Intrapartum transmission after mucosal exposure to HIV was not observed with single-dose nevirapine for mother and child.
Intrapartum transmission of HIV has been reported to be associated with HIV in oropharyngeal secretions (OPSs) of the child. In this study, we analyze the frequency of intrapartum transmission after mucosal exposure to HIV after administration of single-dose nevirapine. Eighty mothers and their children participating in a prevention of mother-to-child transmission of HIV program in Uganda who took a single dose of nevirapine according to the HIVNET012 protocol participated in the study. HIV-1 was quantified by polymerase chain reaction (PCR) in the mothers' and children's plasma, in cervicovaginal secretions (CVSs), and in the children's OPSs. Intrapartum transmission was defined as a positive HIV-1 RNA PCR result at week 1 or 2 after birth and a previously negative PCR result. Ninety-seven percent of children had detectable nevirapine in their OPS (median = 592 ng/mL). Fifty-seven (81%) children had HIV-negative OPSs, and 13 (19%) had HIV-positive OPSs. All children of mothers with HIV-negative CVSs had HIV-negative OPSs. HIV-1 levels of OPSs and CVSs correlated (r = 0.33, P = 0.027). None of the babies with detectable HIV-1 in the OPSs became infected by means of intrapartum transmission. Intrapartum HIV infection was not observed after mucosal exposure to HIV-1 after administration of a single dose of nevirapine to the mother and child.


Contamination of hospital linen by Bacillus cereus.
An investigation into two cases of post-operative Bacillus cereus meningitis revealed that hospital linen laundered by a batch continuous washing machine was heavily contaminated by B. cereus spores. The washing machine, detergents, other chemical additives and the water supply were eliminated as the source of contamination. It was found that the linen introduced into the washing machine had a high B. cereus spore content and that this was still present after the wash process. The spores were not killed by either the heat disinfection stage of the wash or the addition of chemical disinfectants and were not removed by the dilution in the process. The multiplication of B. cereus was thought to have occurred on used, damp linen stored in plastic bags, particularly when ambient temperatures were high. An increase in the water flow through the washing machine was the only measure associated with a decrease in B. cereus on laundered linen.


Robust microbial cell segmentation by optical-phase thresholding with minimal processing requirements.
High-throughput imaging with single-cell resolution has enabled remarkable discoveries in cell physiology and Systems Biology investigations. A common, and often the most challenging step in all such imaging implementations, is the ability to segment multiple images to regions that correspond to individual cells. Here, a robust segmentation strategy for microbial cells using Quantitative Phase Imaging is reported. The proposed method enables a greater than 99% yeast cell segmentation success rate, without any computationally-intensive, post-acquisition processing. We also detail how the method can be expanded to bacterial cell segmentation with 98% success rates with substantially reduced processing requirements in comparison to existing methods. We attribute this improved performance to the remarkably uniform background, elimination of cell-to-cell and intracellular optical artifacts, and enhanced signal-to-background ratio-all innate properties of imaging in the optical-phase domain. © 2017 International Society for Advancement of Cytometry.


"Winner takes it all": strongest node rule for evolution of scale-free networks.
We study a model for evolution of complex networks. We introduce information filtering for reduction of the number of available nodes to a randomly chosen sample, as a stochastic component of evolution. New nodes are attached to the nodes that have maximal degree in the sample. This is a deterministic component of network evolution process. This fact is unusual for evolution of scale-free networks and depicts a possible route for modeling network growth. We present both simulations and theoretical results for network evolution. The obtained degree distributions exhibit an obvious power-law behavior in the middle with the exponential cut off in the end. This highlights the essential characteristics of information filtering in the network growth mechanisms.


Interventional treatment of iatrogenic lesions and hepatic arteries.
The aim of this study was to evaluate the angiographic findings and the results of interventional treatment in iatrogenic lesions of the hepatic artery. Twelve patients (6 men and 6 women), aged 46 to 75 years (mean age 56.3 years), with acute hepatic bleeding secondary to percutaneous, surgical or laparoscopic procedures, were diagnosed using angiography and treated with endovascular percutaneous procedures. Angiography revealed 7 pseudoaneurysms, 3 arterial lacerations, 1 arterio-portal fistula e 1 arterio-biliary fistula that were treated by Trans-catheter Arterial Embolization (TAE) (n=11) and stentgraft placement (n=1). Only one patient had a relapse two days after TAE and died of haemorrhagic shock. The other patients had a benign clinical course with an average follow-up of 9.6 months. Interventional radiological procedures are effective in the management of iatrogenic lesions of the hepatic arterial vessels since they are minimally invasive, have a high success rate, and a low incidence of complications compared to the more complex and dangerous surgical or laparoscopic options.


Effects of topical phenylephrine and tafluprost on optic nerve head circulation in monkeys with unilateral experimental glaucoma.
To compare the effects of a topical alpha agonist (vasoconstrictor) and a prostaglandin receptor (FP) agonist (vasodilator) on circulation in the optic nerve head (ONH) in experimental glaucomatous and normal eyes of monkeys. Tissue blood velocity in the ONH (NB(ONH)) was determined using the laser speckle method in both eyes of eight normal cynomolgus monkeys under systemic anesthesia for 180 minutes after bilateral instillation of 5% phenylephrine. The effect of 0.0015% tafluprost, a potent FP agonist, was also studied after single and once-daily 7-day instillations. Measurements were repeated in both eyes of the eight monkeys after establishment of unilateral laser-induced glaucoma. NB(ONH) decreased significantly in both eyes of normal monkeys 30 to 120 minutes after phenylephrine instillation by a maximum of 9% to 11% (P < 0.05) without significant change in intraocular pressure (IOP). A similar decrease in NB(ONH) was found in non-laser-treated eyes in glaucomatous monkeys despite the absence of significant changes in contralateral experimental glaucomatous eyes. NB(ONH) increased by 16% (P < 0.05) 60 minutes after a single instillation and also after 7-day repeated instillations of tafluprost in both eyes of normal monkeys. A similar increase in NB(ONH) occurred in both eyes after the establishment of unilateral glaucoma but was completely abolished by 5 mg/kg indomethacin injected intravenously 15 minutes after tafluprost instillation. Tafluprost significantly reduced IOP only in experimental glaucomatous eyes by 34%. The ONH vasculature in glaucomatous and normal eyes reacts differently to an exogenous alpha agonist, whereas it reacts similarly to an FP agonist.


LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect.
The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1α, which is essential for driving glycolysis under hypoxia, is often up-regulated even in the presence of oxygen. The relationship between these two major regulators of the Warburg effect remains to be fully defined. Here we demonstrate that regulation of a long noncoding RNA (lncRNA), named IDH1-AS1, enables c-Myc to collaborate with HIF1α in activating the Warburg effect under normoxia. c-Myc transcriptionally repressed IDH1-AS1, which, upon expression, promoted homodimerization of IDH1 and thus enhanced its enzymatic activity. This resulted in increased α-KG and decreased ROS production and subsequent HIF1α down-regulation, leading to attenuation of glycolysis. Hence, c-Myc repression of IDH1-AS1 promotes activation of the Warburg effect by HIF1α. As such, IDH1-AS1 overexpression inhibited cell proliferation, whereas silencing of IDH1-AS1 promoted cell proliferation and cancer xenograft growth. Restoring IDH1-AS1 expression may therefore represent a potential metabolic approach for cancer treatment.


Multicenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity.
Fourth-generation assays for the simultaneous detection of human immunodeficiency virus (HIV) antigen and antibody that were available on the international market until now have antigen detection modules with relatively poor sensitivity and produce a higher rate of false-positive results than third-generation enzyme immunoassays (EIAs). The new Cobas Core HIV Combi EIA with an improved sensitivity for HIV p24 antigen was compared to alternative fourth- and third-generation assays, the p24 antigen test, and HIV type 1 (HIV-1) RNA reverse transcriptase PCR (RT-PCR). A total of 94 seroconversion panels (n = 709 sera), samples from the acute phase of infection after seroconversion (n = 32), anti-HIV-1-positive specimens (n = 730) from patients in different stages of the disease, 462 subtyped samples from different geographical locations, anti-HIV-2-positive sera (n = 302), dilutions of cell culture supernatants (n = 62) from cells infected with different HIV-1 subtypes, selected performance panels from Boston Biomedica Inc., 7,579 unselected samples from blood donors, 303 unselected daily routine samples, 997 specimens from hospitalized patients, and potentially interfering samples (n = 1,222) were tested with Cobas Core HIV Combi EIA. The new assay showed a sensitivity comparable to that of the Abbott HIV-1 AG Monoclonal A for early detection of HIV infection in seroconversion panels. The mean time delay of Cobas Core HIV Combi EIA (last negative sample plus 1 day) in comparison to that for HIV-1 RT-PCR for 87 panels tested with both methods was 2.75 days. The diagnostic window was reduced with Cobas Core HIV Combi EIA by between 3.6 and 5.7 days from that for third-generation assays. The specificities of Cobas Core HIV Combi EIA in blood donors were 99.84 and 99.85% (after repeated testing). Overall, 30 repeatedly reactive false-positive results out of 10,031 HIV-negative samples were obtained with Cobas Core HIV Combi EIA. Our results show that a fourth-generation assay with improved specificity such as Cobas Core HIV Combi EIA is suitable for blood donor screening because of its low number of false positives and because it detects HIV p24 antigen with a sensitivity comparable to that of single-antigen assays.


