were connected after the separation column. The sequence of columns could convert dissolved carbon dioxide to KOH having high conductivity response. The enhancement effect for dissolved carbon dioxide could retain even on the vast chromatographic runs, by using the enhancement columns with high ion-exchange capacity above 1.0 meq./ml. The retention time was in 60 s at flow-rate of 1.2 ml/min. The calibration graph of dissolved carbon dioxide estimated as H2CO3- was linear in the range of 0.005-10 mM. The detection limit at signal to noise of 3 was 0.15 microM as H2CO3-. This method was applicable to several rainwater and tap water samples.


Chronic blockade of endothelin ETA receptors improves flow dependent dilation in resistance arteries of hypertensive rats.
Flow (shear stress)-induced dilation (FD) is attenuated in hypertension. Flow triggers the release by endothelial cells of dilators, such as NO or cyclo-oxygenase (COX) derivatives and constrictor factors such as endothelin-1 (ET-1) which might be involved in several cardiovascular diseases. We hypothesized that ET-1 might play a functional role in FD and participate in the endothelial dysfunction in hypertension. We investigated the effect of chronic treatment with the ETA receptor blocker LU135252 (50 mg/kg/day) for 2 weeks on the dilator response to flow in normotensive (Wistar-Kyoto; WKY) or hypertensive (SHR, n = 7 or 8 per group) rats. Systolic arterial pressure was not significantly affected by chronic ETA receptor blockade in both strains. In mesenteric resistance arteries (diameter: approximately 100 microns), isolated in vitro, FD was lower and myogenic tone higher in SHR than in WKY rats. Chronic ETA receptor blockade increased FD by 73% (7.5 +/- 1.5 to 13.0 +/- 2.7 microns dilation with a flow-rate of 150 microliters/min) in SHR (no effect in WKY). The participation of NO to FD was increased in SHR and the participation of dilator COX product(s) (blocked by indomethacin 10 mumol/l) to FD was significantly increased in SHR and in WKY. In control rats FD was improved by acute ETA receptor blockade in WKY rats (18.5 +/- 2.0 to 23.2 +/- 1.8 microns dilation to flow-rate of 150 microliters/min) and significantly more in SHR (6.0 +/- 1.8 to 15.1 +/- 1.6 microns). Acetylcholine-induced dilation was also improved by chronic ETA receptor blockade (no effect of an acute blockade). Myogenic and phenylephrine-induced tone were not affected by chronic or acute ETA receptor blockade. The improvement of endothelium-dependent dilation was not related to a change in blood pressure. Chronic ETA receptor blockade increased flow-induced dilation in SHR possibly by suppressing flow-induced ETA stimulation and by improving the release of dilator products by the endothelium.


Targeting Cell Cycle Checkpoint Kinases to Overcome Intrinsic Radioresistance in Brain Tumor Cells.
Radiation therapy is an important part of the standard of care treatment of brain tumors. However, the efficacy of radiation therapy is limited by the radioresistance of tumor cells, a phenomenon held responsible for the dismal prognosis of the most aggressive brain tumor types. A promising approach to radiosensitization of tumors is the inhibition of cell cycle checkpoint control responsible for cell cycle progression and the maintenance of genomic integrity. Inhibition of the kinases involved in these control mechanisms can abolish cell cycle checkpoints and DNA damage repair and thus increase the sensitivity of tumor cells to radiation and chemotherapy. Here, we discuss preclinical progress in molecular targeting of ATM, ATR, CHK1, CHK2, and WEE1, checkpoint kinases in the treatment of brain tumors, and review current clinical phase I-II trials.


Lymphocyte and granulocyte function in nutritionally depleted patients. The effect of 2 weeks of total parenteral nutrition.
Parenteral nutrition has been reported to restore impaired immune function in nutritionally depleted patients. Lymphocyte and granulocyte function were studied before and after 2 weeks of total parenteral nutrition (TPN) in 9 depleted patients, 5 with gastrointestinal cancer and 4 with benign gastrointestinal disorders. The ability of purified blood lymphocytes to incorporate (14)C-labelled thymidine spontaneously and following mitogenic and antigenic stimulation was studied. Before TPN spontaneous lymphocyte activity was significantly increased and mitogen and antigen responsiveness significantly decreased in comparison to healthy controls. These abnormalities were more pronounced in patients with malignant disorders while the remaining patients showed a moderate impairment. No improvement in lymphocyte capacity was observed following 2 weeks of TPN. Granulocyte function measured as chemotaxis, phagocytosis, NBT-reduction and bactericidal capacity did not differ significantly between patients and controls and no changes were seen following nutritional treatment. These findings support the concept that the underlying disease and/or other factors rather than the secondary nutritional depletion are the main reasons for immune impairment. Furthermore, no immunomodulating effects of lipid emulsions on lymphocyte and granulocyte function, under these experimental conditions, were apparent.


Biosorption of dicloxacillin from pharmaceutical waste water using tannin from Indian almond leaf: Kinetic and equilibrium studies.
This study focused on the use of Indian almond leaf biomass, a local plant widely found in Thailand, on removal of dicloxacillin from pharmaceutical waste water by biosorption. The biosorption characteristics of dicloxacillin were investigated in terms of equilibrium, kinetics and thermodynamics. Optimum biosorption conditions were determined from pH, initial dicloxacillin concentration, biomass dosage, contact time, and temperature. The maximum adsorption capacity was 86.93 % (pH 6.0, 0.1 g/L biomass, dicloxacillin concentration 20 mg/L, contact time 24 h, temperature 283.15 K). The thermodynamic parameters (298.15 K), free energy change, enthalpy change and entropy change were -3475.79 J/mol, -25.36 kJ/mol, and -73.40 J/mol/K, respectively. The best interpretation for the experimental data was given by the Langmuir isotherm with correlation coefficient of 0.965. The results were found to tie in well with pseudo-second-order kinetics. Considering the cost-effectiveness, Indian almond leaf biomass is considered to be suitable to remove dicloxacillin from pharmaceutical waste water.


