Viability, heat stability and immunogenicity of four BCG vaccines prepared from four different BCG strains.
Four BCG strains, French 1173-P2, Danish 1331, Japanese 172 and Glaxo-1077, among those most widely used throughout the world for tuberculosis vaccination, were prepared according to the respective conditions in each BCG-production unit. These 16 vaccine preparations were distributed and compared using standardized in vitro and in vivo conditions, based on optical density and bacillary mass/ml. The results presented in this report concern only the 4 freeze-dried BCG strains prepared by the Institut Pasteur BCG unit. It is shown that these 4 preparations differ in their in vitro characteristics such as growth, morphology, heat stability and viability, tested by colony-forming units and the ATP content. In addition, statistically significant differences were observed in biological control tests performed in guinea-pigs and mice when they were immunized with the same concentrations of 4 reconstituted vaccines. For instance, in tests measuring hallmarks of cell-mediated immunity--such as local granuloma formation, spleen index, delayed-type hypersensitivity to tuberculin, and non-specific immunopotentiation to unrelated antigen--a ranking order of relative immunopotency of the four strains was made, giving the following classification in decreasing order: French 1173-P2, Danish 1331, Japanese 172 and Glaxo-1077. Specific acquired resistance after BCG vaccination in mice was obtained with all four vaccines. However, higher protection was observed in mice vaccinated with Glaxo-1077 and French 1173-P2 strains. No obvious correlation existed between the intensity of cellular post-vaccination resistance and the above CMI tests, except those concerning the three-week index of BCG infection measured in the spleen, which correlated with the protection test.


Primary adnexal angiosarcoma masquerading as periorbital hematoma.
We report an elderly woman who was anticoagulated and presented with a recent history of right-sided orbital contusion and a periorbital hematoma without clinical or radiological evidence of focal mass or orbital involvement. She was initially treated conservatively. Continued progression of adnexal swelling and erythema prompted further investigation, however. There was no improvement with surgical drainage alone; biopsy revealed angiosarcoma. The discovery of this vascular tumor underscores the importance of a reconsideration of the diagnosis in the face of counterintuitive findings. Additionally, we emphasize the need to consider malignancy in the differential diagnosis of prolonged periorbital swelling, regardless of a history of recent trauma.


Prospective cohort study on short-term outcomes of 3D-laparoscopic pancreaticoduodenectomy with stented pancreaticogastrostomy.
Minimally invasive pancreaticoduodenectomy, either laparoscopic or robotic, is a high-risk procedure with demanding learning curve. The aim of this prospective cohort study was to evaluate short-term clinical and oncologic outcomes of 3D-laparoscopic pancreaticoduodenectomy (3dLPD) with stented pancreaticogastrostomy (sPG) and Roux-en-Y gastroenterostomy (ryGES). Between March 2016 and July 2021, 347 consecutive patients underwent 3dLPD for confirmed or suspected pancreatic or periampullary tumors. Pancreatic duct diameter measured 3 mm or less in 221 (64%) and pancreatic texture was soft in 191 (55%) patients. Simultaneous resection of the superior mesenteric or portal vein was performed in 52 (15%) patients. Postoperative complications were observed in 189 (54%) patients, with severe complications (Clavien-Dindo grade > 2) in 68 (20%) including 4 (1.2%) deaths. Clinically relevant pancreatic fistula (cPOPF) occurred in 88 (25%), hemorrhage in 25 (7%), and bile leakage in 10 (3%) patients. Clinical pancreatic fistula was strongly associated with soft pancreatic texture and small pancreatic duct diameter (p < 0.001) and managed by endoscopic trans-gastric drainage in 34 (38.6%) patients, reoperation in 12 (13.6%), and ICU admission in 11 (12.5%). The remaining 31 (35%) patients with cPOPF were managed without invasive intervention. Median length of hospital stay after surgery was 13 (range 5-112; IQR 8-18) days. In pancreatic adenocarcinoma (PDAC) the R0-resection rate was 66/186 (36%), R1-indirect 95/186 (51%), and R1-direct 25 (13%). Median number of locoregional lymph nodes retrieved in PDAC was 21 (IQR 15-28). R0-resection rate for malignancy other than PDAC was 78/86 (91%) with a median of 16 (IQR 12-22) locoregional lymph nodes retrieved. 3dLPD with sPG and ryGES is associated with 1.2% mortality and 25% cPOPF. About two-third of patients with cPOPF were managed with some type of invasive intervention, whereas the intraoperatively placed drains sufficed in one-third of patients. Clinicaltrials.gov NCT02671357.


LASSO type penalized spline regression for binary data.
Generalized linear mixed models (GLMMs), typically used for analyzing correlated data, can also be used for smoothing by considering the knot coefficients from a regression spline as random effects. The resulting models are called semiparametric mixed models (SPMMs). Allowing the random knot coefficients to follow a normal distribution with mean zero and a constant variance is equivalent to using a penalized spline with a ridge regression type penalty. We introduce the least absolute shrinkage and selection operator (LASSO) type penalty in the SPMM setting by considering the coefficients at the knots to follow a Laplace double exponential distribution with mean zero. We adopt a Bayesian approach and use the Markov Chain Monte Carlo (MCMC) algorithm for model fitting. Through simulations, we compare the performance of curve fitting in a SPMM using a LASSO type penalty to that of using ridge penalty for binary data. We apply the proposed method to obtain smooth curves from data on the relationship between the amount of pack years of smoking and the risk of developing chronic obstructive pulmonary disease (COPD). The LASSO penalty performs as well as ridge penalty for simple shapes of association and outperforms the ridge penalty when the shape of association is complex or linear. We demonstrated that LASSO penalty captured complex dose-response association better than the Ridge penalty in a SPMM.


Historical and modern research on propolis and its application in wound healing and other fields of medicine and contributions by Polish studies.
The history of medical application of propolis (also known as bee glue) dates back to the times of ancient Greeks, Romans, Persians and Egyptians. Honey and other bee products, including propolis, occupy an important place in Polish folk medicine. Scientific research on propolis in Poland began in the early 1960s in Zabrze and continues until now. The aim of this review is to provide an overview of information on Polish research on propolis and its medical application with particular emphasis on studies concerning wound healing. Consequently, our goal is also to shed a new light on therapeutic potential of Polish propolis in order to support future research in the field. A systematic review of scientific literature on propolis and its medical application was performed by using the literature databases (PubMed, Web of Science, Google Scholar). We paid special attention to papers describing the effect of propolis on skin wound healing as well as to Polish contribution to research on propolis. Professor Stan Scheller was the first Polish scientist dealing with propolis and its medical potential. His legacy was continued by several research teams that studied the topic in various aspects. They analyzed propolis composition, its antioxidant, anti-inflammatory, antimicrobial, antiapoptotic and anticancer properties as well as its application in dentistry and wound treatment. Burn wound healing physiology after propolis administration was thoroughly studied on pig model, whereas research on patients proved the efficacy of propolis in chronic venous leg ulcer treatment. Polish scientists have made a significant contribution to the research on propolis, its biological properties and influence on wound healing. Propolis ointments can effectively accelerate the healing process and improve healing physiology, so they can be recommended as a promising topical medication for wound treatment in the future clinical and preclinical trials.


Classifying metal-binding sites with neural networks.
To advance our ability to predict impacts of the protein scaffold on catalysis, robust classification schemes to define features of proteins that will influence reactivity are needed. One of these features is a protein's metal-binding ability, as metals are critical to catalytic conversion by metalloenzymes. As a step toward realizing this goal, we used convolutional neural networks (CNNs) to enable the classification of a metal cofactor binding pocket within a protein scaffold. CNNs enable images to be classified based on multiple levels of detail in the image, from edges and corners to entire objects, and can provide rapid classification. First, six CNN models were fine-tuned to classify the 20 standard amino acids to choose a performant model for amino acid classification. This model was then trained in two parallel efforts: to classify a 2D image of the environment within a given radius of the central metal binding site, either an Fe ion or a [2Fe-2S] cofactor, with the metal visible (effort 1) or the metal hidden (effort 2). We further used two sub-classifications of the [2Fe-2S] cofactor: (1) a standard [2Fe-2S] cofactor and (2) a Rieske [2Fe-2S] cofactor. The accuracy for the model correctly identifying all three defined features was >95%, despite our perception of the increased challenge of the metalloenzyme identification. This demonstrates that machine learning methodology to classify and distinguish similar metal-binding sites, even in the absence of a visible cofactor, is indeed possible and offers an additional tool for metal-binding site identification in proteins.


Microcatheter looping technique for coil embolization of complex configuration middle cerebral artery aneurysms.
Protection techniques using stents or microcatheters allow treatment of aneurysms with complex configurations by coil embolization. However, the application of these techniques is occasionally limited in wide-neck middle cerebral artery (MCA) aneurysms with acute angularity of the efferent branch vessel. We describe a looping technique for passage of a microcatheter and microwire into the acutely angled efferent branch vessel without navigating the system through the aneurysm lumen. To select the acutely angulated branch, a looped microcatheter was advanced near the orifice of the distal acutely angled branch vessel, followed by microwire passage through the looped microcatheter into the efferent vessel. The microcatheter loop was straightened after the microwire had been sufficiently advanced. The microcatheter was then navigated into the distal branch vessel over the advanced microwire. A total of 36 wide-neck MCA aneurysms were successfully treated using this looping method. This technique was used to pass the microcatheter for stent protection in 13 patients and for microcatheter protection in 23. The method was most commonly used for aneurysms located at the M1 trunk (n = 21), followed by the MCA bifurcation (n = 15). Complete or near-complete endosaccular occlusion was achieved in 31 aneurysms. There were no complications related to looping the microcatheter. This microcatheter looping technique facilitates safe entry into the distal branch during coil embolization of wide-neck MCA aneurysms incorporating the origins of acutely angulated branches.