Further investigation on the regression method of mapping quantitative trait loci.
The simple regression method of mapping quantitative trait loci (QTL) is further investigated in comparison with the mixture model maximum likelihood method under high heritabilities, dominant and missing markers. No significant difference between the two methods is detected in terms of errors of parameter estimation and statistical powers, with the exception that the estimation of residual variance provided by the regression method is confounded with part of the QTL variance. The test statistic profiles show some difference between the two methods, but the difference is only detectable at the micro level. An alternative method, referred to as iteratively reweighted least squares, is proposed, which can correct the deficiency of parameter confounding in the regression method yet retains the properties of simplicity and rapidity of the ordinary regression method. Like the existing regression method, the weighted least squares method can be useful in QTL mapping in conjunction with the permutation tests and construction of confidence intervals by bootstrapping.


Volume Capnography in the Intensive Care Unit: Physiological Principles, Measurements, and Calculations.
Volume capnography provides a noninvasive and continuous display of the fractional concentration or partial pressure of expired carbon dioxide versus exhaled volume. Derived measurements and calculations include the end-tidal, mean alveolar, and mixed expired carbon dioxide partial pressure (Pco2); the volume of CO2 exhaled per breath and per minute; the airway, alveolar, and physiologic dead space volume; the physiologic dead space to tidal volume ratio; and expired minute ventilation, dead space ventilation, and alveolar ventilation. Thus, volume capnography provides a wealth of information about both respiratory and cardiovascular function, and it has many potential applications in critically ill patients. The effective use of volume capnography, however, requires a thorough understanding of its underlying physiological principles and the meaning and significance of derived measurements and calculations.


The hyperpolarization-activated cyclic nucleotide-gated 4 channel as a potential anti-seizure drug target.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by four genes (HCN1-4) with distinct biophysical properties and functions within the brain. HCN4 channels activate slowly at robust hyperpolarizing potentials, making them more likely to be engaged during hyperexcitable neuronal network activity seen during seizures. HCN4 channels are also highly expressed in thalamic nuclei, a brain region implicated in seizure generalization. Here, we assessed the utility of targeting the HCN4 channel as an anti-seizure strategy using pharmacological and genetic approaches. The impact of reducing HCN4 channel function on seizure susceptibility and neuronal network excitability was studied using an HCN4 channel preferring blocker (EC18) and a conditional brain specific HCN4 knockout mouse model. EC18 (10 mg·kg-1 ) and brain-specific HCN4 channel knockout reduced seizure susceptibility and proconvulsant-mediated cortical spiking recorded using electrocorticography, with minimal effects on other mouse behaviours. EC18 (10 μM) decreased neuronal network bursting in mouse cortical cultures. Importantly, EC18 was not protective against proconvulsant-mediated seizures in the conditional HCN4 channel knockout mouse and did not reduce bursting behaviour in AAV-HCN4 shRNA infected mouse cortical cultures. These data suggest the HCN4 channel as a potential pharmacologically relevant target for anti-seizure drugs that is likely to have a low side-effect liability in the CNS.


Vascular graft selection.
Twenty to thirty per cent of patients with arterial injuries and some patients with venous injuries require interpositional grafting. The first choice of grafting material for both arterial and venous injuries is autogenous vein. Injuries to large vessels such as the aorta and superior vena cava may necessitate synthetic prostheses. Synthetic aortic prostheses have excellent long-term patency rates, but the same materials are much less likely to remain patent in the vena cava. Panel or spiral grafts constructed from saphenous vein appear to be the best replacement for this vessel. Autogenous veins are present in different diameters ranging from a mean of 6.4 mm in the saphenous vein to a mean of 1.8 cm in the internal jugular vein. The thickest autogenous vein is the saphenous vein, and thus it is preferred for medium-sized and small arteries. The authors prefer the larger 7.5-mm cephalic vein for replacement of medium-sized veins. In the absence of suitable saphenous vein, the cephalic vein is also the choice for arterial interposition grafts. Although there are few reports of the use of arterial autografts in vascular trauma, the surgeon should be aware that autografts may be ideal for vascular injuries in children and for isolated injuries with severe contamination. Finally, the use of synthetic grafts in injuries where adequate tissue coverage is not possible may result in immediate limb salvage, but the incidence of limb loss in this situation will be extremely high.


Natural variation explains most transcriptomic changes among maize plants of MON810 and comparable non-GM varieties subjected to two N-fertilization farming practices.
The introduction of genetically modified organisms (GMO) in many countries follows strict regulations to ensure that only safety-tested products are marketed. Over the last few years, targeted approaches have been complemented by profiling methods to assess possible unintended effects of transformation. Here we used a commercial (Affymertix) microarray platform (i.e. allowing assessing the expression of approximately 1/3 of the genes of maize) to evaluate transcriptional differences between commercial MON810 GM maize and non-transgenic crops in real agricultural conditions, in a region where about 70% of the maize grown was MON810. To consider natural variation in gene expression in relation to biotech plants we took two common MON810/non-GM variety pairs as examples, and two farming practices (conventional and low-nitrogen fertilization). MON810 and comparable non-GM varieties grown in the field have very low numbers of sequences with differential expression, and their identity differs among varieties. Furthermore, we show that the differences between a given MON810 variety and the non-GM counterpart do not appear to depend to any major extent on the assayed cultural conditions, even though these differences may slightly vary between the conditions. In our study, natural variation explained most of the variability in gene expression among the samples. Up to 37.4% was dependent upon the variety (obtained by conventional breeding) and 31.9% a result of the fertilization treatment. In contrast, the MON810 GM character had a very minor effect (9.7%) on gene expression in the analyzed varieties and conditions, even though similar cryIA(b) expression levels were detected in the two MON810 varieties and nitrogen treatments. This indicates that transcriptional differences of conventionally-bred varieties and under different environmental conditions should be taken into account in safety assessment studies of GM plants.


PPARγ inhibits small airway remodeling through mediating the polarization homeostasis of alveolar macrophages in COPD.
The role of Peroxisome Proliferator-Activated Receptor-γ (PPARγ) in alveolar macrophages(AMs) polarization homeostasis is closely associated with airway remodeling in COPD, but the definite mechanism remains unclear. In this study, elevated percentage of M1-type AMs and the expression of functionally cytokines were found in COPD patients and mice, which closely related to the disease severity. PPARγ was markedly up-regulated in M2-type AMs and down-regulated in M1-type AMs, and was associated with disease severity in COPD. Co-cultured with M1- or M2-type AMs promoted the epithelial-mesenchymal transition (EMT) of airway epithelial cells and the proliferation of airway smooth muscle cells. Moreover, airway remodeling and functional damage were observed in both IL4R-/- COPD mice with runaway M1-type AMs polarization and TLR4-/- COPD mice with runaway M2-type AMs polarization. Cigarette extract (CS) or lipopolysaccharide (LPS) stimulated PPARγ-/- AMs showed more serious polarization disorder towards M1, as well as CS induced PPARγ-/- COPD mice, which led to more severe airway inflammation, lung function damage, and airway remodeling. Treatment with PPARγ agonist significantly improved the polarization disorder and function activity in CS/LPS stimulated-AMs by inhibiting the JAK-STAT, MAPK and NF-κB pathways, and alleviated the airway inflammation, restored the lung function and suppressed airway remodeling in CS induced-COPD mice. Our research demonstrates that polarization homeostasis of AMs mediated by PPARγ has the protective effect in airway remodeling, and may be a novel therapeutic target for the intervention and treatment of airway remodeling in COPD.


