Potential of plant secondary metabolite-based polymers to enhance wound healing.
There is a global epidemic of non-healing wounds. Chronic inflammation, overexpression of pro-inflammatory cytokines, oxidative stress and bacterial infection are implicated in delayed wound healing. Natural extracts are a rich source of bioactive molecules called plant secondary metabolites (PSMs) that include terpenes and phenols. These molecules may facilitate wound healing through their antioxidant, anti-inflammatory, and antibacterial activity. After briefly outlining the process of wound healing and how it is compromised in chronic wounds, this review focuses on investigating how PSMs-based polymers may improve wound healing. Best methods for incorporating PSMs into wound dressings are reviewed and critically compared. The exiting body of literature strongly suggests that PSMs-based polymers incorporated into wound dressings could have clinical value in aiding wound healing. STATEMENT OF SIGNIFICANCE: Chronic wounds develop by the persistence of inflammation, oxidative stress and infection. Chronic wounds affect the worldwide population, by reducing quality of life of patients with significant cost to healthcare systems. To help chronic wounds to heal and overcome this burden, materials with anti-inflammatory, antioxidant and antibacterial properties are required. Plant secondary metabolites (PSMs) are volatile materials that have all these properties. PSMs-based polymers can be fabricated by polymerization techniques. The present review provides an overview of the state-of-the-art of the wound healing mechanisms of PSMs. Current developments in the field of PSMs-based polymers are reviewed and their potential use as wound dressings is also covered.


Population-based incidence of severe pneumonia in children in Kiel, Germany.
Elaborated data on the descriptive epidemiology of community-acquired pneumonia (CAP) are a prerequisite to estimate the impact of new vaccines. From July 1996 to June 2000, all children (0-16 years) admitted to one of the two pediatric hospitals in Kiel and being resident in the municipal area of Kiel were investigated by cross-sectional studies and prospective testing using a 9-valent in-house m-RT-PCR method. In the 4-year period, 514 children were included (mean age 46, median 40 months): 279 were diagnosed with bronchopneumonia (BPN, median age 26 months), 235 with pneumonia (PN) (47 months); within the latter 69 cases had lobar PN (55 months), 41 atypical PN (51 months) and 28 parapneumonic effusions (74 months). An underlying chronic condition was present in 22.8 % and 10.1 % were born prematurely. The population-based incidence rates (per 100,000 per year) were on average 300 for children 0-16 years, 163 for BPN, 136 for PN, 53 for lobar PN, 24 for atypical PN and 16 for parapneumonic effusions. The rate was stable or slightly declined over the observation period. 61 % of infants and 45 % of children under 5 years of age have to be hospitalized having contracted CAP. The highest fraction of 34 and 25 %, respectively, was attributable to RSV. Viruses were not diagnosed significantly more often in BPN than in PN, if stratified by age. The incidence and the admission rate of severe CAP is lower than in the USA. The high rate of empyema warrants enhanced surveillance as an indicator for antibiotic resistance or changing impact of pneumococcal serotypes. Misclassification, also with ICD codes, is a major issue. Well analyzed epidemiological recruitment areas are a valid tool to generate precise data in Germany.


Prostate tumor delineation using multiparametric magnetic resonance imaging: Inter-observer variability and pathology validation.
Boosting the dose to the largest (dominant) lesion in radiotherapy of prostate cancer may improve treatment outcome. The success of this approach relies on the detection and delineation of tumors. The agreement among teams of radiation oncologists and radiologists delineating lesions on multiparametric magnetic resonance imaging (mp-MRI) was assessed by measuring the distances between observer contours. The accuracy of detection and delineation was determined using whole-mount histopathology specimens as reference. Six observer teams delineated tumors on mp-MRI of 20 prostate cancer patients who underwent a prostatectomy. To assess the inter-observer agreement, the inter-observer standard deviation (SD) of the contours was calculated for tumor sites which were identified by all teams. Eighteen of 89 lesions were identified by all teams, all were dominant lesions. The median histological volume of these was 2.4cm(3). The median inter-observer SD of the delineations was 0.23cm. Sixty-six of 69 satellites were missed by all teams. Since all teams identify most dominant lesions, dose escalation to the dominant lesion is feasible. Sufficient dose to the whole prostate may need to be maintained to prevent under treatment of smaller lesions and undetected parts of larger lesions.


PET [11C]acetate is also a perfusion tracer for kidney evaluation purposes.
Renal positron emission tomography (PET) functional imaging allows non-invasive and dynamic measurements of functional and metabolic parameters. [15O]H2O is used as a perfusion tracer, and [11C]acetate as an oxidative metabolism in this purpose, requiring two injections to assess those fundamental parameters. Yet, in cardiac physiology study, the high first-pass myocardial extraction fraction of [11C]acetate allowed to use its influx rate as a blood flow marker too. Since [11C]acetate has been characterized by a 20-25% single pass renal extraction in dogs, it could be used as a potential tracer for renal perfusion. The aim of this study was to determine whether [11C]acetate influx rate can be used as quantitative in vivo marker of kidney perfusion in human. In 10 healthy subjects, dynamic PET acquisitions were performed after [15O]H2O and [11C]acetate injections spaced by a 15-minute interval. As previously validated, with compartmental modeling of kinetics, renal perfusion and oxidative metabolism were estimated respectively with influx rate of [15O]H2O and efflux rate of [11C]acetate. Additionally, influx rate of [11C]acetate was regressed to influx rate of [15O]H2O. Renal time activity curves of [11C]-acetate was best fitted with a mono compartmental model compared to a bi-compartmental model (p < 0.0001). [11C]acetate influx rate was significantly correlated with perfusion quantified with [15O]H2O (r2 = 0.37, p < 0.001) at baseline. This regression allowed the computation of a renal [11C]acetate extraction fraction (EF), and further the computation of renal blood flow from its influx rate. In healthy subjects, over a wide range of renal perfusion, direct estimates of renal oxygen consumption as well as tissue perfusion can be obtained by PET with a single tracer [11C]acetate. This approach needs to be validated in CKD patients, and would be of great interest to design clinical protocol aiming at evaluating ischemic nephropathies candidate to revascularization.


Towards understanding the cutting temperature in ultrasonic vibration-assisted drilling based on the dynamic contact characteristics between the cutting edge and workpiece.
Compared with conventional drilling (CD), ultrasonic vibration-assisted drilling(UVAD) is experimentally proven a promising method to reduce the cutting temperature. But sometimes cutting temperature also becomes higher in UVAD than in CD. To further make clear the cutting temperature mechanisms in UVAD, this study aims to study the effect of tool's ultrasonic vibration on the cutting heat generation and heat dissipation at a relatively micro level. Firstly, drilling experiments are designed to explore the variations of cutting heat under different ultrasonic vibrations. Then, to analyze the influence of ultrasonic vibration on the cutting heat theoretically, a kinematic model is developed to describe the dynamic contact between the cutting edge and workpiece in UVAD. Besides, a cutting heat analysis model based on the contact characteristics in UVAD is proposed to study and compare the variations of cutting heat generation. The effect of ultrasonic vibration on the cutting heat generation, heat dispassion, and the resultant cutting temperature under different machining in UVAD conditions are discussed. It is indicated from the theoretical analysis that more cutting heat tends to be produced due to the significantly increased sliding velocity on the cutting edge-workpiece interface when the ultrasonic vibration is applied. The analysis agrees with the experimental results that the cutting temperature in dry UVAD is higher than in dry CD. But on the other hand, ultrasonic vibration can also improve the lubrication and cooling effect under appropriate machining conditions, which is beneficial to the reduction in cutting temperature. The investigation shows the multifaceted influences of ultrasonic vibration on the cutting temperature in the drilling process in detail, which provides a reference for UVAD parameter optimization.


Synthesis and potential antidiabetic and lipid-lowering activities of putative asperidine B and its desmethyl analogue.
Putative asperidine B is an unnatural 2,6-disubstituted piperidin-3-ol and a structural isomer of (+)-preussin, a well-known pyrrolidin-3-ol alkaloid. This work reports the first enantioselective synthesis of putative asperidine B and its desmethyl analogue via a chiron approach starting from d-isoascorbic acid as well as evaluation of their free-radical scavenging, antidiabetic, and anti-hyperlipidemic activities. Both putative asperidine B and its desmethyl analogue markedly reduced the total reactive oxygen species (ROS) without cytotoxicity in hepatocellular carcinoma (HepG2) cells. The desmethyl analogue was a potent inducer for two antioxidant gene expression, glutathione peroxidase and superoxide dismutase, whereas putative asperidine B only induced superoxide dismutase. In addition, putative asperidine B exerted potent antidiabetic activity via α-glucosidase inhibition (IC50 = 0.143 ± 0.001 mg/mL) comparable to that of acarbose, an antidiabetic drug. Consistent with the parent asperidine B (preussin), both putative asperidine B and its desmethyl analogue inhibited cholesterol absorption in the intestinal Caco-2 cells. These novel and promising antioxidant, antidiabetic, and lipid-lowering effects of piperidin-3-ols could offer a starting point for this class of compounds for obesity and diabetic drug discovery.


Taxonomic and functional diversity of Dendrobium officinale microbiome in Danxia habitat.
Microbial communities that inhabit plants are crucial for plant survival and well-being including growth in stressful environments. The medicinal plant, Dendrobium officinale grows in the barren soils of the Danxia Habitat. However, the microbiome composition and functional potential for growth of this plant in this environment are still unexplored. In this study, we analysed the taxonomic and functional diversity of the D. officinale Microbiome by metagenomic sequencing of both rhizosphere and endosphere samples. A total of 155 phyla, 122 classes, 271 orders, 620 families and 2194 genera were identified from all samples. The rhizospheric microbes (DXRh) were mainly composed of Proteobacteria and Acidobacteria, while Basidiomycota and Ascomycota were the most dominant phyla in root endosphere (DXRo) and stem endosphere (DXS), respectively. Most of the dominant microbial communities had been reported to have diverse functional potentials that can help plant growth and development in stressful and nutrient-deprived ecological environmental. These include plant growth promoting rhizobacteria (PGPR) such as Massilia, Pseudomonas, Bradyrhizobium, Klebsiella, Streptomyces, Leclercia, Paenibacillus, Frankia and Enterobacter in the DXRh, Tulasnella and Serendipita in the DXRo, Colletotrichum and Burkholderia in the DXS and Paraburkholderia, Rhizophagus and Acetobacter in endosphere. Analysis using the KEGG, eggNOG and CAZy databases showed that metabolic pathways such as carbohydrate metabolism, amino acid metabolism, energy metabolism, genetic information processing and environmental information processing are significantly abundant, which may be related to the survival, growth and development of D. officinale in a stressful environment. We speculated that the microbial community with diverse taxonomic structures and metabolic functions inhabiting in different niches of plants supports the survival and growth of D. officinale in the stressful environment of Danxia Habitat. This study provided an important data resource for microbes associated with D. officinale and theoretical foundation for further studies.