Intraoperative dural irradiation by customized 192iridium and 90yttrium brachytherapy plaques.
After vertebral or paravertebral tumor resection, tumor cells may remain on the dura. Because a tumoricidal dose is difficult to achieve using external beam radiotherapy without exceeding the spinal cord tolerance, we developed intraoperative applicators to deliver additional dose to the dura. Eight patients with vertebral or paravertebral tumor underwent conformal external beam radiotherapy, tumor resection, and intraoperative radiotherapy to the dura involved by tumor. At surgery, vertebra, soft tissue, and epidural tumor were resected. A radioactive applicator plaque was placed on the dura to deliver 7.5-15 Gy, and then removed. Vertebral reconstruction and stabilization was completed. Chemotherapy was administered for large, high-grade sarcomas. We progressed through three plaque designs, initially (192)Ir, subsequently liquid (90)Y, and finally (90)Y foil in a semicylindrical polycarbonate plaque, in the treatment of 8 patients. The low-energy (90)Y beta-emissions provided a more attractive depth dose profile than that achievable with iridium and gave negligible staff radiation exposure. The (90)Y depth dose measured 29% at 2 mm and 9% at 4 mm from the surface of the foil plaque, with acceptable surface dose homogeneity. The average surface dose rate ranged from 18.7 to 47.6 cGy/min for the iridium plaques and 45.2 to 187.5 cGy/min for the (90)Y plaques. The treatments have been without acute or late neurologic complications. The disease of 6 of 8 patients was locally controlled at median potential follow-up of 24 months. The (90)Y foil applicator is technically elegant, easy to use, and superior to the earlier models. It has been incorporated into a protocol for spinal tumor treatment.


The Effects of Mechanical and Thermal Stimuli on Local Field Potentials and Single Unit Activity in Parkinson's Disease Patients.
Chronic pain is a major, debilitating symptom of Parkinson's disease (PD). Although, deep brain stimulation (DBS) has been shown to improve pain outcomes, the mechanisms underlying this phenomenon are unclear. Microelectrode recording allows us to measure both local field potentials (LFPs) and single neuronal unit activity (SUA). In this study, we examined how single unit and LFP oscillatory activity in the basal ganglia are impacted by mechanical and thermal sensory stimuli and explored their role in pain modulation. We assessed changes in LFPs and SUAs in the subthalamic nucleus (STN), globus pallidus interna (Gpi), and globus pallidus externa (Gpe) following exposure with mechanical or thermal stimuli. Sensory thresholds were determined pre-operatively using quantitative sensory testing. Based on these data, patients were exposed to innocuous and noxious mechanical, pressure, and thermal stimuli at individualized thresholds. In the STN, LFP alpha oscillatory activity and SUA increased in response to innocuous mechanical stimuli; SUA further increased in response to noxious mechanical, noxious pressure, and noxious thermal stimuli (p < 0.05). In the Gpe, LFP low betaactivity and SUA increased with noxious thermal stimuli; SUA also increased in response to innocuous thermal stimuli (p < 0.05). In the Gpi, innocuous thermal stimuli increased LFP gammaactivity; noxious pressure stimuli decreased low betaactivity; SUA increased in response to noxious thermal stimuli (p < 0.05). Our study is the first to demonstrate that mechanical and thermal stimuli alter basal ganglia LFPs and SUAs in PD. While STN SUA increases nearly uniformly to all sensory stimuli, SUA in the pallidal nuclei respond solely to thermal stimuli. Similarly, thermal stimuli yield increases in pallidal LFP activity, but not STN activity. We speculate that DBS may provide analgesia through suppression of stimuli-specific changes in basal ganglia activity, supporting a role for these nuclei in sensory and pain processing circuits.


Characteristics of undetected prostate cancer on diffusion-weighted MR Imaging at 3-Tesla with a b-value of 2000s/mm(2): Imaging-pathologic correlation.
To assess the accuracy of Diffusion-Weighted MR Imaging (DW-MRI) at 3-Teslas (3T) with a b-value of 2000s/mm(2) (b-2000 DW-MRI) to detect prostate cancer (PCa) and to describe the histological features of missed tumors. Prior to radical prostatectomy, 35 patients with a mean age of 64±6.2years old [51-77years old] had a b-2000 DW-MRI at 3-T, without rectal coil (acquisition time: 2min, 15s), and were analysed on an eight-sector basis by two independent readers blinded to the rest of the multiparametric-MRI protocol. Pathological tumor foci were matched with high intensity focal areas on MRI and correlated for Gleason score, sector location and largest axial diameter. Of the 280 sectors analysed, histology showed PCa in 113 (113/280, 40%). Overall DW-MRI sensitivity, specificity and accuracy for tumor detection were 79-81%, 99-95% and 92-82% for readers 1 and 2, respectively (kappa test: 0.78). Of all, 28 (28/113, 25%) and 22 (22/113, 20%) tumor foci were not detected by reader 1 and 2 respectively. These undetected tumor foci had a mean pathological axial axis of 5mm (range: 3-15mm) and a Gleason score of 6, 7 (3+4), 7 (4+3) and>7 in 15/28 (54%), 9/28 (32%), 3/28 (10%) and 1/28 (4%) of cases for reader 1, and in 11 (50%), 5 (23%), 5 (23%) and 1 (4%) of cases for reader 2. A normal b-2000 DW-MRI at 3-T may miss small tumors without or with a minor Gleason 4 component.


Experimental study of selective MGMT peptides mimicking TMZ drug resistance in glioma.
Glioblastoma (GBM) is a very frequent primary tumour in the cerebrospinal nervous system. Temozolomide (TMZ) is the first-line treatment for patients with GBM. However, some of GBM patients do not respond to TMZ. O6-methylguanine-DNA-methytransferase (MGMT) remains a major cause. In a previous study, we detected antibodies against MGMT peptides in patients with glioma, and five highly responsive autoantibodies anti-MGMT-02, anti-MGMT-04, anti-MGMT-07, anti-MGMT-10, and anti-MGMT-18 were identified that could be used to dynamically assess chemotherapy-resistant TMZ. Therefore, targeting MGMT peptides may be a potential therapeutic approach for GBM to fight TMZ resistance. First, MGMT-02 and MGMT-04 polypeptides with cell-penetrating peptides were designed and connected to FITC tracer for immunofluorescence localisation. CCK-8 and colony formation assay were performed to evaluate cell proliferation ability. Western blot and immunofluorescence analysis were used to detected the expression of apoptosis-related protein. Flow cytometry was used to detect the proportion of apoptosis in cells. TMZ-resistant effect of MGMT-02/04 peptides was assessed in intracranial xenograft nude mouse model. We also found reduced apoptosis of cells treated with MGMT-02 and MGMT-04 peptides and TMZ compared with those treated separately with TMZ in vivo and in vitro experiences. The results of this study indicate that MGMT-02 and MGMT-04 peptides have a role in glioma resistance and that MGMT peptides may serve as a precise target for TMZ-resistant GBM.