Domain I of beta2-glycoprotein I: its role as an epitope and the potential to be developed as a specific target for the treatment of the antiphospholipid syndrome.
Antiphospholipid syndrome (APS) represents one of the most common acquired causes of thrombophilia and recurrent miscarriages. The only treatment of proven benefit is anticoagulation, often required at high intensity and life-long duration. This therapy can be associated with side effects such as bleeding and is not always effective. Hence, there remains a need for safer, targeted and ideally more effective therapies. Antiphospholipid antibodies (aPL) are pathogenic and promote thrombosis. Independent groups, including our own, have show that the major epitopes that pathogenic aPL targets lie within domain I of the protein beta2-glycoprotein I (beta2GPI). This review focuses on the evidence presented thus far which characterizes the immunodominant epitopes within domain I, demonstrating that the epitope is a conformational one centred around residues R39-G43 and also involving other residues within domain I, such as residues D8 and D9. The hypothesis is proposed that a recombinant domain I molecule, and a recombinant mutant domain I with enhanced aPL binding properties, may be used as an inhibitor of aPL binding and thus inhibit aPL-induced pathogenicity. In vivo proof-of-concept studies within the murine femoral vein injury model are presented supporting this hypothesis, and the rationale as well as potential benefits and problems of employing such an approach to treat APS are discussed.


Does preventive vaccination with engineered tumor cells work in cancer-prone transgenic mice?
The use of genetically modified tumor cells as vaccines has been successful in numerous animal models of grafted syngenic tumors and has provided the groundwork for many clinical trials of gene therapy in cancer patients. To investigate the real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice that express the SV40 large T and small t antigens under the control of hepatic antithrombin III (ASV-B)-regulatory sequences. These mice systematically develop hepatocarcinoma. Hepatoma cells, derived from ASV-B transgenic mice, were gene-transduced to express either interleukin-2, interleukin-4, the granulocyte-macrophage colony-stimulating factor, or the T-cell costimulatory molecule B7.1. First, we demonstrated the vaccine potential of engineered hepatoma cells by immunizing nontransgenic mice with these cells, which prevented the growth of subsequent grafted nontransduced hepatoma cells. However, vaccination of pretumoral transgenic animals with various combinations of engineered hepatoma cells failed to inhibit hepatoma onset and progression. Rather, tumor development in ASV-B mice appears to be dependent on the immune system, since neonatal induction of immunotolerance to tumor in ASV-B mice cells was associated with a moderate, but significant, acceleration of tumor development. These results seriously call into question the efficacy of this strategy of active vaccinotherapy against natural tumors.


Distance to Hospital-based Intrapartum Care and Planned Home Birth in Minnesota.
Loss of hospital-based intrapartum services is associated with increases in out-of-hospital births, but less is known about associations with planned home birth. This study explores the impact of distance to hospital-based intrapartum care on planned home birth. Public-use Minnesota birth certificate data were merged with Minnesota Hospital Annual Report data (2011-2016) to test the relationship of miles from maternal residence to hospital-based intrapartum care with planned home birth in Minnesota. Logistic regression models estimated the odds of a planned home birth versus hospital birth as a function of miles to hospital-based intrapartum care. The number of hospitals offering birth services in Minnesota declined by 11% from 2011 to 2016. Moderate (>20-50 miles) and great (>50 miles) distances to nearest hospital-based intrapartum care were associated with increased odds of planned home birth compared with short distances (≤20 miles). Adjusted odds ratios were 3.31 (95% CI, 3.04-3.61) and 3.89 (95% CI, 2.37-6.37), respectively, after adjusting for maternal education, age, and race. Planned home birth was the intended birth setting in 4.3% of births among those living great distances from hospital-based intrapartum care, compared with 1.0% among those living a short distance from hospital-based intrapartum care. Better understanding of how geographical barriers affect preferred birth settings can inform efforts to reduce the impact of hospital-based intrapartum service loss on rural women and their birth outcomes.


Bilateral acetabular fractures in an adolescent after low-energy trauma.
Pediatric pelvic fractures are rare, accounting for approximately 2.4% to 5.5% of annual admissions at large level I trauma centers. An acetabular fracture is involved in only about 1% to 15% of these cases and is almost exclusively caused by a high-energy trauma. This is a report of an otherwise healthy 15-year-old male adolescent who sustained a nondisplaced bilateral anterior column and wall acetabular fracture after a low-energy mechanism during a hockey game. The patient was managed nonoperatively with non-weight-bearing restrictions and had complete resolution of his symptoms by 10 weeks. This case shows that a low-energy mechanism can create significant bilateral acetabular fractures in the immature skeleton. The presented case may represent an underdiagnosed cause of hip and groin pain in the adolescent patient/athlete when initial radiographs appear normal.


Pharmacology, drug efficacy, and the individual.
The efficacy of drugs has to be demonstrated following the principal approach of statistical evaluation in controlled clinical trials. This scientifically and internationally accepted numerical approach has developed over the years to its importance, in contrast to the more pharmacologically attempt to extrapolate human efficacy of drugs from data obtained in animal experiments or, to the so-called physiological medicine, which did not allow to delineate the suitability of drugs from a given collective to the individual patient. The requirements for the clinical trial are not always met, especially not with so-called surrogate markers. In addition, concerns exist now as ever that the numerically based approach leads to average drugs and information for the "responsible adult" only, to the debit of the individual patient. The concern does not mind the clinical trial as such, which principally can be tailored to the individual as applied with pharmacogenetics. On the other hand, an unbearable situation of increased efforts towards individualization, drug tailoring, and neglect of treatment for patients with neglected diseases, respectively, is immense. The contribution of the pharmacologists is, to present those detailed information which allow proper judgement for the clinical application of drugs for all patients.


'Ear stones' in crocodylians: a cross-species comparative and ontogenetic survey of otolith structures.
The vestibular system of the inner ear is a crucial sensory organ, involved in the sensation of balance and equilibrium. It consists of three semicircular canals that sense angular rotations of the head and the vestibule that detects linear acceleration and gravity. The vestibule often contains structures, known as the otoliths or 'ear stones'. Otoliths are present in many vertebrates and are particularly well known from the fossil record of fish, but surprisingly have not been described in detail in most tetrapods, living or extinct. Here, we present for the first time a survey of the otoliths of a broad sample of extant crocodylian species, based on computed tomography scans. We find that otoliths are present in numerous crocodylian species of different growth stages, and they continue to increase in size during ontogeny, with positive allometry compared to skull length. Our results confirm that otoliths are a common component of the crocodylian vestibular system, and suggest they play an important role in sensory detection. Otoliths are likely common, but overlooked, constituents of the inner ear in tetrapods, and a broader study of their size, shape and distribution promises insight into sensory abilities.


Growth-differentiation factor 15 predicts worsening of albuminuria in patients with type 2 diabetes.
Development of micro- or macroalbuminuria is associated with increased risk of cardiorenal complications, particularly in diabetes. For prevention of transition to micro- or macroalbuminuria, more accurate prediction markers on top of classical risk markers are needed. We studied a promising new marker, growth-differentiation factor (GDF)-15, to predict transition to increasing stage of albuminuria in type 2 diabetes mellitus (T2DM). In addition, we looked at the GDF-15 potential in nondiabetic subjects with hypertension (HT). Case and control subjects were selected from the PREVEND cohort, a large (n = 8,592), prospective general population study on the natural course of albuminuria, with >10 years of follow-up and repeated albuminuria measurements. We found 24 T2DM and 50 HT case subjects transitioning from normo- to macroalbuminuria and 9 T2DM and 25 HT case subjects transitioning from micro- to macroalbuminuria (average follow-up 2.8 years). Control subjects with stable albuminuria were pair matched for age, sex, albuminuria status, and diabetes duration. GDF-15 was measured in samples prior to albuminuria transition. Prior to transition, GDF-15 was significantly higher in case subjects with T2DM than in control subjects (median [IQR] 1,288 pg/mL [885-1,546] vs. 948 pg/mL [660-1,016], P < 0.001). The odds ratio for transition in albuminuria increased significantly per SD of GDF-15 (2.9 [95% CI 1.1-7.5], P = 0.03). GDF-15 also improved prediction of albuminuria transition, with significant increases in C statistic (from 0.87 to 0.92, P = 0.03) and integrated discrimination improvement (0.148, P = 0.001). In HT, GDF-15 was also independently associated with transition in albuminuria stage (2.0 [1.1-3.5], P = 0.02) and improved prediction significantly. We identified GDF-15 as a clinically valuable marker for predicting transition in albuminuria stage in T2DM beyond conventional risk markers. These findings were confirmed in nondiabetic HT subjects.


