Periorbital pain associated with hemifacial spasms that responded to botulinum toxin treatment and microvascular decompression surgery: a case report.
Periorbital pain is unusual in patients with blepharospasms. We report a patient with hemifacial spasms who presented with severe ipsilateral periorbital aching pain. After treatment with botulinum toxin type A, the left hemifacial spasms and left periorbital pain improved temporarily. Microvascular decompression surgery was then performed for the facial spasms. The patient's left hemifacial spasms disappeared immediately after the operation, and his left periorbital pain was also totally resolved.


Artificially intelligent scoring and classification engine for forensic identification.
Despite advances in genotyping technologies, traditional kinship analysis tools utilized in forensic identification have seen limited evolution and lack measures of accuracy. Here, we leverage artificial intelligence (AI) and extend the Elston-Stewart algorithm to deliver a method that provides an unprecedented level of flexibility to matching individuals with pedigrees by likelihood ratio. We designed an AI that utilizes a prediction cascade based on gradient descent logistic regression which allows for iterative solution of multi missing person scenarios. Furthermore, the AI can quantify the confidence underlying likelihood ratios across the spectrum of pedigrees, regardless of the amount of genetic information available and the number of missing persons. The algorithm accommodates an arbitrary number of generations and ancestral relationships, including multiple marriages, mutations, and consanguinity. We demonstrate that a properly trained AI significantly and reproducibly outperforms a human interpreter. We discuss published limitations of existing tools and demonstrate that they are not amenable to the size and complexity of this study. This novel method significantly improves the trade-off between sensitivity and specificity beyond the limits of traditional kinship analysis tools and introduces opportunities beyond the field of forensic genetics.


Course of ATP depletion in hydrazine hepatotoxicity.
The effect of hydrazine on ATP levels has been investigated in rats in vivo and in hepatocytes in vitro. Hydrazine was found to cause a dose-dependent depletion of hepatic ATP in vivo 3 h after dosing. In isolated hepatocytes in vitro hydrazine also caused a concentration-dependent depletion of ATP which preceded cytotoxicity as indicated by loss of cell viability. The ATP depletion in isolated hepatocytes was also significant at a concentration of hydrazine which was not cytotoxic. Attempts to determine hepatic ATP depletion in vivo over time using topical 31P NMR were confounded by the effects of the thiopentobarbitone used to anaesthetise the animals. This was found to ameliorate the effects of hydrazine on ATP depletion but potentiate the lethality of hydrazine. Consequently, although ATP depletion was detected in some hydrazine-treated animals, this was only observed in animals which subsequently died. The results indicate that ATP depletion may underlie the hepatotoxicity of hydrazine.


Disparities in Care Access to Liver-Directed Therapy Among Medicare Beneficiaries with Colorectal Cancer Liver Metastasis.
Liver-directed therapies (LDT) are important components of the multidisciplinary care of patients with colorectal cancer liver metastases (CRCLM) that contribute to improved long-term outcomes. Factors associated with receipt of LDT are poorly understood. Patients > 65 years old diagnosed with CRCLM were identified within the Medicare Standard Analytic File (2013-2017). Patients with extrahepatic metastatic disease were excluded. Mixed-effects analyses were used to assess patient factors associated with the primary outcome of LDT, defined as hepatectomy, ablation, and/or hepatic artery infusion chemotherapy (HAIC), as well as the secondary outcome of hepatectomy. Among 23,484 patients with isolated CRCLM, only 2004 (8.5%) received LDT, although resectability status could not be determined for the entire cohort. Among patients who received LDT, 61.7% underwent hepatectomy alone, 28.1% received ablation alone, 8.5% underwent hepatectomy and ablation, and 1.8% received HAIC either alone (0.8%) or in combination with hepatectomy and/or ablation (0.9%). Patient factors independently associated with lower odds of LDT included older age, female sex, Black race, greater comorbidity burden, higher social vulnerability index, primary rectal cancer, synchronous liver metastasis, and further distance from a high-volume liver surgery center (p < 0.05). Results were similar for receipt of hepatectomy. Despite the well-accepted role of LDT for CRCLM, only a small proportion of Medicare beneficiaries with CRCLM receive LDT. Increasing access to specialized centers with expertise in LDT, particularly for Black patients, female patients, and those with higher levels of social vulnerability or long travel distances, may improve outcomes for patients with CRCLM.


Relationship between plasma atrial and brain natriuretic peptide concentration and hemodynamic parameters during percutaneous transvenous mitral valvulotomy in patients with mitral stenosis.
Brain natriuretic peptide (BNP), a family of peptides with structural and biologic homologies to previously identified atrial natriuretic peptide (ANP), has been found in human cardiac tissue and plasma. To examine the secretion mechanism of these peptides, we have studied the relationship between their plasma concentrations and hemodynamic parameters before and at 0.5 and 24 hours after percutaneous transvenous mitral commissurotomy (PTMC) in 14 patients with mitral stenosis. We have also investigated the validity of measuring plasma natriuretic peptides as a means for estimating changes in hemodynamic parameters after PTMC. The procedure decreased left atrial pressure (p < 0.01) with an elevation in left ventricular end-diastolic pressure (p < 0.05). Plasma ANP levels decreased significantly after PTMC (before, 64.1 +/- 33.7 fmol/ml; at 0.5 hour, 58.9 +/- 27.7 fmol/ml; at 24 hours, 45.7 +/- 18.3 fmol/ml; p < 0.01), whereas plasma BNP levels remained unchanged after the procedure (before, 5.3 +/- 1.5 fmol/ml; at 0.5 hour, 5.6 +/- 1.9 fmol/ml; at 24 hours, 5.0 +/- 1.9 fmol/ml; p = NS). There was a significant relationship between basal plasma ANP and left atrial pressure (r = 0.88; p < 0.001), and changes in plasma ANP were correlated with those in left atrial pressure (r = 0.69; p < 0.01). Basal plasma BNP was significantly correlated with basal left ventricular end-diastolic pressure (r = 0.65; p < 0.05) but not with the other measured hemodynamic parameters or with plasma volume.(ABSTRACT TRUNCATED AT 250 WORDS)


Managing buyer experience in a buyer-supplier relationship in MSMEs and SMEs.
Monitoring buyer experience provides competitive advantages for suppliers as buyers explore the market before reaching a salesperson. Still, not many B2B suppliers monitor their buyers' expectations throughout their procurement journey, especially in MSMEs and SMEs. In addition, the inductive research on evaluating buyer experience in buyer-supplier relationships is minimal, leaving an unexplored research area. This study explores antecedents of buyer experience during the buyer-supplier relationship in MSMEs and SMEs. Further, we investigate the nature of the influence of extracted precursors on the buyer experience. Firstly, we obtain the possible antecedents from the literature on buyer-supplier experience and supplier selection criteria. We also establish hypotheses based on transaction cost theory, resource-based view (RBV), and information processing view. Secondly, we employ an investigation based on the social media analytics-based approach to uncover the antecedents of buyer experience and their nature of influence on MSMEs and SME suppliers. We found that buyer experience is influenced by sustainable orientation, management capabilities (such as crisis management and process innovation), and suppliers' technology capabilities (digital readiness, big data analytical capability).


Condylar stabilizing technique for intra-articular fracture of distal radius.
I previously reported a new reduction and fixation technique for extra-articular distal radius fracture associated with osteoporosis. I developed the technique and applied it to intra-articular fracturea. I present here the technique and verify its reliability, comparing the functional results of intra-articular fracture cases to those of extra-articular cases.


Biomass-based superhydrophobic coating with tunable colors and excellent robustness.
Multicolored superhydrophobic coating with high durability has been receiving tremendous attention in decorative applications. Herein, a facile method to fabricate multicolored superhydrophobic coating with excellent robustness has been developed by using cellulose and chitosan. The multicolored coatings can be obtained through single dyeing or mixed dyeing based on three primary dyes. The coating can be applied on hard substrates (e.g. glass, aluminum sheet) and soft substrates (e.g. cotton fabric) by diverse methods including spraying, dip-coating and painting. The colorful coating firmly adheres to the substrates due to the multiple interactions (siloxane covalent bonds and hydrogen bonds). The colorful coating exhibits water-repellant behaviors and can withstand sandpaper abrasion, tape-peeling cycles, water impact, salt spray test and UV environments. Furthermore, the multicolored coating can be used as a new type of pigment for painting on different substrates and is expected to have a huge potential application in technological design or decoration.


The clinical value of monoclonal protein in ANCA-associated vasculitis with renal involvement.
The value of monoclonal protein (M-protein) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with renal involvement has not been investigated. We analyzed AAV patients with renal involvement from 2013 to 2019 in our center. Patients with immunofixation electrophoresis were divided into M-protein positive group and M-protein negative group. The clinicopathological features and outcomes of the two groups were compared. Ninety-one AAV patients with renal involvement were enrolled for analysis, and 16 patients (17.6%) had a positive test for M-protein. Compared with M-protein negative patients, M-protein positive patients had lower hemoglobin (77.6 vs 88.4 g/L, p = 0.016), mean corpuscular hemoglobin concentration (313 vs 323 g/L, p = 0.002),serum albumin (29.4 vs 32.5 g/L, p = 0.026) and complement 3 (C3) (0.66 vs 0.81 g/L, p = 0.047), while higher platelets (252 vs 201 109/L, p = 0.048) and incidence of pulmonary infection (62.5% vs 33.3%, p = 0.029). However, renal pathological features between the two groups had no significant difference. In addition, during a median follow-up of 33 months, Kaplan-Meier survival analysis showed that, compared with M-protein negative patients, M-protein positive patients had a higher risk of all-cause mortality (log-rank test, p = 0.028), especially for patients who were not dialysis-dependent at the time of admission (log-rank test, p = 0.012). Our results indicate that M-protein is associated with different clinicopathological features and increased all-cause mortality in AAV patients with renal involvement. Testing M-protein and rigorous diagnosing of the significance of the presence of M-protein may be helpful for assessing the survival of AAV patients with renal involvement.