Patient-adapted respiratory training: Effect on navigator-triggered 3D MRCP in painful pancreatobiliary disorders.
To compare the image quality of navigator-triggered (NT) 3D MR cholangiopancreatography (MRCP) with and without a patient-adapted respiratory training, in clinical patients with painful pancreatobiliary disorders. With institutional review board approval, hospitalized patients with painful pancreatobiliary disorders who were scheduled for MRCP study were prospectively enrolled. The numerical rating scale (NRS) of abdominal pain during the examination was recorded. Special patient-adapted respiratory training was conducted before the examination. A control group of patients was enrolled with the same criteria, who received ordinary instructions only (n=60 for each group). A subgroup of patients (n=10) underwent MRCP studies with ordinary instructions first and with patient-adapted training later. Acquisition time was recorded. General image quality, degree of artifacts and visualization of 12 segments of the pancreatobiliary tree were rated on a five-point scale and compared between the groups. Both groups had similar NRS of pain. There was a significant improvement in image quality (p<0.01) as well as visualization of right posterior hepatic duct (p=0.045), left lateral hepatic duct (p=0.037), and pancreatic duct (p<0.01 for head, body and tail segments) in patients receiving respiratory training. The other segments showed no significant differences. The percentage of patients with severe and extensive imaging artifacts decreased from 18.3%(11/60) to 8.3%(5/60). The acquisition time was shorter (175±54s vs 249±67s, p<0.01) in patients with respiratory training. Patient-adapted respiratory training improves the image quality of NT-MRCP in patients with painful pancreatobiliary disorders.


A review of the evidence from comparative studies of levocetirizine and desloratadine for the symptoms of allergic rhinitis.
Levocetirizine and desloratadine are newer antihistamines indicated for the treatment of allergic rhinitis and chronic idiopathic urticaria. This article discusses the pharmacokinetics and pharmacodynamics of levocetirizine and desloratadine and reviews studies that have directly compared the effects of these 2 drugs in allergic rhinitis and urticaria. Relevant articles were identified through a search of MEDLINE from 1999 through 2004 using the main search terms levocetirizine and desloratadine. Levocetirizine is absorbed rapidly and reaches a steady-state plasma concentration more quickly than does desloratadine. It is also metabolized to a lesser extent than desloratadine, has a lower V(d), and has higher specificity for histamine(1) receptors. Eight well-controlled trials were identified that directly compared the effects of levocetirizine and desloratadine in the skin and nose of healthy individuals and patients with allergic rhinitis. Drug activity was measured in terms of wheal, flare, and itch reactions; nasal symptoms or symptom scores; increases in concentrations of inflammatory markers; or facial thermography. In most of these trials, levocetirizine had a faster onset and greater consistency of effect than desloratadine. The differences in the pharmacokinetic and pharmacodynamic profiles of the 2 drugs may partially explain these clinical findings. Levocetirizine may be preferred to desloratadine as a treatment option for allergic rhinitis because of its faster onset of action and greater consistency of effect. Although comparative studies in chronic idiopathic urticaria are not available, data from histamine-induced wheal and flare studies in healthy volunteers suggest that levocetirizine may be more effective in preventing itching than desloratadine.


Screening the Sargasso Sea metagenome for data to investigate genome evolution in Ostreococcus (Prasinophyceae, Chlorophyta).
The Sargasso Sea water shotgun sequencing unveiled an unprecedented glimpse of marine prokaryotic diversity and gene content. The sequence data was gathered from 0.8 microm filtered surface water extracts, and revealed picoeukaryotic (cell size<2 microm) sequences alongside the prokaryotic data. We used the available genome sequence of the picoeukaryote Ostreococcus tauri (Prasinophyceae, Chlorophyta) as a benchmark for the eukaryotic sequence content of the Sargasso Sea metagenome. Sequence data from at least two new Ostreococcus strains were identified and analyzed, and showed a bias towards higher coverage of the AT-rich organellar genomes. The Ostreococcus nuclear sequence data retrieved from the Sargasso metagenome is divided onto 731 scaffolds of average size 3917 bp, and covers 23% of the complete nuclear genome and 14% of the total number of protein coding genes in O. tauri. We used this environmental Ostreococcus sequence data to estimate the level of constraint on intronic and intergenic sequences in this compact genome.


The Escherichia coli QseB/QseC signaling is required for correct timing of replication initiation and cell motility.
The Escherichia coli QseB/QseC signaling regulates expressions of more than 50 genes encoding flagellar proteins and proteins associated with virulence. Here we found that absence of the QseB/QseC signaling led to an early initiation of chromosomal replication and higher concentration of DnaA which is initiator for replication. The upstream region of dnaA promoter contains three potential QseB binding sites and absence of these binding sites increased transcription of the dnaA gene in wild-type cells but not in the cells lacking the qseB/qseC genes, showing that the QseB/QseC signaling regulates dnaA expression through the QseB binding sites. Also increased cell motility but neither cell size nor growth rate in ΔqseBC and ΔqseB cells was observed and these effects were reversed by ectopic expression of QseBC. Further, it was found that QseB interacted with the DnaK chaperone and FtsZ cell division protein in vivo, and absence of DnaK or partial inactivation of FtsZ decreased cell motility. Thus, we conclude that the QseB/QseC signaling modulates timing of replication initiation by regulating expression of DnaA, coordinates cell motility with cell division through interacting with the DnaK and FtsZ protein.


Correction: Tbx18 Regulates the Differentiation of Periductal Smooth Muscle Stroma and the Maintenance of Epithelial Integrity in the Prostate.
[This corrects the article DOI: 10.1371/journal.pone.0154413.].