Morphological difference of Escherichia coli non-heme ferritin iron cores reconstituted in the presence and absence of inorganic phosphate.
The iron core of Escherichia coli ferritin was reconstituted in the presence and absence of phosphate. The core formed in the presence of phosphate contained phosphate in amounts comparable to the iron content. The size distribution of the core was analyzed by analytical ultracentrifugation. A continuous size distribution was observed in the presence of phosphate, whereas a multimodal distribution was found in the absence of phosphate. In the presence of phosphate, the core size observed by electron microscopy was consistent with the inner diameter of ferritin. In contrast to this, clusters of several smaller particles were observed in the absence of phosphate. The small-angle X-ray scattering was measured under contrast matching conditions to obtain information on the iron core shape. A fringe was observed in the scattering profile in the presence of phosphate, but it was not observed in the absence of phosphate. Combining all results, we conclude that a hollow spherical core was formed in the presence of phosphate, while several small particles were formed within the inner cavity in the absence of phosphate.


Considerations to comprehensive care for the older individual with myelofibrosis.
Over the last decade, we have witnessed a massive increase in available clinical agents, both in the clinical trial setting and following commercial use approval, directed to reduced life expectancy as well as the considerable symptom, splenic and anaemia burden associated with myelofibrosis. Given the median age of onset of the disease, coupled with an ageing population globally, we will be caring for an increasingly aged myelofibrosis cohort in future years. We will need to adapt our approach, emphasizing the holistic management of the older individual with myelofibrosis accordingly. Out with the pharmacological management of the disease, consideration needs to be given to interventions based on concurrent illness, comprehensive geriatric assessments, frailty, polypharmacy and drug-drug interactions, nutritional issues, psychological concerns (depression, anxiety or distress), cognitive decline and social/economic aspects. Within this review, we summarise available data addressing these issues, outline knowledge gaps and suggest a summative and holistic approach to the older individual with myelofibrosis.


Pulsatile tympanic membrane displacement is associated with cognitive score in healthy subjects.
To test the hypothesis that pulsing of intracranial pressure has an association with cognition, we measured cognitive score and pulsing of the tympanic membrane in 290 healthy subjects. This hypothesis was formed on the assumptions that large intracranial pressure pulses impair cognitive performance and tympanic membrane pulses reflect intracranial pressure pulses. 290 healthy subjects, aged 20-80 years, completed the Montreal Cognitive Assessment Test. Spontaneous tympanic membrane displacement during a heart cycle was measured from both ears in the sitting and supine position. We applied multiple linear regression, correcting for age, heart rate, and height, to test for an association between cognitive score and spontaneous tympanic membrane displacement. Significance was set at P < 0.0125 (Bonferroni correction.) A significant association was seen in the left supine position (p = 0.0076.) The association was not significant in the right ear supine (p = 0.28) or in either ear while sitting. Sub-domains of the cognitive assessment revealed that executive function, language and memory have been primarily responsible for this association. In conclusion, we have found that spontaneous pulses of the tympanic membrane are associated with cognitive performance and believe this reflects an association between cognitive performance and intracranial pressure pulses.


Injectable glycol chitosan thermogel formulation for efficient inner ear drug delivery.
We prepared a new injectable thermogel to enhance the efficiency of inner ear delivery of dexamethasone (DEX). Hexanoyl glycol chitosan (HGC) was synthesized and evaluated as an amphiphilic thermogel (Tgel ~ 32 °C) for use as a solubilizing agent as well as an injectable carrier for intratympanic delivery of the hydrophilic and hydrophobic forms of DEX. Various thermogel formulations with different drug types and concentrations were prepared, and their physicochemical and thermogelling properties were characterized by 1H NMR, ATR-FTIR, and rheometer. They exhibited versatile release kinetics from several hours to more than 2 weeks, depending on drug type and concentration. Our formulations further showed good residual stability for more than 21 days without any cytotoxicity or inflammation in the middle and inner ear and could deliver a considerably high drug concentration into the inner ear. Therefore, HGC thermogel has great potential as an effective and safe formulation for inner ear drug delivery.


Estrogen controls PKCepsilon-dependent mechanical hyperalgesia through direct action on nociceptive neurons.
Protein kinase C epsilon (PKCepsilon) is an important intracellular signaling molecule in primary afferent nociceptors, implicated in acute and chronic inflammatory as well as neuropathic pain. In behavioral experiments inflammatory mediators produce PKCepsilon-dependent hyperalgesia only in male rats. The mechanism underlying this sexual dimorphism is unknown. We show that the hormone environment of female rats changes the nociceptive signaling in the peripheral sensory neuron. This change is maintained in culture also in the absence of a gender-simulating environment. Stimulation of beta(2)-adrenergic receptors (beta(2)-AR) leads to PKCepsilon activation in cultured dorsal root ganglia (DRG) neurons derived from male but not from female rats. Addition of estrogen to male DRG neurons produces a switch to the female phenotype, namely abrogation of beta(2)-AR-initiated activation of PKCepsilon. Estrogen interferes downstream of the beta(2)-AR with the signaling pathway leading from exchange protein activated by cAMP (Epac) to PKCepsilon. The interfering action is fast indicating a transcriptional-independent mechanism. Estrogen has a dual effect on PKCepsilon. If applied before beta(2)-AR or Epac stimulation, estrogen abrogates the activation of PKCepsilon. In contrast, estrogen applied alone leads to a brief translocation of PKCepsilon. Also in vivo the activity of estrogen depends on the stimulation context. In male rats, intradermal injection of an Epac activator or estrogen alone induces mechanical hyperalgesia through a PKCepsilon-dependent mechanism. In contrast, injection of estrogen preceding the activation of Epac completely abrogates the Epac-induced mechanical hyperalgesia. Our results suggest that gender differences in nociception do not reflect the use of generally different mechanisms. Instead, a common set of signaling pathways can be modulated by hormones.


Could age modify the effect of genetic variants in IL6 and TNF-α genes in multiple myeloma?
Cytokines play a central role in multiple myeloma (MM) pathogenesis thus genetic variations within cytokines coding genes could influence MM susceptibility and therapy outcome. We investigated the impact of 8 SNPs in these genes in 202 MM cases and 235 controls also evaluating their impact on therapy outcome in a subset of 91 patients. Despite the overall negative findings, we found a significant age-modified effect of IL6 and TNF-α SNPs, on MM risk and therapy outcome, respectively. Therefore, this observation suggests that genetic variation in inflammation-related genes could be an important mediator of the complex interplay between ageing and cancer.


Systematic review and meta-analysis of the efficacy of clinically tested protectants of cisplatin nephrotoxicity.
Cisplatin is a potent antineoplastic drug that has been widely used to treat a number of solid tumors. However, a high incidence of renal damage observed in patients has led researchers to search for alternate strategies that prevent or at least reduce the cisplatin-induced nephrotoxicity. The objective of the present study was to conduct a systematic review and a subsequent meta-analysis to evaluate and identify compounds with effective antitumor activity and lesser side effects that could provide protection against cisplatin-induced nephrotoxicity. The study included all placebo-controlled trials published up to December 2017 that met the inclusion criteria. A total of 22 articles were finally included to extract the following information: number of patients, doses of cisplatin and protectant, qualitative (acute kidney injury incidence) and quantitative (plasma creatinine, blood urea nitrogen, and creatinine clearance) indicators of renal function. The odds ratio or the mean difference (95% confidence interval) of each parameter was calculated for each study and group of studies. The results of this meta-analysis show that there is great variability in the nephroprotective capacity of a variety of products evaluated. Of all the compounds tested, only magnesium sulfate and cystone were found to exert protective effects. However, more studies need to be conducted to confirm these results. The administration of 1 g of Mg i.v. seems to be the best strategy for the prevention of cisplatin nephrotoxicity.


Corrigendum: Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids.
[This corrects the article DOI: 10.3389/fbioe.2022.917726.].


A clinical comparative evaluation of periodontally accelerated osteogenic orthodontics with piezo and surgical bur: An interdisciplinary approach.
The orthodontic treatment in adult for the treatment of malocclusion is becoming more common. However, the disadvantages of conventional orthodontics are the time consumed for the treatment (18-24 months), root resorption, and formation of fenestrations and dehiscence. Periodontally accelerated osteogenic orthodontics (PAOO) is a surgical technique resulting in increased alveolar bone width, shorter treatment time, increase posttreatment stability, and decrease amount of apical root resorption. The aim of the study is to compare the treatment time, root resorption, bone density, and presence/absence of fenestrations and dehiscence after PAOO with surgical bur and PAOO with piezocision. Forty participants with bimaxillary protrusion undergoing orthodontic treatment were randomly selected and divided into two groups. Group I: 20 participants selected for PAOO with surgical bur and Group II: 20 participants selected for PAOO with piezocision. Patients were recalled at baseline 3, 6, 9, and 12 months and evaluated for treatment time and bone density, root resorption, and detection of fenestration and dehiscence using cone-beam computerized tomography (CBCT). Participants in Group I had less treatment time compared to Group II. Rate of retraction was 7.07 mm/20.81 weeks and 5.99 mm/28.48 weeks in Group I and Group II, respectively. CBCT showed a statistically significant increase in bone density in both groups, 12 months after the surgery. Root resorption was negligible in Group I (0.34 mm) and in Group II (0.51 mm). CBCT revealed increase in thickness of alveolar bone and coverage of fenestrations and dehiscence. PAOO provides an efficient and stable orthodontic tooth movement.