Repair of porcelain-fused-to-metal restorations.
Three techniques have been described which may be used to repair many porcelain-fused-to-metal restorations. These techniques provide an avenue of repair for extensive porcelain-fused-to-metal restorations without remaking the entire prosthesis. The success of the overlay and pin-retained ceramo-metal repairs should be comparable to that of a newly constructed porcelain-fused-to-metal restoration. The composite resin bonded to porcelain repair technique will not have as favorable a prognosis, as composite resins are more subject to wear and are not color stable, and the chemical bond created with silance bonding agents is much weaker than the bond created when porcelain is fused to metal. Success of silance-bonded repairs should not be expected for periods longer than 2 to 3 years.


Novel Clinical Anatomic Consideration of the Superficial and Deep Layers of the Deep Temporal Fascia.
The deep temporal fascia provides anchoring during thread lifting, which is a minimally invasive facelifting procedure. However, anatomic studies involving the deep temporal fascia as well as effective and safe thread lifting procedures are scarce. We clarified the anatomy of the superficial layer of the deep temporal fascia and its surrounding structure using ultrasonography, histologic sections, and cadaveric dissection to propose an effective thread lifting procedure guideline. We included 20 healthy young South Korean participants. Real-time, two-dimensional, B-mode ultrasonography was performed. Longitudinal scanning was performed along three vertical lines: the line passing through the jugale, the anterior margin of the condylar process of the mandible, and the midpoint between the jugale and anterior margin of the condylar process. Histologic samples from three fresh adult cadavers were harvested from 2.5 cm above and below the zygomatic arch. Eighteen fresh adult hemifaces of South Korean cadavers (six males, three females; age, 67.3 ± 7.2 years) were used to confirm the morphology of the deep temporal fascia. The superficial layer of the deep temporal fascia crossed the zygomatic arch and was connected to the origin of the zygomaticus major muscle at the line passing through the jugale. The superficial layer continued inferiorly to the parotidomasseteric fascia at the line passing through the midpoint and condylar process of the mandible. This study yielded the novel anatomy of the superficial layer of the deep temporal fascia, and this anatomic structure may be used for an ideal thread lifting procedure.


Patient, primary care physician and specialist expectations of primary care physician involvement in cancer care.
In Canada, many health authorities recommend that primary care physicians (PCP) stay involved throughout their patients' cancer journey to increase continuity of care. Few studies have focused on patient and physician expectations regarding PCP involvement in cancer care. To compare lung cancer patient, PCP and specialist expectations regarding PCP involvement in coordination of care, emotional support, information transmission and symptom relief at the different phases of cancer. Canadian survey of lung cancer patients, PCPs and cancer specialists A total of 395 patients completed questionnaires on their expectations regarding their PCP participation in several aspects of care, at different phases of their cancer. Also, 45 specialists and 232 community-based PCP involved in these patients' care responded to a mail survey on the same aspects of cancer care. Most specialists did not expect participation of the PCP in coordination of care in the diagnosis and treatment phases (65% and 78% respectively), in contrast with patients (83% and 85%) and PCPs (80% and 59%) (p < 0.0001). At these same phases, the best agreement among the 3 groups was around PCP role in emotional support: 84% and more of all groups had this expectation. PCP participation in symptom relief was another shared expectation, but more unanimously at the treatment phase (p = 0.85). In the advanced phase, most specialists expect a major role of PCP in all aspects of care (from 81% to 97%). Patients and PCP agree with them mainly for emotional support and information transmission. Lung cancer patient, PCP and specialist expectations regarding PCP role differ with the phase of cancer and the specific aspect of cancer care. There is a need to reach a better agreement among them and to better define PCP role, in order to achieve more collaborative and integrated cancer care.


Development of an antimicrobial bioactive paper made from bacterial cellulose.
Bacterial cellulose (BC) has emerged as an attractive adsorptive material for antimicrobial agents due to its fine network structure, its large surface area, and its high porosity. In the present study, BC paper was first produced and then lysozyme was immobilized onto it by physical adsorption, obtaining a composite of lysozyme-BC paper. The morphology and the crystalline structure of the composite were similar to that of BC paper as examined by scanning electron microscopy and X-ray diffraction, respectively. Regarding operational properties, specific activities of immobilized and free lysozyme were similar. Moreover, immobilized enzyme showed a broader working temperature and higher thermal stability. The composites maintained its activity for at least 80 days without any special storage. Lysozyme-BC paper displayed antimicrobial activity against Gram-positive and Gram-negative bacteria, inhibiting their growth by 82% and 68%, respectively. Additionally, the presence of lysozyme increased the antioxidant activity of BC paper by 30%. The results indicated that BC is a suitable material to produce bioactive paper as it provides a biocompatible environment without compromising the activity of the immobilized protein. BC paper with antimicrobial and antioxidant properties may have application in the field of active packaging.


Exposure to perfluoroalkyl substances and women's fertility outcomes in a Singaporean population-based preconception cohort.
Experimental models have demonstrated a link between exposure to perfluoroalkyl substances (PFAS) and decreased fertility and fecundability; however, human studies are scarce. We assessed the associations between preconception plasma PFAS concentrations and fertility outcomes in women. In a case-control study nested within the population-based Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), we measured PFAS in plasma collected in 2015-2017 from 382 women of reproductive age trying to conceive. Using Cox proportional hazards regression (fecundability ratios [FRs]) and logistic regression (odds ratios [ORs]) models, we assessed the associations of individual PFAS with time-to-pregnancy (TTP), and the likelihoods of clinical pregnancy and live birth, respectively, over one year of follow-up, adjusting for analytical batch, age, education, ethnicity, and parity. We used Bayesian weighted quantile sum (BWQS) regression to assess the associations of the PFAS mixture with fertility outcomes. We found a 5-10 % reduction in fecundability per quartile increase of exposure to individual PFAS (FRs [95 % CIs] for clinical pregnancy = 0.90 [0.82, 0.98] for PFDA; 0.88 [0.79, 0.99] for PFOS; 0.95 [0.86, 1.06] for PFOA; 0.92 [0.84, 1.00] for PFHpA). We observed similar decreased odds of clinical pregnancy (ORs [95 % CIs] = 0.74 [0.56, 0.98] for PFDA; 0.76 [0.53, 1.09] for PFOS; 0.83 [0.59, 1.17] for PFOA; 0.92 [0.70, 1.22] for PFHpA) and live birth per quartile increases of individual PFAS and the PFAS mixture (ORs [95 % CIs] = 0.61 [0.37, 1.02] for clinical pregnancy, and 0.66 [0.40, 1.07] for live birth). Within the PFAS mixture, PFDA followed by PFOS, PFOA, and PFHpA were the biggest contributors to these associations. We found no evidence of association for PFHxS, PFNA, and PFHpS and the fertility outcomes examined. Higher PFAS exposures may be associated with decreased fertility in women. The potential impact of ubiquitous PFAS exposures on infertility mechanisms requires further investigation.


The anatomy of transcription sites.
Patterns of gene expression in multicellular eukaryotes are regulated by numerous extremely sophisticated mechanisms. Over the past year, developments in our ability to monitor the organisation and dynamic properties of the components involved in gene expression have emphasised how both global nuclear architecture and chromosome structure can influence this fundamental process.


Have risk factors for mortality after heart transplantation changed over time? Insights from 19 years of Cardiac Transplant Research Database study.
The Cardiac Transplant Research Database (CTRD) collected data from 26 U.S. institutions from January 1, 1990 to December 31, 2008 providing the opportunity for construction of a comprehensive multivariable model of risk for death after transplantation. We analyzed risk factors for death over 19 years of experience to determine how risk profiles have changed over time and how they interact with age. A multivariable parametric hazard model for death was created for 7,015 patients entered into the CTRD. Variables collected over 19 years of experience were examined as potential risk factors and tested for interaction with date of transplantation to determine if their relative risk (RR) changed over time. The hazard for death post-transplant occurred in 2 phases: an early phase of acute risk lasting <1 year, and a late phase of relatively low, gradually increasing risk (<0.1 event/year). In the early phase, predictive models showed that ventricular assist device (VAD) at the time of transplant did not increase the RR of death for recipient transplant at 30 years of age, but the RR of death was increased by 60% (p = 0.04) at 60 years of age. Of the late-phase variables found to be risk factors, the RR of age, date of transplant and pulmonary vascular resistance changed with respect to transplant year. The overall risk of death dropped importantly over the study period, but the RR of all other variables remained unchanged. RR was 2.6 (p < 0.0001) for 25-year-old African-American (AA) versus non-AA recipients and 1.6 for 60-year-old AA recipients (p = 0.02). Over 19 years, the baseline risk of death has decreased, but the specific risk factors and the magnitudes of their RR have remained unchanged. Therefore, despite advances in clinical management and improvement in overall survival, the risk profile for death after cardiac transplantation is similar to that in 1990.


Reconstruction of auricular defect with perichondrial graft: a new technique. Case report.
A new technique is introduced to reconstruct defects of the auricle. The neochondrogenic capacity in a free graft of the auricular perichondrium is used to build the cartilaginous framework in the missing part of the auricle. By using local flaps and skin grafts for coverage of the newly formed cartilage the missing part of the auricle is satisfactorily reconstructed.


Time-resolved fluorescence polarization from ordered biological assemblies.
We calculate the time dependence of the polarized fluorescence signal from fluorescent-labeled elements of a biological assembly that are rotationally diffusing in an arbitrary three-dimensional angular potential. We have formulated this calculation using the model-independent description of the angular potential wherein the angular potential is described by an expansion in a complete set of orthonormal functions with the expansion coefficients (or order parameters) determined by time-independent methods (Burghardt, T. P., 1984, Biopolymers, 23:2382-2406). We have applied the calculation to fluorescent-labeled myosin cross-bridges in relaxed muscle fibers. In a related paper we describe the experimental observation of the myosin cross-bridges rotationally diffusing in an angular potential (Burghardt, T. P., and N. L. Thompson, 1985, Biochemistry, 24:3731-3735).