Acute administration of antibiotics modulates intestinal capillary perfusion and leukocyte adherence during experimental sepsis.
Antibiotic treatment represents a mainstay of therapy for clinical sepsis. Distinct from their antimicrobial effects, antibiotics may impact the inflammatory process in sepsis, e.g. within the intestinal microcirculation. The impact of seven antibiotics relevant to clinical sepsis on intestinal leukocyte recruitment and capillary perfusion was studied in rats with colon ascendens stent peritonitis (CASP)-induced sepsis or after endotoxin [lipopolysaccharide (LPS)] challenge. The following antibiotics were included: daptomycin; erythromycin; imipenem; linezolid; tigecycline; tobramycin; and vancomycin. The number of rolling and adherent leukocytes in intestinal submucosal venules and the functional capillary density (FCD) in three layers of the intestinal wall were assessed using intravital microscopy. CASP-induced sepsis reduces the intestinal FCD by 30-50%. Single administration of daptomycin, tigecycline or linezolid increased the intestinal FCD. CASP sepsis increased the number of rolling leukocytes by 4.5-fold, which was reduced by erythromycin but increased by vancomycin. The number of adherent leukocytes increased 3-fold in rats with CASP sepsis. It was reduced following administration of daptomycin, tigecycline (in V1 and V3 venules), erythromycin and linezolid (in V1 venules). However, following tobramycin and vancomycin, leukocyte adhesion was further enhanced. Administration of tigecycline and linezolid reduced the LPS-induced increase in the number of adherent leukocytes by 50%. However, imipenem did not affect leukocyte adherence. In conclusion, this work highlights the beneficial impact of the antibiotics daptomycin, tigecycline, erythromycin and linezolid in that they improve intestinal capillary perfusion and/or reduce leukocyte recruitment, whilst the antibiotics imipenem, tobramycin and vancomycin do not exert these properties.


Continuous abdominal fascial closure: a randomized controlled trial of poly(L-lactide/glycolide).
The objective was to compare the handling characteristics and </=6 month clinical outcome using a No. 1 long-term absorbable multifilament suture poly(L-lactide/glycolide) (PLG) or the permanent monofilament (No. 1) polypropolene using a continuous fascial closure. During the 13-month study interval, 203 high-risk patients were enrolled in this randomized prospective trial. All were managed under a strict perioperative management protocol. There was no clinically significant difference in patient demographics. Seventy percent carried a diagnosis of abdominal malignancy. The mean body mass index of the population was 33.1. Wound variables including incision length, incision site, measured subcutaneous tissue thickness, and method of subcutaneous dissection did not differ. During the evaluation of suture handling properties PLG was judged to be statistically superior (P < 0.001) in lack of springback, knot tie-down smoothness, knot security, knot strength, and surgical hand. The monofilament suture was judged superior (P < 0001) in ease of tissue passage. There was no difference in incisional pain, suture rejection, superficial wound dehiscence, infection, seroma, or hernia. PLG suture represents a suitable nonpermanent suture alternative for fascial closure in patients at risk for poor wound outcome.


Bacterial translation inhibitors, 1-acylindazol-3-ols as anthranilic acid mimics.
The discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents has been described in a recent series of papers. This paper describes the discovery of 1-acylindazol-3-ols as a novel bioisostere of an anthranilic acid. The synthesis and structure-activity relationships of the indazol bioisosteres are described herein.


A longitudinal analysis of the relationship between housing insecurity and physical health among midlife and aging adults in the United States.
A large body of work demonstrates the impact of housing instability on health by exploring the effects of evictions and homelessness on psychological wellbeing of young adults and children. However, limited research leverages national longitudinal data to examine whether and how experiences of a range of housing insecurity events, rather than just eviction or homelessness, affect physical health among midlife and older adults. The current study examines (1) prevalence of housing insecurity among midlife and older adults by age and race, (2) linkages between housing insecurity experiences and facets of physical health, and (3) age and race moderations on these effects. This study employs regression models to examine whether experiences of housing insecurity affect self-rated physical health and chronic physical conditions among midlife and older adults (N = 2598) leveraging two waves of the National Study of Midlife in the United States (MIDUS). Models revealed that housing insecurity experiences predicted poorer self-rated physical health and additional chronic conditions, even when controlling for previous physical health. Moderation analyses indicated that housing insecurity has a stronger relationship with chronic conditions among midlife adults as compared to older adults, and among Black adults as compared to white adults. These results suggest that experiences of housing insecurity leave adults vulnerable to compromised physical health, and that housing insecurity experiences may be particularly detrimental to the health of midlife Black adults. This research adds to the extant literature by introducing a comprehensive measure of housing insecurity experiences, and contributes to a life course perspective regarding how housing insecurity can affect physical health. This research has implications for policy that addresses housing insecurity as a public health concern, especially in the aftermath of the 2008 recession and the economic and housing crisis caused by the COVID-19 pandemic.


New technique for femtosecond laser creation of clear corneal incisions for cataract surgery.
To evaluate the changes in corneal topography and corneal higher-order wavefront aberrations with the use of a new technique in which clear corneal incisions (CCIs) for cataract surgery are created with a femtosecond laser. IRCCS Fondazione G.B. Bietti, Rome, Italy. Prospective randomized case series. Cataract surgery patients were randomized into 2 groups. In the study group, a 3-plane CCI was created with a femtosecond laser. In the control group, the single plane-angled CCI was created manually using disposable knives. Simulated keratometry (K) values and corneal higher-order wavefront aberrations with 3.5 mm and 6.0 mm pupils were compared between groups. Each group comprised 10 eyes. At 6 months, the mean change in K values from preoperatively was 0.16 diopter (D) ± 0.14 (SD) in the study group and 0.34 ± 0.16 D in the control group, with no differences between groups (P > .05). The manual CCI significantly increased corneal higher-order wavefront aberrations with 3.5 mm and 6.0 mm pupils (both P < .05). In the study group, corneal higher-order wavefront aberrations increased significantly with a 6.0 mm pupil only (P ≤ .02). The induced changes in corneal higher-order wavefront aberrations were significantly different between groups over both pupil sizes (P < .05). The femtosecond laser-created CCI did not induce significant changes in simulated K or corneal higher-order wavefront aberrations over the mesopic pupil size. The lower amount of induced corneal higher-order wavefront aberrations with the new technique than with manual CCI could be related to the different geometry of the 2 techniques.


Serum Phenobarbitone Levels in Term and Near Term Neonates with Seizures.
To evaluate serum phenobarbitone levels in neonates with seizures and to evaluate the effect of repeated loading dose on serum phenobarbitone levels. In this prospective observational study conducted in a tertiary care centre of Northern India during 2011- 2012, 99 neonates admitted with seizureswere included.Serum phenobarbitone levels in neonates with seizures at 20 minutes and 12 hours after the first loading dose of phenobarbitone were measured. Serum phenobarbitone levels [mean (SD)] at 20 min and 12 hours was 27.3 (28.4) ug/mL and 23 (19.1) ug/mL, respectively (P=0.07). The mean serum phenobarbitone levels 12 hours after the loading dose, and proportion of neonates with toxic levels increased with each loading dose of intravenous phenobarbitone. Monitoring of serum level of phonobarbitone may not be essential because seizure control in neonates appears to be independent of whether serum level is subtherapeutic, therapeutic or toxic range.