Contaminant profiles for surface water, sediment, flora and fauna associated with the mangrove fringe along middle and lower eastern Tampa Bay.
Contaminant concentrations are reported for surface water, sediment, flora and fauna collected during 2010-2011 from the mangrove fringe along eastern Tampa Bay, Florida. Concentrations of trace metals, chlorinated pesticides, atrazine, total polycyclic aromatic hydrocarbons, and polychlorinated biphenyls were species-, chemical- and location-specific. Contaminants in sediments did not exceed proposed individual sediment quality guidelines. Most sediment quality assessment quotients were less than one indicating the likelihood of no inhibitory effect based on chemical measurements alone. Faunal species typically contained more contaminants than plant species; seagrass usually contained more chemicals than mangroves. Bioconcentration factors for marine angiosperms were usually less than 10 and ranged between 1 and 31. Mercury concentrations (ppm) in blue crabs and fish did not exceed the U.S. Environmental Protection Agency fish tissue criterion of 0.3 and the U.S. Food and Drug Administration action level of 1.0. In contrast, total mercury concentrations in faunal species often exceeded guideline values for wildlife consumers of aquatic biota.


Mode-locked Yb:YAG thin-disk oscillator with 41 µJ pulse energy at 145 W average infrared power and high power frequency conversion.
We demonstrate the generation of 1.1 ps pulses containing more than 41 µJ of energy directly out of an Yb:YAG thin-disk without any additional amplification stages. The laser oscillator operates in ambient atmosphere with a 3.5 MHz repetition rate and 145 W of average output power at a fundamental wavelength of 1030 nm. An average output power of 91.5 W at 515 nm was obtained by frequency doubling with a conversion efficiency exceeding 65%. Third harmonic generation resulted in 34 W at 343 nm at 34% efficiency.


Properties and biotechnological applications of microbial deacetylase.
Deacetylases, a class of enzymes that can catalyze the hydrolysis of acetylated substrates to remove the acetyl group, used in producing various products with high qualities, are one of the most influential industrial enzymes. These enzymes are highly specific, non-toxic, sustainable, and eco-friendly biocatalysts. Deacetylases and deacetylated compounds have been widely applicated in pharmaceuticals, medicine, food, and the environment. This review synthetically summarizes deacetylases' sources, characterizations, classifications, and applications. Moreover, the typical structural characteristics of deacetylases from different microbial sources are summarized. We also reviewed the deacetylase-catalyzed reactions for producing various deacetylated compounds, such as chitosan-oligosaccharide (COS), mycothiol, 7-aminocephalosporanic acid (7-ACA), glucosamines, amino acids, and polyamines. It is aimed to expound on the advantages and challenges of deacetylases in industrial applications. Moreover, it also serves perspectives on obtaining promising and innovative biocatalysts for enzymatic deacetylation. KEYPOINTS: • The fundamental properties of microbial deacetylases of various microorganisms are presented. • The biochemical characterizations, structures, and catalyzation mechanisms of microbial deacetylases are summarized. • The applications of microbial deacetylases in food, pharmaceutical, medicine, and the environment were discussed.


Resilience to climate-induced disasters and its overall impact on well-being in Southern Africa: a mixed-methods systematic review protocol.
Southern Africa has long been vulnerable to climate-induced disasters, especially droughts and floods. The severity and frequency of disasters increased in the early 1980s, continuously eroding livelihoods, which in turn invoked humanitarian intervention. A systematic review of the relationship between resilience to drought and well-being will be undertaken. Studies will be included if they were conducted between January 1980 and December 2017; used quantitative and/or qualitative methods; were peer reviewed or comprise grey literature; covered Southern Africa; and measured resilience and its relationship to well-being. Data extraction will be informed by the Cochrane Public Health Group and the Joanna Briggs Institute manuals. The quality of evidence of the studies included will be assessed for risk bias, psychometric properties of tools used, and their suitability. The findings will be summarised into themes and narrated. This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. The protocol gives insight of the scope and parameters for the systematic review to be carried out. The systematic review will establish how resilience to climate-induced disasters affects well-being. It will also provide recommendations to improve humanitarian coordination in Southern Africa. The protocol was registered by the PROSPERO international prospective register of systematic reviews, reference CRD42017064396 .


Synthesis and chemistry of 4,5-dimagnesioimidazole dianions.
An experimentally convenient procedure for the generation of 4,5-dimagnesioimidazoles is described. N-Protected 2-substituted 4,5-diiodoimidazoles were treated with i-PrMgCl (2.4 equiv) in THF at 0-5 degrees C. The resulting vicinal dianions reacted with electrophiles to give 4,5-disubstituted imidazoles in 27-71% yields.


Prognostic value of white-coat and masked hypertension diagnosed by ambulatory monitoring in initially untreated subjects: an updated meta analysis.
The prognostic relevance of white-coat hypertension (WCH) and masked hypertension (MH) is controversial. The aim of this study was to perform an updated meta-analysis on the prognostic value of WCH and MH diagnosed by ambulatory monitoring in initially untreated subjects. We searched for articles evaluating cardiovascular outcome in WCH or MH or sustained hypertension (SH) in comparison with normotension, investigating untreated subjects at baseline or performing separate analysis for untreated or treated subjects, and reporting adjusted hazard ratio (HR) and 95% confidence interval (CI). Eight studies were identified. Five whole studies and untreated groups of three others were included in the meta-analysis. The pooled population consisted of 7,961 subjects who experienced 696 events. When compared with normotension, the overall adjusted HR was 0.96 (95% CI 0.65-1.42) for WCH (P = 0.85), 2.09 (1.55-2.81) for MH (P = 0.0001), and 2.59 (2.0-3.35) for SH (P = 0.0001). There was no significant difference between WCH and normotension according to normotensive subjects source (same or different study population) and follow-up length. Where reported, prevalence of drug therapy was higher in subjects with WCH than in those with normotension at follow-up. Cardiovascular risk is not significantly different between WCH and normotension, regardless of normotensive population type and follow-up length. However, at follow-up drug therapy was more frequent in WCH than in normotension and its possible impact on outcome should be evaluated in future studies. MH shows significantly higher risk than normotension, although the best way for its detection and treatment remains to be established.


Tricalcium phosphate-based biocomposites for mandibular bone regeneration--A histological study in sheep.
The present study investigated the suitability of three different absorbable biocomposites for the repair of critical sized bone defects created at the mandibular angle of adult sheep. Each biocomposite was composed of a three-dimensional individualized polylactide scaffold, containing a tricalcium phosphate biomaterial (chronOS). Either autologous bone marrow (chOS/BoneMarrow) or coagulation factor XIII (chOS/FactorXIII) was added to the biomaterial for osteopromotion. Venous whole blood (chOS/Blood) added to the biomaterial served as a control. A total of 18 adult sheep were used for implantation studies, subdivided into three groups of six animals each. After 12 weeks of observation, the animals were sacrificed and the mandibles were retrieved for qualitative and quantitative histologic assessment within three regions of interest (transitional zone, center, and periphery) throughout the biocomposites. Successful bone regeneration was defined by the absence of scaffold deformation and the presence of new bone formation within the biocomposites. In histomorphometry, only chOS/BoneMarrow showed elevated area fractions of newly formed bone in all regions of interest (transitional zone 50.7 ± 7.5, center 31.9 ± 9.3, periphery 23.1 ± 13.5). This led to preservation of the macroscopic scaffold structure in all specimens. Zero hurdle regression confirmed this by validating the factor biocomposite as significant (p < 0.001) for regeneration success. In our experiment, chOS/BoneMarrow was the only biocomposite passing the hurdle of regeneration in all three regions of interest. In contrast, bone formation was less pronounced and uniform in chOS/FactorXIII and chOS/blood-containing specimens. In these groups, scaffolds showed obvious to significant deformation. Overall, autologous bone marrow showed the most promising results in our experimental setting. As opposed to reports in the literature, we could not confirm the suitability of coagulation factor XIII to promote bone formation, since bone formation rates were comparable only to those of the control venous blood.


Projected structure of unstained, frozen-hydrated T-layer of Bacillus brevis.
This paper presents the projected structure of the T-layer of Bacillus brevis, obtained from electron microscopic studies of the unstained protein layer in the frozen-hydrated state. Computer image processing is used to correct for the effects of the contrast transfer function, and to increase the signal-to-noise ratio by lattice averaging. The results obtained show a good agreement with those previously obtained using negatively stained specimens. It is shown that the contrast of T-layer embedded in ice can be approximated to pure phase contrast.


Cruelty begins at home.
The abuse of children is presumed by most mental health professionals to occur at the hands of parents who were themselves harshly traumatized by abuse or neglect. A 14-month-old child is presented who was well treated by his family and developed well until 6.5 months of age, after which, due to traumatization of his mother, the child became neglected and physically abused. In a therapeutic-observational environment, as the child recovered from his massive depression, much explosive destructive behavior not seen in him before was observed. From his past studies and those of other psychoanalysts, the author presents the collectively advanced hypothesis that excessive unpleasure mobilizes hostility in humans and suggests that this hypothesis may be fruitfully applied to explain why the abused become abusers. The hypothesis may also serve to guide the treatment of abused children so as to prevent their becoming tomorrow's abusers. Furthermore, the hypothesis suggests that strategies can be proposed toward preventing child abuse.


Effects of temperature and salinity on haemocyte activities of the Pacific oyster, Crassostrea gigas (Thunberg).
The Pacific oyster, Crassostrea gigas, is extensively cultivated and represents an important economic activity. Oysters are reared in estuarine areas, subjected to various biotic and abiotic factors. One of the limiting factors in aquaculture is mortality outbreaks, which may limit oyster production, and the causes of these outbreaks are not completely understood. In this context, the effects of temperature and salinity on Pacific oyster, C. gigas, haemocytes, were studied. Haemocytes are the invertebrate blood cells and thus have been shown to be involved in defence mechanisms. Flow cytometry was used for monitoring several haemocyte parameters. An increase of temperature induced an increase of haemocyte mortality, in both in vitro and in vivo experiments. Temperature modulated aminopeptidase activity. An in vitro decrease of salinity was associated with cell mortality. During the course of in vivo experiments, an increase of phagocytic activity was reported at 15 per thousand and 50 per thousand. Environmental physical parameters may modulate haemocyte activities.