Treatment of talus osteochondral defects in chronic lateral unstable ankles: small-sized lateral chondral lesions had good clinical outcomes.
To assess and compare the clinical and MRI outcomes of patients with talus osteochondral defect (OCD) and patients without OCD in a cohort with chronic lateral ankle instability. All patients who underwent open or arthroscopic anterior talofibular ligament repair of the lateral ligament complex by a single surgeon were included in this study. Ankle arthroscopic surgery was initially performed to manage any intra-articular OCD, including debridement and microfracture. Functional scores (AOFAS, Karlsson score) and Tegner activity level scores were determined. An MRI scan was performed at follow-up to assess talus OCD after treatment. Spearman's correlation coefficients were calculated between functional scores and various factors. A total of 104 patients with chronic ankle instability were included in this study. Among them, 33 patients had cartilage injury on the talus (OCD group), and the other 71 patients had no cartilage injury (control group). After surgery, there was a significant increase in the AOFAS scores (p < 0.001), the Karlsson scores (p < 0.001), and the Tegner activity scores (p < 0.001) in both the OCD group and the control group. However, there was no significant difference in the AOFAS scores (90.7 ± 6.6 vs. 92.5 ± 8.5; n.s.), the Karlsson scores (89.7 ± 9.3 vs. 91.2 ± 9.1; n.s.), or the Tegner activity scores (5 vs. 6; n.s.) between the OCD group and the control group postoperatively. In the OCD group, there was a significant negative association between the functional scores (AOFAS, Karlsson score, or Tegner score) and the number of intra-articular lesions. For the lateral OCD, the mean lesion area significantly decreased from 49.0 ± 10.7 mm2 preoperatively to 18.3 ± 13.1 mm2 at the final follow-up (p < 0.001). No significant difference in functional outcomes was found between the OCD group and the control group postoperatively. Arthroscopic microfracture is a good option for the long-term treatment of lateral talus OCD. III.


Partners for Vulnerable Youth and the Alliance for Children in Trafficking: Using the Policy Circle Model as a Framework for Change.
The National Association of Pediatric Nurse Practitioners (NAPNAP) was the first-ever professional organization for nurse practitioners (NPs) and remains dedicated to advancing the NP role to improve child health. In 2016, NAPNAP Partners for Vulnerable Youth (NPVY) was established as a 501(c)(3) to take a leadership role in advocacy and education efforts for at-risk pediatric populations. NPVY launched the Alliance for Children in Trafficking (ACT), with far-reaching implications for nursing leadership to leverage expertise from collective organizational membership to improve health. This paper will demonstrate use of the Policy Circle model as a framework for planned policy change.


A bicyclic peptide scaffold promotes phosphotyrosine mimicry and cellular uptake.
While peptides are promising as probes and therapeutics, targeting intracellular proteins will require greater understanding of highly structured, cell-internalized scaffolds. We recently reported BC1, an 11-residue bicyclic peptide that inhibits the Src homology 2 (SH2) domain of growth factor receptor-bound protein 2 (Grb2). In this work, we describe the unique structural and cell uptake properties of BC1 and similar cyclic and bicyclic scaffolds. These constrained scaffolds are taken up by mammalian cells despite their net neutral or negative charges, while unconstrained analogs are not. The mechanism of uptake is shown to be energy-dependent and endocytic, but distinct from that of Tat. The solution structure of BC1 was investigated by NMR and MD simulations, which revealed discrete water-binding sites on BC1 that reduce exposure of backbone amides to bulk water. This represents an original and potentially general strategy for promoting cell uptake.


Blood levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha and cognitive functions in patients with obsessive compulsive disorder.
Cognitive dysfunction and immune system disorders are two actual issues for the patients with Obsessive Compulsive Disorder (OCD). The cognitive dysfunctions have been considered to substantial part of clinical phenomenon of OCD but exploration of various etiopathogenesis of cognitive dysfunction is needed. Immune dysfuncion has been implicated to be important part of pathopysiology of OCD and different lines of evidence suggests immune abnormalities in OCD. But whether these immune changes are traits of disease or secondary to clinical burden of the disease such as cognitive dysfunctions has not been determined. Data regarding relation between the cognitive dysfunctions and immune system disorders in OCD is unsatisfied. In this study we aimed to investigate the relation of blood levels of interleukin 1-beta (IL-1ß), interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) with various neurocognitive functions in patients with OCD in comparison with its autogenous/reactive subtypes and healthy controls. Further exploration of the effects of various clinical variables on cognitive functioning in patients with OCD and additional investigation of whether the cognitive dysfunction associated with this disorder differs from or overlap with that in other anxiety disorders are needed. Forty-two patient with OCD and 45 age, sex and educational level matched healthy control were enrolled in the study. The diagnosis of OCD was made with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Yale- Brown Obsessive-Compulsive Scale, Beck Anxiety and Depression Inventory Scales were administered. Neuropsychological test battery including Wisconsin Card Sorting Test (WCST), Trail Making Test A and B (TMT-A, TMT-B) were used for evaluation of the patients and healthy control. The plasma of interleukin-1beta (IL-1ß), interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-α) of both groups were measured with ELISA kits. Blood levels of IL-1ß, IL-6 and TNF-α were significantly higher in patients with OCD than the healthy control. There was significant difference in IL-1ß, IL-6 but not in TNF-α between autogenous/reactive subtypes and healthy controls. TNF-α is positively correlated with TMT-A, TMT-B and Stroop Test Part 5, negatively correlated with immediate memory, verbal learning, interference effect, immediate recall, delayed recall and recognition in RAVLT. IL-1ß was positively correlated with TMT-A score. IL-6 was positively correlated with scores of TMT-A, TMT-B. IL-6 was negatively correlated with immediate memory, verbal learning, interference effect, immediate recall and delayed recall in RAVLT, positively correlated with number of perseverative error and negatively correlated with the number of categories completed in WCST. This is the first study that investigates the relation of IL- 1ß, IL-6 and TNF-α levels with cognitive functions in OCD. There may be a contribution to pathogenesis of OCD and subtypes then new choices for treatment might be developed. Moreover, uncovering the effect of cytokine blood levels on cognitive function of OCD, new data concerning etiopathogenesis and further treatment choices can be gained.


Intraoperative radiotherapy versus no radiotherapy for early stage low-risk breast cancer patients undergoing breast-conserving surgery: a propensity score matching study based on the SEER database.
To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery. According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The Kaplan-Meier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences. A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41 months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p < 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p < 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p < 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p < 0.05). For patients aged 50 years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups.


Operation in patients with incurable colon cancer--is it worthwhile?
This study was designed to identify objective criteria that might help surgeons decide which patients with incurable colon cancer will benefit from palliative surgery and which will not. Charts of 68 patients with incurable colon cancer were reviewed. Fifty-seven patients underwent resection, six had a bypass of a nonresectable cancer, and five had no surgery at all. Time to death was the major end point of the study. Minor end points were postoperative morbidity and mortality. Independent variables analyzed were comorbidity, preoperative carcinoembryonic antigen, liver function tests, extent of liver metastases, stage and site of tumor, and tumor cell differentiation. There were six postoperative deaths, and six patients had complications. Mean survival after palliative resection was 10.6 months, after bypass was 3.4 months, and after diagnosis in patients not operated on was 2 months. Patients with > 50 percent of their liver replaced by cancer had significantly worse survival than those with < 50 percent involvement (mean, 4.2 +/- 4 standard deviation (SD) vs. 14.4 +/- 10.6 SD; P < 0.003, Wilcoxon's rank-sum test). Tumor differentiation also influenced survival (poor, mean 8.4 +/- 8.2 SD; well/moderate, 12.5 +/- 9.2 SD; P < 0.02). No other variable had a significant effect on survival. Resection of primary colon cancer in patients with incurable disease has a relatively high postoperative mortality but is worthwhile as long as hepatic metastases occupy less than 50 percent of liver volume.


Diethylstilbestrol enhances melanogenesis via cAMP-PKA-mediating up-regulation of tyrosinase and MITF in mouse B16 melanoma cells.
It is well known that melanin synthesis in melanoma cells is controlled by melanogenic enzymes, which regulate the cAMP-PKA signaling pathway. Estrogen was previously reported to upregulate melanogenesis that is associated with human skin pigmentation. To investigate the influence and mechanism of diethylstilbestrol (DES) on melanogenesis in mouse B16 melanoma cells. The effects of diethylstilbestrol on cell viability, melanin content, tyrosinase activity, cAMP level, expression of the tyrosinase family and microphthalmia related transcription factor (MITF) were measured in B16 melanoma. Estrogen receptor (ER) expression were detected in B16 melanoma and A375 melanoma. Diethylstilbestrol-induced melanin synthesis were evaluated in the presence and absence of H89 (a PKA-specific inhibitor) and ICI182, 780 (a pure ER antagonist). Tyrosinase activity, the mRNA levels of tyrosinase and MITF were evaluated in the presence and absence of H89. In B16 cells, diethylstilbestrol increased cell proliferation, melanin synthesis, tyrosinase activity and expression of the tyrosinase family and MITF. ER expression have not difference in human and mouse melanoma. When ER were inhibited by ICI182, 780, DES-induced melanogenesis was significantly reduced. Diethylstilbestrol enhanced the level of cAMP. The upregulation of melanin content and tyrosinase activity stimulated by diethylstilbestrol was significantly attenuated in the presence of H89. Further, diethylstilbestrol-induced upregulation of tyrosinase and MITF were significantly attenuated when the PKA pathway was blocked. Diethylstilbestrol can enhance melanin synthesis in melanoma cells. This effect is associated with activation of the cAMP-PKA pathway and upregulation of expression and activity of the melanogenesis-related enzyme tyrosinase and MITF.


The crystal structure of hypothetical protein MTH1491 from Methanobacterium thermoautotrophicum.
As part of our structural proteomics initiative, we have determined the crystal structure of MTH1491, a previously uncharacterized hypothetical protein from Methanobacterium thermoautotrophicum. MTH1491 is one of numerous structural genomics targets selected in a genome-wide survey of uncharacterized proteins. It belongs to a family of proteins whose biological function is not known. The crystal structure of MTH1491, the first structure for this family of proteins, consists of an overall five-stranded parallel beta-sheet with strand order 51234 and flanking helices. The oligomeric form of this molecule is a trimer as seen from both crystal contacts and gel filtration studies. Analysis revealed that the structure of MTH1491 is similar to that of dehydrogenases, amidohydrolases, and oxidoreductases. Using a combination of sequence and structural analyses, we showed that MTH1491 does not belong to either the dehydrogenase or the amidohydrolase superfamilies of proteins.