The impact of pre-evacuation ultrasound examination in histologically confirmed hydatidiform mole in missed abortion.
Early detecting hydatidiform mole in missed abortion is challenge. In this retrospective observational study, we analysed the sensitivity of detecting hydatidiform mole by pre-evacuation ultrasound examination or naked eye after surgical uterine evacuation in missed abortion. Data on 577 cases with histologically confirmed hydatidiform mole were collected over a 10-year period and analysed. Data included serum β-hCG level before surgical evacuation, the ultrasound examination findings, histology findings and naked eye findings. In addition, serum β-hCG level on 2398 cases without hydatidiform mole was also collected. The median maternal age was 29 (range, 17-53) years and the range of gestational age was 6 to 12 weeks. The sensitivity of detecting hydatidiform mole by ultrasound examination or by naked eye was 25% or 60% respectively. This sensitivity was not increased by the combination of ultrasound and naked eye. There was no difference in the sensitivity of detecting subtypes of hydatidiform mole. The higher β-hCG level was seen in cases with hydatidiform mole, compared to cases without hydatidiform mole. However, there was a lot of overlap in the distributions of β-hCG between the two groups. In this study, we found lower sensitivity of detecting hydatidiform mole by ultrasound in missed abortion. β-hCG level was higher in hydatidiform mole than in non- hydatidiform mole in missed abortion. Although higher sensitivity of detecting hydatidiform mole is seen by naked eye (60%), in order to minimise missed opportunity of detecting hydatidiform mole, our study suggests that routine histopathological examination is necessary in missed abortion.


Repeat interventions for maintenance of transjugular intrahepatic portosystemic shunt function in patients with Budd-Chiari syndrome.
The authors report the role of transjugular intrahepatic portosystemic shunts (TIPS) and consecutive interventions, including brachytherapy (n = 2) and stent-graft placement (n = 3), to increase secondary patency and consequently postpone orthotopic liver transplantation (OLT) in the treatment of Budd-Chiari syndrome in eight patients. Two patients (with hematologic diseases) died 2 weeks after the TIPS procedure. Median follow-up in the six survivors was 42.5 months (range, 11-79 mo). Multiple TIPS occlusions occurred in three patients (range, 2-7 revisions). Reocclusions occurred despite brachytherapy and Hemobahn stent-graft placement and necessitated OLT in one patient. Revision-free patency was achieved in the other two patients after VIATORR stent-graft placement (16 and 32 months after TIPS creation). All patients with stable TIPS (n = 5) are without ascites, no liver failure occurred, and no patients are currently on the transplant list.


Painless piezoelectric extracorporeal lithotripsy.
A total of 693 stones in 438 renoureteral units from 426 patients 4 months to 84 years old was treated with a mobile piezoelectric lithotriptor using ultrasound stone localization. Of the units 37 per cent had solitary stones smaller than 1.5 cm. in diameter, (group 1), 32 per cent had multiple stones up to this size (group 2), 21 per cent had stones 1.6 to 2.5 cm. in diameter (group 3) and 10 per cent had calculi larger than 2.5 cm. in diameter (group 4). No sedation or analgesics were necessary in 96.2 per cent of the treatments. Of all stones 97.2 per cent were disintegrated, with 39 per cent of the units requiring repeat treatments usually on an outpatient basis. Of the patients 82 per cent had transient hematuria, 6 per cent had fever and 28 per cent temporarily took some type of analgesics within the first 3 months after treatment. Nine per cent of the patients required postoperative ancillary interventions. After 3 months 92 per cent of the renoureteral units in group 1, 73 per cent in group 2, 74 per cent in group 3 and 50 per cent in group 4 were free of stones. Piezoelectric extracorporeal lithotripsy proved to be as efficient as spark-gap lithotripsy, yet it was essentially painless. Ultrasound localization permits treatment of all renal stones but it restricts lithotripsy of ureteral stones to the most proximal and distal fourths of the ureter.


Prediction of the structure of a receptor-protein complex using a binary docking method.
To validate procedures of rational drug design, it is important to develop computational methods that predict binding sites between a protein and a ligand molecule. Many small molecules have been tested using such programs, but examination of protein-protein and peptide-protein interactions has been sparse. We were able to test such applications once the structures of both the maltose-binding protein (MBP) and the ligand-binding domain of the aspartate receptor, which binds MBP, became available. Here we predict the binding site of MBP to its receptor using a 'binary docking' technique in which two MBP octapeptide sequences containing mutations that eliminate maltose chemotaxis are independently docked to the receptor. The peptides in the docked solutions superimpose on their original positions in the structure of MBP and allow the formation of an MBP-receptor complex. The consistency of the computational and biological results supports this approach for predicting protein-protein and peptide-protein interactions.


Molecular characterization in the toll-like receptor 9 gene of Cape Mountain Zebra (Equus zebra zebra) from three populations.
Toll-like receptors (TLR) are a family of proteins that signal activation of the innate immune response through the recognition of a variety of pathogen molecular compounds. Here, we characterized the complete TLR9 gene in Cape mountain zebra (Equus zebra zebra) from three populations in South Africa and compared sequences to a variety of horse and donkey breeds. Overall, we identified six single nucleotide polymorpHisms (SNPs). A single SNP (G586S) was non-synonymous, whereas the remaining SNPs were synonymous. The G586S alteration was detected in Cape mountain zebra populations with varying frequency. In addition, adaptive diversity was found to be discordant with variation based on neutral markers. The mutation is unique to the Cape mountain zebra when compared to other equid species. The structure of TLR9 is relatively conserved and the resulting amino acid substitution was found to have minimal interaction with active sites in the protein. Future studies can explore the effects of this potentially functional mutation which will contribute to our understanding of genetic diversity within adaptive sites of the Cape mountain zebra genome.


A promoter assay system using gene targeting in agaricomycetes Pleurotus ostreatus and Coprinopsis cinerea.
A novel promoter assay was developed for Agaricomycetes, using a gene-targeting approach, with or without the CRISPR/Cas9 technique. It enables precise evaluation of promoter activity at the original site of the chromosome without random and multiple integrations in conventional transformation experiments.