Malignant fibrous histiocytoma of the clivus: case report.
A case of malignant fibrous histiocytoma of the clivus in a 2 1/2-year-old boy is reported. There are no prior reports of this tumor in this location. The child was treated with operation, radiation therapy, and chemotherapy. The tumor recurred locally 21 months later. The recurrence was palliated by operation and chemotherapy, permitting an additional 20-month survival.


Human endonuclease III/NTH1: focusing on the [4Fe-4S] cluster and the N-terminal domain.
Human Endonuclease III (EndoIII), hNTH1, is an FeS containing enzyme which repairs oxidation damaged bases in DNA. We report here the first comparative biophysical study of full-length and an N-terminally truncated hNTH1, with a domain architecture homologous to bacterial EndoIII. Vibrational spectroscopy, spectroelectrochemistry and SAXS experiments reveal distinct properties of the two enzyme forms, and indicate that the N-terminal domain is important for DNA binding at the onset of damage recognition.


Subepidermal calcified nodule on the periungual finger successfully treated with ablative carbon dioxide laser.
Subepidermal calcified nodules are lesions that primarily affect children and are most commonly located on the head. The current standard of treatment for these is surgical excision. However, surgical excision is not always possible and may not be cosmetically favorable. We describe the use of a CO2 laser as a successful treatment for a subepidermal calcified nodule of the finger.


Emerging public health threat of e-waste management: global and Indian perspective.
Background Electrical and electronic waste or e-waste is emerging as a major public health threat worldwide because of rapid advances in technology leading to the generation of large amount of wastes and a lack of knowledge in handling of these wastes. Objective The current review discusses the current e-waste problem worldwide, as a public health concern, with a specific focus on India and recommendations to have effective e-waste management. Methods This is a traditional review study. The burden of e-waste, regulations and its impact on health and the environment at the global and country level were identified using various search engines such as PubMed, Google Scholar, Scopus and ScienceDirect. Books, case studies, legislation documents, reports, original articles and other documents from international organizations and specific governmental agency websites were retrieved. In total, 33 original articles, reports, case studies and documents were used for this review. Results In 2016, 44.7 million tonnes of e-waste was generated with 2 million tonnes produced in India alone. Out of this, only 20% of the e-waste generated globally was handled properly. The situation is worse in India where more than 90% of the e-waste was handled by informal sector workers. An important problem with the process is that they do not take necessary precautionary measures before handling e-waste. Components which are not suitable for reuse are burnt openly or disposed of through open dumping. Most of the informal sector workers are illiterate making them unaware of the hazardous chemicals that can be released later into the water sources and the environment. Conclusion The current review shows that the e-waste poses a serious global public health threat leading to significant environmental and health risks. Most of the developing countries including India were found to be lagging behind in the implementation of environmentally sound formal recycling processes. Hence, a better life cycle assessment model which have been successfully implemented in other developing countries should be introduced in India.


Surfing the Blood Coagulation Cascade: Insight into the Vital Factor Xa.
Factor Xa (FXa) plays a key role in haemostasis, it is a central part of the blood coagulation cascade which catalyzes the production of thrombin and leads to clot formation and wound closure. Therefore, FXa is an attractive target for the development of new anticoagulant agents. In this review, we will first describe the molecular features of this fundamental protein in order to understand its mechanism of action, an essential background for the design of novel inhibitors by means of synthetic organic chemistry or using peptides obtained from recombinant methodologies. Then, we will review the current state of the synthesis of novel direct FXa inhibitors along with their mechanisms of action. Finally, approved reversal agents that aid in maintaining blood haemostasis by using these commercial drugs will also be discussed.


[Clinical symptoms and differential diagnosis of acute arterial vascular occlusion in the limbs].
The acute arterial vascular occlusion is relatively rare, but without any exception it belongs to the medical emergency situations. The early diagnosing is decisive, since embolectomy is to be regarded as method of choice during the first 10 hours. After demonstration of the most frequent sources of embolism and their clinical manifestation symptomatology and most essential differential diagnoses of the acute arterial vascular occlusion are discussed. As consequence for practice must be demanded that at the least supposition on the presence of an acute arterial vascular occlusion the immediate hospitalisation is necessary.


A finite element model on effects of impact load and cavitation on fatigue crack propagation in mechanical bileaflet aortic heart valve.
Pyrolytic carbon mechanical heart valves (MHVs) are widely used to replace dysfunctional and failed heart valves. As the human heart beats around 40 million times per year, fatigue is the prime mechanism of mechanical failure. In this study, a finite element approach is implemented to develop a model for fatigue analysis of MHVs due to the impact force between the leaflet and the stent and cavitation in the aortic position. A two-step method to predict crack propagation in the leaflets of MHVs has been developed. Stress intensity factors (SIFs) are computed at a small initiated crack located on the leaflet edge (the worst case) using the boundary element method (BEM). Static analysis of the crack is performed to analyse the stress distribution around the front crack zone when the crack is opened; this is followed by a dynamic crack analysis to consider crack propagation using the finite element approach. Two factors are taken into account in the calculation of the SIFs: first, the effect of microjet formation due to cavitation in the vicinity of leaflets, resulting in water hammer pressure; second, the effect of the impact force between the leaflet and the stent of the MHVs, both in the closing phase. The critical initial crack length, the SIFs, the water hammer pressure, and the maximum jet velocity due to cavitation have been calculated. With an initial crack length of 35 microm, the fatigue life of the heart valve is greater than 60 years (i.e. about 2.2 x 10(9) cycles) and, with an initial crack length of 170 microm, the fatigue life of the heart valve would be around 2.5 years (i.e. about 9.1 x 10(7) cycles). For an initial crack length greater than 170 microm, there is catastrophic failure and fatigue cracking no longer occurs. A finite element model of fatigue analysis using Patran command language (PCL custom code) in MSC software can be used to evaluate the useful lifespan of MHVs. Similar methodologies can be extended to other medical devices under cyclic loads.


Abnormalities of right ventricular function following Mustard's operation for transposition of the great arteries.
Postoperative data were obtained at cardiac catheterization in twelve patients studied 6-29 months following Mustard's operation for transposition of the great arteries (TGA) to assess the incidence and severity of abnormalities of right ventricular (RV) function. Age at operation was 5-13 months in seven patients (infant group) and 19-25 months in the remaining five patients. RV end-diastolic volume (EDV) decreased in all patients following surgery and averaged 123% of normal in the postoperative group (NS). RV ejection fraction (EF) was depressed postoperatively averaging 0.45 (69% of normal (P less than 0.001) as was RV systolic output (78% of normal, P less than 0.01). LVEDV averaged 65% of normal (P less than 0.001), LVEF 0.67 (103% of normal, NS), and LV systolic output 67% of normal (P less than 0.001) following operation. Left atrial (systemic venous) volume was decreased in all postoperative patients averaging only 39% of normal (P less than 0.001). A high incidence (greater than 50%) of partial baffle obstruction was found and LV systolic output showed a significant negative correlation with baffle gradients. The low output postoperatively may be related to decreased LV filling pressure, a small LV reservoir, and thus a small atrial "booster pump." Pressure-velocity indices of RV contractile function in four patients showed a poor correlation with pump function. Long-term follow-up will be required to determine the clinical significance of the abnormalities of venous return and ventricular function.


Congenital tuberculosis because of misdiagnosed maternal pulmonary tuberculosis during pregnancy.
We report the death of an infant due to severe sepsis caused by congenital tuberculosis following treatment with antituberculous drugs and antibiotics, who was born to a mother with misdiagnosed symptomatic pulmonary tuberculosis during pregnancy. Therefore, pregnant women with chronic cough and constitutional symptoms must be examined for pulmonary tuberculosis, particularly in tuberculosis endemic areas.


Time-resolved X-ray diffraction investigation of the modified phonon dispersion in InSb nanowires.
The modified phonon dispersion is of importance for understanding the origin of the reduced heat conductivity in nanowires. We have measured the phonon dispersion for 50 nm diameter InSb (111) nanowires using time-resolved X-ray diffraction. By comparing the sound speed of the bulk (3880 m/s) and that of a classical thin rod (3600 m/s) to our measurement (2880 m/s), we conclude that the origin of the reduced sound speed and thereby to the reduced heat conductivity is that the C44 elastic constant is reduced by 35% compared to the bulk material.