Neurovirulence of mumps virus: intraspinal inoculation test in marmosets.
An intraspinal inoculation test of mumps virus using marmosets was performed in order to develop a neurovirulence test of mumps vaccines. In the group inoculated with non-neurovirulent Jeryl Lynn vaccine strain at 10(2.0) pfu/dose, there were only minimal histopathological changes in 3 of the 5 marmosets. In contrast, all marmosets inoculated with neurovirulent Urabe and NK-M46 vaccine strains developed extensive encephalitis and meningitis. Thus, this marmoset model, which can distinguish between non-neurovirulent and neurovirulent vaccine strains, is useful for evaluating neurovirulence of vaccine strains and elucidating the molecular pathogenesis of mumps.


The prevalence and burden of Rome IV faecal incontinence in ulcerative colitis: A cross-sectional study.
Despite advances in ulcerative colitis (UC) therapies, a relatively undefined proportion of patients experience faecal incontinence (FI) in the absence of active inflammation. For this group, there remains a significant unmet need with a limited evidence base. We aimed to estimate the prevalence and impact of FI in UC. In a prospective cross-sectional study, patients with UC completed a series of validated questionnaires, including Rome IV FI criteria, an inflammatory bowel disease (IBD)-specific FI questionnaire (ICIQ-IBD), Hospital Anxiety and Depression Scale and IBD-Control. UC remission was defined as faecal calprotectin (FCP) ≤250 μg/g, or IBD-control 8 score ≥13 and IBD-Control-VAS ≥ 85. Of 255 patients with UC, overall, 20.4% fulfilled Rome IV criteria for FI. Rome IV FI prevalence did not differ between active and quiescent UC regardless of whether disease activity was defined by IBD-Control scores ± FCP (p = 0.25), or objectively with FCP thresholds of 250 μg/g (p = 0.86) and 100 μg/g (p = 0.95). Most patients (75.2%) reported FI when in 'remission' and during 'relapse' (90.6%) according to ICIQ-IBD. Those who reported FI according to both ICIQ-IBD and Rome IV definitions had higher anxiety, depression and worse quality-of-life (QoL) scores (p < 0.05). In those with Rome IV FI, there was a strong correlation between FI symptom severity and impaired QoL (r = 0.809, p < 0.001). The prevalence of FI in UC is high, even in remission, and associated with significant psychological distress, symptom burden and impaired QoL. These findings highlight the urgent need for further research and development of evidence-based treatments for FI in UC.


Revealing the nature of thio-click reactions on the solid phase.
Thiol- and yne-functionalized beads were manufactured in a simple microfluidic setup. While CuAAC and thiol-yne reactions were performed on yne-functionalized beads, 9 different thiol-X reactions were compared, in terms of kinetics and conversion, on thiol-functionalized beads.


Hierarchical cell-type-specific functions of caspase-11 in LPS shock and antibacterial host defense.
Caspase-11 sensing of intracellular lipopolysaccharide (LPS) plays critical roles during infections and sepsis. However, the key cell types that sense intracellular LPS and their contributions to the host responses at the organismal level are not completely clear. Here, we show that macrophage/monocyte-specific caspase-11 plays a dominant role in mediating the pathological manifestations of endotoxemia, including gasdermin D (GSDMD) activation, interleukin (IL)-1β, IL-18, and damage-associated molecular pattern (DAMP) release, tissue damage, and death. Surprisingly, caspase-11 expression in CD11c+ cells and intestinal epithelial cells (IECs) plays minor detrimental roles in LPS shock. In contrast, caspase-11 expression in neutrophils is dispensable for LPS-induced lethality. Importantly, caspase-11 sensing of intracellular LPS in LyzM+ myeloid cells and MRP8+ neutrophils, but not CD11c+ cells and IECs, is necessary for bacterial clearance and host survival during intracellular bacterial infection. Thus, we reveal hierarchical cell-type-specific roles of caspase-11 that govern the host-protective and host-detrimental functions of the cytosolic LPS surveillance.


New "persona" concept helps site designers cater to target user segments' needs.
Using the relatively new "persona" design concept, Web strategists create a set of archetypical user characters, each one representing one of their site's primary audiences. Then, as their site is constructed or upgraded, they champion the personas, arguing on their behalf and forcing the design team to take each audience's needs and wants into account.


Repair of transverse sternal nonunions using metal plates and autogenous bone graft.
Transverse sternal nonunion is a complication of sternal fracture or partial sternotomy, and requires surgical treatment. Three patients with repeated failure of standard sternal repair were treated with a technique using metal plates and autogenous bone graft, which resulted in bone union in all patients. Metal plating of the sternum, accompanied by autogenous bone graft, is an effective method of treating transverse sternal nonunion.


Reactive electrically conducting membranes for phosphorus recovery from livestock wastewater effluents.
We present a novel 'proof-of-concept' electrochemically based membrane filtration process for the recovery of nitrogen and phosphorus from livestock wastewater following an anaerobic digestion step. Reactive electrically conducting membranes are shown to precipitate and separate struvite, an eco-friendly fertilizer from synthetic livestock wastewater, resulting in the production of a solid fertilizer and a high-quality water stream, fit for irrigation. The recovery process is based on electrochemical hydrolysis and control of local pH in proximity to the surface of the membrane, and therefore, does not require chemical additives for pH adjustment. The system was assessed at varying concentrations of nitrogen and phosphorus corresponding to diluted and concentrated livestock wastewater (up to 1000 mg/L of N and P). Experimental results show up to 65% removal of phosphorus and nitrogen in the first 30 min of electrochemical filtration, and the precipitates were analytically confirmed to be struvite. In addition, the recovery process was shown efficient as it resulted in limited membrane fouling and flux reduction. Fouling and precipitation results were explained by a mathematical model describing the concentration of N, P, Mg ions in the presence of an external electric field. Accordingly, precipitation takes place in proximity to the membrane's surface but not directly on it, thus, limiting surface fouling. The electrochemical filtration system does not require chemical additives for pH adjustment, and the cost associated with electrochemical membrane-based struvite recovery was calculated to be $158 per ton of dry struvite, which is about 1.4 times lower in comparison to conventional recovery approaches. Overall, the electrochemical filtration system may be a promising alternative for nutrient recovery from livestock wastewater in terms of operational costs, recovery efficiency, and fouling mitigation.


Phosphoglycerate mutase 5 facilitates mitochondrial dysfunction and neuroinflammation in spinal tissues after spinal cord injury.
Spinal cord injury (SCI) is a high incidence worldwide that causes a heavy physical and psychological burden to patients. It is urgent to further reveal the pathological mechanism and effective treatment of SCI. Mitochondrial dysfunction plays an important role in the disease progression of SCI. As a mitochondrial membrane protein, phosphoglycerate mutase 5 (PGAM5) is mainly involved in mitochondrial function and mitosis to modulate cellular physiological functions, but the roles of PGAM5 in spinal tissues remain to be unreported after SCI. The purpose of this study was to evaluate the role of PGAM5 in SCI mice and its relationship with neuroinflammation. The results showed that the mitochondrial membrane protein PGAM5 was involved in microglia activation after SCI, and PGAM5 deletion could improve mitochondrial dysfunction (including abnormal mtDNA, ATP synthases, and ATP levels, Cyt C expression, and ROS and rGSH levels) in spinal cord tissue after SCI, Arg1/iNOS mRNA level, iNOS expression, and pro-inflammatory cytokines TNF-α, IL-1β, and IL-18 levels. In vitro, H2O2 increased TNF-α, IL-1β, and IL-18 levels in BV2 cells, and PGAM5-sh and Nrf2 activators significantly reversed H2O2-induced iNOS expression and proinflammatory cytokine production. Furthermore, IP/Western blotting results revealed that PGAM5-sh treatment significantly reduced the interaction of PGAM5 with Nrf2 and enhanced the nuclear translocation of Nrf2 in BV2 cells. The data suggested that PGAM5 was involved in the cascade of oxidative stress and inflammatory response in microglia via facilitating the expression level of Nrf2 in the nucleus after SCI. It provided a reference for clarifying the pathological mechanism and therapeutic target of SCI.


Biodegradable capsules as non-viral vectors for in vitro delivery of PEI/siRNA polyplexes for efficient gene silencing.
The efficiency of siRNA delivery is demonstrated to be improved by encapsulating the siRNA within a non-viral carrier based on layer-by-layer assembly of oppositely charged biodegradable and biocompatible polyelectrolytes. In comparison to other non-viral delivery vehicles such as polycation-based complexes, a smaller amount of siRNA was necessary to produce in vitro gene silencing as early as 20-30 h after incubation. Colloidal carriers based on assembled biodegradable polyelectrolytes offer several advantages, such as efficient intracellular delivery after endocytosis followed by release to the cytosol, as well as protection of the siRNA, which is crucial for its therapeutic activity.


Highly efficient sub-nanometer RuxCuyP2 nanoclusters designed for hydrogen evolution under alkaline media.
Design of highly active and stable non-precious electrocatalysts towards hydrogen evolution reaction (HER) is a hot research topic in low cost, clean and sustainable hydrogen energy field, yet remaining the important challenge caused by the sluggish reaction kinetics for water-alkali electrolyzers. Herein, a robust electrocatalyst is proposed by designing a novel sub-nanometer of copper and ruthenium bimetallic phosphide nanoclusters (RuxCuyP2) supported on a graphited carbon nanofibers (CNF). Uniform RuxCuyP2 (~1.90 nm) on the surface of CNF are obtained by introducing the dispersed Ru, thereby improving the intrinsic activity for HER. On optimizing the Ru ratio, the (x = y = 1) RuCuP2/CNF catalyst exhibits an excellent HER electroactivity with an overpotential of 10 mV in 1.0 M NaOH electrolyte to produce 10 mA cm-2 current density, which is lower than commercial 20% Pt/C in alkaline solution. Moreover, the kinetic study demonstrated that electrochemical activation energies for HER of RuCuP2/CNF is 20.7 kJ mol-1 highest among different ratio bimetallic phosphide. This simple, cost-effective, and environmentally friendly methodology can pave the way for exploitation of bimetallic phosphide nanoclusters for catalyst design.