Physician patient-sharing networks and the cost and intensity of care in US hospitals.
There is substantial variation in the cost and intensity of care delivered by US hospitals. We assessed how the structure of patient-sharing networks of physicians affiliated with hospitals might contribute to this variation. We constructed hospital-based professional networks based on patient-sharing ties among 61,461 physicians affiliated with 528 hospitals in 51 hospital referral regions in the US using Medicare data on clinical encounters during 2006. We estimated linear regression models to assess the relationship between measures of hospital network structure and hospital measures of spending and care intensity in the last 2 years of life. The typical physician in an average-sized urban hospital was connected to 187 other doctors for every 100 Medicare patients shared with other doctors. For the average-sized urban hospital an increase of 1 standard deviation (SD) in the median number of connections per physician was associated with a 17.8% increase in total spending, in addition to 17.4% more hospital days, and 23.8% more physician visits (all P<0.001). In addition, higher "centrality" of primary care providers within these hospital networks was associated with 14.7% fewer medical specialist visits (P<0.001) and lower spending on imaging and tests (-9.2% and -12.9% for 1 SD increase in centrality, P<0.001). Hospital-based physician network structure has a significant relationship with an institution's care patterns for their patients. Hospitals with doctors who have higher numbers of connections have higher costs and more intensive care, and hospitals with primary care-centered networks have lower costs and care intensity.


Exercise intolerance establishment in pulmonary hypertension: Preventive effect of aerobic exercise training.
1) Characterize the progression of exercise intolerance in monocrotaline-induced pulmonary hypertension (PH) in mice and 2) evaluate the therapeutic effect of aerobic exercise training (AET) on counteracting skeletal and cardiac dysfunction in PH. Wild type C57BL6/J mice were studied in two different time points: 2 months and 4 months. Exercise tolerance was evaluated by graded treadmill exercise test. The AET was performed in the last month of treatment of 4 months' time point. Cardiac function was evaluated by echocardiography. Skeletal muscle cross-sectional area was assessed by immunofluorescence. The diameter of cardiomyocytes and pulmonary edema were quantified by staining with hematoxylin-eosin. The variables were compared among the groups by two-way ANOVA or non-paired Student's t-test. Significance level was set at p < 0.05. After 2 months of MCT treatment, mice presented pulmonary edema, right cardiac dysfunction and left ventricle hypertrophy. After 4 months of MCT treatment, mice showed pulmonary edema, right and left cardiac dysfunction and remodeling associated with exercise intolerance and skeletal muscle atrophy. AET was able to reverse cardiac left ventricle dysfunction and remodeling, prevent exercise intolerance and skeletal muscle dysfunction. Thus, our data provide evidence of skeletal muscle abnormalities on advanced PH. AET was efficient in inducing an anti-cardiac remodeling effect besides preventing exercise intolerance. Our study provides a robust model of PH in mice, as well as highlights the importance of AET as a preventive strategy for exercise intolerance and, skeletal and cardiac muscle abnormalities in PH.


Incidence and risk factors of infections associated with peripheral intravenous catheters.
To study the incidence and risk factors of bacterial colonisation of peripheral venous catheters during the early neonatal period. Prospective observational clinical study. Level II neonatal intensive care unit. Consecutive neonates in whom peripheral catheter was inserted were recruited. The insertion site was cleaned with isopropyl alcohol and chlorhexidine for 30 s consecutively. A needleless catheter access device was attached to peripheral catheters. A dedicated observer reviewed the catheter sites regularly for complications. On removal, the tip of the catheter was cut under sterile conditions and sent to the laboratory for culture. Only catheters indwelling for >12 h were sent for culture. Bacteria were isolated from 22 out of 154 catheter tips. Methicillin-sensitive Staphylococcus aureus (n = 13) was the most common organism constituting more than 50% of isolates. In five out of 22 isolates, the organism from the catheter tip was identical to the one from the skin. Systemic sepsis at enrolment was positively associated with colonisation of peripheral catheter. None of the neonates developed peripheral catheter-related bloodstream infection. When proper infection control measures are in place, risk of peripheral venous catheter-related infection appears extremely low in spite of frequent colonisation of the catheter.


Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor.
G-protein-coupled receptors (GPCRs) respond to external stimuli by activating heterotrimeric G proteins inside the cell. There is increasing evidence that many GPCRs exist as dimers or higher oligomers, but the biochemical nature of such dimers and what roles they have, if any, in signal transduction remains unclear. We conducted a comprehensive study of dimerization of the 5HT2c serotonin receptor using disulphide-trapping experiments. We found a dimer interface between transmembrane (TM) helices IV and V that is markedly sensitive to the state of receptor activation. This dimer seems to be quasisymmetrical in interfacial geometry and asymmetrical in its association with its cognate G alpha protein. We also found a second interface at TM I helices, which is insensitive to the state of activation.


Protection from genetic diathesis in attention-deficit/hyperactivity disorder: possible complementary roles of exercise.
The degree of functional impairment and adverse developmental outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD) likely reflect interplay between genes and environment. To establish whether physical exercise might reduce the level of ADHD symptoms or ADHD-related impairments, we conducted a comprehensive review of the effect of exercise in children with ADHD. Findings on the impact of exercise in animals and typically developing human beings, and an overview of putative mechanisms involved, are also presented to provide the context in which to understand this review. The electronic databases PubMed, OVID, and Web of Knowledge were searched for all studies investigating the effect of exercise in children and adolescents with ADHD, as well as animal models of ADHD behaviors (available in January 2013). Of 2,150 initially identified records, 16 were included. Animal studies indicate that exercise, especially early in development, may be beneficial for ADHD symptom reduction. The limited research investigating the effect of exercise in children and adolescents with ADHD suggests that exercise may improve executive functioning and behavioral symptoms associated with ADHD. Although animal research suggests that brain-derived neurotrophic factor (BDNF) and catecholamines (CAs) play a role in mediating these effects, the association between BDNF and ADHD remains unclear in human beings. The potential protective qualities of exercise with regard to reducing symptoms and impairments commonly associated with ADHD may hold promise for the future. Further research is needed to firmly establish whether there are clinically significant effects of exercise on the severity of ADHD symptoms, impairments, and associated developmental outcomes.