Computer assisted minimally invasive surgery: is medical computer vision the answer to improving laparosurgery?
Minimally Invasive Surgery (MIS) is one of the most effective methods of modern surgical intervention that has considerable advantages compared with open surgery, including reduced trauma, pain, and post-operative recovery time. MIS has improved substantially over the years, chiefly due to new hardware innovations, including HD cameras and flexible head endoscopes. However, MIS continues to be hindered by several problems. In addition to hardware innovation, Computer Vision (CV) has been proposed as a way to overcome some of its current limitations. However, the research literature lacks a coherent picture of how the limitations can be best overcome by hardware, CV or a combination of the two. In this paper we focus on laparoscopic MIS, and list these limitations into 5 clear categories. We detail the effectiveness of hardware and CV solutions with respect to each limitation, from which we base the following hypothesis: CV is both complementary and necessary to hardware development, to overcome all 5 limitations in laparoscopy. Our paper is of value to laparoscopy surgeons, by conveying what is expected to be achieved in computer-aided laparoscopy over the next decade. It is also of value to medical CV researchers, by clarifying which problems are best solved with CV, in light of the hardware developments likely to occur over the next decade.


The antidepressant and anxiolytic effect of GPER on translocator protein (TSPO) via protein kinase a (PKA) signaling in menopausal female rats.
Postmenopausal depression is mainly caused by the deprivation of ovarian hormones during menopausal transition, it is of great importance to study on the treatment that could effectively relieve symptoms of menopausal depression with fewer side effects. Activation of G-protein-coupled estrogen receptor (GPER) has long been reported to facilitate neuronal plasticity and improve cognition in animals. Meanwhile, it could participate in regulation of intracellular signaling pathways through the characteristic of GPER, ameliorate intracellular mitochondrial function and oxidative stress. However, the impact of GPER on regulating estrogen deprived-depressant and anxious behaviors is still largely unknown. Here we used the ovariectomized female rats to imitate the condition of menopause. Owing to the lateral ventricle administration of G-1 which specifically react with GPER receptor intracerebrally, Ovariectomized (OVX) female rats showed depressive- or anxiety-like phenotypes with attenuated mitochondrial function. In addition, G-1 facilitated PKA activation, which further accelerated TSPO phosphorylation and alleviated menopausal depression- and anxiety-like behaviors. Moreover, PKA inhibitor PKI could partially antagonized the anti-anxiety and anti-depression effects of G-1. Taken together, we concluded that GPER activation might exhibit antidepressant and anxiolytic effect by elevating TSPO phosphorylation via protein kinase A signaling and rescuing the redox status in menopausal female rats.


Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation.
Fibroblasts maintain the extracellular matrix homeostasis and may couple to cardiomyocytes through gap junctions and thereby increase the susceptibility to slow conduction and cardiac arrhythmias, such as atrial fibrillation (AF). In this study, we used an equine model of persistent AF to characterize structural changes and the role of fibroblasts in the development of an arrhythmogenic substrate for AF. Eleven horses were subjected to atrial tachypacing until self-sustained AF developed and were kept in AF for six weeks. Horses in sinus rhythm (SR) served as control. In terminal open-chest experiments conduction velocity (CV) was measured. Tissue was harvested and stained from selected sites. Automated image analysis was performed to assess fibrosis, fibroblasts, capillaries and various cardiomyocyte characteristics. Horses in SR showed a rate-dependent slowing of CV, while in horses with persistent AF this rate-dependency was completely abolished (CV•basic cycle length relation p = 0.0295). Overall and interstitial amounts of fibrosis were unchanged, but an increased fibroblast count was found in left atrial appendage, Bachmann's bundle, intraatrial septum and pulmonary veins (p < 0.05 for all) in horses with persistent AF. The percentage of α-SMA expressing fibroblasts remained the same between the groups. Persistent AF resulted in fibroblast accumulation in several regions, particularly in the left atrial appendage. The increased number of fibroblasts could be a mediator of altered electrophysiology during AF. Targeting the fibroblast proliferation and differentiation could potentially serve as a novel therapeutic target slowing down the structural remodeling associated with AF.


Automating Vancomycin Monitoring to Improve Patient Safety.
Intravenous vancomycin is a frequently used antibiotic and a common cause of medication-related harm because of its narrow therapeutic range. Improving monitoring of drug levels with automation in the electronic health record (EHR) may decrease this harm. After examining the existing state of vancomycin ordering, administration, and monitoring, an automated process was created in the EHR that, on initiation of a new vancomycin order, automatically ordered a vancomycin trough level 30 minutes before the fourth dose. In addition, a nursing alert was integrated into the bar coding medication administration process that, if no trough level had been drawn by the time of the administration of the fourth dose, prompted the nurse to draw a trough level. Data from a three-month, post-implementation period was compared to data from a preceding three-month period. The frequency of trough levels drawn between the third and fourth dose increased from 58.6% to 75.8% (p < 0.01). However, the percentage of trough levels drawn within one hour of the fourth dose remained unchanged, possibly because nursing staff waited for the result of the level prior to administering the next dose of vancomycin. A minority of patients in both groups had trough levels that were in range (difference between groups, p = 0.46). Automation of vancomycin monitoring was associated with improvement in the frequency of monitoring and only delayed medication dosing by six minutes. Because vancomycin is high risk, this type of process should be broadly implemented, and outcomes should be assessed to identify unexpected outcomes and necessary further refinements.


Acoustic rhinometry, spirometry and nitric oxide in relation to airway allergy and smoking habits in an adolescent cohort.
This study aimed to analyze upper and lower airway function and the impact of smoking habits in a cohort of allergic and healthy adolescents. The influence of smoking habits on the outcomes of rhinitis and asthma is well documented, but only few reports are available showing smoke related upper airway impairment by rhinometric measurements, and none with focus on early changes in adolescents. A cohort followed from infancy was re-examined at the age of 18 years concerning allergy development. Acoustic rhinometry (VOL2), spirometry (FEV(1)) and measurements of nitric oxide levels from the upper (nNO) and lower airways (eNO) were performed before and after physical exercise, and smoking habits were registered. Active smoking habits were reported by 4/21 subjects suffering from allergic rhinitis, by 1/4 from probable allergic rhinitis, by 0/3 subjects with atopic dermatitis and by 2/10 healthy controls. Smoking habits were reported as daily by 2 and occasional by 5 of the 7 active smokers. VOL2 did not increase in smokers after exercise as in non-smokers, resulting in a post-exercise group difference (7.3±1.1cm(3) vs. 8.8±1.5cm(3); p=0.02), and FEV(1) values were lower in smokers compared to non-smokers (89±7% vs. 98±8%; p=0.02). The nNO and eNO levels were, however, only slightly reduced in smokers. Airway allergy was discerned only in subjects with current allergen exposure by increased eNO levels compared to healthy controls (41±44ppb vs. 13±5ppb). The levels of VOL2, nNO and FEV(1) did not differentiate allergic subjects from healthy controls. Low levels of tobacco smoke exposure resulted in reduced airway functions in this adolescent cohort. Acoustic rhinometry and spirometry were found to be more sensitive methods compared to nitric oxide measurements in early detection of airway impairment related to smoke exposure. A possible difference in airway vulnerability between allergic and healthy subjects due to smoke exposure remains to be evaluated in larger study groups.


A systematic review and critical evaluation of reported pathogenic sequence variants in hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a severe chronic inflammatory disorder characterized by recurrent painful deep-seated nodules with a predilection to the apocrine-bearing areas of skin. A minority of cases of HS are due to mutations in the γ-secretase complex. Contention exists surrounding the pathogenicity of sequence variants and their effects upon Notch signalling. This systematic review was registered with PROSPERO (CRD42016041425) and was conducted in line with the PRISMA statement. Eligibility criteria for this review included published case reports, case series and reviews that identified sequence variants or protein or functional studies from patients with HS. Sixty-two articles were identified reporting a total of 41 sequence variants - heterozygous missense (nine), splice site (nine), insertion resulting in frameshift (one), premature termination codon (19) and promoter region PSTPIP1 (three) - with 18 associated protein or functional studies. The American College of Medical Genetics and Genomics standards and guidelines on the interpretation of sequence variants were applied to each identified variant to assess evidence for pathogenicity. Twenty-three variants were assessed as likely pathogenic, 17 of uncertain significance and one benign. The large number of variants of 'uncertain significance' is largely due to the variable number of functional studies. Four studies used Notch as a proxy for γ-secretase function, with conclusions of nonpathogenicity based on the assumption of Notch signalling as the sole pathogenic process. The role of Notch-independent signalling mechanisms requires further research. Limitations to this study include identification of variants of Mendelian inheritance and not complex polygenic traits.


Plain access to justice and the orthodontist's activity in Brazil: vulnerability in the professional practice in the face of risks of malpractice lawsuits.
the present study aimed at evaluating the risks and vulnerability of orthodontists to legal compensation actions and verifying the hypothesis of these health care professionals having little knowledge concerning their rights and obligations as service providers. Three groups were formed to participate in a semi-structured interview. The first group had thirteen law professionals, the second group was composed of eleven orthodontists and the third group was made up of nine randomly selected orthodontic patients. Relevant aspects related to the exercise of the professional activity of orthodontists that influence on the vulnerability of orthodontists in lawsuits were identified. After transcription, reading, and comparing the answers of the interviews, items capable of influencing judicial decisions, from the standpoint of Brazilian Justice Courts, were evaluated. It was verified that Brazilian orthodontists do not have adequate formation concerning the legal consequences of the exercise of their professional activity. Orthodontists also failed to establish proper contractual relationship, organize orthodontic records, and, most importantly, failed in communicating the risks and the therapeutic processes to patients during all phases of treatment.


Temporal transcriptome profiling of developing seeds reveals candidate genes involved in oil accumulation in safflower (Carthamus tinctorius L.).
The investigation of molecular mechanisms involved in lipid metabolism plays a critical role for the genetic engineering of safflower (Carthamus tinctorius L.) to increase the oil accumulation level or to change the oil composition. Although transcript sequences are currently available for the leaves and flowers of safflower, a wide range scan of temporal transcripts at different stages of seed development has not been conducted for safflower. In this study, temporal transcriptome sequencing was executed at 10, 14, 18, and 22 days after flowering (DAF) to uncover the molecular networks concerned in the biosynthesis of unsaturated fatty acids (USFAs). The results revealed that the biosynthesis of fatty acids is a dominant cellular process from 10 to 14 DAF, while degradation mainly happens after 18 DAF. Significant expression changes of two genes, stearoyl-[acyl-carrier-protein] 9-desaturase gene (SAD) from 10 to 14 DAF and oleate desaturase (FAD2-1) from 14 to 18 DAF, were detected at the transcriptomic levels, and the temporal expression patterns revealed by the transcriptomic analysis were confirmed using quantitative real-time PCR experiments. In addition, 13 candidate transcription factors (TFs) involved in regulating the expression level of the FAD2-1 gene were identified. These results create a link between fatty acid biosynthesis and gene expression at different developmental stages of the seeds, provide insight into the underlying lipid metabolism, and meanwhile lay an important foundation for the genetic engineering of safflower varieties. We have identified novel candidate genes, including TFs, that are worthy of further exploration.