Successful treatment of vasospastic acute ischaemia with intra-arterial nicardipine.
Accidental intra-arterial injection of a colouring agent (Bonney's blue) in a 28-year-old male patient induced acute ischaemia of the lower limb, resistant to standard therapy. Its successful treatment was finally obtained by intra-arterial infusion of nicardipine.


A Chinese family with phenylketonuria and maternal phenylketonuria detected by family screening.
A 16-year-old boy with classical phenylketonuria (PKU) and mild mental retardation (IQ 69) was detected by the screening of mentally retarded school children in Taiwan with Guthrie's bacterial inhibition assay. The follow-up family study showed that one of his married elder sisters suffered from borderline mental retardation (IQ 75) and was also diagnosed as a classical case of PKU. She had borne one boy and one girl, both suffering from mild mental retardation, microcephaly, delay in linguistic development and severe growth retardation. This is the first known Chinese family with maternal PKU. To prevent future mental retardation caused by maternal PKU, the simultaneous establishment of a register system with a neonatal screening programme, is indicated for the follow-up of PKU girls, screening of the whole family of newly discovered PKU cases, and to exclude unrecognized maternal PKU in women who have given birth to a microcephalic child.


Gastroesophageal and laryngopharyngeal reflux profiles in patients with obstructive sleep apnea/hypopnea syndrome as determined by combined multichannel intraluminal impedance-pH monitoring.
The profiles of gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) have never been explored. The aim of the study was to investigate the reflux profile in OSAHS patients. Consecutive snoring out-patients suspected with having OSAHS and 20 healthy volunteers were included. All subjects underwent simultaneous 24-h combined multichannel intraluminal impedance-pH (MII-pH) monitoring and polysomnography. Obstructive sleep apnea/hypopnea syndrome was defined when the apnea/hypopnea index was over 5. Stepwise multiple logistic regression analysis was performed to determine the predictor for OSAHS. Fifty-three patients were included, 37 with and 16 without OSAHS. The prevalence of reflux symptoms was similar between OSAHS (35.1%) and non-OSHAS (37.5%) patients. More OSAHS patients, compared with non-OSAHS patients and healthy volunteers, had pathologic acid GER, nocturnal acid GER, and prolonged acid clearance (P < 0.001). However, no difference in non-acid reflux episodes was observed among the three groups. Laryngopharyngeal reflux was detected in 51.4%, 43.8%, and 35.0% of OSAHS, non-OSAHS, and healthy volunteers, respectively (P = 0.034). In OSAHS patients, there was no difference in the sleep parameters between patients with and without LPR. Body mass index was the only predictor of OSAHS in the regression analysis. OSAHS patients have more pathologic acid GER and prolonged acid clearance than non-OSAHS patients whereas non-acid reflux was similar between the two groups. However, BMI, not GER, is the only independent predictor for OSAHS. Laryngopharyngeal reflux occurs in more than half of OSAHS patients despite no significant association with OSAHS.


Genotyping of Toxoplasma gondii isolates in meningo-encephalitis affected striped dolphins (Stenella coeruleoalba) from Italy.
This study reports the occurrence of Toxoplasma gondii in the brain of three striped dolphins (Stenella ceoruleoalba) found stranded on the Ligurian Sea coast of Italy between 2007 and 2008. These animals showed a severe, subacute to chronic, non-purulent, multifocal meningo-encephalitis, with the cerebral parenchyma of two dolphins harbouring protozoan cysts and zoites immunohistochemically linked to T. gondii. Molecular, phylogenetic and mutation scanning analyses showed the occurrence of Type II and of an atypical Type II T. gondii isolates in one and two dolphins, respectively. In spite of the different molecular patterns characterizing the above T. gondii genotypes, the brain lesions observed in the three animals showed common microscopic features, with no remarkable differences among them. The role of T. gondii in causing the meningo-encephalitis is herein discussed.


Biomonitoring as a Nature-Based Solution to Assess Atmospheric Pollution and Impacts on Public Health.
The control of air pollution remains a challenge to the planning of cities and fossil fuel burning is the main cause of air degradation. Particulate matter (PM) is the contaminant commonly used as an indicator of pollution, but environmental agencies may face difficulties in operating surveillance networks due to the lack of resources and infrastructure. As an alternative to conventional networks, scientific studies have pointed out that nature itself can contribute to the diagnosis and reduction of air pollution. Nature-based solutions (NbS) are proposals that use natural processes and structures to meet different environmental challenges. In this study, biomonitoring with Tillandsia usneoides was applied as a NbS tool to evaluate air quality in an important port urban area in the city of Guarujá, Brazil, affected by industrial and vehicular emissions. It was observed that cadmium mass fractions were at least forty times higher than the control area with one-month exposition.


Effect of feeding corn distillers dried grains with solubles naturally contaminated with deoxynivalenol on growth performance, meat quality, intestinal permeability, and utilization of energy and nutrients in broiler chickens.
The objective of this experiment was to investigate the effect of feeding corn distillers dried grains with solubles (DDGS) naturally contaminated with deoxynivalenol (DON) on growth performance, meat quality, intestinal permeability, and utilization of energy and nutrients in broiler chickens. Two trials (growth and metabolism trials) were conducted. In the growth trial, a total of four hundred 7-day-old Ross 308 broiler chicks were allotted to 1 of 5 dietary treatments with 8 replicates in a completely randomized design. The diets were formulated to contain 5 inclusion levels of 0, 5, 10, 15, or 20% DON-contaminated DDGS in diets and were fed to birds for 21 d. Results indicated that increasing inclusion levels of DON-contaminated DDGS decreased (linear, P < 0.01) BW gain and feed efficiency of broiler chickens. The relative organ weights of the liver and breast were decreased (linear and quadratic, P < 0.05) by increasing inclusion levels of DON-contaminated DDGS in diets. The transepithelial electrical resistance values as a measure of intestinal permeability were decreased (linear, P < 0.05) by increasing inclusion levels of DON-contaminated DDGS in diets. In the metabolism trial, a total of twenty four 22-day-old Ross 308 broiler chickens were allotted to 1 of 3 dietary treatments consisting of 0, 10, or 20% inclusion of DON-contaminated DDGS in diets. Each treatment had 8 replicates. Increasing inclusion levels of DON-contaminated DDGS in diets decreased (linear and quadratic, P < 0.05) MEn (AMEn and TMEn) and apparent total tract retention of nitrogen and acid-hydrolyzed ether extract in diets. In conclusion, feeding diets containing more than 10% DON-contaminated DDGS to broiler chickens has negative effects on growth performance, intestinal permeability, and utilization of energy and nutrients in diets. Therefore, it is suggested that if DDGS is contaminated with DON, inclusion level of DDGS should be limited, possibly at less than 5.0% in broiler diets.


Development and Primary Evaluation of a Smartphone Application for Blood Glucose Control in Hospitalized Patients.
Diabetes is one of the major causes of morbidity and mortality. Diabetes and hyperglycemia are leading causes for cardiovascular diseases, chronic infections, and other serious problems. The use of smartphone is dramatically increasing, and as such, it is sensible to use an application for management of hospitalized patients with diabetes or hyperglycemia. We designed a software for physicians by use of which they educate to take appropriate decisions in management of patients with diabetes and evaluated the quality of the application using a questionnaire. Application is designed in a cascade framework to help in management of patients with diabetes and hyperglycemia. The treatment protocols presented in the program were extracted from diabetes management guidelines and valid review articles. Furthermore, we developed a questionnaire to assess the quality of the program. Physicians (n = 36) used this program for 1 week after which they completed the questionnaire. The physicians described the application to be useful and understandable. A high percentage of physicians and health providers are aware of the problems when it comes to hospitalized patients with diabetes and our application was designed to resolve the associated difficulties.


Hydrolysis and oxidation of lipids in mussel Mytilus edulis during cold storage.
Change in quality of mussels (Mytilus edulis) meat when stored at 4 °C was evaluated by determining volatile basic nitrogen (TVB-N), peroxide value (POV), thiobarbituric acid reactive substance (TBARS), total oxidation (TOTOX), lipid class, fatty acid (FA), phosphatidylcholine (PC) and phosphatidylcholine (PE) content, and glycerophospholipid (GP) molecular species. After 4 days of storage, the percentages of triacylglycerol and polar lipid as well as the contents of PC, PE and major GP molecular species significantly decreased (P < 0.05), while the percentages of free FA and monoacylglycerol significantly increased (P < 0.05), indicating the hydrolysis of lipids. The increase in activities of phospholipase and lipase during storage suggests that they may contribute to the hydrolysis of lipids. The cold storage also resulted in significantly increased POV, TBARS and TOTOX as well as lipoxygenase activity (P < 0.05) but slightly decreased percentage of polyunsaturated FA (PUFA), indicating the occurrence of lipid oxidation.


Evaluation of the relationship of chronic otitis media with the Körner's septum, auditory tube angle, and tubotympanic angle.
This study aimed to evaluate the relationships between chronic otitis media (COM) and the characteristics of Auditory tube (Eustachian) angle (ATa), tubotympanic angle (TTa), and Körner's septum (KS). A retrospective research was conducted between January 2019 and October 2019. The computed tomography (CT) results and medical files of 210 patients were evaluated. According to CT results and medical files, the patients were evaluated regarding the presence of COM, KS, ATa, and TTa. There were 113 (53.81%) males and 97 (46.19%) females in the study group, and the mean age of the patients was 42.05 ± 10.77 years. The frequency of the KS was significantly higher in patients who were diagnosed with COM (35.66% vs. 7.41%, p < 0.001). The patients diagnosed with COM were found to have a narrower ATa and a wider TTa than the patients who were not diagnosed with COM. ATa was narrower and TTa was wider in patients with KS. The presence of KS and higher TTa value were considered as risk factors for COM (p < 0.001, p < 0.001, respectively) CONCLUSION: Our findings indicate that ATa was narrower, TTa was wider and KS was more frequent in patients with COM. Analysis of risk factors demonstrated that increased TTa and the presence of KS were associated with increased risk for COM.