Comparison of Survival Outcomes After Deceased Donor Split Versus Whole Liver Transplant for Hepatocellular Carcinoma.
To mitigate waiting time forlivertransplant for hepatocellular carcinoma, partial or split liver transplant has been utilized. There was concern that regeneration of these grafts would negatively affect oncologic outcomes. We compared posttransplant graft survival between hepatocellular carcinoma whole livertransplant and partial/splitlivertransplant using Scientific Registry of Transplant Recipients data (2002-2017). The 330 partial/split liver transplant recipients were compared with a logistic regressionbased propensity score 1:1 matched whole liver transplant cohort (n = 330) and a random unmatched whole livertransplant cohort(n = 4143). Kaplan-Meier and multivariable Cox regression models evaluated the effects of partial/split and whole liver transplant on survival. Unadjusted analysis demonstrated no difference in graft survivalbetween thepartial/split and whole liver transplant cohorts (overall log-rank P = .78). After adjustments for recipient age, last laboratory Modelfor End-stage LiverDisease score, hepatitisBviral infection co-diagnosis, liver donor risk index, donor historyofdiabetes, anddonorbodymass index category were made (all P ⟨ .05), multivariable analysis demonstrated no statistically significant difference in the risk of graftfailure in thepartial/splitlivertransplant cohort compared with either the matched or random whole livertransplant cohort (both P ≥ .23). Partial/split liver transplant was not an independent risk factor for graft failure. Additional studies are needed to further elucidate differences in these populations to determine the "right" candidate for partial/split liver transplant.


[Cost savings derived from the participation in clinical trials].
Medical care of patients with essential hypertension implies considerable expenses for the National Health System (NHS). During the performance of clinical trials (CT), the promoter (usually the pharmaceutical industry) covers the expenses of patient care, which implies savings for the NHS. In this work, we quantitated cost savings derived from the participation of patients in clinical trials on essential hypertension in a tertiary care level Insalud hospital. Savings were defined as the difference between the economical expenses of a patient before being enrolled in a clinical trial (CT) and that generated during his/her participation in the CT. Expenses of a given patient to the NHS were calculated from his/her clinical record during a time period equal to CT length in which the patient participated. Three financial allottments in four CT were analyzed (three with a 52-week duration and one of 14 weeks) that meant cost savings (total or partial): a) antihypertensive drugs; b) complementary tests, and c) medical visits. Seventy-three patients with essential hypertension were enrolled in the 4 CT; 59 (81%) patients were randomly assigned and 57 patients concluded the CT. The overall savings derived from the participation of the 57 patients was 2,950,423 pesetas. Most of these savings corresponded to drugs (70.7%). Savings derived from laboratory tests (14.1%) and medical visits (15.1%) were similar. The mean savings derived from the participation of one patient in a CT for 12 months was, at least, 70,564 pesetas (5,880 pesetas/patient/month). The participation of patients with essential AH implies considerable savings for the NHS.


New records of the family Dascillidae (Coleoptera) from China.
New geographical records for 13 species of Dascillidae in China are provided, of which two, Dascillus vittatus (Pic, 1914) and D. russus Jin et al., 2013 are new Country records. In addition, we provide 10 new province records for 13 species of Chinese Dascillidae. The Yunnan Province holds the richest generic and species diversity of Dascillinae (3 genera, 20 species). A total of 32 species (74%) are Chinese endemics and Yunnan is also found to be the area with the highest endemicity (13 species).


Significant activity of single agent vinorelbine against small-cell cancer of the bladder as second line chemotherapy: a case series and review of the literature.
Small-cell carcinoma of the urinary bladder is an extremely uncommon form of urologic malignancy, accounting for less that 1% of new cases of bladder cancer. It is an aggressive malignancy which, like its pulmonary counterpart, tends to spread with distant metastases. This malignancy is generally chemotherapy and radiotherapy sensitive. Metastatic disease is typically treated with regimens active against small-cell carcinoma of the lung, such as cisplatin and etoposide. There are no data regarding second-line treatment of this cancer. We report our experience in 3 patients using the second generation vinca alkaloid, vinorelbine, in refractory metastatic small-cell carcinoma of the bladder. These 3 patients had extensive prior therapy but all 3 responded to weekly vinorelbine, with a complete response (CR) in 1, near CR in the second, and partial response in the third. Of note, the patient who sustained a CR has remained without disease and with excellent quality of life for nearly 4 years since starting vinorelbine. Indeed, the therapy was very well tolerated in all 3 patients with grade 2 cytopenia being the only toxicity. We conclude that vinorelbine is well tolerated and has activity in this case series in the second-line treatment of metastatic small-cell carcinoma of the bladder.


Vasculitis following implantation of a ventriculoperitoneal shunt tube made of silicone.
Abstract A 56-year-old man presented with hyperproteinemia and renal dysfunction associated with antineutrophil cytoplasmic antibodies (ANCA). He had had a ventriculoperitoneal shunt tube made of silicone implanted 4 years earlier. In his renal biopsy, necrotizing crescentic glomerulonephritis was identified: tests for both myeloperoxidase ANCA and proteinase 3 ANCA were initially weakly positive. Antinuclear and other autoantibodies were also present. We diagnosed ANCA-associated vasculitis, probably induced by the silicone tube.


Exploring predictors of COVID-19 vaccine acceptance among students, faculty, and staff at a Southeastern University in the United States.
Explore predictors of early COVID-19 vaccine adoption on a university campus. Students, faculty, staff, and administration (N = 1,234) completed an online survey exploring COVID-19 vaccine-related experiences, perspectives, and knowledge, from September to October 2021. Based on vaccination status participants were identified as vaccine hesitant or early vaccine adopters. Binary logistic regression was used to examine association between independent variables and vaccine adoption status. Democrats (OR = 4.3, p = <.001), participants without a positive COVID-19 test (OR = 2.5, p = <.001), noted seeing/hearing COVID-19 misinformation (OR = 1.8, p = 0.27), and reported trust in public health agencies (OR = 26.2, p = <.001) were more likely to be early COVID-19 vaccine adopters, compared to Republicans, those with a positive COVID-19 test, those who had not seen/heard COVID-19 misinformation, and those reporting distrust in public health agencies, respectively. Findings indicate that COVID-19 vaccine adoption is multifactorial. Future research should focus on vaccination status-related trust and health communication.


Novel cerebroprotective agents with central nervous system stimulating activity. 2. Synthesis and pharmacology of the 1-(acylamino)-7-hydroxyindan derivatives.
In a continuous search for a novel cerebroprotective drug with a central nervous system (CNS) stimulating activity, a series of 1-(acylamino)-7-hydroxyindan derivatives has been synthesized and tested for its dual activities. The cerebroprotective activities of the compounds in this series were evaluated in terms of their effect on the survival of mice in hypoxic conditions (210 mmHg), and their CNS stimulating activities were examined by evaluating their promotional effects on the recovery from coma induced by cerebral concussion in mice. Several compounds prolonged the survival of mice in the hypoxic conditions at a dose of 30 mg/kg po. Four compounds in this series showed the CNS-stimulating effect at the same dose. Among them, 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetyl]amino]-2,2,4, 6-tetramethylindan (18, OPC-14117), which was active in the two tests with no side effect up to 500 mg/kg po daily for 2 weeks of administration to rats, was selected for preclinical investigations.


cDNA cloning of two different serine protease inhibitor precursors in the migratory locust, Locusta migratoria.
Recently, a novel serine protease-inhibiting peptide family, designated as the 'pacifastin family', has been described in locusts and crayfish. All members of this family possess a characteristic cysteine-rich domain. The present study describes the cDNA cloning, sequencing and transcript distribution of two novel pacifastin-related peptide precursors in the migratory locust, Locusta migratoria. Only one of the encoded peptides (HI) was identified previously, whereas six others represent new members of the pacifastin family. Northern blot analysis showed that both precursor transcripts are present in adult locust fat body. These could not be detected in the midgut. Interestingly, an in silico data mining approach of the expressed sequence tags (EST) database revealed the existence of Manduca sexta and Bombyx mori cDNAs that display pronounced sequence similarities with these locust pacifastin-related transcripts.