Local variation in absolute water content of human and rabbit eye lenses measured by Raman microspectroscopy.
Raman spectra were obtained from fresh, fixed and sliced rabbit lenses and from human lens slices. For all lenses and lens slices the ratio R, defined as the Raman intensity at 3390 cm-1 divided by the Raman intensity at 2935 cm-1, was measured at different locations along the visual and equatorial axis. The ratios R were transformed to absolute water mass percentages by measuring solutions with known protein concentrations. It was shown that fixation and slicing have very little effect on the absolute water content of the lenses. The values obtained for the absolute water content are comparable to values given in literature. It was also shown that the water content in rabbit and human lenses rapidly decreases from the immediate anterior and posterior subsurface region to the deep superficial cortex and is relatively constant in the nucleus. Raman microspectroscopy appears to be a reliable method for the measurement of the absolute water content of small volumes on defined positions in the lens. This can be very useful when analyzing the possible relation between local variations in water content and the occurrence of opacities in the lens.


Transcriptional regulation of IL-5 gene by nontransformed human T cells through the proximal promoter element.
IL-5 is strongly involved in the eosinophilic inflammation in bronchial asthma and atopic dermatitis. We have previously reported that IL-5 synthesis in atopic and nonatopic asthmatics is significantly enhanced compared to control subjects. T cell IL-5 synthesis is regulated through several transcriptional elements, one of which is the proximal human IL-5 promoter (-62 to -46). The present study was undertaken to delineate the transcriptional regulation through this element using nontransformed human T cells. Con A blast lymphocytes which tolerate electroporation were derived from peripheral blood lymphocytes. Luciferase reporter analysis and gel shift analysis were performed. The proximal promoter element is the overlapping binding site for the constitutive binding factor, Oct-1, and the inducible one, AP-1. The transcriptional induction was ascribed to the inducible binding, while the constitutive binding was rather inhibitory. A mutant element which lost the constitutive binding but retained the inducible binding exerted 3 times more transcriptional activity compared to the wild type element. In contrast, another mutant element which lost the inducible binding and retained the constitutive binding exhibited no transcriptional induction. Gel shift analysis clarified that the inducible binding was more prominent and the constitutive binding was less in IL-5-producing T cells derived from asthma patients compared to IL-5-nonproducing cells derived from control subjects. The ratio of the inducible/constitutive binding to the proximal promoter element may determine the capacity of human Th cells to transcribe IL-5 gene, and its regulation may control eosinophilic inflammation.


Trans-Oval-Window Implants, A New Approach for Drug Delivery to the Inner Ear: Extended Dexamethasone Release From Silicone-based Implants.
The purpose of this study was to develop a new strategy to deliver drugs to the inner ear from dexamethasone (DXM)-loaded silicone implants and to evaluate the distribution of the drug in the cochlea with confocal microscopy. Systemic drug administration for the treatment of inner ear disorders is tricky because of the blood-cochlear barrier, a difficult anatomical access, the small size of the cochlea, and can cause significant adverse effects. An effective way to overcome these obstacles is to administer drugs locally. In vitro, the drug release from DXM-loaded silicone-based thin films and tiny implants into artificial perilymph was thoroughly analyzed by high-performance liquid chromatography. In vivo, a silicone implant loaded with 10% DXM and 5% polyethylene glycol 400 was implanted next to the stapes's footplate of gerbils. Delivery of DXM into the inner ear was proved by confocal microscopy imaging of the whole cochlea and the organ of Corti. The study showed a continuous and prolonged release during 90 days in vitro. This was confirmed by confocal microscopy that allowed detection of DXM by fluorescence labeling in the cell body of the hair cells for at least 30 days. Interestingly, fluorescence was already observed after 20 minutes of implantation, reached a climax at day 7, and could still be detected 30 days after implantation. Thus, we developed a new device for local corticosteroids delivery into the oval window with an extended drug release of DXM to the inner ear.


Diagnosis and treatment of the Mirizzi syndrome.
The aim of this paper is to describe the clinical characteristics, diagnostic procedure and operative management of Mirrizi syndrome. Sixteen cases of Mirrizi syndrome were selected and reviewed from 1987 to 1997. In the 16 cases, 6 cases were male, 10 cases were female, the average age was 62.7 years old. Ten cases were diagnosed to be Mirrizi syndrome preoperatively (62.5%); 3 cases were considered to bile duct tumor, the other 3 cases were emergency, they were confirmed the diagnosis after the operation. Ultrasound is recommended as the first choice of screening method, while ERCP may confirm the diagnosis. Surgical approach is considered to be the choice and technical procedures are suggested to prevent intraoperative injury and to repair defects of the common bile duct.


Activity of bile-salt-stimulated human milk lipase in the presence of liposomes and mixed taurocholate-phosphatidylcholine micelles.
(1) The interaction of bile-salt-stimulated human milk lipase and liposomal membranes has been investigated in the presence or absence of sodium taurocholate. Freshly purified enzyme enhances the permeability of liposomal membranes but thermally inactivated enzyme does not. (2) The ability of the enzyme to catalyze the hydrolysis of a relatively hydrophilic substrate, 4-nitrophenyl acetate, and a more hydrophobic substrate, 4-nitrophenyl palmitate, has also been measured in media containing small unilamellar vesicles of egg phosphatidylcholine in both the absence and presence of taurocholate, and also in the presence of free taurocholate in the absence of liposomes. (3) The enzyme-catalyzed hydrolysis of 4-nitrophenyl acetate is enhanced in all of these systems, but 4-nitrophenyl palmitate is protected from enzymic attack in the phosphatidylcholine-bile salt systems. If free taurocholate be present in the system before 4-nitrophenyl palmitate is added, then, and only then, is enzymic activity observed. (4) These results have been interpreted in terms of the importance of the microenvironment around the substrate and the role played by the bile salt surfactant in stimulating the enzyme.


A simple technique for multiorgan preservation.
A simple technique for multiorgan preservation with no ischemic time was developed. In five mongrel dogs, the heart and lungs were separated and removed with the liver, pancreas, kidneys, and a small portion of intestine en bloc while they were being self-perfused. A respirator was used for oxygenation. Arterial and venous blood pressures were measured by indwelling catheters. Fresh blood, glucose, electrolytes, mannitol, prednisolone, and a fat emulsion (Soyacal) were infused through the portal vein. The organs were experimentally perfused for 12 hours. Aortic systolic pressure ranged from 75 to 125 mm Hg, central venous pressure from 0 to 5 mm Hg, portal venous pressure from 0 to 3 mm Hg, bile output from 5 to 20 ml/hr, urine output from 10 to 70 ml/hr, and hematocrit value from 35% to 55%. The heart and lungs were normal and physiologically functional during the preservation time. The pancreas and small intestine appeared normal. Three of the livers showed some congestion. The kidney in one organ block appeared to have some edematous swelling after 16 hours. The technique for multiorgan preservation presented here is simple and effective. The preliminary data are encouraging and suggest further evaluation.