Multifaceted interventions are likely to be more effective to increase adherence to the ventilator care bundle: A systematic review of strategies to improve care bundle compliance.
The implementation of ventilator care bundles has remained suboptimal. However, it is unclear whether improving adherence has a positive relationship with patient outcomes. To identify the most effective implementation strategies to improve adherence to ventilator bundles and to investigate the relationship between adherence to ventilator bundles and patient outcomes. A systematic review followed the PRISMA guidelines. A systematic literature search from the inception of ventilator care bundles 2001 to January 2021 of relevant databases, screening and data extraction according to Cochrane methodology. In total, 6035 records were screened, and 24 studies met the eligibility criteria. The implementation strategies were provider-level interventions (n = 15), included educational activities, checklist, and audit/feedback. Organizational-level interventions include (n = 8) included change of medical record system and multidisciplinary team. System-level intervention (n = 1) had motivation and reward. The most common strategies were education, checklists, audit feedback, which are probably effective in improving adherence. We could not perform a meta-analysis due to heterogeneity of the strategies and types of adherence measurement. Most studies (n = 7) had a high risk of bias. There were some conflicting results in determining the associations between adherence and patient outcomes because of the poor quality of the studies. Multifaceted interventions are likely to be effective for consistent improvement in adherence. It remains uncertain whether improvements in adherence have positive outcomes on patients due to limited evidence of low to moderate uncertainty. We recommend the need for robust research methodology to assess the effectiveness of implementation strategies on improving adherence and patient outcomes.


Demonstration of an olfactory bulb-brain translocation pathway for ZnO nanoparticles in rodent cells in vitro and in vivo.
ZnO nanoparticles (ZnO-NPs) are widely used in the engineering and cosmetic industries, and inhaled airborne particles pose a known hazard to human health; their translocation into humans is a recognized public health concern. The pulmonary-blood pathway for ZnO-NP toxicity is well documented, but whether translocation of these particles can also occur via an olfactory bulb-brain route remains unclear. The potential toxicity of ZnO-NPs for the human central nervous system (CNS) is predicated on the possibility of their translocation. Our study investigated translocation of ZnO-NPs both in vitro using the neuronal cell line PC12 and in vivo in a Sprague-Dawley rat model. Our findings indicate that the zinc-binding dye, Newport-Green DCF, binds ZnO stoichiometrically and that ZnO-NP concentration can therefore be measured by the fluorescence intensity of the bound dye in confocal fluorescence microscopy. Confocal data obtained using Newport-Green DCF-2 K(+)-conjugated ZnO-NPs along with the membrane probe FM1-43 demonstrated endocytosis of ZnO-NPs by PC12 cells. In addition, Fluozin-3 measurement showed elevation of cytosolic Zn(2+) concentration in these cells. Following in vivo nasal exposure of rats to airborne ZnO-NPs, olfactory bulbs and brains that were examined by Newport-Green fluorescence and TEM particle measurement clearly showed the presence of ZnO-NPs in brain. We conclude that an olfactory bulb-brain translocation pathway for airborne ZnO-NPs exists in rats, and that endocytosis is required for interneuron translocation of these particles.


Using C-JAMP to Investigate Epistasis and Pleiotropy.
Unraveling the complex biological mechanisms underlying human health and disease is a great challenge. With genomic data, many aspects can be investigated in great detail, such as interactions between different genetic variants as well as their effects on one or multiple traits. Modeling epistasis and pleiotropy jointly necessitates appropriate statistical methods. A suitable tool for this is C-JAMP, which is a recently proposed method based on copula functions. In this chapter, we outline C-JAMP and how it can be applied to investigate epistatic effects on multiple traits to advance our understanding of biological processes. We further discuss important aspects of this area of research, such as polygenic risk scores and ancestry-specific modeling, which we propose to include in future extensions of the software.


ATP-stimulated tetraethylammonium transport by rabbit renal brush border membrane vesicles.
These studies examined the ability of ATP to stimulate transport of the organic cation tetraethylammonium (TEA) into proximal tubular brush border membrane vesicles. ATP markedly enhanced TEA uptake for 1 h or more to values severalfold above those observed in the absence of ATP. The poorly hydrolyzable analogue of ATP, AMP-PNP (adenyl-5'-yl imidodiphosphate), reduced the effect of ATP but alone did not stimulate TEA uptake. GTP and ITP also stimulated TEA uptake, whereas other nucleotides did not. ATP-stimulated TEA uptake was saturable, temperature-dependent, and markedly reduced by the organic cations amiloride, quinidine, cimetidine, and verapamil, but only modestly reduced by the organic cations N'-methylnicotinamide and choline. Some inhibitors of other transport ATPases, including N-ethylmaleimide, N,N'-dicyclohexylcarbodiimide, and oligomycin, reduced the effect of ATP, whereas ouabain, vanadate, and azide did not. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid also reduced TEA uptake in the presence of ATP. Vinblastine, but not actinomycin D and colchicine (all inhibitors of P-glycoprotein-mediated transport), reduced TEA uptake. The reduction of TEA transport by amiloride and cimetidine was most consistent with competitive inhibition, whereas the inhibition produced by N-ethylmaleimide and vinblastine evidently was not. ATP also stimulated uptake of N'-methylnicotinamide but not that of vinblastine. These studies have identified a previously unrecognized process by which ATP hydrolysis may directly energize the reabsorption of organic cations from the renal tubule lumen.


Prevalence and characteristics of pain in patients with chronic obstructive pulmonary disease compared to the Norwegian general population.
The purpose of this study was to evaluate the prevalence and characteristics of pain in patients with chronic obstructive pulmonary disease (COPD) compared to a sample from the Norwegian general population. This cross-sectional study evaluated 100 COPD patients with and without pain and 333 individuals from the Norwegian population with pain. After controlling for age and sex, a significantly higher percentage of patients with COPD (45%) reported pain than the general population (34%; P = .02). No differences were found in pain intensity scores, pain interference score, or number of pain locations between COPD patients and the general population. COPD patients reported moderate-to-severe pain located primarily in the chest, shoulders, neck, and thorax. For both groups, the most common pain treatment was analgesic use. Acupuncture/transcutaneous electrical nerve stimulation was used more frequently by COPD patients (P < .001) while physiotherapy was used more frequently by the general population (P = .007) to treat their pain. Pain is a significant problem for COPD patients. Additional research is warranted to replicate these findings and to provide a more detailed characterization of how pain changes over time and influences COPD patients' ability to function and their quality of life. Compared to the general population, pain is more common in patients with COPD and ranges from moderate to severe in its intensity.


Biological anti-psoriatic therapy profoundly affects high-density lipoprotein function.
Psoriasis is a common chronic inflammatory skin disease linked to increased cardiovascular risk. Functional impairment of high-density lipoprotein (HDL) may contribute to excessive cardiovascular mortality in psoriasis patients. Anti-cytokine therapies with biologics have been efficiently used for the management of psoriasis, however little data is available on the effects of biologic anti-psoriatic therapies on the composition and functionality of HDL. Blood samples were taken from 17 healthy volunteers and from 27 real-world psoriasis patients at baseline (no therapy with biologics) and after short-term (3 to 6 months) and intermediate-term (1 to 2 years) therapy. The biologics used included anti-interleukin (IL)-12/23p40 (ustekinumab), anti-IL17A (secukinumab) or anti-tumor necrosis factor-α (etanercept or adalimumab) antibodies. We observed that in psoriasis patients at baseline, metrics of HDL function including cholesterol efflux capacity of apolipoprotein B-depleted serum (p = 0.021), paraoxonase (p < 0.001) and lecithin-cholesterol acyltransferase (p < 0.001) activities were impaired, when compared to controls. Unexpectedly, we observed that short- and especially intermediate-term therapy with biologics markedly reduced HDL cholesterol efflux capacity (p < 0.001) and rendered HDL pro-inflammatory (p < 0.001), but increased paraoxonase (p = 0.009) and lecithin-cholesterol acyltransferase (p = 0.019) activities. All biologics caused similar changes in HDL composition, subclass distribution and cholesterol efflux capacity. Our results provide evidence that anti-psoriatic therapy with biologic agents is associated with changes in HDL functionality, particle composition and subclass distribution.


Lipoprotein-mediated regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesteryl ester metabolism in the adrenal gland of the rat.
In the adrenal gland of the rat, the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme of cholesterol synthesis, is shown to be regulated by cholesteerol carried in plasma lipoproteins. When plasma cholesterol levels were lowered 90% by administration of the drug 4-aminopyrazolopyrimidine, the cholesteryl ester content of the adrenal gland declined by more than 90% and this was associated with a 150- to 200-fold increase in the activity of adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase and a 30-fold increase in cholesterol synthesis from [14C]acetate. The subsequent intravenous infusion of cholesterol contained in either rat or human high density or low density lipoproteins restored the adrenal content of cholesteryl esters and reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase to basal levels. The depletion of adrenal cholesteryl esters and the enhancement in the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that occurred in the 4-aminopyrazolopyrimidine-treated rat required the action of adrenocorticotropic hormone (ACTH) since neither was observed when ACTH secretion was blocked by administration of dexamethasone. The current data indicate that the low rate of cholesterol synthesis normally observed in the rat adrenal gland is due to a suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that is mediated by plasma lipoproteins.


The Role of Adjunct Imaging in Endoscopic Detection of Dysplasia in Barrett's Esophagus.
Advances in imaging technologies have demonstrated promise in early detection of dysplasia and cancer in Barrett's esophagus (BE). Optical chromoendoscopy, dye-based chromoendoscopy, and novel technologies have provided the opportunity to visualize the cellular and subcellular structures. Only narrow-band imaging and acetic acid chromoendoscopy have reached benchmarks for clinical use. Volumetric laser endomicroscopy and molecular imaging are not established for routine use. Best practice in management of BE should be focused on careful endoscopic examination, resection, or ablation of the entire abnormal lesion, as well as the use of available imaging technique that has good diagnostic accuracy.