Apparent absence of recombinogenic activity of nitropyrenes for yeast.
Nitropyrenes have been shown to be potent bacterial and mammalian mutagens. However, they failed to induce any recombinogenic activity in Saccharomyces cerevisiae D4 even at elevated concentrations and following extended periods of exposure. A plausible explanation for this lack of activity is the absence or the lack of activation of the enzyme required for the activation of nitropyrenes in this test system under the experimental (aerobic) conditions employed.


Geographic Distribution of Alcohol Use Among Chinese Adults - China, 2015.
Alcohol use is attributed to more than 200 diseases and injury conditions. Recent conventional and genetic evidence is beginning to counter the benefit of moderate drinking. The prevalence of current alcohol use was 35.7% in 2007 among the Chinese population aged 18-69 years, but comparable estimations on a provincial-level has not been reported in China. The prevalence of current alcohol use in the preceding year was 41.3% among the Chinese population aged 18 years and above in 2015. The prevalence of current alcohol use and the average level of daily pure alcohol intake among drinkers showed clustered and diversified geographic distribution across provinces. Given diversified demographics and geographic characteristics of the current alcohol drinking population, the alcohol control policies and intervention strategies should be adopted at a provincial level to reduce alcohol-related mortality and disability.


[Fracture of the collum of femur as a consequence of disturbed function in patients with resected stomach (Billroth II) (author's transl)].
Disturbed metabolism of bones like osteoporosis are not completely physiological in elder persons. In all cases it is needed to search for the origin. Under the intestinal factors is a slight calcium deficiency with food of a great importance for genesis of osteoporosis stimulating a occult secondary hyperparathyroidism. If vitamin D-deficiency is added a osteomalacic component is following called "Osteoporomalacia". This mixed form is typical for intestinals. Especially elder patients are endangered because the supplying of calcium and vitamin D also the calcium absorption are decreasing with getting elder. The calcium absorption is also smaller in patients with resected stomach (Billroth II). When the function in resected stomach is disturbed like in our case of afferent-loop-syndrome a osteoporosis with osteomalacic component and pathological fractures can develop. In such cases teamwork is worthwhile.


Simple preparation of a cadmium selenide-montmorillonite hybrid.
The immobilization of organically modified cadmium selenide on montmorillonite was investigated by the reaction of modified cadmium selenide nanoparticles with montmorillonite. The intercalation of the nanoparticles was indicated by the expansion of the interlayer space and spectroscopic observations. The diffuse reflectance absorption spectrum of the product showed absorption onset at 567 nm. In comparison to the bulk cadmium selenide, the blue shift of the absorption onset of the hybrid was ascribed to the quantum size effect of the modified cadmium selenide nanoparticles. This study provides a new method for introducing nanoparticles into the interlayer space of layered inorganic materials.


X-ray structure determination and comparison of two crystal forms of a variant (Asn115Arg) of the alkaline protease from Bacillus alcalophilus refined at 1.85 A resolution.
The X-ray structure determination, refinement and comparison of two crystal forms of a variant (Asn115Arg) of the alkaline protease from Bacillus alcalophilus is described. Under identical conditions crystals were obtained in the orthorhombic space group P2(1)2(1)2(1) (form I) and the rhombohedral space group R32 (form II). For both space groups the structures of the protease were solved by molecular replacement and refined at 1.85 A resolution. The final R-factors are 17.9% and 17.1% for form I and form II, respectively. The root-mean-square deviation between the two forms is 0.48 A and 0.86 A for main-chain and side-chain atoms, respectively. Due to differences in crystal lattice contacts and packing, the structures of the two crystal forms differ in intermolecular interaction affecting the local conformation of three flexible polypeptide sequences (Ser50-Glu55, Ser99-Gly102, Gly258-Ser259) at the surface of the protein. While the two overall structures are very similar, the differences are significantly larger than the errors inherent in the structure determination. As expected, the differences in the temperature factors in form I and II are correlated with the solvent accessibility of the corresponding amino acid residues. In form II, two symmetry-related substrate binding sites face each other, forming a tight intermolecular interaction. Some residues contributing to this intermolecular interaction are also found to be involved in the formation of the complex between subtilisin Carlsberg and the proteinaceous inhibitor eglin C. This demonstrates that the two symmetry-related molecules interact with each other at the same molecular surface area that is used for binding of substrates and inhibitors.


Fluorescence enhancement of CdSe/ZnS quantum dots induced by mercury ions and its applications to the on-site sensitive detection of mercury ions.
The significant fluorescence enhancement of CdSe/ZnS quantum dots (QDs) induced by Hg2+ was observed for the first time based on a CdSe/ZnS QD-modified fiber nanoprobe. The fluorescence enhancement mechanism contributed to the Zn-to-Hg cation exchange in the ZnS shell, which allowed to form a HgxZn1-xS/CdSe heterojunction and increase the separation of electrons and holes and reduce the recombination rate. High concentrations of Hg2+ accelerated the generation of the fluorescence signal and lead to higher fluorescence intensity. The maximum fluorescence intensity increased more than eight times when Hg2+ concentration was 1 µM. The characteristic time (θc), i.e., the rising time to achieve the maximum fluorescence intensity, was linearly dependent on initial concentration of Hg2+ solution in accordance with our proposed theory. When the evanescent wave optofluidic fluorescence platform was used, the linear detection range and detection limit of Hg2+ were 5.0-1000 nM and 0.80 nM, respectively. The fiber nanoprobe can be applied to the rapid, sensitive, and accurate on-site detection of Hg2+ in real water samples without significant matrix effect. Our work paves a novel way to develop a simple and reliable nanoprobe for mercuric pollution control, and achieve the high quantum efficiency of QDs by limiting the diffusion of Hg2+ in the ZnS shell.


The Data Behind Popular Diets for Weight Loss.
Both scientific evidence and popular diet trends have sought to identify the ideal diet for weight loss with strategies focused on either restricting carbohydrates or fat. While there is a strong physiologic rationale for either carbohydrate restriction or fat restriction to achieve a calorie deficit needed for weight loss, evidence from randomized controlled trials suggest either type of diet is effective for weight loss. The level of adherence, rather than macronutrient content, is the driver of successful weight loss.


Novel Humanized Biosimulator to Predict Coronary Obstruction in High-Risk Valve-in-Valve Procedures.
We developed humanized biosimulator to predict the risk of coronary obstruction among high-risk patients undergoing valve-in-valve (ViV) procedures. In this case, based on unchanged instantaneous wave-free ratio values measured during a ViV simulation session, the procedure was performed safely in the patient the day afterward, without coronary artery issues and with good hemodynamic results. (Level of Difficulty: Advanced.).


Psychometric properties of the revised Piper Fatigue Scale in Dutch cancer patients were satisfactory.
To examine the psychometric properties of the revised Piper Fatigue Scale (PFS) in Dutch cancer patients. Participants were 64 patients with lung (any stage, nonsurgery) and breast (any stage) cancer, selected for curative high-dose radiotherapy (> or =50 Gy). Prior to radiotherapy, patients completed the revised PFS (translated into Dutch), the Multidimensional Fatigue Inventory (MFI), and the Rotterdam Symptom Checklist (RSCL). Reliability and construct and criterion validity of the PFS were investigated. Overall, the structure of the Dutch revised PFS appeared appropriate, with corrected item-subscale correlations being higher than the correlations of the same item with the three other subscales; furthermore, internal consistency was excellent (Cronbach's alpha > or =0.90). Lung cancer patients were significantly more tired then breast cancer patients, supporting construct validity. Criterion validity was also satisfactory, with highest correlations of PFS total fatigue with the MFI subscale general fatigue (0.84) and RSCL overall quality of life score (0.74). Internal consistency was similar in Dutch and U.S. breast cancer patients; fatigue scores were lower on several PFS subscales in the Dutch study population. Psychometric properties of the Dutch version of the revised PFS, as tested in cancer patients prior to radiotherapy, were satisfactory.


HLA class II high-resolution genotyping in Greek children with celiac disease and impact on disease susceptibility.
Celiac disease (CD) has been associated with HLA class II heterodimers. This study aimed at determining the HLA genotypic and allelic distribution in Greek children with CD as compared with the general population. A total of 118 children with CD and 120 healthy individuals serving as controls were included in the study. Higher frequencies for HLA-DQB1*02:01 (40.25 vs. 9.58%, P < 0.001) and DQB1*02:02 (20.34 vs. 5.42%, P < 0.001) were observed in patients with CD, whereas HLA-DQB1*03:01 (16.53 vs. 30.42%, P < 0.001), DQB1*05:01 (0.85 vs. 10%, P < 0.001), and DQB1*05:02 (5.51 vs. 17.92%, P < 0.001) were significantly lower, as compared with the controls. DQA1*02:01 (patients with CD vs. controls: 20.76 vs. 6.67%, P < 0.001) and DQA1*05:01 (40.25 vs. 9.58%, P < 0.001) were significantly more frequent in patients. The frequencies of HLA-DQA1* 01:01, *01:02, *01:04, and *05:05 were significantly lower in patients (P < 0.001). The haplotype mainly associated with CD was DRB1*03-DQB1*02:01-DQA1*05:01; patients with CD vs. controls: 39.83 vs. 9.58%, P < 0.001. In total, 84.75% of patients carried DQ2 (vs. 21.67% in controls, P < 0.001), whereas 11.02% were DQ8 positive/DQ2 negative. This study confirms the existing data and provides additional evidence supporting a strong genetic predisposition for CD associated with the class II alleles DQB1*02 and DQA1*05 encoding the serological specificity DQ2.


Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma.
Conventional chemotherapy is commonly used to treat non-small cell lung cancer (NSCLC) however it increases therapeutic resistance. In contrast, metronomic chemotherapy (MET) is based on frequent drug administration at lower doses, resulting in inhibition of neovascularization and induction of tumor dormancy. This study aims to evaluate the inhibitory effects, adverse events, and potential mechanisms of MET Vinorelbine (NVB) combined with an angiogenesis inhibitor (Endostar). Circulating endothelial progenitor cells (CEPs), apoptosis rate, expression of CD31, vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1α) were determined using flow cytometry, western blot analysis, immunofluorescence staining and Enzyme-linked immunosorbent assay (ELISA) analysis. And some animals were also observed using micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) to identify changes by comparing SUVmax values. In addition, white blood cell (WBC) counts and H&E-stained sections of liver, lungs, kidney, and heart were performed in order to monitor toxicity assessments. We found that treatment with MET NVB + Endo was most effective in inhibiting tumor growth, decreasing expression of CD31, VEGF, HIF-1α, and CEPs, and reducing side effects, inducing apoptosis, such as expression of Bcl-2, Bax and caspase-3. Administration with a maximum tolerated dose of NVB combined with Endostar (MTD NVB + Endo) demonstrated similar anti-tumor effects, including changes in glucose metabolism with micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) imaging, however angiogenesis was not inhibited. Compared with either agent alone, the combination of drugs resulted in better anti-tumor effects. These results indicated that MET NVB combined with Endo significantly enhanced anti-tumor and anti-angiogenic responses without overt toxicity in a xenograft model of human lung cancer.


Blood group O and black race are independent risk factors for thrombotic thrombocytopenic purpura associated with severe ADAMTS13 deficiency.
It has been postulated that blood group O subjects may be partially protected against thrombotic thrombocytopenic purpura (TTP) because they have lower plasma levels of von Willebrand factor. The Oklahoma TTP Registry enrolled 301 consecutive patients from November 13, 1995 (when systematic ADAMTS13 measurements began), through 2009; 281 (93%) patients had ADAMTS13 measurements. Patients were designated as having severe ADAMTS13 deficiency when the activity measurement by either method was less than 10%. ABO blood group was determined in all 281 patients. The observed frequency of blood group O was compared to the expected frequency. The association between severe ADAMTS13 deficiency and blood group, race, sex, and age were analyzed by logistic regression. The frequency of blood group O was unexpectedly and significantly greater than the race-ethnicity-adjusted expected frequency in 65 patients with severe ADAMTS13 deficiency (60.0% vs. 47.4%, p = 0.042) but not in 216 patients without severe ADAMTS13 deficiency (44.9% vs. 46.5%, p = 0.639). Blood group O and race-ethnicity were independently associated with severe ADAMTS13 deficiency among patients with TTP. The probability for severe ADAMTS13 deficiency was 45.8% with O and 32.1% with non-O blood groups for black patients and 24.1% with O and 15.1% with non-O blood groups for white patients. Among patients with TTP and severe ADAMTS13 deficiency the relative frequency of patients with blood group O was greater than expected, suggesting that blood group O may be a risk factor for TTP associated with severe ADAMTS13 deficiency.


Gene-set analysis identifies master transcription factors in developmental courses.
Transcriptional regulation plays key roles in many biological processes. The regulation is dynamic in time and space. Identifying transcription factors that play major roles in a developmental time course is very important for understanding the regulation. This cannot be realized by studying the relation between the expression of individual genes. We developed a gene-set analysis approach to study master regulators and their actively regulated targets during a time course from gene expression data. We applied the method to a mouse liver development data and a mouse embryonic stem cell (mESC) development data, and identified 14 and 9 transcription factors that play major regulatory roles in the two development courses, respectively. Some transcription factors could not be identified as active in the process by studying their correlation with individual targets. The method was also extended for studying other regulation factors or pathways from time-course expression data.


Differential regulation of fibrinogen γ chain splice isoforms by interleukin-6.
Fibrinogen is a major structural protein in blood clots, and is also a well-known acute phase reactant. The γ chain gene of fibrinogen has two alternative splice variants, γA and γ' chains. γ' fibrinogen constitutes about 7% of total fibrinogen. Total fibrinogen levels and γ' fibrinogen levels have been associated with cardiovascular disease, but the mechanisms regulating the production of the two isoforms are unknown. Several inflammatory cytokines are known to influence the production of total fibrinogen, but the role of cytokines in the production of γ' fibrinogen has not been examined. However, epidemiologic studies have shown an association between γ' fibrinogen levels and inflammatory markers in humans. The expression of γ' fibrinogen and total fibrinogen by HepG2 liver cells was quantitated after treatment with interleukin-1β, transforming growth factor-β, tumor necrosis factor-α, and interleukin-6. Interleukin-1β, transforming growth factor-β, and tumor necrosis factor-α, known down-regulators of total fibrinogen synthesis, also downregulate γ' fibrinogen synthesis in HepG2 cells. However, interleukin-6 differentially up-regulates the production of total and γ' fibrinogen, leading to a 3.6-fold increase in γA mRNA, but an 8.3-fold increase in γ' mRNA. These findings indicate that γ' fibrinogen is disproportionately up-regulated by inflammatory responses induced by interleukin-6.


Does HER2 immunoreactivity provide prognostic information in locally advanced urothelial carcinoma patients receiving adjuvant M-VEC chemotherapy?
To evaluate the impact of HER2 immunoreactivity on clinical outcome in locally advanced urothelial carcinoma patients who received surgery alone, or methotrexate, vinblastine, epirubicin, and cisplatin (M-VEC) as adjuvant chemotherapy. We studied 114 formalin-fixed paraffin-embedded specimens obtained from locally advanced urothelial carcinoma patients receiving surgery alone or adjuvant M-VEC. The authors evaluated HER2 immunoreactivity using immunohistochemical staining and explored the influence of pathological parameters and HER2 immunoreactivity on progression-free survival (PFS) and disease-specific overall survival (OS) using univariate and multivariate Cox's analyses. Urothelial carcinoma of the bladder had a significantly higher frequency of HER2 immunoreactivity than that of the upper urinary tract (60.7 vs. 20.7%, p < 0.0001). Overall, nodal status was a strong and independent prognostic indicator for clinical outcome. The HER2 immunoreactivity was significantly associated with PFS (p = 0.02) and disease-specific OS (p = 0.005) in advanced urothelial carcinoma patients. As for patients with adjuvant M-VEC, HER2 immunoreactivity was a significant prognostic factor for PFS (p = 0.03) and disease-specific OS (p = 0.02) using univariate analysis, but not multivariate analysis, and not for patients receiving watchful waiting. HER2 immunoreactivity might have a limited prognostic value for advanced urothelial carcinoma patients with adjuvant M-VEC.


Mixed incontinence: comparing definitions in women having stress incontinence surgery.
To develop an empirically derived definition of mixed urinary incontinence (MUI) for use in incontinence outcomes research. Participants in a randomized trial comparing the fascial sling and. Burch colposuspension were assessed using standardized measures including the Medical, Epidemiologic and Social Aspects of Aging (MESA), UI questionnaire, the Urogenital Distress Inventory (UDI), 3-day urinary diary and urodynamic studies (UDS). Participants were required to have stress incontinence with a MESA stress subscale score > MESA urge subscale score. Several definitions of MUI were considered. Logistic and linear regression analysis methods were used to predict clinical outcomes based on the different MUI definitions. Analyses were carried out using SAS (SAS Institute, Inc., Cary, NC, Version 9.1). Statistical significance was defined at P-value <0.05. In 655 participants, the proportion of women with MUI varied from 8.3% to 93.3% depending on the MUI definition All definitions were associated with severity as measured by the frequency of incontinence episodes at baseline; however little of the variability was explained by any single definition. No strict cut-off value for these baseline measures was identified to predict clinical outcomes. These MUI definitions do not adequately categorize clinically relevant UI subgroups. For research reporting, MUI subcomponents of stress and urge UI should be described separately rather than as a single dimension.


Increased morbidity and mortality after bilateral femoral shaft fractures: myth or reality in the era of damage control?
Bilateral femoral shaft fractures have been reported to be an independent risk factor for morbidity and mortality; however, the value of these studies is limited due to small sample sizes and the timing of these studies before the establishment of damage control orthopaedics. The objective of this study was to compare the incidence of morbidity and mortality in patients with bilateral vs. unilateral femoral shaft fractures in the era of damage control orthopaedics. Retrospective analysis of the TraumaRegister DGU from 2002 to 2005. Inclusion criteria were uni- or bilateral femoral shaft fractures and complete demographic data documentation. Univariate data analysis and logistic regression analysis were performed with SPSS. Between 2002 and 2005, 776 patients with unilateral and 118 patients with bilateral femoral shaft fractures were identified. Patients with bilateral femoral shaft fractures had a significantly higher Injury Severity Score (ISS) (29.5 vs. 25.7 points), a significantly higher incidence of pulmonary (34.7% vs. 20.6%) and multiple organ failure (25.0% vs. 14.6%) as well as a significantly higher mortality rate (16.9% vs. 9.4%). In the overall patient population, early total care (ETC) was significantly more often performed in patients with unilateral femoral shaft fractures (50.9% vs. 33.6%). Logistic regression analysis revealed no significant association between bilateral femoral shaft fractures and multiple organ failure or mortality; however, bilateral femoral shaft fractures are an independent risk factor for pulmonary failure. Subgroup analysis revealed that the impact of the bilateral femoral shaft fracture was especially pronounced in patients with an ISS<25 points. Bilateral femoral shaft fractures are an independent risk factor for pulmonary failure but not for multiple organ failure or mortality. The impact of the additional femoral shaft fracture for pulmonary failure appears to be especially pronounced in the less severely injured patients, whose injuries are often underestimated when stratified with the ISS. Patients with bilateral femoral shaft fractures have significantly more often severe abdominal injuries as well as severe blood loss which may account for the increased mortality rate. Therefore, the presence of bilateral femoral shaft fractures should be recognised as an increased risk for systemic complications.