Determination of D-glucaric acid and/or D-glucaro-1,4-lacton in different apple varieties through hydrophilic interaction chromatography.
d-Glucaric acid (GA) derivatives exhibit anti-cancerogenic properties in vivo in apples, but quantitative information about these derivatives is limited. Hydrophilic interaction-based HPLC with ultraviolet detection or mass spectrometry was developed to quantify GA and/or D-glucaro-1,4-lacton (1,4-GL) in apples. Although the formation of 1,4-GL from GA could be the prerequisite to exert biological effects in vivo, only a small portion of GA (<5%) was identified and converted to 1,4-GL in the rat stomach. The 1,4-GL content in apples ranged from 0.3 mg/g to 0.9 mg/g, and this amount can substantiate health claims associated with apples. The amount of 1,4-GL was 1.5 times higher in Gala and the ratio of 1,4-GL to GA was lower in Green Delicious apples than those in the other varieties. Our findings suggested that the variety and maturity of apples at harvest are factors that determine 1,4-GL content.


Use of solid-phase extraction to eliminate interferences in the determination of mercury by flow-injection CV AAS.
Solid-phase extraction with two-step elution has been developed for effective elimination of copper and iron interference with mercury determination by flow-injection cold vapour atomic absorption spectrometry (CV AAS). Sodium tetrahydroborate(III) was used as reducing agent. Cation-exchanger Dowex 50Wx4 was applied for the sorption of mercury and both interfering ions. In the first step elution of Cu(II) and Fe(III) was performed using 0.5 mol L(-1) KF solution. Then mercury was eluted with 0.1% thiourea in 8% HCl. The detection limit (3 delta) for Hg(II) was 27 ng L(-1). The expanded uncertainty estimated for the whole procedure was about 6%. The accuracy of the proposed method was evaluated by determination of the recovery of known amount of mercury added to mineral, spring, and tap waters, and by analysis of a certified reference material BCR-144R (sewage sludge).


Arterial hypertension as a risk factor for chronic symmetric polyneuropathy.
To assess whether arterial hypertension (AH) is an independent risk factor for chronic symmetric polyneuropathy (CSP) in the elderly. A strong relationship has been detected between AH and distal symmetric polyneuropathy in insulin-dependent and non-insulin-dependent diabetes. However, the correlation between AH and polyneuropathy caused by other clinical conditions has not yet been studied. Four thousand one hundred and ninety-one subjects aged > or = 55 years seen in office consultations by 25 general practitioners (GPs) from two separate areas in Italy were interviewed, using a pretested semistructured questionnaire covering conditions commonly associated with neuropathy and symptoms of peripheral nerve disease. A neurologist later visited individuals with > or = 2 symptoms of polyneuropathy and a diagnosis of CSP was made in the presence of bilateral, fairly symmetric impairment of at least two among strength, sensation and tendon reflexes. AH was ascertained when known to the GP and/or if the patient was being treated with antihypertensive drugs. One hundred and fifty one subjects had CSP (3.6%). Diabetes was the commonest associated condition (18%). AH was present in 47 patients with CSP (31%). The odds ratio (OR) of AH in patients with CSP was 4.5 [95% confidence interval (CI) 3.1-6.6]. The OR of AH was 3.2 (95% CI 1.5-6.9) in patients with diabetes, and 5.7 (95% CI 3.6-9.3) in those without diabetes. The OR of AH was 4.8 (95% CI 4.4-5.2) after adjusting for the commonest risk factors for CSP. AH may be an independent risk factor for CSP in the elderly.


Driving Simulator Brake Reaction Parameters After Total Hip Arthroplasty According to Different Surgical Approaches.
The aim of this study is to validate the point of normalization of braking following total hip arthroplasty (THA) and to determine the relevance of the surgical approach. Brake reaction parameters (BRPs), including brake reaction time, total brake time, and brake pedal depression force were measured in 90 patients who underwent primary arthroplasty of the right hip (42 with direct anterior approach and 48 with posterolateral approach) using a modern driving simulator. The driving parameters were measured preoperatively and every 2 weeks postoperatively until the eighth week. BRPs were measured in 40 subjects without hip problems, and the results were used as a control. Statistical assessment was performed to analyze when the patients' reaction to braking recovered to that of the control group with respect to different surgical approaches and also according to the pain. Preoperative BRPs of the patients undergoing THA were prolonged compared to the control group and were normalized at the sixth week following the operation. Although BRPs of the direct anterior approach group showed significantly better improvement compared to the posterolateral approach group (total brake time at week 2, brake reaction time and brake pedal depression at week 4), both groups reached baseline value at week 6. In addition, we found no correlation between the pain score and BRPs. The results of the current study indicate that the response to braking events normalizes at 6 weeks following THA in young active patients and is irrelevant to the surgical approach.


The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer.
Antitumor T lymphocytes play an essential part in immune surveillance of cancer cells. Cytotoxic T lymphocyte-associated Protein 4 (CTLA-4) is a negative regulator of T cell activation and proliferation and therefore influences immune surveillance of carcinogenesis of pancreas. Thus, this study examined the association between functional CTLA-4 49G-to-A (49G>A) single-nucleotide polymorphism and pancreatic cancer risk. Genotypes were determined in 368 patients with pancreatic cancer and 926 controls, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. A significant increased risk of pancreatic cancer was found to be associated with the CTLA-4 49G>A single-nucleotide polymorphism. Compared with noncarriers, the OR of developing pancreatic cancer for CTLA-4 49 GA or AA carriers was 1.75 (95% CI = 1.34-2.30, P = 4.83 × 10(-5) ) or 2.54 (95% CI = 1.67-3.87, P = 1.36 × 10(-5) ), respectively. In stratified analyses, the association was more pronounced in GA and AA carriers aged ≤60 years (OR = 3.10, 95% CI = 2.15-4.47, P(interaction) = .002), smokers with GA and AA genotypes (OR = 3.92, 95% CI = 2.39-6.43, P(interaction) = .037), and drinkers with GA and AA genotypes (OR = 4.55, 95% CI = 2.65-7.82, P(interaction) = .042), compared with GG carriers. Moreover, a supermultiplicative interaction between the CTLA-4 49AA genotype and smoking plus drinking was also evident in intensifying risk of pancreatic cancer (P(interaction) = 5.64 × 10(-12) ). These results suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to developing pancreatic cancer, alone and in a gene-environment interaction manner.


Langerhans cell histiocytosis involving the corpus callosum and cerebellum: gadolinium-enhanced MRI.
Langerhans cell histiocytosis is a systemic disorder consisting of abnormal histiocyte proliferation, in the form of focal deposits. Central nervous system involvement is most common in the hypothalamus, although other sites have been described, such as the cerebellum and the meninges. We present a case with presumed involvement of the corpus callosum and cerebellum, demonstrating gadolinium enhancement on MRI.


Tampon culture for quantitation of cervicovaginal herpes simplex virus.
From 10(1) to 10(6) TCID50 (mean tissue culture infective doses) per ml HSV I and II can be quantitatively recorded from vaginal tampons. Tampons and sterile cotton swabs are equally sensitive in recovering HSV I and II. Direct cotton swab cultures of the cervix and cervicovaginal tampon cultures from the same patients recovered similar quantities of HSV, ranging from 1.5 to 6.5 log10 TCID50/ml in 5 patients.


Formation and propagation of brain oedema fluid around human brain metastases. A CT Study.
Computerized tomography (CT) was used to examine the time-course of the propagation of extravasated contrast medium from small brain metastases into the peritumoural oedematous white matter, following infusion of 200 ml of meglumine amidtrizoate for 3 hours. Four patients with a metastatic brain tumour were examined. CT scans at identical levels were taken 1.5, 3, 6, 9, and 12 hours after start of contrast infusion. Following 4-7 days of dexamethasone treatment (8-12 mg/day i.v.) the examination was repeated. A contrast-enhanced area was observed surrounding the clearly delineated tumours, expanding gradually in a circular fashion into the peritumoural white matter oedema. The expanding circular enhancement was measured planimetrically on the various scans. From these values, the increase in radius/hr respectively in volume/hr was calculated, assuming a spherical geometry. This enabled a determination of the rate of oedema fluid formation and of the speed of oedema fluid propagation. The formation rate of oedema fluid amounted to 0.5-3.2 ml/hour and the speed of oedema fluid spreading to 1.9 mm/hour. Following treatment with dexamethasone the formation rate of oedema fluid is reduced by 30-50%. The important clinical implications of these new findings are discussed.


3D-printed titanium implant with pre-mounted dental implants for mandible reconstruction: a case report.
This clinical case presented a novel method of segmental mandible reconstruction using 3D-printed titanium implant with pre-mounted dental implants that was planned to rehabilitate occlusion. A 53-year-old male who suffered osteoradionecrosis due to the radiation after squamous cell carcinoma resection. The 3D-printed titanium implant with pre-mounted dental implant fixtures was simulated and fabricated with selective laser melting method. The implant was successfully inserted, and the discontinuous mandible defect was rehabilitated without postoperative infection or foreign body reaction during follow-ups, until a year. The 3D-printed titanium implant would be the one of the suitable treatment modalities for mandible reconstruction considering all the aspect of mandibular functions.


Myeloid differentiation factor 88-dependent post-transcriptional regulation of cyclooxygenase-2 expression by CpG DNA: tumor necrosis factor-alpha receptor-associated factor 6, a diverging point in the Toll-like receptor 9-signaling.
The immune stimulatory unmethylated CpG motifs present in bacterial DNA (CpG DNA) induce expression of cyclooxygenase-2 (cox-2). The present study demonstrates that CpG DNA can up-regulate cox-2 expression by post-transcriptional mechanisms in RAW264.7 cells. To determine the CpG DNA-mediated signaling pathway that post-transcriptionally regulates cox-2 expression, a cox-2 translational reporter (COX2-3'-UTR-luciferase) was generated by inserting sequences within the 3'-untranslated region (UTR) of cox-2 to the 3' end of the luciferase gene under control of the SV40 promoter. CpG DNA-induced COX2-3'-UTR-luciferase activity was completely inhibited by an endosomal acidification inhibitor chloroquine, a Toll-like receptor 9 antagonist inhibitory CpG DNA, or overexpression of a dominant negative (DN) form of MyD88. However, overexpression of DN-IRAK-1 or DN-TRAF6 resulted in substantial, but not complete, inhibition of the CpG DNA-induced COX2-3'-UTR-luciferase activity. Activation of all three MAPKs (ERK, p38, and JNK) was required for optimal COX2-3'-UTR-luciferase activity induced by CpG DNA. Overexpression of DN-TRAF6 suppressed CpG DNA-mediated activation of p38 and JNK, but not ERK, explaining the partial inhibitory effects of DN-TRAF6 on CpG DNA-induced COX2-3'-UTR-luciferase activity. Co-expression of DN-TRAF6 and N17Ras completely inhibited CpG DNA-induced COX2-3'-UTR-luciferase activity, indicating the involvement of Ras in CpG DNA-mediated ERK and COX2-3'-UTR regulation. Collectively, our results suggest that MyD88 and MAPKs play a key regulatory role in CpG DNA-mediated cox-2 expression at the post-transcriptional level and that TRAF6 is a diverging point in the Toll-like receptor 9-signaling pathway for CpG DNA-mediated MAPK activation.