Clinical characteristics of severe community-acquired pneumonia among younger patients: an analysis of 18 years at a community hospital.
Unlike elderly patients with community-acquired pneumonia whose outcomes are markedly affected by their background characteristics, it appears that the severity of the infection itself contributes to outcomes in younger patients with community-acquired pneumonia. In order to identify clinical characteristics of severe community-acquired pneumonia in younger patients under 60 years old, among such cases prospectively collected at our hospital over a period of 18 years, those meeting the criteria for severe community-acquired pneumonia, as defined in the Infectious Diseases Society of America/American Thoracic Society Guidelines for community-acquired pneumonia, were retrospectively examined and compared to elderly patients with severe community-acquired pneumonia. Younger patients with severe pneumonia accounted for 12.9% of younger hospitalized patients. Although the incidence of severe pneumonia in younger patients was lower than that in elderly patients, its severity may be underestimated by severity assessment based on the conventional guidelines. Thus, attention is required. While Streptococcus pneumoniae and Legionella species were important causative pathogens, atypical pathogens and viruses were also frequently detected. There were only 11 deaths over a period of 18 years. Based on multivariate analysis, the risk factors for aggravation of community-acquired pneumonia among younger patients were age 50 years or older, diabetes mellitus, chronic liver disease, and Legionella pneumonia. Although the mortality rate from community-acquired pneumonia is extremely low in previously healthy younger patients, outcomes might be poor for patients with underlying diseases and those with rapid progression. Multimodal treatments including respiratory management may be appropriate.


Clinical pretreatment risk factors and Ga-67 scintigraphy early during treatment for prediction of outcome of patients with aggressive non-Hodgkin lymphoma.
Clinical pretreatment risk factors indicate the severity of disease in patients with aggressive non-Hodgkin lymphoma (NHL). Ga-67 scintigraphy during treatment is an early indicator of treatment-related features of lymphoma cells. The ability of risk factors and Ga-67 to predict disease outcome was compared in 139 patients with aggressive NHL. Pretreatment clinical risk factors and Ga-67 scintigraphy performed after one cycle and at mid-treatment were evaluated for their correlation with response rate and as predictors of 5-year failure-free survival (FFS). Univariate analysis was performed to determine the ability of pretreatment risk factors and Ga-67 early during treatment to predict FFS. Subsequently, multivariate analysis was performed on the variables with significant univariate results using the Cox proportional hazards method. The predictive value of risk factors and Ga-67 scintigraphy was calculated to determine their suitability in selecting patients with poor outcome. Response rate correlated with stage of disease (P < 0.01) and the international prognostic index (IPI) score (P < 0.05). Five-year FFS was predicted by stage of disease (P < 0.004), performance status (P < 0.02), and the IPI score (P < 0.01). Response rate correlated with results of Ga-67 scintigraphy after one cycle of chemotherapy (P < 0.001) and at mid-treatment (P < 0.001). Five-year FFS was predicted by Ga-67 after one cycle of chemotherapy (P < 0.0004) and at mid-treatment (P < 0.0001). Positive Ga-67 after the first cycle of treatment predicted 64% of patients who had failure of treatment. A positive study at mid-treatment predicted 77% of patients who had treatment failure. Cox analysis showed Ga-67 after one course (P < 0.0012) and at mid-treatment (P < 0.0002) as being the most significant variables in predicting FFS. Ga-67 scintigraphy demonstrates early the effect of treatment in patients with aggressive NHL. It is a better predictor than pretreatment risk factors of both response rate and FFS. Positive Ga-67 early during treatment may be used as an independent test in selecting patients who will not respond favorably to current protocol treatment for early therapeutic modifications.


Optimising RGP lens fitting in normal eyes using 3D topographic data.
To analyse, retrospectively, the effect of fitting characteristics on comfort of wear and the role that 3D topographic data can play in attaining an optimal lens fit with rigid gas permeable (RGP) contact lenses in normal eyes. Included were 60 normal myopic eyes (1.00-5.00 D) with astigmatism limited to 2.00 D. Lenses were ordered empirically, based on traditional fitting rules. The initial fit based on traditional computation was accepted in 40% of the eyes. To achieve an acceptable fit, 15% of the eyes needed an adaptation of the back optic zone radius, in 28% switching from a multicurve to an aspheric lens design was indicated and in 17% a non-rotational symmetric lens design was favoured. The reason for changing the lens parameters could in 88% be attributed to mid-peripheral differences between corneal shape as found with 3D corneal topography. Average comfort of wear improved statistically significantly (chi(2), P<0.05) from 5.2 initially to 7.7 after 3 months in the group with optimal lens fits, while comfort slightly decreased (not significant) in the group with sub-optimal fits. Switching to a non-rotational symmetric lens design, when indicated, improved comfort significantly (chi(2), P<0.05) from 5.0 to 7.3. In normal eyes, the measurement of corneal shape, especially in the mid-peripheral regions, is of importance to optimise RGP lens fit. Optimised lens fits increases comfort of wear.


Histochemical localization of heme oxygenase-2 protein and mRNA expression in rat brain.
Heme oxygenase (HO) proteins are members of the HSP30 family and consist of 2 isozymes identified to date, termed HO-1 and HO-2. Separate genes encode the isozymes and protein products which are immunochemically distinct, share less than 50% similarity at the amino acid sequence level. Each form, however, shows greater than 90% similarity among species, including human and the rat (reviewed in ref.). Furthermore, these isozymes function in a well-defined role to carry out oxidation of the heme molecule (Fe-protoporphyrin IX) in concert with NADPH-cytochrome P450 reductase. The oxidation of heme is isomer specific and results in the formation of bile pigments, carbon monoxide, and iron. The heme molecule constitutes the prosthetic moiety of hemoproteins, such as hemoglobin, myoglobin, catalase, soluble guanylate cyclase, cytochrome b5, cytochromes P450 and NO synthase. HO-1 also known as heat shock protein (HSP) 32 is encoded by a gene which is exquisitely stress-responsive and a host of stimuli that mediate oxidative stress cause induction of the protein both in vivo and in vitro. The HO-2 form shows a unique pattern of regulation from that of HO-1. HO-2 is a constitutive protein and its expression is not affected by the inducers of HO-1 tested to date; rather, the only known regulator of HO-2 yet identified is adrenal glucocorticoids. The two isozymes display vast differences in tissue distribution and under normal conditions HO-1 is present in the whole brain at the limit of immunodetection and is discreetly localized in select neuronal populations. HO-1 protein (approximately 32 kDa) and its approximately 1.8 kb transcript are increased, however, in response to stressful stimuli primarily in non-neuronal cell populations. The heme oxygenase system serves in both a catabolic and anabolic capacity in the cell. In the former capacity, it down-regulates cellular heme and hemoprotein levels. And, as such it inactivates the most effective catalyst for formation of free radicals, the heme molecule. In its anabolic role, as noted above, heme oxygenase produces bile pigments, carbon monoxide, and iron, all of which are biologically active: bile pigments function as antioxidants; the carbon monoxide generated by HO activity has been correlated with the generation of cGMP; and iron regulates expression of various genes, including that of HO-1 itself, as well as transferrin receptors, ferritin, and NO synthase. We used rabbit anti-rat HO-2 polyclonal antibody and HO-2 cDNA to localize HO-2 immunoreactive protein and the 1.3- and 1.9 kb homologous transcripts, respectively, in rodent brain as visualized by histochemical staining procedures. These protocols provide the first detailed description of methodologies successfully used to define the pattern of HO-2 expression at the transcriptional and translational levels in the adult rat brain and glucocorticoid-treated newborn rats. The procedures described herein have the virtue of being non-radioactive, as well as applicability to the systemic organs, such as the cardiovascular system and the male reproductive organs. Visualization of cellular HO-2 expression aids in assessment of potential sites of carbon monoxide, iron, and bilirubin production within the nervous system.


Association of the prognosis and severity of idiopathic sudden sensorineural hearing loss with cervical ultrasonographic findings.
The aim of this study was to investigate the association of the prognosis and severity of idiopathic sudden sensorineural hearing loss (ISSNHL) with cervical ultrasonographic findings suggestive of cardiovascular risk. Seventy-four inpatients with ISSNHL were included in our study. Cervical ultrasonography was performed to evaluate the common carotid artery (CCA), internal carotid artery (ICA), and vertebral artery (VA). The peak systolic velocity, end diastolic velocity, intima-media thickness, pulsatility index (PI), and resistance index (RI) were evaluated. We investigated the relationship of these variables with the severity and prognosis of ISSNHL. ICA-PI, ICA-RI, and CCA-RI were significantly higher in patients with poor hearing prognosis than in those with good prognosis. The variables of VA were not related to the prognosis of ISSNHL. There were no statistically significant differences between ISSNHL severity and cervical ultrasonographic findings. We found that PI and RI might be prognostic factors for ISSNHL.


Ultrasound as a Diagnostic Tool in the Assessment of Lisfranc Joint Injuries.
Ligamentous Lisfranc injuries are frequently overlooked because of subtle clinical presentations and diagnostic difficulties. The dorsal Lisfranc ligament (DLL) is easily visualized with ultrasound (US), which can provide quick, cost-effective diagnoses of disorders but is not considered standard clinical practice. This study sought to compare DLL measurement accuracy between US and cadaveric dissection. Ultrasound images of 22 embalmed cadaveric feet were obtained with an M-Turbo US machine and a 6-13-MHz linear array (FUJIFILM SonoSite, Inc, Bothell, WA). Images were measured in the US unit and again with ImageJ software (National Institutes of Health, Bethesda, MD). Specimens were dissected, and DLL morphologic characteristics were recorded. Twenty-two specimens were scanned, however 4 were excluded, leaving a sample of 11 male and 7 female cadaveric specimens (mean age ± SD, 80.3 ± 14.03 years). The DLL length differences between SonoSite (8.39 ± 1.27 mm) and ImageJ (8.25 ± 1.84 mm) were not significant (P > .05). Both US DLL measurements significantly differed from the gross dissection measurement (10.8 ± 1.85 mm; P < .001). The morphologic characteristics of the DLL at dissection were consistent. Overall, 70% to 80% of the ligament length was represented by US compared to dissection. The dorsal joint space did not differ significantly between SonoSite (2.19 ± 0.49 mm) and ImageJ (2.05 ± 0.52; P > .05). Both US measurements were also significantly larger than dissection measurements (1.04 ± 0.24; P < .001). Intraclass correlation coefficients indicated good reliability for the DLL length (0.835) and moderate reliability for the dorsal joint space (0.714). The DLL is underrepresented but easily distinguished by US, demonstrating its utility in Lisfranc injury diagnosis. Thus, we propose a 4-component assessment involving US, which may provide more rapid, cost-effective diagnoses of subtle Lisfranc injuries.