Risk factors for unsuccessful atropine therapy in hypertrophic pyloric stenosis.
I.v. atropine (IA) for infantile hypertrophic pyloric stenosis (IHPS) is a good alternative to pyloromyotomy but has not been broadly accepted. The lower success rate is one of the greatest disadvantages of IA. We investigated the risk factors for unsuccessful results following IA for IHPS. Medical records of patients with IHPS who were admitted to Kimitsu Chuo Hospital between 2002 and 2016 and were initially given atropine sulfate were retrospectively reviewed. Atropine was given i.v. (0.1 mg/kg/day in eight divided doses). Oral feeding of milk was started with a small amount and increased in a stepwise fashion to full feed. IA therapy was defined as unsuccessful in the presence of projectile vomiting more than three times a day or intolerance to a predetermined amount of milk. Of the 48 patients with IHPS, 33 patients were successfully treated with IA and 15 patients needed surgical intervention. On univariate analysis the risk factors for unsuccessful IA therapy were younger age, lower bodyweight, and shorter duration of symptoms before diagnosis. On multivariate analysis age at diagnosis < 30 days was the only significant risk factor for unsuccessful IA therapy (OR, 5.7 l P = 0.03). Age at diagnosis < 30 days is a risk factor for unsuccessful IA therapy in IHPS. This might be considered when IA therapy is used for neonates with IHPS.


Research of electrosurgical ablation with antiadhesive functionalization on thermal and histopathological effects of brain tissues in vivo.
Thermal injury and tissue sticking are two major concerns in the electrosurgery. In the present study, the effect of lateral thermal injury caused by different electrosurgical electrodes on wound healing was investigated. An electrosurgical unit equipped with untreated (SS) and titanium oxide layer-coated (TiO2-coated) stainless steel needle-type electrodes was used to create lesions on the rat brain tissue. TiO2 layers were produced by radiofrequency plasma and magnetron sputtering in the form of amorphous (TO-SS-1), anatase (TO-SS-2), and rutile (TO-SS-3) phase. Animals were sacrificed for evaluations at 0, 2, 7, and 28 days postoperatively. TO-SS-3 electrodes generated lower levels of sticking tissue, and the thermographs showed that the recorded highest temperature in brain tissue from the TO-SS-3 electrode was significantly lower than in the SS electrode. The total injury area of brain tissue caused by TO-SS-1 and TO-SS-3 electrodes was significantly lower than that caused by SS electrodes at each time point. The results of the present study reveal that the plating of electrodes with a TiO2 film with rutile phases is an efficient method for improving the performance of electrosurgical units and should benefit wound healing.


One-Step Synthesis of Ultrasmall Nanoparticles in Glycerol as a Promising Green Solvent at Room Temperature Using Omega-Shaped Microfluidic Micromixers.
Despite innovations in the synthesis protocol of nanoparticles (NPs), the size distribution and uniformity of particles still remain as crucial attributes. Homogeneous and rapid nucleation is a critical phenomenon to obtain monodisperse nanoparticles. Herein, we have carried out the synthesis of metal nanoparticles in a customized microfluidic (MF) chip, with 18 omega-shaped micromixers, by using glycerol as a promising green solvent and reducing agent at various concentrations (10-80%), and simultaneous comparison of the results from batch synthesis. Initially, mixing characterization for 10-80% glycerol was obtained by adjusting the Peclet (Pe) number. Further, the effect of the Pe number, time, and concentrations of polyvinylpyrrolidone, metal source, and glycerol on the NP size was investigated. Interestingly, the experimental findings depicted that by varying different parameters, the spherical nanoparticles with an average ultrasmall particle diameter of <2 nm were obtained at all glycerol concentrations (10-80%), as compared to batch synthesis (giving a yield of ∼10-fold larger particles). The mixing efficiency in this MF chip design was analyzed by using a fluorescent dye in glycerol, while the particle morphology and size were characterized by using dynamic light scattering, transmission electron microscopy, and ultraviolet-visible spectroscopy. Hence, compared to the conventional benchtop-assisted NP synthesis, this study unveils the significant effect of the microfluidic technique on the synthesis of ultrasmall and homogeneous nanoparticles in a single step, using an environmentally friendly solvent.


Biogenic iron sulfide functioning as electron-mediating interface to accelerate dissimilatory ferrihydrite reduction by Shewanella oneidensis MR-1.
Microbially driven iron and sulfur geochemical cycles co-exist ubiquitously in subsurface environments and are of environmental relevance. Shewanella species (dissimilatory metal-reducing bacteria) are capable of reducing Fe(III)-(oxyhydr)oxide minerals and diverse sulfur sources using corresponding metabolic pathways and producing FeS secondary minerals. In spite of the ability in promoting bacterial extracellular electron transfer (EET), the specific role of FeS in mediating EET between microbe/mineral interface is still unclear. In this work, the electron-mediating function of biogenic FeS on promoting the reduction of ferrihydrite by S. oneidensis MR-1 using thiosulfate as sulfur source was investigated in terms of Fe(III) reduction percentage, X-ray diffraction and scanning electron microscopy. The results showed that the microbial ferrihydrite reduction was pH-dependent and positively correlated with the addition of thiosulfate. In the presence of thiosulfate, biogenic FeS in nano-scale were formed and deposited on the surfaces of S. oneidensis MR-1 and ferrihydrite to build an interfacial electron transfer bridge between them. The addition of either thiosulfate and in-vitro FeS could rescue the entirely inactivated ability of the mutant (△omcA/mtrC) in ferrihydrite reduction to some extent, but which was obviously inferior to the wild-type strain. Meanwhile, the effect of the biogenic FeS in-situ coating on the surfaces of S. oneidensis MR-1 cells on promoting microbial ferrihydrite reduction was significantly superior to the in-vitro ones. Thus, the in-situ formed biogenic FeS secondary minerals were demonstrated to mediate and accelerate interfacial electron transfer from S. oneidensis MR-1 cells to ferrihydrite through interfacing with the bacterial EET routes, especially Mtr pathway. This work provides an insight into the secondary minerals-mediating interfacial electron transfer between microbes and minerals in the presence of biological S (-II), which has important biogeochemical and environmental implications.


Data-driven decision support for radiologists: re-using the National Lung Screening Trial dataset for pulmonary nodule management.
Real-time mining of large research trial datasets enables development of case-based clinical decision support tools. Several applicable research datasets exist including the National Lung Screening Trial (NLST), a dataset unparalleled in size and scope for studying population-based lung cancer screening. Using these data, a clinical decision support tool was developed which matches patient demographics and lung nodule characteristics to a cohort of similar patients. The NLST dataset was converted into Structured Query Language (SQL) tables hosted on a web server, and a web-based JavaScript application was developed which performs real-time queries. JavaScript is used for both the server-side and client-side language, allowing for rapid development of a robust client interface and server-side data layer. Real-time data mining of user-specified patient cohorts achieved a rapid return of cohort cancer statistics and lung nodule distribution information. This system demonstrates the potential of individualized real-time data mining using large high-quality clinical trial datasets to drive evidence-based clinical decision-making.


Undescribed ecdysteroids and phenolic glycosides from the roots of Cyathula officinalis Kuan and their anti-inflammatory activity in LPS-induced RAW 264.7 macrophages in vitro.
Six undescribed compounds, including four undescribed ecdysteroids (cyathsterones A-D) and two undescribed phenolic glycosides (cyathglucosides A-B), were isolated from the roots of Cyathula officinalis Kuan. Their structures were based on chemical analyses, NMR spectroscopic evidence, DP4+ calculations, and hydrolysis products. All compounds inhibited NO release in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro. Among them, cyathsterone A showed the strongest inhibitory effects. Moreover, cyathsterone A has been shown to inhibit the release of the proinflammatory cytokines TNF-α, IL-6, and IL-1β in LPS-induced RAW 264.7 macrophages in vitro. Further studies found that cyathsterone A present concentration-dependent suppression of the protein expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells in vitro and exerted anti-inflammatory activity via the NF-κB signalling pathway.


Regulation of macromolecular synthesis in Morris hepatomas.
In this review, some studies are discussed in which an attempt has been made to determine the nature of changes in macromolecular synthesis in Morris hepatomas. The incorporation of isotope labeled precursors into nucleic acids and proteins has suggested greatly increased rates of DNA synthesis in comparison with rat liver of normal and tumor bearing rats, but for RNA and proteins the changes may be impressive for individual macromolecular species but total synthesis is not greatly changed. Fractionation of nuclear proteins has indicated altered patterns of synthesis which are related to the growth rates of the tumors and are much more pronounced than in regenerating liver despite a growth rate similar to that of the most rapidly growing hepatomas. Investigations with drugs which inhibit synthesis of macromolecules has suggested that liver neoplasia may be accompanied by changes in response which may make the tumor less sensitive or more sensitive to regulation than the tissue of origin.


Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial.
Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.


[Management of Delirium in Patients with Cancer].
Delirium is a condition in which the main symptom is a mild disturbance of consciousness caused by a physical abnormality or medication, and various symptoms such as cognitive dysfunction, hallucinations, delusions, and mood swings appear with any disease. Delirium is frequently observed in patients with cancer, especially in the terminal stage, and is observed in about 90% of patients just before death. Hypercalcemia due to bone metastases, brain metastases, and the use of opioids and steroids for symptom relief are direct factors in the development of delirium. Furthermore, there are many opportunities to encounter delirium at the end of life caused by conditions that are difficult to recover from, such as brain metastasis, liver failure, and hypoxic encephalopathy. In the management of delirium, "search for the cause(s)and its treatment"and"environmental adjustment"are the most important. Then, pharmacotherapy is considered to reduce the severity of delirium. Antipsychotics are the basic medication of choice. The route of administration, half-life, dosage form, adverse events of medication, as well as patient factors such as the presence or absence of diabetes and the subtype of delirium should be comprehensively considered when selecting a medication. The timing of medication discontinuation should also be kept in mind once medication therapy is initiated. On the other hand, when delirium is caused by factors that are difficult to recover from, the goal of treatment is to alleviate the painful symptoms caused by delirium, and it is important to take a holistic approach for patients and family members.