Determination of subjective similarity for pairs of masses and pairs of clustered microcalcifications on mammograms: comparison of similarity ranking scores and absolute similarity ratings.
The presentation of images that are similar to that of an unknown lesion seen on a mammogram may be helpful for radiologists to correctly diagnose that lesion. For similar images to be useful, they must be quite similar from the radiologists' point of view. We have been trying to quantify the radiologists' impression of similarity for pairs of lesions and to establish a "gold standard" for development and evaluation of a computerized scheme for selecting such similar images. However, it is considered difficult to reliably and accurately determine similarity ratings, because they are subjective. In this study, we compared the subjective similarities obtained by two different methods, an absolute rating method and a 2-alternative forced-choice (2AFC) method, to demonstrate that reliable similarity ratings can be determined by the responses of a group of radiologists. The absolute similarity ratings were previously obtained for pairs of masses and pairs of microcalcifications from five and nine radiologists, respectively. In this study, similarity ranking scores for eight pairs of masses and eight pairs of microcalcifications were determined by use of the 2AFC method. In the first session, the eight pairs of masses and eight pairs of microcalcifications were grouped and compared separately for determining the similarity ranking scores. In the second session, another similarity ranking score was determined by use of mixed pairs, i.e., by comparison of the similarity of a mass pair with that of a calcification pair. Four pairs of masses and four pairs of microcalcifications were grouped together to create two sets of eight pairs. The average absolute similarity ratings and the average similarity ranking scores showed very good correlations in the first study (Pearson's correlation coefficients: 0.94 and 0.98 for masses and microcalcifications, respectively). Moreover, in the second study, the correlations between the absolute ratings and the ranking scores were also very high (0.92 and 0.96), which implies that the observers were able to compare the similarity of a mass pair with that of a calcification pair consistently. These results provide evidence that the concept of similarity for pairs of images is robust, even across different lesion types, and that radiologists are able to reliably determine subjective similarity for pairs of breast lesions.


Importance of specimen size in accurate needle liver biopsy evaluation of patients with chronic hepatitis C.
In patients with chronic hepatitis C (CHC), percutaneous needle liver biopsy examination establishes the severity of necroinflammatory activity and fibrosis, thus guiding treatment decisions. Optimal biopsy specimen size remains controversial. We sought to determine how varying lengths of biopsy specimens influence the grading and staging of CHC. We used 100 liver biopsy specimens from patients with CHC. The slides were evaluated blindly using the METAVIR scoring system, after being covered with paper, so that only specific specimen lengths (5 mm, 10 mm, 15 mm, and > or =20 mm) were visible. In each case, the scores obtained with biopsies 5 mm, 10 mm, or 15 mm long were compared with the scores at 20 mm or greater by weighted kappa statistics (kappa of >.75 signified excellent agreement). A subset of specimens 20 mm or greater was selected for a blinded repeat scoring to assess intraobserver agreement. The kappa statistics for the designated features and lengths were compared using analysis of variance. In assessing the stage of fibrosis, the weighted kappa statistics for agreement with the 20-mm or greater score at 5 mm, 10 mm, and 15 mm were .75, .85, and .92, respectively. In assessing the histologic activity score, the corresponding figures were .73, .81, and .77, respectively. Average kappa statistic comparisons showed that intraobserver agreement was significantly better than agreement between the 20-mm or greater scores and those at shorter lengths; the 5-mm kappa scores were significantly lower than the others; and there was no significant difference between the 10-mm and 15-mm kappa scores. Liver biopsy specimens measuring at least 10 mm usually reflect the grade and stage of CHC reliably. Relatively little improvement in diagnostic accuracy is obtained with longer specimens.


Erb's Syphilitic Paraplegia.
A 45 years old married lady was admitted with spastic paraplegia of insidious onset without any sensory deficit. Serological studies of blood and CSF for syphilis were positive and cerebrospinal fluid showed increased cells and protein content. She responded well to parenteral penicillin therapy, showed gradual subjective improvement and appreciable decrease in cellular and protein content of the CSF. Her husband also was found to have latent syphilitic infection. Review of relevant literature showed no report of such paraplegia following syphilis in recent times. The case is being reported with a short discussion of the clinical features of neurosyphilis.


Considerations for the application of artificial intelligence in vascular surgical education.
The rapid adoption of artificial intelligence (AI) into everyday use has presented multiple issues for surgical educators to consider. In this article, the authors discuss some of the ethical aspects of academic integrity and the use of AI. These issues include the importance of understanding the current limits of AI and the inherent biases of the technology. The authors further discuss the ethical considerations of the use of AI in surgical training and in clinical use, with an emphasis on vascular surgery.


[Antihypertensive therapy and drug-drug interactions].
Adverse drug reactions (ADR) have increasing clinical implications and are a permanent challenge for general practitioners. Data suggest that ADR cause 3 to 18% of all hospital admissions with potentially serious consequences. Polymedication, female sex, multiple pathologies with age-related changes are predisposing factors. Antihypertensive drugs with a low bioavailability, a high protein binding capacity and specific elimination pathways are particularly prone to pharmacokinetic interactions. ACE-inhibitors, atenolol, moxonidine and diuretics have few pharmacokinetic interactions. Calcium channel blockers and beta-blockers are associated with an increased risk of pharmacokinetic drug-drug interactions. Diltiazem and verapamil are particularly prone to interactions, as they strongly inhibit the elimination of drugs undergoing the CYP3A4 and P-glycoprotein pathways.


Does the timing and method of rapid maxillary expansion have an effect on the changes in nasal dimensions?
The aim of this study was to assess the effects of rapid maxillary expansion (RME) and surgical assisted rapid maxillary expansion (SARME) on nasopharyngeal area. The study group consisted of 30 subjects in the permanent dentition who had both maxillary constriction and a posterior cross-bite. The patients were divided into two groups, RME and SARME. The subjects in the RME group consisted of 15 patients (eight girls, seven boys) whose average age was 12.1 +/- 1.1 years. The SARME group also consisted of 15 patients (eight boys, seven girls) whose mean age was 18.4 +/- 1.4 years. An acrylic bonded RME appliance was used in both groups. Surgery was performed using lateral cortical osteotomies in the SARME group. The nasopharyngeal and respiratory area was determined using a digital planimeter on lateral cephalometric radiographs taken before and after RME. Nasal cavity width was evaluated on postero-anterior radiographs. Nasal dimension was measured using planimeter measurements of the respiratory and nasopharyngeal areas before and after treatment. The data obtained were analyzed using SPSS. Comparisons within the groups were carried out with paired t-tests and comparisons between the groups were with a Student's t-test. In both groups, the respiratory area and the ratio of the respiratory area to nasopharyngeal (RA/NA) area increased following RME. There were no statistically significant differences between the groups. Nasal cavity width and maxillary width also increased, but the difference between the groups was not significant. Following RME, various differences in both the maxilla and surrounding bones occurred and nasal width increased with a decrease in nasal airway resistance. At the end of treatment there were increases in the width of the nasal floor near the midpalatal suture and nasal cavity. As the maxillary structures separated, the outer walls of the nasal cavity moved laterally resulting in an increase in internasal volume. Nasal resistance decreased and respiratory area increased in patients treated with RME.


Molecular Complexity and Retrosynthesis.
An atom-environment complexity measure, CA, to assess local changes in complexity during synthetic transformations is described. The complexity measure is based on applying Shannon's equation to the number and diversity of paths up to two bonds in length emanating from an atom node. The method requires no explicit accounting for bond type, stereochemistry, ring membership, symmetry, or molecular size. CA varies with expectation across a number of basic reaction examples and may identify the key disconnections to guide retrosynthesis.


Crystallography and Its Impact on Carbonic Anhydrase Research.
X-ray and neutron crystallography are powerful techniques utilized to study the structures of biomolecules. Visualization of enzymes in complex with substrate/product and the capture of intermediate states can be related to activity to facilitate understanding of the catalytic mechanism. Subsequent analysis of small molecule binding within the enzyme active site provides insight into mechanisms of inhibition, supporting the design of novel inhibitors using a structure-guided approach. The first X-ray crystal structures were determined for small, ubiquitous enzymes such as carbonic anhydrase (CA). CAs are a family of zinc metalloenzymes that catalyze the hydration of CO2, producing HCO3 - and a proton. The CA structure and ping-pong mechanism have been extensively studied and are well understood. Though the function of CA plays an important role in a variety of physiological functions, CA has also been associated with diseases such as glaucoma, edema, epilepsy, obesity, and cancer and is therefore recognized as a drug target. In this review, a brief history of crystallography and its impact on CA research is discussed.


A new species of Hangangbathynella (Crustacea, Bathynellacea, Parabathynellidae) from South Korea.
A new parabathynellid bathynellacean species, Hangangbathynella mihoensis sp. nov., was found in the groundwater of the Geumgang River in South Korea. This is the first report of Hangangbathynella from a tributary of the Geumgang River. All previously-reported species were found in the Hangang River and the origins of the two rivers are distinct from each other. The new species can be distinguished from its congeners by the two-segmented mandibular palp and the absence of epipods on thoracopod II. In this study, we provide a description of the new species and an identification table for the genus Hangangbathynella. In addition, we obtained partial sequences of the mitochondrial cytochrome c oxidase subunit I gene for DNA barcoding.