The clinical potential of circulating microRNAs in obesity.
Obesity is a complex condition that is characterized by excessive fat accumulation, which can lead to the development of metabolic disorders, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease and cardiovascular diseases. Evidence is accumulating that circulating microRNAs (miRNAs) act as a new class of endocrine factor. These miRNAs are released by many types of tissue, including adipose tissues. miRNAs might serve as endocrine and paracrine messengers that facilitate communication between donor cells and tissues with receptor cells or target tissues, thereby potentially having important roles in metabolic organ crosstalk. Moreover, many miRNAs are closely associated with the differentiation of adipocytes and are dysregulated in obesity. As such, circulating miRNAs are attractive potential biomarkers and hold promise for the development of miRNA-based therapeutics (such as miRNA mimetics, anti-miRNA oligonucleotides and exosomes loaded with miRNA) for obesity and related disorders. Here we review the latest research progress on the roles of circulating miRNAs in metabolic organ crosstalk. In addition, we discuss the clinical potential of circulating miRNAs as feasible biomarkers for the assessment of future risk of metabolic disorders and as therapeutic targets in obesity and related diseases.


Intra-articular pressures during arthroscopic knee surgery.
Arthroscopic surgery of the knee requires effective joint distention. No reports exist in the literature relating to optimal fluid pressure and dynamics of joint distention during arthroscopic knee surgery. Static and dynamic laboratory studies were performed on a knee model to establish an accurate method of measuring pressures from the arthroscopic cannula. A prospective study of 107 subjects who underwent arthroscopic surgery by one surgeon (J.W.E.) was then performed using saline distention from a saline bag wrapped with a pneumatic cuff. Intra-articular pressures ranged from 0 to 750 mm Hg, but usually fell into the zone from 70 to 120 mm Hg. A minimum pressure of 30 mm Hg was required for visualization. Variations in pressure magnitudes as well as flow rates during the procedures were studied. Technical suggestions based upon these data include maintenance of pressure between 70 and 100 mm Hg; avoidance of abrupt changes in position of the distended knee; and maintenance of lower pressure levels (35-50 mm Hg) if the synovium has been violated as in the performance of a lateral release procedure.


Quantitative structure-activity relationship and molecular docking studies on designing inhibitors of the perforin.
Quantitative structure-activity relationship (QSAR) studies were performed on a series of 5-arylidene-2thioxoimidazolidin-4-ones derivatives as the inhibitors of perforin and to gain insights about the structural determinants for designing new drug molecules. The heuristic method could explore the descriptors responsible for bioactivity and gain a best linear model with R2 .82. Gene expression programming method generated a novel nonlinear function model with R2 .92 for training set and R2 .85 for test set. The predicted IC50 by QSAR, molecular docking analysis, and property explorer applet show that 42a acts as a well-pleasing potent inhibitor for perforin. This study may lay a reliable theoretical foundation for the development of designing perforin inhibitor structures.


Purification of household water using a novel mixture reduces diarrhoeal disease in Matlab, Bangladesh.
In Bangladesh, one of the main causes of waterborne diseases is related to the use of contaminated surface water. This pilot study was conducted to determine the acceptability and effectiveness of a recently developed surface water purifying mixture to prevent diarrhoeal diseases in a rural community in Bangladesh. The mixture, using a combination of alum potash, bleaching powder and lime, is added to 15 l of surface water and mixed; the water becomes suitable for drinking after 30 min. A total of 420 households from 15 villages were provided with the mixture and were taught how to use it. Episodes of diarrhoeal disease from study families were determined from hospital records of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) in Matlab and were compared with diarrhoea episodes among 1613 control families who were not provided with the mixture. A total of 83 diarrhoeal patients were treated at Matlab Hospital from 1613 control families, but only one patient was treated for diarrhoea from among the intervention families. Among the intervention families, 73 families decided to shift from using tube well water to surface water using the mixture. The mixture could be used as a cheaper, easier and simpler point-of-use water treatment strategy in Bangladesh.


Formation of automatic letter-colour associations in non-synaesthetes through likelihood manipulation of letter-colour pairings.
Grapheme-colour synaesthesia is a well-characterized phenomenon in which achromatic letters and/or digits automatically and systematically trigger specific colour sensations. Models of its underlying mechanisms diverge on a central question: whether triggered sensations reflect (1) an overdeveloped capacity in normal cross-modal processing (i.e., sharing characteristics with the general population), or rather (2) qualitatively deviant processing (i.e., unique to a few individuals). To test to what extent synaesthesia-like (automatic) letter-colour associations may be learned by non-synaesthetes into adulthood, implied by (1), we developed a learning paradigm that aimed to implicitly train such associations via a visual search task that employed statistical probability learning of specific letter-colour pairs. In contrast to previous synaesthesia-training studies (Cohen Kadosh, Henik, Catena, Walsh, & Fuentes, 2009; Meier & Rothen, 2009), here all participants were naïve as to the end-goal of the experiment (i.e., the formation of letter-colour associations), mimicking the learning conditions of acquired grapheme-colour synaesthesia (Hancock, 2006; Witthoft & Winawer, 2006). In two experiments, we found evidence for significant binding of colours to letters by non-synaesthetes. These newly-formed associations showed synaesthesia-like characteristics, because they correlated in strength with performance on individual synaesthetic Stroop-tasks (experiment 1), and because interference between the learned (associated) colour and the real colour during letter processing depended on their relative positions in colour space (opponent vs. non-opponent colours, experiment 2) suggesting automatic formation on a perceptual rather than conceptual level, analogous to synaesthesia. Although not evoking conscious colour percepts, these learned, synaesthesia-like associations in non-synaesthetes support that common mechanisms may underlie letter-colour associations in synaesthetes and non-synaesthetes.


Unmasking misunderstandings: Strategies for better communication with patients.
Positive patient outcomes depend on successful communication. Increased use of personal protective equipment such as face masks during the COVID-19 pandemic can exacerbate communication difficulties. This article describes situations in which miscommunications may occur, identifies sources of communication breakdowns, and offers strategies to prevent them in real-life scenarios.


Integrating RIS/PACS: the web-based solution at University Hospital of Ribeirão Preto, Brazil.
Integration of a Radiology Information System (RIS) and a Picture Archiving and Communication System (PACS) reduces the risk of inconsistent data by reducing interfaces among databases that contain largely redundant information. Furthermore, RIS/PACS integration is the basis for a filmless radiology facility. Web technology is based on international standards and supplies the main features for the RIS/PACS integration task based on a client/server model. This article presents a web-based system developed to manage and distribute images and diagnostic information within the University Hospital of Ribeirão Preto (HCRP) at the University of Sao Paulo.


Omnivory and the stability of food webs.
The ecological concept of omnivory, feeding at more than a single trophic level, is formulated as an intermediate stage between any two of three classical three-dimensional species interaction systems-tritrophic chain, competition, and polyphagy. It is shown that omnivory may be either stabilizing or destabilizing, depending, in part, on the conditions of the parent systems from which it derives. It is further conjectured that the tritrophic to competition gradient cannot be entirely stable, that there must be an instability at some level of intermediate omnivory.


Sex differences in the association between serum lipids and depressive symptoms: A longitudinal population-based study.
Depression is an important global public health problem. Whether sex differences exist in the association between serum lipids and depressive symptoms is controversial. This study aimed to investigate sex differences in the association between dyslipidemia and depressive symptoms in the middle-aged and elderly population in China. Data from the China Health and Retirement Longitudinal Study, which included 2 630 males and 2 929 females, were used. Serum lipids were measured using a standard enzymatic colorimetric technique. Depressive symptoms were evaluated by the 10-item Center for Epidemiologic Studies Depression Scale. Multivariable logistic regression was performed to evaluate the association between serum lipids and depressive symptoms in men and women separately. To preclude the effects of hypertension and diabetes, the above analysis was also performed among those free of hypertension and diabetes. Total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not associated with depressive symptoms. High-level triglycerides showed a marginally significant association with depressive symptoms in men (adjusted OR 1.35, 95% CI 0.91 to 1.99). In the population without hypertension and diabetes, high-levels TGs were only associated with the development of depressive symptoms in men (adjusted OR 2.04, 95% CI 1.20 to 3.47). Depression and chronic diseases were respectively identified by CESD-10 and self-report, which were subjective to some extent. High-level triglycerides increased the risk of depressive symptoms in men, especially in the nonhypertensive and nondiabetic population. This study provided a basis for formulating sex-specific prevention strategies and treatment measures for depressive symptoms.


Prediction of stable radon fluoride molecules and geometry optimization using first-principles calculations.
Noble gases possess extremely low reactivity because their valence shells are closed. However, previous studies have suggested that these gases can form molecules when they combine with other elements with high electron affinity, such as fluorine. Radon is a naturally occurring radioactive noble gas, and the formation of radon-fluorine molecules is of significant interest owing to its potential application in future technologies that address environmental radioactivity. Nevertheless, because all isotopes of radon are radioactive and the longest radon half-life is only 3.82 days, experiments on radon chemistry have been limited. Here, we study the formation of radon molecules using first-principles calculations; additionally, possible compositions of radon fluorides are predicted using a crystal structure prediction approach. Similar to xenon fluorides, di-, tetra-, and hexafluorides are found to be stabilized. Coupled-cluster calculations reveal that RnF6 stabilizes with Oh point symmetry, unlike XeF6 with C3v symmetry. Moreover, we provide the vibrational spectra of our predicted radon fluorides as a reference. The molecular stability of radon di-, tetra-, and hexafluoride obtained through calculations may lead to advances in radon chemistry.