Mood disorders and urban/rural settings: comparisons between two French regions.
A review of the main large-scale mental health surveys does not give full support to the idea of urbanicity as a risk factor in mood disorders. Lack of agreement between findings can be attributed, at least in part, to heterogeneous operationalisation of urbanicity, as different ways to define urban and rural areas are likely to lead to different morbidity rates and to have an effect on the respective weight of other risk factors. A total of 2,638 subjects sampled from two French regions (Basse-Normandie and Ile-de-France) were interviewed using face-to-face parts of the Composite International Diagnostic Interview covering demographic and certain life event questions. Urbanicity was defined according to (1) official index based on population density or (2) type of dwelling. Participation rates were 85 and 79%. When gender, age, marital status and certain early life events, such as being placed in an institution, as well as events concerning close family members are entered into a logistic regression, the urbanicity association with DSM-IV MDE and especially severe forms disappeared. This finding tends to support the theory that what happens to individuals is more relevant to depression than the place where they live. It may be wiser to rely on social indicators than on a rural/urban component for planning for mental health care in the various areas; this remark should not prevent to evaluate the topographic situations of the diverse settings to take them into account to provide appropriate resources.


Bioelectrochemical removal of carbon dioxide (CO2): an innovative method for biogas upgrading.
Innovative methods for biogas upgrading based on biological/in-situ concepts have started to arouse considerable interest. Bioelectrochemical removal of CO2 for biogas upgrading was proposed here and demonstrated in both batch and continuous experiments. The in-situ biogas upgrading system seemed to perform better than the ex-situ one, but CO2 content was kept below 10% in both systems. The in-situ system's performance was further enhanced under continuous operation. Hydrogenotrophic methanogenesis and alkali production with CO2 absorption could be major contributors to biogas upgrading. Molecular studies showed that all the biocathodes associated with biogas upgrading were dominated by sequences most similar to the same hydrogenotrophic methanogen species, Methanobacterium petrolearium (97-99% sequence identity). Conclusively, bioelectrochemical removal of CO2 showed great potential for biogas upgrading.


Mobile apps as a sustainable shopping guide: The effect of eco-score rankings on sustainable food choice.
Consumers often struggle to assess food's environmental impact. A product ranking based on a standardized scoring approach (aggregating multiple indicators) that is easily accessible, for instance, via a mobile app, could serve as a simple decision aid for consumers. However, to avoid information overload, research is needed in which format such information should be presented. This paper examines how different information levels of an eco-score ranking influence decision uncertainty and sustainable food choice. In an online experiment (n = 332, representative by age and gender), we compared a basic eco-ranking and an extended eco-ranking (eco-rank plus additional indicators: transportation distance and eco-certifications) against a control group (no eco-ranking) in three different food categories: milk, juice, and eggs. The basic eco-ranking successfully lowered decision uncertainty compared to the two other groups. In contrast, the extended eco-ranking did not reduce consumers' decision uncertainty level. Further, the basic (extended) eco-ranking increased the likelihood of choosing a sustainable product by 26 (17) percentage points compared to the control group. Thus, providing access to a simple eco-ranking can help avoid information overload and increase sustainable consumption.


Age-related increase in haemoglobin A1c and fasting plasma glucose is accompanied by a decrease in beta cell function without change in insulin sensitivity: evidence from a cross-sectional study of hospital personnel.
To examine the influence of age on glucose homeostasis in a population of healthy, non-diabetic hospital personnel. One hundred and twenty female and 71 male non-diabetic individuals (fasting plasma glucose < 7.0 mmol/l) were fasted overnight prior to blood sampling. Glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and fasting plasma insulin (FPI) were measured using a BioRad Diamat automated HPLC, a Hitachi 747 analyser and a sensitive in-house radioimmunoassay, respectively. Mathematical modelling of the fasting glucose and insulin pairs (homeostasis model assessment (HOMA)) generated indices of pancreatic beta cell function, HOMA-B and tissue insulin sensitivity HOMA-S. Spearman rank correlation analysis showed that in the whole group there was a significant negative correlation between age and HOMA-B (rs = -0.218, P = 0.0022) and a significant positive correlation between age and both HbA1c (rs = 0.307, P = 0.0001) and FPG (rs = 0.26, P = 0.0003). There was no correlation between age and either FPI (rs = -0.08, P = 0.266) or HOMA-S (rs = 0.024, P = 0.75). Analysis by gender showed the above associations to be present in the females (rs = -0.243, P = 0.0076; rs = 0.304, P = 0.0007; rs = 0.32, P = 0.0004 for age vs. HOMA-B, HbA1c, and FPG, respectively). Again there was no correlation of age with FPI or insulin sensitivity. In the males there was a significant correlation of HbA1c with age (rs = 0.35, P = 0.002), but no significant correlation of age with any of the other parameters. Glycaemic control deteriorates with age in healthy, non-diabetic individuals. Age-related rises in FPG and haemoglobin A1c result from a small but steady decline in pancreatic beta cell function.


Treatment of Malignant Adnexal Tumors of the Skin: A 12-Year Perspective.
Malignant adnexal cancers of the skin-extremely rare neoplasms-are mostly reported as non-symptomatic, slow-growing nodules. These carcinomas occur mainly in the middle-aged (50-60 years of age); they are mostly localized on the upper part of the body and are locally aggressive, infiltrate surrounding tissue, and metastasize to regional lymph nodes. The patients' outcomes depend on multiple prognostic factors, including the size of the primary tumor and its mitotic count. Surgical resection of the primary tumor with or without regional lymph nodes is the treatment method of choice; however, due to aggressive tumor behavior, perioperative treatment may be considered. The role and efficacy of radiotherapy in the treatment of skin adnexal malignancies are not yet fully defined. Some authors suggest that adjuvant radiotherapy may be considered in locally advanced and regional disease. The aim of this study was to evaluate treatment outcomes and assess the efficacy of combined therapy in patients with adnexal malignancies. Our analysis covered all cases of cutaneous adnexal tumor patients diagnosed and provided with multidisciplinary treatment with surgery and radiotherapy since the beginning of 2009.


Use of three-dimensional segmented FLASH sequence with magnetization transfer contrast to improve Gd-DTPA-enhanced intrahepatic MR portography.
Twenty healthy volunteers underwent gadopentetate dimeglumine (gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA))-enhanced MR angiography (MRA) using three-dimensional-segmented fast low angle shot images (FLASH) with magnetization transfer contrast (MTC) pulses. MRA was obtained at 75 seconds (early phase) and 135 seconds (late phase) after bolus injection of Gd-DTPA (MTC+ group) during one period of breath-holding. Within 1 week. MRA without MTC was performed under the same scanning conditions. Visualization of intrahepatic portal branches with these methods was compared in both phases. Portal vein-liver contrast-to-noise ratios were significantly higher in the MTC+ group in both phases. For third- and fourth-order portal branches, visualization was significantly better in the MTC+ group in both phases. Use of three-dimensional-segmented FLASH shortened acquisition time and facilitated imaging during breath-holding and also reduced whole-body average specific absorption rate values. Visualization of intrahepatic portal vein branches was improved by MTC pulses, and effective imaging time was prolonged.


Identifying the psychological determinants of risky riding: an application of an extended Theory of Planned Behaviour.
The Theory of Planned Behaviour (TPB) plus moral norms, anticipated regret, past behaviour, self-identity and perceived susceptibility was applied to predicting motorcyclists' intention to ride above the speed limit and ride at inappropriate speeds. Past behaviour, control beliefs, attitudes, moral norm, normative beliefs, age and self-identity explained 60% of the variance in motorcyclists' intention to exceed the speed limit on motorways (N=1381). A total of 62% of the variance in motorcyclists' intention to really go for it on rural roads was accounted for, with past behaviour, attitudes, control beliefs, age, normative beliefs, anticipated regret, self-identity, behavioural beliefs and training status being significant (N=1116). Finally, attitudes, past behaviour, control beliefs, moral norm, anticipated regret, behavioural beliefs, normative beliefs, engine size and self-identity explained 57% of the variance in motorcyclists' intention to ride faster than felt safe in order to keep up with the group (N=1940). The belief-based measures also successfully differentiated between those who intended to speed and those who did not. Theoretical and practical implications of the findings are discussed.


Microcomposition of human urinary calculi using advanced imaging techniques.
Common methods of commercial urolithiasis analysis, such as light microscopy and Fourier transform infrared spectroscopy, provide limited or no information on the molecular composition of stones, which is vital when studying early stone pathogenesis. We used synchrotron radiation based microfocused x-ray fluorescence, x-ray absorption and x-ray diffraction advanced imaging techniques to identify and map the elemental composition, including trace elements, of urinary calculi on a μm (0.0001 cm) scale. Human stone samples were obtained during serial percutaneous nephrolithotomy and ureteroscopy procedures. A portion of each sample was sent for commercial stone analysis and a portion was retained for synchrotron radiation based advanced imaging analysis. Synchrotron radiation based methods of stone analysis correctly identified stone composition and provided additional molecular detail on elemental components and spatial distribution in uroliths. Resolution was on the order of a few μm. Knowledge of all elements present in lithogenesis at this detail allows for better understanding of early stone formation events, which may provide additional insight to prevent and treat stone formation.


Magnesium sulfate reduces postoperative pain in women with cesarean section: A meta-analysis of randomized controlled trials.
The use of magnesium sulfate (MgSO4 ) as an adjunct in different anesthetic regimens for cesarean section (CS) delivery often reports conflicting results. This study aimed to review the effectiveness of MgSO4 on improving postoperative analgesia after CS systematically. PubMed, Embase, and the Cochrane library were searched for randomized controlled trials (RCTs) published from inception to February 2020. A total of 880 women were included (440 in each group). MgSO4 had a statistically significant effect compared to the control group on the highest VAS (weighted mean difference [WMD] = -0.74, 95% confidence interval [CI] = -1.03 to -0.46, p < 0.001, I2 = 91.7%, pheterogeneity < 0.001) and the last VAS (WMD = -0.47, 95% CI = -0.71 to -0.23, p < 0.001, I2 = 95.0%, pheterogeneity < 0.001). MgSO4 prolonged the time to the first use of analgesia compared to the control group (standardized mean difference [SMD] = -3.03 min, 95% CI = -4.32 to -1.74, p < 0.001, I2 = 96.3%, pheterogeneity < 0.001). MgSO4 decreased the consumption of analgesia compared to the control group (SMD = -3.20 mg of IV morphine equivalent, 95% CI: -5.45 to -0.95, p = 0.005, I2 = 97.6%, pheterogeneity < 0.001). MgSO4 decreases the highest VAS in women who underwent general anesthesia, spinal anesthesia, or epidural for CS (all p < 0.05). Additional MgSO4 significantly reduces postoperative pain in women undergoing CS.