[Efficacy of sivelestat for acute lung injury due to severe bacterial pneumonia with systemic inflammatory response syndrome].
Neutrophil elastase is believed to play an important role in acute lung injury (ALI). Sivelestat is a small molecular weight neutrophil elastase inhibitor. Although some authors reported its efficacy in ALI, it is unclear whether sivelestat has good effects in ALI, especially in cases due to severe bacterial pneumonia. The purpose of this study is to investigate the effect of sivelestat to ALI due to severe bacterial pneumonia. We performed a retrospective study of 28 patients who were admitted for severe bacterial pneumonia (pneumonia severity index; PSI class V). We investigated the patients' background, pneumonia severity score, the days from diagnosis of systemic inflammatory response syndrome (SIRS) to sivelestat administration, P/F ratio, SIRS score, and compared two groups: those who survived and those who died. There were no significant background differences between the two groups. In pneumonia severity score, chest X-ray film score was higher in the group of fatalities than in the survival group. In the survival cases, sivelestat had been administered earlier than in the cases that died. In the survival cases, improvement in P/F ratio, body temperature, heart rate, and respiratory rate were shown. The total number of SIRS scores also decreased in survival cases. This study suggested the possibility that early administration of sivelestat may improve the ALI survival rate in severe pneumonia.


Chalcopyrite Nanoparticles as a Sustainable Thermoelectric Material.
In this report, copper iron sulfide nanoparticles with various composition were synthesized by a thermolysis based wet chemical method. These inherently sustainable nanoparticles were then fully characterized in terms of composition, structure, and morphology, as well as for suitability as a thermoelectric material. The merits of the material preparation include a straightforward bulk material formation where particles do not require any specialized treatment, such as spark plasma sintering or thermal heating. The Seebeck coefficient of the materials reveals P-type conductivity with a maximum value of 203 µV/K. The results give insight into how to design and create a new class of sustainable nanoparticle material for thermoelectric applications.


[Improved expression and catalytic efficiency of (R)-carbonyl reductase in Escherichia coli by secondary structure optimization of mRNA translation initiation region].
To improve the expression level and catalytic efficiency of (R)-carbonyl reductase from Candida parapsilosis in Escherichia coli, we optimized the mRNA secondary structure of (R)-carbonyl reductase gene in translation initiation region (from +1 to +78), and constructed the corresponding variant. The formation of hairpin structure was significantly reduced and the Gibbs free energy was dramatically decreased from -9.5 kcal/mol to -5.0 kcal/mol after optimization. As a result, the expression level of (R)-carbonyl reductase in the variant was increased by 4-5 times and its specific activity in cell-free extract was enhanced by 61.9% compared to the wild-type strain. When using the whole cells as catalyst and 2-hydroxyacetophenone as substrate with a high concentration of 5.0 g/L, the variant showed excellent performance to give (R)-1-phenyl-1, 2-ethanediol with optical purity of 93.1% enantiomeric excess and a yield of 81.8%, which were increased by 27.5% and 40.5% respectively than those of the wild-type. In conclusion, the optimization of mRNA secondary structure in translation initiation region can overcome the steric hindrance of translation startup, promote translation smoothly to acquire high expression of target protein, and favor protein folding correctly to efficiently improve the enzyme specific activity and biotransformation function.


Efficient Removal of Carcinogenic Azo Dyes from Water Using Iron(II) Clathrochelate Derived Metalorganic Copolymers Made from a Copper-Catalyzed [4 + 2] Cyclobenzannulation Reaction.
A novel synthetic strategy is disclosed to prepare a new class of metalorganic copolymers that contain iron(II) clathrochelate building blocks by employing a mild and cost-effective copper-catalyzed [4 + 2] cyclobenzannulation reaction, using three specially designed diethynyl iron(II) clathrochelate synthons. The target copolymers CBP1-3 were isolated in high purity and excellent yields as proven by their structural and photophysical characterization, namely, Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and UV-VIS absorption and emission spectroscopies. The thermogravimetric analysis (TGA) of CBP1-3 revealed an excellent chemical stability. Investigation of the adsorption properties of the target copolymers towards the carcinogenic methyl red dye from aqueous solution revealed a quantitative uptake in 30 min. Isothermal adsorption studies disclosed that methyl red uptake from aqueous solution followed the Langmuir model for all of the target copolymers, reaching a maximum adsorption capacity (qm) of 431 mg g-. Kinetic investigation revealed that the adsorption followed pseudo-first-order with an equilibrium adsorption capacity (qe,cal) of 79.35 mg g- and whose sorption property was sustained even after its reuse several times.


Analysis of the long-term outcomes of nonsyndromic bicoronal synostosis.
Isolated nonsyndromic bicoronal synostosis is a relatively rare entity that produces a characteristic turribrachycephalic skull shape. The purpose of this study was to evaluate the long-term outcomes of the isolated nonsyndromic bicoronal synostosis patients treated at the authors' institution. A retrospective chart review of all patients who underwent cranial vault remodeling for nonsyndromic bicoronal synostosis was performed at the Children's Hospital of Philadelphia from 1991 to 2011. Fifteen patients were identified for this study, and information regarding their demographic, perioperative, and postoperative details were analyzed. Four boys and 11 girls were identified for inclusion in this study. The average age at the time of the initial surgery was 9 months, with an average follow-up of 13.4 years. There were no reported complications. Six patients with at least a 10-year follow-up (six of 10 patients) underwent revision for contour improvement in the forehead and temporal regions, and two patients required a repeated fronto-orbital advancement. Four patients underwent subsequent strabismus surgery. No patients were documented to have midface hypoplasia requiring orthognathic surgery. One patient with an associated diagnosis of autism was noted to have significant developmental delay. Isolated nonsyndromic bicoronal synostosis confers a high rate of revisions for contour deformities but is associated with a low risk of complications. Overall, nonsyndromic patients require less secondary fronto-orbital advancement when compared with syndromic patients. In contrast to the syndromic population, there were no instances of midface hypoplasia necessitating surgery. There did not appear to be significant correlation between bicoronal synostosis and developmental abnormalities or delays.


Expression of the zinc-finger antiviral protein inhibits alphavirus replication.
The rat zinc-finger antiviral protein (ZAP) was recently identified as a host protein conferring resistance to retroviral infection. We analyzed ZAP's ability to inhibit viruses from other families and found that ZAP potently inhibits the replication of multiple members of the Alphavirus genus within the Togaviridae, including Sindbis virus, Semliki Forest virus, Ross River virus, and Venezuelan equine encephalitis virus. However, expression of ZAP did not induce a broad-spectrum antiviral state as some viruses, including vesicular stomatitis virus, poliovirus, yellow fever virus, and herpes simplex virus type 1, replicated to normal levels in ZAP-expressing cells. We determined that ZAP expression inhibits Sindbis virus replication after virus penetration and entry, but before the amplification of newly synthesized plus strand genomic RNA. Using a temperature-sensitive Sindbis virus mutant expressing luciferase, we further showed that translation of incoming viral RNA is blocked by ZAP expression. Elucidation of the antiviral mechanism by which ZAP inhibits Sindbis virus translation may lead to the development of agents with broad activity against alphaviruses.


A Highly Ionic Conductive, Healable, and Adhesive Polysiloxane-Supported Ionogel.
A new kind of polysiloxane-supported ionogel is successfully designed via locking ionic liquids (ILs), 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][Tf2 N]), into poly(aminopropyl-methylsiloxane) (PAPMS) grafted with [2-(methacryloyloxy)ethyl] trimethylammonium chloride (METAC) in the presence of tannic acid (TA). The novel ionogel exhibits good mechanical and recovery properties, as well as high ionic conductivity (1.19 mS cm-1 ) at 25 °C. In addition, the totally physical dual-crosslinked network based on ionic aggregates among METAC and the hydrogen bonds between PAPMS and TA provides excellent self-healing ability, which allows the damaged ionogel to almost completely heal (≈83%) in 12 h at room temperature. Interestingly, the obtained ionogel also shows satisfactory adhesive behavior to various solid materials. Moreover, this novel ionogel can maintain its high ionic conductivity and recovery property even at subzero temperatures. Therefore, this polysiloxane-supported ionogel is anticipated to be advantageous in flexible electronic devices such as sensors and supercapacitors, even at low temperatures.