An action spectrum for UV-B radiation and the rat lens.
To determine an action spectrum for UV-B radiation and the rat lens and to show the effect of the atmosphere and the cornea on the action spectrum. One eye of young female rats was exposed to 5-nm bandwidths of UV-B radiation (290, 295, 300, 305, 310, and 315 nm). Light scattering of exposed and nonexposed lenses was measured 1 week after irradiation. A quadratic polynomial was fit to the dose-response curve for each wave band. The dose at each wave band that produced a level of light scattering greater than 95% of the nonexposed lenses was defined as the maximum acceptable dose (MAD). Transmittance of the rat cornea was measured with a fiberoptic spectrophotometer. The times to be exposed to the MAD in Stockholm (59.3 degrees N) and La Palma (28 degrees N) were compared. Significant light scattering was detected after UV-B at 295, 300, 305, 310, and 315 nm. The lens was most sensitive to UV-B at 300 nm. Correcting for corneal transmittance showed that the rat lens is at least as sensitive to UV radiation at 295 nm as at 300 nm. The times to be exposed to the MAD at each wave band were greater in Stockholm than in La Palma, and in both locations the theoretical time to be exposed to the MAD was least at 305 nm. After correcting for corneal transmittance, the biological sensitivity of the rat lens to UV-B is at least as great at 295 nm as at 300 nm. After correcting for transmittance by the atmosphere, UV-B at 305 nm is the most likely wave band to injure the rat lens in both Stockholm and La Palma.


Selective detrending method for reducing task-correlated motion artifact during speech in event-related FMRI.
Task-correlated motion artifacts that occur during functional magnetic resonance imaging can be mistaken for brain activity. In this work, a new selective detrending method for reduction of artifacts associated with task-correlated motion (TCM) during speech in event-related functional magnetic resonance imaging is introduced and demonstrated in an overt word generation paradigm. The performance of this new method is compared with that of three existing methods for reducing artifacts because of TCM: (1) motion parameter regression, (2) ignoring images during speech, and (3) detrending time course datasets of signal components related to TCM (deduced from artifact corrupted voxels). The selective detrending method outperforms the other three methods in reducing TCM artifacts and in retaining blood oxygenation level dependent signal.


Impact of decreasing energy intakes in major burn patients: A 15-year retrospective cohort study.
Nutritional therapy is particularly important after major burn injury and specific nutritional guidelines have been developed. The study aimed at evaluating the impact of the changes in our nutritional practice, general compliance with the guidelines and potential consequences. Retrospective analysis of prospectively collected data in burn patients requiring intensive care (ICU) between 1999 and 2014. admission on day 1, full treatment and length of ICU stay >7 days. Four periods (P) were defined by protocol changes (P1: 1999-2001, P2: 2002-2005, P3: 2006-2010, P4: 2011-2014). Collected data: demographic and nutritional data, infectious complications, weights, CRP and prealbumin concentrations during the first 21 days. 240 patients were included (median age 43 years, burned area 25%). Measured energy expenditure (MEE) was stable through all periods but the prescribed caloric target decreased significantly, and below MEE (P1: 33 kcal/kg, IQR 7, P4: 28 kcal/kg, IQR 8, p < 0.001). Energy delivery ended decreasing below 30 kcal/kg/day (P1: 30 kcal/kg, IQR 23, P4: 25 kcal/kg, IQR 12, p < 0.001). Protein intakes increased due the use of high protein solutions and glutamine (P1: 1.04 g/kg, IQR 0.90, P4: 1.26, IQR 0.99, p < 0.001). Weight loss by day 21 increased significantly according to area under the curve (P1: 701, IQR 38, P2: 722, IQR 51, P4: 689 IQR 63, p = 0.02). Prealbumin levels decreased with energy decrease (P1: 150 mg/L, IQR 110, P4: 80 mg/L, IQR 70, p = 0.003). The observed reduction of the energy delivery <30 kcal/kg was associated with a supplemental weight loss and lower prealbumin concentrations.


Standard ophthalmology residency training in China: an evaluation of resident satisfaction on training program in Guangdong Province.
National standardized training for resident doctors (STRD) in mainland China has been formally established since 2014 as a kind of postgraduate education. The purpose of this survey was to assess the satisfaction of the training residents in Guangdong Province on the ophthalmology STRD program after a duration of 5 years. A 48-item survey was sent to all postgraduate ophthalmology residents from bases in Guangdong Province to inquire about their attitude towards the program. The survey contained questions about demographic and work-related information, job satisfaction, psychological resilience, and job performance. All responses were verified, and invalid questionnaires were excluded. Statistical analyses were performed using SPSS software version 22.0 (SPSS, Inc., Chicago, IL). Multiple logistic regression analysis was used to evaluate the factors (demographic information, working environment, clinical exposure, supervision and hands-on training opportunities, and involvement in academic activities) impacting the overall satisfaction. P < 0.05 was considered statistically significant. A total of 471/635 (74.17%) valid questionnaires were returned from all the STRD bases of Guangdong Province, which included 38 hospitals. 60.3% of the respondents reported overall satisfaction with their training. The satisfaction with operative teaching (60.7%) was slightly lower than the other settings of teaching experience (above 65%). Meanwhile, the satisfaction on different secessions of operative experience was all below 70%, of which in the areas of cornea and orbit were 55.42% and 57.53%, respectively. Some potential factors were found to affect general satisfaction, including the training grade, marriage, working time, income level, the doctor-patient relationship, family members working as doctors, the time proportion spent on writing medical documents during clinical work, and the frequency of attending academic meetings. Improvement was observed in both performing and reporting clinical examinations in the last year of training in comparison to the first year. Finally, 82.8% of the residents acknowledged this training was helpful for future clinical work. The first five career preferences for residents were cataract (67.1%), refractive surgery (42.3%), vitreo-retina (36.5%), optometry (28.7%), and oculoplastic (27.2%). Ophthalmology residents in Guangdong Province expressed comparable satisfaction with the STRD program. To further improve satisfaction, factors such as resident subsidy, harmonious marriage, the patient-doctor relationship, and chances of attending academic conferences should be emphasized.