Circannual rhythms of acetylcholinesterase (AChE) activity in the freshwater fish Cnesterodon decemmaculatus.
The use of biomarkers as a tool to assess responses of organisms exposed to pollutants in toxicity bioassays, as well as in aquatic environmental risk assessment protocols, requires the understanding of the natural fluctuation of the particular biomarker. The aim of this study was to characterize the intrinsic variations of acetylcholinesterase (AChE) activity in tissues of a native freshwater teleost fish to be used as biomarker in toxicity tests, taking into account both seasonal influence and fish size. Specific AChE activity was measured by the method of Ellman et al. (1961) in homogenates of fish anterior section finding a seasonal variability. The highest activity was observed in summer, decreasing significantly below 40% in winter. The annual AChE activity cycle in the anterior section was fitted to a sinusoidal function with a period of 11.2 months. Moreover, an inverse relationship between enzymatic activity and the animal size was established. The results showed that both the fish length and seasonal variability affect AChE activity. AChE activity in fish posterior section showed a similar trend to that in the anterior section, while seasonal variations of the activity in midsection were observed but differences were not statistically significant. In addition, no relationship between AChE and total tissue protein was established in the anterior and posterior sections suggesting that the circannual rhythms observed are AChE-specific responses. Results highlight the importance of considering both the fish size and season variations to reach valid conclusions when AChE activity is employed as neurotoxicity biomarker.


Antibody for the prevention of neonatal noscocomial staphylococcal infection: a review of the literature.
Staphylococci, especially coagulase negative staphylococci (CONS), are responsible for over 75 % of late-onset infections in very low birth weight infants. These infections cause increased length of hospital stay, need for antibiotics, and cost of medical care. Several drug companies have developed and evaluated hyperimmune polyclonal and monoclonal antibodies for the prevention of neonatal staphylococcal infection including 1) Altastaph by North American Biologics Inc., 2) Veronate by Inhibitex Inc., and 3) Pagibaximab by Biosynexus Inc, and Glaxo Smith Kline Inc. We will review the development and status of these potential products. Altastaph is a S. aureus serotype 5 and 8 vaccine induced hyperimmune polyclonal antibody whose development has been placed on hold due to its failure to demonstrate any trend toward efficacy in a recently completed Phase II study. Veronate is a polyclonal antibody obtained by plasmapheresis from donors with high titers of MSCRAMM (microbial surface components recognizing adhesion matrix molecules) activity against CONS whose development has been placed on hold due to its failure to demonstrate effectiveness in a recently completed Phase III study. Pagibaximab is a humanized mouse chimeric monoclonal antibody (previously known as BSYX-A110) directed against lipoteichoic acid (LTA), a major cell wall component of gram-positive bacteria, that has recently completed a Phase II study suggesting efficacy and is being developed further for clinical investigation.


AQP8 is a crucial H2O2 transporter in insulin-producing RINm5F cells.
Peroxiporins are distinct aquaporins (AQP) which, beside water, also facilitate the bidirectional transport of hydrogen peroxide (H2O2) across cellular membranes. H2O2 serves as the major reactive oxygen species that mediates essential cell signaling events. In pancreatic β-cells, H2O2 has been associated with the regulation of cell growth but in excess it leads to failure of insulin secretion, making it important for diabetes mellitus (DM) pathogenesis. In the present study, the role of aquaporin-8 (AQP8) as a peroxiporin was investigated in RINm5F cells. The role of AQP8 was studied in an insulin-producing cell model, on the basis of stable AQP8 overexpression (AQP8↑) and CRISPR/Cas9-mediated AQP8 knockdown (KD). A complete AQP8 knock-out was found to result in cell death, however we demonstrate that mild lentiviral re-expression through a Tet-On-regulated genetically modified AQP8 leads to cell survival, enabling functional characterization. Proliferation and insulin content were found to be increased in AQP8↑ cells underlining the importance of AQP8 in the regulation of H2O2 homeostasis in pancreatic β-cells. Colocalization analyses of V5-tagged AQP8 proteins based on confocal microscopic imaging revealed its membrane targeting to both the mitochondria and the plasma membrane, but not to the ER, the Golgi apparatus, insulin vesicles, or peroxisomes. By using the fluorescence H2O2 specific biosensor HyPer together with endogenous generation of H2O2 using d-amino acid oxidase, live cell imaging revealed enhanced H2O2 flux to the same subcellular regions in AQP8 overexpressing cells pointing to its importance in the development of type-1 DM. Moreover, the novel ultrasensitive H2O2 sensor HyPer7.2 clearly unveiled AQP8 as a H2O2 transporter in RINm5F cells. In summary, these studies establish that AQP8 is an important H2O2 pore in insulin-producing RINm5F cells involved in the transport of H2O2 through the mitochondria and cell membrane and may help to explain the H2O2 transport and toxicity in pancreatic β-cells.


Quantification of free serum cortisol based on equilibrium dialysis and isotope dilution-liquid chromatography-tandem mass spectrometry.
Only unbound serum cortisol is bioactive and protein binding of cortisol is highly variable. Thus, the quantification of free serum cortisol (FSC) is of superior biological relevance compared to total serum cortisol quantification. Consequently, the development of automated routine tests for FSC for endocrine testing is desirable - along the lines of free thyroid hormone measurement. Since the availability of a reliable and matrix-independent method is an important tool for this goal, we have developed a highly standardised mass spectrometric FSC method. We used equilibrium dialysis (ED) to obtain a protein-free fraction from serum samples. The cortisol content of the dialysate was quantified using isotope-dilution two dimensional liquid chromatography (LCxLC-MS/MS). Comprehensive evaluation characterised the method as reliable and robust; using commercially available dialysis cells, convenient handling was realised. The method described in this article can be suggested for the implementation of a reference measurement system for FSC.


Comparative Analysis of the Interaction of Silver Nanoparticles with Hexokinase from Trypanosoma brucei and Humans.
Regardless of the efforts to ease cases of human African trypanosomiasis (HAT), an increased number of cases get reported annually. This is because of drug resistant Trypanosoma brucei (Tb), the causative agent of the illness. This has renewed the need for creative methods to find new anti-trypanosomal drugs. The blood stream form (BSF) of the parasite depends exclusively on the glycolytic pathway for energy production while it is in the human host. Interruptions in this pathway efficiently kills the parasite. Trypanosoma brucei hexokinase (TbHK) is the first enzyme in glycolysis, and any effectors or inhibitors of TbHK would have potential as anti-trypanosomal agents. TbHK and human glucokinase (hGCK) were over-expressed with a 6 histidine-tag in E. coli BL21(DE3) cells having the pRARE2 plasmid. TbHK had thermal and pH stability between 30°C and 55°C and 7.5 and 8.5, respectively, while hGCK exhibited thermal and pH stability between 30°C and 40°C and 7.0 and 8.0, respectively. Kinetically, TbHK had a Km of 39.3 µM, Vmax of 0.066 µmol.min-1.mL-1, kcat of 2.05 min-1 and kcat/Km of 0.0526 min-1.µmol-1. hGCK exhibited a Km of 4.5 µM, Vmax of 0.032 µnmol.min-1.mL-1, kcat of 11.25 min-1, and kcat/Km of 2.5 min-1.µmol-1. Interaction kinetic studies of silver nanoparticles (AgNPs) (0.1 µM) of average size of 6 nm with TbHK and hGCK were conducted. AgNPs selectively inhibited TbHK over hGCK. TbHK showed a non-competitive inhibition with a 50% and 28% decrease in Vmax, and kcat/km, respectively. HsGCK showed a 33% increase in affinity, 9% decrease in Vmax, and a 50% increase in enzyme efficiency. The observed pattern of hGCK and AgNPs falls under the uncompetitive inhibition. The observed highly selective inhibitory effects of AgNPs between TbHK and hGCK may be used in development of new anti-trypanosomal drugs.


Gradual activation of the response regulator DegU controls serial expression of genes for flagellum formation and biofilm formation in Bacillus subtilis.
In natural environments, bacteria fluctuate between growth as motile cells and growth as sessile, biofilm-forming cells. However, what controls the transition between these two-growth modes in Bacillus subtilis is not well understood yet. The degU mutation prevents both flagellum formation and biofilm formation, suggesting that one of the transition mechanisms may underlie regulation of the DegU activity. The expression profiles of DegU-regulated genes differed; flagellar genes and several unknown genes were expressed during the exponential phase, whereas other genes were induced in the stationary phase. The degS mutation did not affect transcription of the flgB-sigD operon, but reduced transcription of sigma(D)-dependent flagellar genes, degU and other DegU-regulated genes. In addition, the degQ mutation did not affect transcription of flagellar genes but reduce transcription of other DegU-regulated genes. Purified DegQ protein stimulated phosphotransfer from phospho-DegS to DegU in vitro. Moreover, DegU binds the promoter region of flgB with a high affinity, whereas DegU binds to the promoter regions of other DegU-regulated genes with a low affinity and in a DegS-dependent manner. Taken together, we propose that a gradual increase in DegU and phospho-DegU levels induces a transition from growth as motile cells to growth as sessile, biofilm-forming cells.


Motivational interviewing to reduce substance-related consequences: effects for incarcerated adolescents with depressed mood.
The impact of depressed mood on Motivational Interviewing (MI) to reduce risky behaviors and consequences in incarcerated adolescents was examined in this brief report. Adolescents (N=189) were randomly assigned to receive MI or Relaxation Training (RT). At 3-month follow-up assessment, MI significantly reduced risks associated with marijuana use, with a trend towards reducing risks associated with alcohol use. There was also a trend for depressive symptoms to be associated with reduced risks after release. Interaction effects were non-significant, indicating no moderating effects for depressed mood on treatment outcome. MI may be a useful treatment for incarcerated adolescents in order to reduce risks and consequences associated with substance use after release.