Long-term Outcomes of Titanium Ossiculoplasty in Chronic Otitis Media.
The primary objective is to report long-term hearing outcomes (>2 years) after titanium ossiculoplasty in patients with chronic otitis media. Case series with chart review. Tertiary care hospital. In total, 156 patients with chronic otitis media undergoing titanium ossiculoplasty were included. The primary outcome measure was the long-term postoperative ABG. The stability of hearing over time was determined by comparing short-term and long-term postoperative air-bone gap (ABG). Secondary outcome measures included ΔABG, postoperative speech reception thresholds, air-conduction pure-tone average (AC PTA), word recognition scores, and percentage of patients achieving ABG ≤20 dB. Revision and extrusion rates were examined. At short-term follow-up (<6 months), mean postoperative ABG was 18.4 ± 10.6 dB and AC PTA was 31.7 ± 15.2 dB; 67% of patients achieved ABG ≤20 dB. At long-term follow-up (>2 years), mean ABG was 20.0 dB ± 15.4 and AC PTA was 35.3 ± 16.1 dB; 60% of patients achieved ABG ≤20. At both short- and long-term follow-up, ABG and AC PTA were significantly improved compared with preoperative values. No difference in hearing outcomes was observed when comparing partial titanium ossicular prostheses (PORPs) to total titanium ossicular prostheses (TORPs) at either short- or long-term follow-ups. In patients with both short- and long-term follow-up (n = 50), deterioration in hearing was noted (3.4 dB, P = .04). When analyzed by type of prosthesis, PORPs demonstrated statistically significant deterioration in ABG over time (4.9 dB, P = .02), while TORPs did not (2.5 dB, P = .50). The long-term extrusion rate was 3.2%. With a minimum follow-up of 2 years, titanium ossiculoplasty provides good long-term hearing results. Modest deterioration in hearing is noted over time.


Human antibody libraries in Escherichia coli.
A potentially vast pool of human antibodies with novel specificities for diagnostic and therapeutic purposes can be generated in Escherichia coli. Antibodies to infectious agents have already been isolated by amplifying the heavy and light chain repertoires of donor lymphocytes and they have even been rescued many years after the initial infection from memory cells cultivated in SCID mice. Eventually, however, the creation of extremely large and diverse libraries from the naive antibody repertoire of unactivated B lymphocytes or by gene synthesis using random oligonucleotides for the hypervariable regions could provide a rapid means of obtaining human antibodies to any particular antigen. An important breakthrough for exploiting the potential size and diversity of these libraries has been the development of systems for the surface display of antibodies that are physically linked to their own genes. This allows large numbers of clones to be screened simultaneously and antibodies with affinities of up to 10(8) M-1 have already been obtained using these vectors. It seems quite feasible, therefore, that antibodies with affinities approaching those obtained in the secondary immune response can be obtained by systematically optimizing the strategies for making antibody libraries. Furthermore, it might be possible to establish extremely large antibody repertoires in E. coli by the in vivo recombination of phage and plasmid antibody libraries. The affinity of the selected antibodies could be increased by chain shuffling or random mutagenesis followed by several rounds of selection under increasingly stringent conditions.


Clinical features of young women with hypergonadotropic amenorrhea.
One hundred fifteen women under age 40 presenting with hypergonadotropic amenorrhea (follicle-stimulating hormone greater than 40 mIU/mL) were evaluated. Incomplete pubertal maturation and chromosomal abnormalities were more likely in the 18 women (15.7%) with primary amenorrhea than in those with secondary amenorrhea. The 97 women with secondary hypergonadotropic amenorrhea were significantly more apt to complain of symptoms of estrogen deficiency, have been pregnant before diagnosis, and have evidence of ovulation after diagnosis. Withdrawal bleeding occurred commonly (greater than 48%) in those women administered exogenous progestin. Immune abnormalities occurred with approximately equal frequency (17.4%), and spinal bone density was decreased in both groups.


A study of illness referral in a Spanish-speaking community.
In an anthropologic study of illness referral among Latin-American immigrants three phases were ascertained: First, there was extended use of self-treatment. Second, referrals were made to the social network, particularly to people from the same country of origin. Finally, referrals to the professional network were made to professionals with the same cultural heritage. Latin-American immigrant families living in a cooperative were studied over a 14-month period, utilizing the method of participant observation, a family health calendar, and interviews. This report focuses on the results of the family health calendar. Most illnesses reported by families did not go beyond self-treatment. Cultural influences including language, social network, priorities of daily living were related to the alternatives selected by families when illness incidents occurred.


Tirzepatide as Monotherapy Improved Markers of Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes (SURPASS-1).
Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for treatment of type 2 diabetes (T2D). SURPASS-1, a phase 3 trial of tirzepatide monotherapy in people with early T2D, enables evaluating effects of tirzepatide on pancreatic beta-cell function and insulin sensitivity (IS) without other background antihyperglycemic medications. Explore changes in biomarkers of beta-cell function and IS with tirzepatide monotherapy. Post hoc analyses of fasting biomarkers with analysis of variance and mixed model repeated measures. Forty-seven sites in 4 countries. Four hundred seventy-eight T2D participants. Tirzepatide (5, 10, 15 mg), placebo. Analyze biomarkers of beta-cell function and IS at 40 weeks. At 40 weeks, markers of beta-cell function improved with tirzepatide monotherapy vs placebo with reductions from baseline in fasting proinsulin levels (49-55% vs -0.6%) and in intact proinsulin/C-peptide ratios (47-49% vs -0.1%) (P < .001, all doses vs placebo). Increases from baseline in homeostatic model assessment for beta-cell function (computed with C-peptide) (77-92% vs -1.4%) and decreases in glucose-adjusted glucagon levels (37-44% vs +4.8%) were observed with tirzepatide vs placebo (P < .001, all doses vs placebo). IS improved as indicated by reductions from baseline in homeostatic model assessment for insulin resistance (9-23% vs +14.7%) and fasting insulin levels (2-12% vs +15%), and increases in total adiponectin (16-23% vs -0.2%) and insulin-like growth factor binding protein 2 (38-70% vs +4.1%) with tirzepatide vs placebo at 40 weeks (P ≤ .031, all doses vs placebo, except for fasting insulin levels with tirzepatide 10 mg). As monotherapy for early T2D, tirzepatide achieved significant improvements in biomarkers of both pancreatic beta-cell function and IS.


Chinese college students' SCL-90 scores and their relations to the college performance.
Since the Symptom Checklist-90 (SCL-90) was introduced in China about 30 years ago, most studies with the instrument were conducted among clinical samples. This study tried to explore factor structure in a non-clinical and college student sample. We also planned to find if the SCL-90 scores are correlated with any school performance of the college students, such as grades and extra curriculum activities. The instrument together with a full-length questionnaire was administered to 1125 undergraduate students in a four-year university in China. Principal component factor analyses yielded a factor structure with some differences from those previously reported for other populations. We only derived four distinct factors: depression, somatization, obsessive-compulsive, and phobic anxiety. interpersonal sensitivity, anxiety, hostility, paranoid ideation, and psychoticism all failed to yield. Reliability and validity tests proved that SCL-90 could be used on the sample of Chinese college students. Results showed that Rural/urban location, the only child status, attending sports competition, and winning an award in publishing articles are significantly associated with the SCL-90 scores. Students who attended sports competition had lower SCL-90 scores while students who won an award from publishing articles had higher SCL-90 scores than students who did not.


Identification of penumbra in acute ischemic stroke using multimodal MR imaging analysis: A case report study.
Ischemic etiology of stroke is the most common health issue. Differentiating the ischemic core from the associated penumbra is tremendously important in tailoring an effective therapeutic strategy and potential intervention. Additionally, the degree of cell damage adjacent to the ischemic core may be either reversible or irreversible, which may also affect clinical outcomes. We describe a case of a 58-year-old female, who was diagnosed with global aphasia and fluctuating right-sided hypoesthesia. Multimodal MR imaging analysis was obtained, with cerebral blood flow and mean transit time , demonstrating an infarcted core with an even larger penumbra, suggesting potentially salvageable tissue. We concluded that quantified perfusion imaging data should be used in combination with other MR protocols to determine at-risk tissues. This case substantiates the role of multimodal imaging of the penumbra as a routine part of acute stroke workup and management.


Wastewater-derived biohydrogen: Critical analysis of related enzymatic processes at the research and large scales.
Organic-rich wastewater is a feasible feedstock for biohydrogen production. Numerous review on the performance of microorganisms and the diversity of their communities during a biohydrogen process were published. However, there is still no in-depth overview of enzymes for biohydrogen production from wastewater and their scale-up applications. This review aims at providing an insightful exploration of critical discussion in terms of: (i) the roles and applications of enzymes in wastewater-based biohydrogen fermentation; (ii) systematical introduction to the enzymatic processes of photo fermentation and dark fermentation; (iii) parameters that affect enzymatic performances and measures for enzyme activity/ability enhancement; (iv) biohydrogen production bioreactors; as well as (v) enzymatic biohydrogen production systems and their larger scales application. Furthermore, to assess the best applications of enzymes in biohydrogen production from wastewater, existing problems and feasible future studies on the development of low-cost enzyme production methods and immobilized enzymes, the construction of multiple enzyme cooperation systems, the study of biohydrogen production mechanisms, more effective bioreactor exploration, larger scales enzymatic biohydrogen production, and the enhancement of enzyme activity or ability are also addressed.