MRI-directed biopsy for primary detection of prostate cancer in a population of 223 men: MRI In-Bore vs MRI-transrectal ultrasound fusion-targeted techniques.
To compare the detection rates of overall prostate cancer (PCa) and clinically significant PCa (csPCa) and the median percentage of cancer per biopsy core between MRI-guided In-bore and MRI-TRUS fusion-targeted biopsy (TBx). In this retrospective study, 223 patients who underwent prostate multiparametric MRI (mpMRI) and subsequent MR-directed biopsy were included. For PCa and csPCa detection rate (DR), contingency tables were tested via the Pearson's chi-squared to explore the variance of the outcome distribution. The percentage of cancer per biopsy core was tested with a two-tailed Mann-Withney test. One hundred and seventeen and 106 patients underwent MRI-TRUS fusion or MRI In-bore TBx, respectively. 402 MRI biopsy targets were identified, of which 206 (51.2%) were biopsied with the MRI-TRUS TBx and 196 (48.8%) with the MRI In-bore TBx technique. Per-patient PCa and csPCa detection rates were 140/223 (62.8%) and 97/223 (43.5%), respectively. PCa-DR was 73/117 (62.4%) and 67/106 (63.2%) for MRI-TRUS and MRI In-Bore TBx (p = 0.9), while csPCa detection rate reached 50/117 (42.7%) and 47/106 (44.3%), respectively (p = 0.81). The median per-patient percentage of malignant tissue within biopsy cores was 50% (IQR: 27-65%) for PCa and 60% (IQR: 35-68%) for csPCa, with a statistically significant difference between the techniques. No statistically significant difference in the detection rate of MRI In-bore and MRI-TRUS fusion TBx was found. MRI In-bore TBx showed higher per-core percentage of malignant cells. MRI In-bore biopsy might impact risk stratification and patient management considering the higher per-core percentage of malignant cells, especially for patients eligible for active surveillance or focal therapy.


Identification of Blood miR-216a, miR-377 and Their Target Genes ANGPTL4, GAP-43 and Serum of PPARG as Biomarkers for Diabetic Peripheral Neuropathy of Type 2 Diabetes.
Diabetic peripheral neuropathy (DPN) is one of the most common and complex chronic complications of diabetes, but it is clinically lacking effective means for early diagnosis and early treatment. MicroRNA, in the occurrence and development of the disease, has an important regulatory role. Its role in diabetes has been reported more. However, specific research on microRNA in DPN is rare. Based on the results of bioinformatics screening, miR-377 and miR-216a, their respective target molecules growth association protein 43 (GAP-43) and angiopoietin-like 4 protein (ANGPTL4), and related pathways peroxisome proliferator activated receptor gamma (PPARG) and chemerin were tested by RT-qPCR and ELISA in blood samples of DPN to analyze the correlation between these differentially expressed molecules and clinico-pathological factors of DPN. In this study, we found that miR-377, miR-216a, GAP-43, ANGPTL4, and PPARG were significantly differentially expressed genes for DPN. The correlation analysis showed that they were closely related to the clinical indicators of DPN suggesting that they may be involved in the development of DPN. In addition, receiver operating characteristic (ROC) curves generated for miR216a, miR377, ANGPTL4, GAP43, PPARG revealed that they can be used as new molecular diagnostic markers of DPN. miR-216a, miR-377, ANGPTL4, GAP-43, and PPARG could potentially be biomarkers of DPN.


Studies of variability in the islet amyloid polypeptide gene in relation to Type 2 diabetes.
To explore whether the coding region of the islet amyloid polypeptide (IAPP) gene contains genetic variants associated with Type 2 diabetes and whether a previously reported association of the promoter variant -132g-->a with Type 2 diabetes could be reproduced in Danish Caucasians. The coding region was analyzed using single strand conformation polymorphism (SSCP) and heteroduplex analysis in 192 Type 2 diabetic patients. Restriction fragment length polymorphism (RFLP) was employed to screen for the promoter variant in 414 Type 2 diabetic patients and 182 glucose-tolerant control subjects. The SSCP analysis identified an IVS+75a-->g variant in two patients. The frequency of heterozygous carriers of the promoter variant in the case-control study was 4.1% (17/414) and 7.1% (13/182), respectively. Odds ratio of the prevalence of Type 2 diabetes in carriers compared with non-carriers was estimated to be 0.47 (95% confidence interval 0.19, 1.15). Neither variability in the coding region of the IAPP gene nor the -132g-->a promoter variant was associated with Type 2 diabetes among the studied Danish Caucasians.


The incidence, risk factors and outcomes of acute kidney injury in critically ill patients undergoing emergency surgery: a prospective observational study.
Without sufficient evidence in postoperative acute kidney injury (AKI) in critically ill patients undergoing emergency surgery, it is meaningful to explore the incidence, risk factors, and prognosis of postoperative AKI. A prospective observational study was conducted in the general intensive care units (ICUs) from January 2014 to March 2018. Variables about preoperation, intraoperation and postoperation were collected. AKI was diagnosed using the Kidney Disease: Improving Global Outcomes criteria. Among 383 critically ill patients undergoing emergency surgery, 151 (39.4%) patients developed postoperative AKI. Postoperative reoperation, postoperative Acute Physiology and Chronic Health Evaluation (APACHE II) score, and postoperative serum lactic acid (LAC) were independent risk factors for postoperative AKI, with the adjusted odds ratio (ORadj) of 1.854 (95% confidence interval [CI], 1.091-3.152), 1.059 (95%CI, 1.018-1.102), and 1.239 (95%CI, 1.047-1.467), respectively. Compared with the non-AKI group, duration of mechanical ventilation, renal replacement therapy, ICU and hospital mortality, ICU and hospital length of stay, total ICU and hospital costs were higher in the AKI group. Postoperative reoperation, postoperative APACHE II score, and postoperative LAC were independent risk factors of postoperative AKI in critically ill patients undergoing emergency surgery.


Neuronal mechanism for acute mechanosensitivity in tactile-foraging waterfowl.
Relying almost exclusively on their acute sense of touch, tactile-foraging birds can feed in murky water, but the cellular mechanism is unknown. Mechanical stimuli activate specialized cutaneous end organs in the bill, innervated by trigeminal afferents. We report that trigeminal ganglia (TG) of domestic and wild tactile-foraging ducks exhibit numerical expansion of large-diameter mechanoreceptive neurons expressing the mechano-gated ion channel Piezo2. These features are not found in visually foraging birds. Moreover, in the duck, the expansion of mechanoreceptors occurs at the expense of thermosensors. Direct mechanical stimulation of duck TG neurons evokes high-amplitude depolarizing current with a low threshold of activation, high signal amplification gain, and slow kinetics of inactivation. Together, these factors contribute to efficient conversion of light mechanical stimuli into neuronal excitation. Our results reveal an evolutionary strategy to hone tactile perception in vertebrates at the level of primary afferents.


Prostate cancer screening: a survey of attitudes and practices among Finnish physicians in 1999 and 2007.
To evaluate the attitudes and practices related to prostate-specific antigen (PSA) screening for prostate cancer (PC) among Finnish physicians in 1999 and 2007. The first questionnaire survey was conducted in 1999 with a mailing to 102 urologists, 679 community physicians and 684 occupational health physicians identified from the membership files of three medical associations. The area of residence was divided into the study area of the Finnish PC screening trial and the rest of Finland. The second survey was carried out in 2007 targeting 168 urologists, 1039 community physicians and 938 occupational health physicians. The response proportion was 48% in 1999 and 50% in 2007. In both rounds, urologists regarded PC as a more important public health issue than other physicians. On the other hand, the non-urologists considered early diagnosis and screening more important than the urologists. PC was rated by all physicians as a less important public health problem in 2007 than in 1999. A smaller proportion of urologists found routine PSA testing indicated for asymptomatic men, compared with other physicians (40% versus 74-60% in 1999, P < 0.001 and 35% versus 44-37% in 2007, P = 0.005). The proportion of physicians reporting regular PSA screening in asymptomatic men was reduced from 1999 to 2007 (from 18% to 9%, P < 0.0001). Based on reported practices of Finnish urologists, community physicians and occupational health physicians, popularity of PSA testing declined between 1999 and 2007. Urologists found PSA testing among asymptomatic men justified less frequently than the other physicians.


Gateways to clinical trials.
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate.


Characterization of a protein kinase-phosphoprotein system in free cytoplasmic ribonucleoprotein particles of plasma cell tumours.
A protein kinase, associated with free cytoplasmic ribonucleoprotein particles (free dRNP) has been purified from mouse plasma cell tumours. This protein kinase is able to phosphorylate in vitro endogenous protein from free dRNP. Some characteristics of this protein kinase have been studied. This protein kinase behaves as being cyclic AMP independent. The properties of this protein kinase were compared with other protein kinases: soluble, ribosome-bound, and nuclear protein kinases. Although there are minor differences it is very similar to a ribosome-associated protein kinase from the plasma cell tumours.


[The State of Hemostasis and Immune System in Patients With Acute Coronary Syndrome Combined With Anxiety-Depressive Disorder].
Anxiety-depressive disorders (DD) have a negative impact on the course and prognosis of patients with ischemic heart disease, but the mechanisms of their correlation are not studied enough. The purpose of this study was to elucidate special characteristics of hemostasis and immune system in patients with acute coronary syndrome (ACS) combined with ADD. We included into the study 60 patients during first 24 hours of ACS. ADD was identified in 27 patients (45%). Parameters of plasma and vascular-platelet hemostasis and phenotype.


Relationship between urinary excretion of fibronectin degradation products and proteinuria in diabetic patients, and their suppression after continuous subcutaneous heparin infusion.
To explore the possibility that the excretion of urinary fibronectin degradation products (U-FnDP) can be an indicator of the progression of diabetic nephropathy, U-FnDP and urinary protein(U-P) were determined in 64 diabetic patients and 11 healthy volunteers. Moreover, to determine whether continuous subcutaneous heparin infusion (CSHI) reduces elevated U-FnDP and U-P in diabetic patients with persistent proteinuria, heparin sodium was administered as a bolus subcutaneous injection of 5000 IU, followed by subcutaneous infusion of 250 IU/kg per 24 h heparin sodium for 7 days. U-FnDP excretion rate elevated proportionally to the degree of U-P. CSHI reduced significantly elevated U-FnDP from 172.68 +/- 15.79 to 100.04 +/- 14.93 micrograms/24 h (P < 0.01) and U-P from 1.76 +/- 0.13 to 1.20 +/- 0.12 g/24 h (P < 0.01). No significant changes in blood pressure and diurnal mean plasma glucose levels were found. APTT was prolonged with a decrease of AT-III activity during the treatment. These findings suggest that U-FnDP can be one of the indicators which reflects the degree of progression of diabetic nephropathy, and that CSHI may be useful for the normalization of elevated U-FnDP and reduction in U-P in diabetic nephropathy.