Association of β-blocker use with survival and pulmonary function in patients with chronic obstructive pulmonary and cardiovascular disease: a systematic review and meta-analysis.
The aim of this study was to clarify the effect of β-blockers (BBs) on respiratory function and survival in patients with chronic obstructive pulmonary disease with cardiovascular disease (CVD), as well as the difference between the effects of cardioselective and noncardioselective BBs. We searched for relevant literature in four electronic databases, namely, PubMed, EMBASE, Cochrane Library, and Web of Science, and compared the differences in various survival indicators between patients with chronic obstructive pulmonary disease taking BBs and those not taking BBs. Forty-nine studies were included, with a total sample size of 670 594. Among these, 12 studies were randomized controlled trials (RCTs; seven crossover and five parallel RCTs) and 37 studies were observational (including four post hoc analyses of data from RCTs). The hazard ratios (HRs) of chronic obstructive pulmonary disease exacerbation between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.77 [95% confidence interval (CI) 0.67, 0.89], 0.72 [95% CI 0.56, 0.94], and 0.98 [95% CI 0.71, 1.34, respectively] (HRs <1 indicate favouring BB therapy). The HRs of all-cause mortality between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.70 [95% CI 0.59, 0.83], 0.60 [95% CI 0.48, 0.76], and 0.74 [95% CI 0.60, 0.90], respectively (HRs <1 indicate favouring BB therapy). Patients with Chronic obstructive pulmonary disease treated with cardioselective BBs showed no difference in ventilation effect after the use of an agonist, in comparison with placebo. The difference in mean change in forced expiratory volume in 1 s was 0.06 [95% CI -0.02, 0.14]. The use of BBs in patients with chronic obstructive pulmonary disease is not only safe but also reduces their all-cause and in-hospital mortality. Cardioselective BBs may even reduce chronic obstructive pulmonary disease exacerbations. In addition, cardioselective BBs do not affect the action of bronchodilators. Importantly, BBs reduce the heart rate acceleration caused by bronchodilators. BBs should be prescribed freely when indicated in patients with chronic obstructive pulmonary disease and heart disease.


Pediatric spinal cord injury: approach for urological rehabilitation and treatment.
As proposed in this report, early urological rehabilitative management of patients with spinal cord injuries (SCIs) is mandatory, in order to prevent a poorly compliant bladder with related upper urinary tract complications and secondary renal failure. Moreover, the approach to treating this traumatic condition in children must be as much rapid as appropriate. We evaluated our experience of the last 5 years with 17 patients (12 males and five females), with a mean age of 9.6 years at injury (range 6 months-18 years), all affected by an SCI and with direct trauma involved in more than 50%. Mechanism of injury, lesional level, the mean interval between injury and bladder management onset, and the mean interval between bladder management onset and our last control were evaluated. A standardized diagnostic approach was instituted, and all patients received at least a video-urodynamic evaluation before and after the start of urological management. A continence score was established and evaluated before and at least 6 months after the application of rehabilitation treatments (catheterization, medication). Follow-up ranged from 12 to 60 months (average 29.6 months). Sixteen of the 17 patients showed, at first urodynamic evaluation, a neurogenic overactive bladder. Mean bladder maximum capacity was 287.7 ml+/-146.4 SD. Mean reflex volume and end filling pressure were 119.7 ml+/-76.4 SD and 44.6 cmH(2)O+/-25 SD, respectively. Detrusor sphincter dyssynergia was present in 16 out of 17 of the cases. All patients but one began self-catheterization and medication (anticholinergics). Urinary continence improved in all patients but one. An adjunctive endoscopic procedure for continence was carried out in five out of 17 cases. The upper urinary tract was involved in two out of 17 cases. A prompt and standardized urological approach to pediatric SCIs is mandatory. The aims of this initial management are the prevention of further secondary damage to the upper tract and the achievement of a socially acceptable degree of urinary continence as soon as possible after the traumatic event.


A serum exosomal microRNA panel as a potential biomarker test for gastric cancer.
The findings from several studies have suggested that circulating miRNAs are imbalanced with the genesis of gastric cancer (GC). Both normal and cancer cells can generate and secrete exosomes, which are nanosized membrane vesicles that can transport microRNAs and proteins. Emerging evidence indicates that the exosomes secreted by cancer cells can be released into the circulatory system. In this study, we investigated whether circulating exosomal miRNAs can be used to discriminate individuals with GC from healthy controls (NCs). Based on the quantitative reverse transcription polymerase chain reaction (qRT-PCR), four miRNAs (miR-19b-3p, miR-17-5p, miR-30a-5p, and miR-106a-5p) related to GC pathogenesis were identified in serum-circulating exosomes from a cohort of 20 healthy controls and 20 individuals with GC in the initial screening phase. The distinguished miRNAs were further validated in the training (90 GC vs. 90 NCs) and blinded phases 20 GC vs. 20 NCs), and the area under receiver operating characteristic (ROC) curves of these miRNAs were analyzed. We found that miR-19b and miR-106a were markedly overexpressed in individuals with GC compared to NCs (P < 0.0001). Besides, the ROC analyses yielded the AUC values of 0.786 for miR-106a-5p, 0.769 for miR-19b-3p and combined ROC analysis revealed the highest AUC value of 0.814 in discriminating GC patients from NCs. Furthermore, based on the model developed from the data, a signature composed of the 2 miRNAs (miR-19b-3p and miR-106a-5p) correctly discriminated 19 out of 20 GC serum samples (95% sensitivity) and 18 out of 20 normal samples (90% specificity) in the blinded phase. Moreover, the validated miRNAs were related to GC lymphatic metastasis (P < 0.01) and expressed at higher levels in stages III and IV compared to I and II stages (P < 0.05). These results suggest that serum exosomal miR-19b-3p and miR-106a-5p are novel potential biomarkers for detecting GC.


Enhanced biodegradation resistance of biomodified jute fibers.
A bio-catalyzed process has been developed for treating jute fibers to enhance their tensile strength and resistance against biodegradation. Lipolytic bacteria were used in the process to transesterify jute fibers by replacing hydrophilic hydroxyl groups within cellulose chains with hydrophobic fatty acyl chains. Transesterification of some of the hydroxyl groups within the fiber was confirmed with FTIR, UV-vis spectroscopy, (13)C solid state NMR, gas chromatography and analytical determination of ester content. Biomodified fibers exhibited remarkably smaller affinity to water and moisture and retained 62% of their initial tensile strengths after being exposed to a composting environment over 21 days. The corresponding figure for untreated fibers was only 30%. Efficacy of the process reported herein in terms of tensile strength and biodegradation resistance enhancement of fibers achieved after treatment appears to be comparable with similar chemical processes and better than the enzyme-catalyzed alternatives.


The proteasome metabolizes peptide-mediated nonviral gene delivery systems.
The proteasome is a multisubunit cytosolic protein complex responsible for degrading cytosolic proteins. Several studies have implicated its involvement in the processing of viral particles used for gene delivery, thereby limiting the efficiency of gene transfer. Peptide-based nonviral gene delivery systems are sufficiently similar to viral particles in their size and surface properties and thereby could also be recognized and metabolized by the proteasome. The present study utilized proteasome inhibitors (MG 115 and MG 132) to establish that peptide DNA condensates are metabolized by the proteasome, thereby limiting their gene transfer efficiency. Transfection of HepG2 or cystic fibrosis/T1 (CF/T1) cells with CWK18 DNA condensates in the presence of MG 115 or MG 132 resulted in significantly enhanced gene expression. MG 115 and MG 132 increased luciferase expression 30-fold in a dose-dependent manner in HepG2 and CF/T1. The enhanced gene expression correlated directly with proteasome inhibition, and was not the result of lysosomal enzyme inhibition. The enhanced transfection was specific for peptide DNA condensates, whereas Lipofectamine- and polyethylenimine-mediated gene transfer were significantly blocked. A series of novel gene transfer peptides containing intrinsic GA proteasome inhibitors (CWK18(GA)n, where n=4, 6, 8 and 10) were synthesized and found to inhibit the proteasome. The gene transfer efficiency mediated by these peptides in four different cell lines established that a GA repeat of four is sufficient to block the proteasome and significantly enhance the gene transfer. Together, these results implicate the proteasome as a previously undiscovered route of metabolism of peptide-based nonviral gene delivery systems and provide a rationale for the use of proteasome inhibition to increase gene transfer efficiency.


Synergistic influence of cytokine gene polymorphisms over the risk of dementia: A multifactor dimensionality reduction analysis.
Evidence supports the important role of neuroinflammation in some types of dementia. This study aimed to evaluate the effect of epistasis of gene cytokines such as interleukin (IL)-α, IL-6, tumor necrosis factor (TNFα), and interferon-gamma (IFN-γ) on the susceptibility to the development of dementia. In the study, 221 patients diagnosed with dementia and 710 controls were included. The multifactor-dimensionality reduction (MDR) analysis was performed to identify the epistasis between SNP located in genes of IL-α (rs1800587), IL-6 (rs1800796), TNFα (rs361525 and rs1800629), and IFNγ (rs2069705). The best risk prediction model was identified based on precision and cross-validation consistency. Multifactor-dimensionality reduction analysis detected a significant model with the genes TNFα, IFNγ, IL1α, and IL6 (prediction success: 72%, p < 0.0001). When risk factors were analyzed with these polymorphisms, the model achieved a similar prediction for dementia as the genes-only model. These data indicate that gene-gene interactions form significant models to identify populations susceptible to dementia.


Changes in baroreflex control of renal sympathetic nerve activity in high-fat-fed rats as a predictor of hypertension.
There is evidence that obesity is associated with increased sympathetic activity and hypertension. However, the mechanisms responsible for these changes are not fully understood. Therefore, the aim of the present study was to evaluate the cardiovascular function and the baroreceptor reflex control of renal sympathetic nerve activity (rSNA) in rats exposed to a high-fat diet over different periods (10 and 20 weeks) compared to control rats. Serum leptin levels were assessed for all time points. Male Wistar rats weighing 150-180 g were used. Four groups of rats were studied: control 10 weeks (Ct10), obese 10 weeks (Ob10), control 20 weeks (Ct20), and obese 20 weeks (Ob20). Blood pressure (BP) and rSNA were recorded in urethane-anesthetized rats (1.4 g/kg, intravenous).The sensitivity of rSNA responses to baroreceptor reflex was assessed by changes in BP induced by increasing doses of phenylephrine or sodium nitroprusside. Significant and progressive increases in serum leptin levels were found in the obese rats, but not in the control rats. No changes in basal BP or rSNA were found in the Ob10 and Ob20 groups; however, a significant impairment in the baroreceptor sensitivity was observed in the Ob20 group for phenylephrine (slope Ob20: -0.78 ± 0.12 vs. Ct20: -1.00 ± 0.08 potential per second (pps)/mm Hg, P < 0.05) and sodium nitroprusside (slope Ob20: -0.82 ± 0.09 vs. 1.13 ± 0.13 pps/mm Hg, P < 0.05). The results suggest that the baroreceptor dysfunction that controls the rSNA is an initial change in the obesity induced in high-fat-fed rats, which might be a predictor of sympathoexcitation and hypertension associated to obesity.


Tumors of the epididymis.
Tumors of the epididymis, both primary and secondary, whether benign or malignant are very rare. The elements of the spermatic duct system, whether inside the testis or outside it in the epididymis and spermatic cord, exhibit only 1/20th of that of the germinal epithelium. In accordance with the mesodermal, or mesothelial origin of the whole spermatic ducr system, tumors of the epididymis and spermatic cord are - with few exceptions - mesenchymal tumors, the most frequent of these being the so-called adenomatoid tumor, a benign slowly growing tumor. With regard to the relative frequency of the various extratesticular tumors, a British panel has shown that one quarter of its cases are adenomatoid tumors, a second quarter sarcomas of children and juveniles (rhabdomyosarcomas and embryonic sarcomas), a third quarter sarcomas of adults and aged, while the last quarter includes simple benign mesenchymal tumors, mixed tumors, metastatic tumors, and others. There is only one extremely rare epithelial tumor of the epididymis, the papillary cystadenoma, which seems to be a partial menifestation or forme fuste of Hippel-Lindau's disease. So far only 40 cases have been described in the world literature. Therapy of intrascrotal but extratesticular tumors always ought to be surgical: if the tumor proves to be benign, simple excision suffices. In cases of malignancy, immediate inguinal lymphadenectomy and - as with testicular tumors - lymphography followed by retroperitoneal lymphadenectomy. Whether one should, in principle, then continue treatment either chemotherapeutically or radiotherapeutically, or do so only when there is evidence of metastasis, is a question whiich still remains open.


Early and frequent exposure to antibiotics in children and the risk of obesity: systematic review and meta-analysis of observational studies.
Background: This study aimed to systematically evaluate the available evidence on prenatal and early infancy antibiotic exposure and the association with overweight and obesity in later childhood. Methods: We conducted a comprehensive search of Embase, MEDLINE, and Web of Science for observational studies assessing prenatal and early antibiotic exposure on the risk of overweight and obesity. We independently assessed the risk of bias using the ROBINS instrument and the overall quality of evidence using the GRADE approach. Results: Our search identified thirteen observational studies including 554,983 participants; most studies were at moderate risk of bias. We found a statistically significant impact of early antibiotic exposure and the risk of being overweight later in childhood (OR 1.18; 95% CI 1.05 to 1.34) (very low quality evidence). We also found that early childhood antibiotic exposure was associated with the risk for childhood obesity (OR 1.14; 95% CI 1.04 to 1.24) (very low quality evidence). Conclusions: Very low quality evidence suggests that exposure to antibiotics early in life may be associated with an increased risk of being overweight and obese in later childhood. However, very low quality evidence raises serious questions about the plausibility of prenatal and early infancy antibiotic exposure being causally related to weight in children. PROSPERO registration: CRD42016050011 (14/12/2016).


Diagnostic capacity for viral haemorrhagic septicaemia virus (VHSV) infection in rainbow trout (Oncorhynchus mykiss) is greatly increased by combining viral isolation with specific antibody detection.
Detection of disease specific antibodies in farmed rainbow trout (Oncorhynchus mykiss) has been proposed as an alternative or supplement to the currently approved procedures for diagnosis and surveillance in this species. In samples from natural outbreaks of the disease viral haemorrhagic septicaemia (VHS) at two freshwater farms in southern Denmark serologic testing was used to broaden the diagnostic window from outbreak to diagnosis in the laboratory as compared to traditional procedures of isolation and identification of the virus. The serologic assay clearly increased the chance of detecting present or previous infections where the pathogen could not be isolated by standard methods (indicating older infections where the virus had been cleared). Our data allowed us to monitor the levels of neutralising antibodies in relation to the presence of the virus in fish experiencing two different types of outbreaks at two different farms. By sequence analysis of the viral glycoprotein from selected isolates we found no evidence for escape mutants having developed in the fish showing high titres of neutralising antibodies.


Subcellular localization of squalene synthase in human hepatoma cell line Hep G2.
Using the Hep G2 cell line as a model for the human hepatocyte the question was studied whether Hep G2-peroxisomes could be able to synthesize cholesterol. Hep G2 cell homogenates were applied to density gradient centrifugation on Nycodenz, resulting in good separation between the organelles. The different organelle fractions were characterized by assaying the following marker enzymes: catalase for peroxisomes, glutamate dehydrogenase for mitochondria and esterase for endoplasmic reticulum. Squalene synthase activity was not detectable in the peroxisomal fraction. Incubation of Hep G2 cells with U18666A, an inhibitor of the cholesterol synthesis at the site of oxidosqualene cyclase, together with heavy high density lipoprotein, which stimulates the efflux of cholesterol, led to a marked increase in the activity of squalene synthase as well as HMG-CoA reductase, whereas no significant effect on the marker enzymes was observed. Neither enzyme activity was detectable in the peroxisomal density gradient fraction, suggesting that in Hep G2-peroxisomes cholesterol synthesis from the water-soluble early intermediates of the pathway cannot take place. Both stimulated and non-stimulated cells gave rise to preparations where squalene synthase activity was comigrating with the reductase activity at the lower density side of the microsomal fraction; however, it was also present at the high density side of the microsomal peak, where reductase activity was not detected.


Response characteristics of tooth pulp-driven postsynaptic neurons in the spinal trigeminal subnucleus interpolaris of the cat: comparison with primary afferent fiber, subnucleus caudalis, reflex, and sensory responses.
Tooth pulp-evoked single neuron responses were recorded in the spinal trigeminal subnucleus interpolaris of the cat. The thresholds to monopolar electric pulses of varying duration (0.2-20 ms) were determined using a constant current stimulator. The thresholds were comparable with those of primary afferent A-fibers, although the most sensitive primary afferent fibers have lower thresholds. The thresholds and latencies showed that none of the interpolaris neurons received their input solely from intradental C-fibers. The most sensitive subnucleus interpolaris neurons had lower thresholds than the respective subnucleus caudalis neurons studied in our previous work. The thresholds and strength-duration curves of the most sensitive interpolaris neurons and of the tooth pulp-elicited jaw-opening reflex are nearly similar, although the jaw reflex can be elicited at an intensity which is slightly lower than that needed to activate the most sensitive interpolaris neurons of the present sample. The most sensitive interpolaris neurons were activated at current intensities that were below the intensity needed to produce liminal dental pain in man, and the strength-duration curves of these neurons were flatter than the curve depicting liminal dental pain sensation in man. The relationship between stimulus intensity and response magnitude could be well described by power functions, the median exponent of which was 1.251. A conditioning stimulation of the tooth pulp at low intensity produced a short (less than 25 ms) enhancement of the response to the following test stimulus, whereas a high intensity conditioning stimulus produced a longer (greater than 40 ms) suppression of the response to the following stimulus. The threshold of 33% of the neurons was elevated during a noxious tail pinch, and this elevation was not reversed by naloxone, an opioid antagonist. The results indicate that in the trigeminal subnucleus interpolaris there are tooth pulp-driven neurons with an input from intradental A-fibers and that a considerable temporal summation of impulses from primary afferent fibers is needed to activate most of them. Human dental pain thresholds cannot be explained by the liminal response properties of the most sensitive interpolaris neurons, but they may be important in the mediation of near-threshold reflex events. It is possible, however, that the high-threshold interpolaris neurons may have a role in the mediation of sensory responses.


4D printing of biocompatible, hierarchically porous shape memory polymeric structures.
Conventional implants tend to have significant limitations, as they are one-size-fits-all, require monitoring, and have the potential for immune rejection. However, 4D Printing presents a method to manufacture highly personalized, shape-changing, minimally invasive biomedical implants. Shape memory polymers (SMPs) with a glass transition temperature (Tg) between room and body temperature (20-38 °C) are particularly desirable for this purpose, as they can be deformed to a temporary shape before implantation, then undergo a shape change within the body. Commonly used SMPs possess either an undesirable Tg or lack the biocompatibility or mechanical properties necessary to match soft biological tissues. In this work, Poly(glycerol dodecanoate) acrylate (PGDA) with engineered pores is introduced to solve these issues. Pores are induced by porogen leaching, where microparticles are mixed with the printing ink and then are dissolved in water after 3D printing, creating a hierarchically porous texture to improve biological activity. With this method, highly complex shapes were printed, including overhanging structures, tilted structures, and a "3DBenchy". The porous SMP has a Tg of 35.6 °C and a Young's Modulus between 0.31 and 1.22 MPa, comparable to soft tissues. A one-way shape memory effect (SME) with shape fixity and recovery ratios exceeding 98 % was also demonstrated. Cultured cells had a survival rate exceeding 90 %, demonstrating cytocompatibility. This novel method creates hierarchically porous shape memory scaffolds with an optimal Tg for reducing the invasiveness of implantation and allows for precise control over elastic modulus, porosity, structure, and transition temperature.


Root growth and water relations of oak and birch seedlings.
First year seedlings of English oak (Quercus Cobur) and silver birch (Betula pendula) were subjected to pressure-volume analysis to investigate the water potential components and cell wall properties of single leaves. It was hoped that this rapid-drying technique would differentiate between reductions in plant solute potential resulting from dehydration and the effects of solute accumulation.Comparison of results from these experiments with those of slow drying treatments (over a number of days) with plants growing in tubes of soil, indicated that some solute accumulation may have occurred in drying oak leaves. High leaf turgor and leaf conductance were maintained for a significant period of the drying cycle. Roots of well-watered oak plants extended deep into the soil profile, and possibly as a result of solute regulation and therefore turgor maintenance, root growth of unwatered plants was greater than that of their well-watered counterparts. This was particularly the case deep in the profile. As a result of deep root penetration, water deep in the soil core was used by oak plants to maintain plant turgor, and quite low soil water potentials were recorded in the lower soil segments.Root growth of well-watered birch seedlings was prolific but roots of both well-watered and unwatered plants were restricted to the upper part of the profile. Root growth of unwatered plants was reduced despite the existence of high soil water potentials deep in the profile. Shallow rooting birch seedlings were unable to use this water.Pressure-volume analysis indicated that significant reductions of water potential, which are required for water uptake from drying soil, would occur in oak with only a small reduction in plant water content compared to the situation in birch. This was a result of the low solute potential in oak leaves combined with a high modulus of elasticity of cell walls. Deep rooting of oak seedlings, combined with these characteristics, which will be particularly important when soil deep in the profile begins to dry, mean that this species may be comparatively successful when growing on dry sites.


Prognostic significance of cytokine receptor-like factor 2 alterations in acute lymphoblastic leukemia: a meta-analysis.
Cytokine receptor-like factor 2 (CRLF2) has been shown to play a role in the pathogenesis of acute lymphoblastic leukemia (ALL). Studies have examined the relationship between CRLF2 alterations such as over-expression or deregulation and clinical outcome in childhood ALL, but the results are conflicting. This meta-analysis aimed to explore the association between CRLF2 alterations and survival of pediatric patients with ALL. Electronic databases updated to March 2014 were searched for relevant studies. A meta-analysis was made of twelve studies including 5945 patients to evaluate the prognostic significance of CRLF2 alterations on survival in childhood ALL. Hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled across the studies using a fixed-effects model. CRLF2 over-expression in childhood ALL was associated with poor prognosis in terms of relapse-free survival (RFS; HR=1.70, 95% CI=1.28-2.24, P=0.000), event-free survival (EFS; HR=1.78, 95% CI=1.05-3.01, P=0.032), and overall survival (OS; HR=2.28, 95% CI=1.42-3.65, P=0.001). The combined data also suggested that CRLF2 deregulation in childhood ALL was correlated with poor EFS (HR=1.95, 95% CI=1.46-2.61, P=0.000), RFS (HR=2.20, 95% CI=1.53-3.18, P=0.000), and OS (HR=1.89, 95% CI=1.24-2.87, P=0.003). Subgroup analysis on multivariate HRs showed that CRLF2 deregulation independently predicted a poor prognosis for childhood ALL. The present meta-analysis reveals that both CRLF2 over-expression and deregulation are associated with poor prognosis in pediatric patients with ALL.


Effect of oxidative stress on protein thiols in the blue mussel Mytilus edulis: proteomic identification of target proteins.
Protein thiols are targets of oxidative stress. Their modification was analysed in gill extracts of the mussel Mytilus edulis, exposed to menadione. Diagonal gel electrophoresis revealed two clusters of carbonylated proteins involved in interchain disulphide linkages. Immunoblotting identified these as being associated with protein disulphide isomerase (PDI) and actin and this was confirmed by immunoprecipitation. Protein free thiols (-SH) were identified in 2-DE separations by labelling with 5-iodoacetamidofluorescein (IAF). Cysteines involved in disulphide bridges were identified by blocking free -SH with N-ethylmaleimide, reducing disulphides with DTT and IAF labelling. Several protein spots containing free thiols disappeared on exposure to menadione. Conversely, new protein spots containing disulphides appeared in response to menadione which may be protective against oxidative stress. In-gel tryptic digestion followed by LC/MS-MS and database searching identified some of the free thiol targets: PDI; hsp gp96; calreticulin; heavy metal binding protein. Tubulin, PDI, enolase and gelsolin contained new disulphide bridges in response to menadione. Our findings indicate a protein level response to oxidative stress principally involving PDI, chaperone-like and cytoskeletal proteins. Since many environmental pollutants cause oxidative stress, studies on PDI and structural proteins may be particularly relevant to understanding toxicity in this popular sentinel species.


Villous adenoma of the duct of Wirsung.
A patient presenting with recurrent pancreatitis was found to have a benign polypoid villous adenoma of the duct of Wirsung. The tumor was excised locally via transduodenal access to the duct. The patient has now remained free of pancreatitis for 24 months. Obstruction of the pancreatic duct by this rare tumor appears to have been the cause of pancreatitis. Villous adenomas of the pancreatic duct epithelium may be premalignant.


Reliability of stemless shoulder arthroplasty in rheumatoid arthritis: observation of early lysis around the humeral component.
To evaluate whether stemless shoulder implants in rheumatoid arthritis (RA) patients provide comparable functional outcomes to patients with osteoarthritis or post-traumatic arthritis. In addition, the study assessed for differences in incidence of radiolucent lines or proximal humeral bone loss during radiographic follow-up. Consecutive stemless shoulder arthroplasties performed in RA patients and a matched control group were retrospectively identified between February 2012 and 2018. Thirty-five patients were included in each group: 24 total shoulder arthroplasty (TSA) and 11 hemiarthroplasty (HA). Patients were evaluated annually using the Oxford Shoulder Score (OSS) and radiographically. The mean OSS significantly improved in all groups until 24 months. The mean improvement for RA TSA and HA patients at 24 months was 19.86 (95% CI 10.66-29.05, p = 0.0004) and 19.71 (95% CI 7.33-32.31, p = 0.0084), respectively. The mean improvement in the control TSA and HA patients at 24 months was 20.86 (95% CI 17-24.71, p = 0.0001) and 17.86 (95% CI 1.36-34.35, p = 0.0381), respectively. During the study period, two patients in the RA TSA group (8%), one patient in the control TSA group (4%) and one patient in the control HA group (9%) required revision. The proportion of progressive proximal humeral bone loss after TSA was 33% in the RA group and 13% in the control group. Stemless shoulder implants can provide significant improvement in functional scores in RA patients in the short term. However, early bone loss around the humeral implant is a concern and the authors recommend long-term clinical and radiological follow-up.


Real-world experience with Grazoprevir/Elbasvir in the treatment of previously "difficult to treat" patients infected with hepatitis C virus genotype 1 and 4.
Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real-world experience, particularly in previously "difficult-to-treat" patients with chronic kidney diseases, human immunodeficiency virus-coinfected, cirrhotics, and treatment-experienced. The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer-2 database, large national real-world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online. A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV-coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent-to-treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult-to-treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation. GZR/EBR treatment carried-out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult-to-treat populations.


Screening for Atrial Fibrillation Using Economical and Accurate Technology (From the SAFETY Study).
The prevalence of atrial fibrillation (AF) is estimated at more than 3% in the adult population and there has been increased interest in screening for AF. In the SAFETY trial we chose to evaluate if inexpensive, wearable, consumer electrocardiography (ECG) sensing devices (Polar-H7 [PH7] and Firstbeat Bodyguard 2 [BG2]), could be used to detect AF accurately. We undertook a case-control study of 418 participants aged >65 (82 with AF and/or flutter at the study visit and 336 without) attending 3 general practice surgeries in Hampshire, UK for a single screening visit. The PH7 and BG2 devices were tested alongside 2 established AF detection devices (AliveCor and WatchBP) in random order and the diagnosis of AF was confirmed by 12-Lead ECG interpreted by a panel of cardiologists. The sensitivity (95% confidence interval [CI] range), specificity (95% CI range), and overall accuracy (95% CI range) of the 4 devices were: AliveCor: 87.8% (78.7% to 94.0%), 98.8% (97.0% to 99.7%), 96.7% (94.4% to 98.2%); WatchBP: 96.3% (89.7% to 99.2%), 93.5% (90.3% to 95.9%), 94.0% (91.3% to 96.1%): PH7: 96.3% (89.7% to 99.2%), 98.2% (96.2% to 99.3%), 97.9% (96.0% to 99.0%). BG2: 96.3% (89.7% to 99.2%), 98.5% (96.6% to 99.5%), 98.1% (96.3% to 99.2%). The PH7 and BG2 devices were highly reliable (the devices acquired sufficient data and obtained a diagnostic result in all but 1 participant on the first attempt). In conclusion, inexpensive, consumer heart rate monitoring devices (PH7 and BG2) can be used to detect AF accurately with sensitivity and specificity >95%. The consumer devices performed as well or better than WatchBP and AliveCor and have the capability to store or transmit ECG data which could be used to confirm AF.


Anaemia of chronic diseases: Pathophysiology, diagnosis and treatment.
Anaemia of chronic disease (ACD) is generated by the activation of the immune system by autoantigens, microbial molecules or tumour antigens resulting in the release of cytokines that cause an elevation of serum hepcidin, hypoferraemia, suppression of erythropoiesis, decrease in erythropoietin (EPO) and shortening of the half-life of red blood cells. Anaemia is usually normocytic and normochromic, which is the most prevalent after iron deficiency anaemia, and it is the most frequent in the elderly and in hospitalized patients. If the anaemia is severe, the patient's quality of life deteriorates, and it can have a negative impact on survival. Treatment is aimed at controlling the underlying disease and correcting anaemia. Sometimes intravenous iron and EPO have been used, but the therapeutic future is directed against hepcidin, which is the final target of anaemia.


Synthesis and in vitro muscarinic activities of a series of 1,3-diazacycloalkyl carboxaldehyde oxime derivatives.
A series of 1,3-diazacycloalkyl carboxaldehyde oxime derivatives was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (OXO-M) and [3H]-pirenzepine (PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies measuring their potencies to inhibit the binding of OXO-M and PZ. Preferential inhibition of OXO-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs.


Central processing technician internship--a unique learning opportunity.
A critical shortage of qualified central processing technicians and the opening of a new central processing department (CPD) were driving forces behind the development of a CPD technician internship program at one facility. Classes focused on the principles and practices of central processing, and an OR observation gave interns the opportunity to see the impact that the work of the CPD has on OR function and patient care and safety. Program evaluations have been positive, and staff vacancies have been filled with the graduates of the internship program.


Successful treatment of pulmonary Nocardia farcinica infection with linezolid: case report and literature review.
Nocardia infection is rare but potentially fatal. Therapy of Nocardia infection remains difficult. Linezolid, a novel oxazolidinone antibiotic, has proven to be effective, but clinical data are limited. Here we describe a case of a 45-year-old man with pulmonary N. farcinica infection following a liver transplantation. The initial therapy was trimethoprim-sulfamethoxazole, which showed no effect. According to susceptibility test, linezolid was administered with clearly improving the patient's condition. The treatment was stopped for anemia as drug related adverse event, and the therapy lasted for as long as 5 months. At the end of treatment clinical cure was confirmed and anemia reversed after discontinuation of linezolid. We also analyzed the clinical data of previously published reports by literature review, focusing on the efficacy and safety of linezolid treatment for Nocardia infection.