Electrochemiluminescence of dimethylaminonaphthalene-oxazaborine donor-acceptor luminophores.
Donor-acceptor (D-A) type molecules with a skeleton consisting of a dimethylaminonaphthalene donor and an oxazaborine acceptor were designed as efficient electrochemiluminescence (ECL) luminophores with tunable intramolecular charge transfer (ICT). The D-A ECL luminophores demonstrated that the ICT characteristics play a critical role in the electrochemistry and ECL of luminophores in the presence of tri-n-propylamine, which was rationalised experimentally and computationally. Furthemore, dual-peaked ECL-potential behaviours of the luminophores were rationalised using two competitive pathway ECL mechanisms, elucidated through the use of spooling ECL spectroscopy.


A Standardized Positive Physical Approach to Improve Oral Hygiene for Nursing Home Residents With Alzheimer's Disease and Related Dementias.
Residents with Alzheimer's disease and related dementias (ADRD) in nursing homes (NHs) rely on direct care workers (DCWs) to assist with activities of daily living, such as oral hygiene. The current quality improvement project was implemented to evaluate the effectiveness of teaching a standardized positive physical approach to oral hygiene completion for patients with ADRD residing in a NH. A pre-/postintervention evaluation incorporating a video presentation coupled with a hands-on simulation experience showed a statistically significant improvement in DCWs' overall Sense of Competency in Dementia score, as well as all subcategories of the Sense of Competence in Dementia Care Staff survey. In addition, residents' day shift oral hygiene care completion rates increased monthly pre- to postintervention. NHs should consider implementing training that includes hands-on experiences to equip DCWs with the knowledge and skill needed to improve oral hygiene among residents with ADRD. [Journal of Gerontological Nursing, 48(11), 15-20.].


Simian malaria: a narrative review on emergence, epidemiology and threat to global malaria elimination.
Simian malaria from wild non-human primate populations is increasingly recognised as a public health threat and is now the main cause of human malaria in Malaysia and some regions of Brazil. In 2022, Malaysia became the first country not to achieve malaria elimination due to zoonotic simian malaria. We review the global distribution and drivers of simian malaria and identify priorities for diagnosis, treatment, surveillance, and control. Environmental change is driving closer interactions between humans and wildlife, with malaria parasites from non-human primates spilling over into human populations and human malaria parasites spilling back into wild non-human primate populations. These complex transmission cycles require new molecular and epidemiological approaches to track parasite spread. Current methods of malaria control are ineffective, with wildlife reservoirs and primarily outdoor-biting mosquito vectors urgently requiring the development of novel control strategies. Without these, simian malaria has the potential to undermine malaria elimination globally.


Portraiture Brought Introspection and Perspective.
This article describes the perspectives of a scientist-patient and patient-caregiver when sitting for their portrait and also considers the value of this experience for facilitating healing and observation of patient-caregiver relationships.


The role of uric acid in the pathogenesis of hypertension in the young.
Uric acid has been suspected to be a risk factor for hypertension since the 1870s. Numerous epidemiological studies demonstrate an association between uric acid and both incident and prevalent hypertension in diverse populations. Studies in elderly patients have had more variable results, raising the possibility that uric acid may be more significant to hypertension in the young. Animal models support a two-phase mechanism for the development of hyperuricemic hypertension. Initially, uric acid induces vasoconstriction by activation of the renin-angiotensin system and reduction of circulating nitric oxide, which can be reversed by lowering uric acid. Over time, uric acid uptake into vascular smooth muscle cells causes cellular proliferation and secondary arteriolosclerosis that impairs pressure natriuresis, causing sodium-sensitive hypertension. Consistent with the animal model data, small clinical trials performed in adolescents with newly diagnosed essential hypertension demonstrate that at least in certain young patients, reduction of serum uric acid can mitigate blood pressure elevation. While more research is clearly necessary, the available data suggest that uric acid is likely causative in some cases of early-onset hypertension.


From student to doctor: An analysis of chiropractic oaths as an allegory of the transition from academic integrity to ethical professionalism.
This article examined current chiropractic oaths, particularly topics related to aspects of integrity, ethics, and professional behavior. The oaths were then compared for their individual inclusion and emphasis of these components. Data were obtained from 1988 and 2019 papers describing components of the oaths used at each existing chiropractic college as well as those used in the past by colleges that are no longer operational. Additionally, colleges founded after 2019 were contacted to obtain their oaths. Nine oath components related to ethics and professional conduct were selected from 26 topics originally studied. Each oath was evaluated for the presence of and specific wording used to describe those components. The oaths were compared for their inclusion and emphasis of these components. Some topics, such as "keeping a patient's confidence" and "refrain from wrongdoing," demonstrated a high rate of occurrence. Others, including "serving humanity" and "respecting teachers," were less frequent. The oath of 1 program contained 8 of the topics, 4 program's oaths used 7 topics, 11 schools had 6 topics in their oath, and the oaths of 5 schools included 2 topics. There is wide variation in the occurrence and emphasis of themes relating to ethics, integrity, and professionalism in the different chiropractic oaths. This study provides information for institutions to consider with regard to the content of the oath they administer. It is hoped that this article may encourage the creation of a universally accepted chiropractic oath that will help each graduate commit to a fulsome, all-encompassing pledge to become an ethical professional who optimally represents chiropractic.


The crucial role of catheters in micrococcal bloodstream infections in cancer patients.
Micrococcus bacteria are frequently isolated from blood cultures and could represent a cause of infections associated with medical devices, particularly in immunocompromised patients; however, there is a lack of information on the management of micrococcal bacteremia. We report what is, to our knowledge, the largest series of cases of micrococcal bacteremia ever studied and the great impact of catheter removal on its outcome.


[A smoker with progressive knee complaints].
A 70-year-old smoker was referred for X-rays of both painful knees. Both femora showed signs of hypertrophic osteoarthropathy. Chest radiography demonstrated a tumour in the upper lobe of the right lung. The patient was diagnosed with hypertrophic pulmonary osteoarthropathy (Marie-Bamberger syndrome).


Expression and promoter analysis of SLC19A2 in the human intestine.
The molecular mechanism and regulation of the intestinal uptake process of dietary thiamine is not well understood. Previous studies have established the involvement of a carrier-mediated system for thiamine uptake in the human intestine. Recently a human thiamine transporter, SLC19A2, was cloned from a number of human tissues. Little, however, is known about expression of the SLC19A2 message along the native human gastrointestinal tract, and no analysis of its promoter in intestinal tissue is available. Therefore, the current studies were aimed at investigating the expression of SLC19A2 in the human gastrointestinal tract and at analyzing the promoter of this potential intestinal thiamine transporter. First we cloned SLC19A2 cDNA from a human intestinal cell line (Caco-2) by reverse transcriptase-polymerase chain reaction, then used this cDNA as a probe in Northern blot analysis. SLC19A2 message was found to be expressed in all gastrointestinal tissues in the following order: liver>stomach>duodenum>jejunum>colon>cecum>rectum>ileum. SLC19A2 was also expressed at the protein level in Caco-2 cells and in native human small intestine by Western blot analysis. We also cloned the 5'-regulatory region of the SLC19A2 gene and confirmed activity of its promoter following transfection into intestinal epithelial Caco-2 cells. Furthermore, we identified the minimal promoter region required for basal activity of SLC19A2 in these cells which was found to be mainly encoded in a sequence between -356 and -36, and included multiple cis-regulatory elements. Transcription initiation sites of the SLC19A2 gene in intestinal epithelial Caco-2 cells were also identified by 5'-rapid amplification of cDNA ends. These results demonstrate that SLC19A2 is expressed in various regions of the human gastrointestinal tract. In addition, the results provide the first characterization of the SLC19A2 promoter. These findings raise the possibility that SLC19A2 may play a role in the normal intestinal thiamine absorption process.


Isolation of Aeromonas salmonicida from paddlefish, Polyodon spathula.
Aeromonas salmonicida was isolated from paddlefish (Polyodon spathula) mortalities collected during an epizootic of furunculosis at the Spring River State Hatchery, Arkansas (USA), in 1992. Isolates of the bacterium were obtained from culture of gill and kidney tissue. This is the first epizootic of bacterial etiology to be reported in paddlefish.


Type 2 diabetes is associated with the accumulation of senescent T cells.
Type 2 diabetes is a global health priority, given that it is driven, in part, by an ageing population, the role of immune senescence has been overlooked. This is surprising, as the functional impairments of senescent T cells show strong similarities to patients with hyperglycaemia. Immune senescence is typified by alterations in T cell memory, such as the accumulation of highly differentiated end-stage memory T cells, as well as a constitutive low-grade inflammation, which drives further immune differentiation. We show here in a preliminary study that people living with type 2 diabetes have a higher circulating volume of senescent T cells accompanied with a higher level of systemic inflammation. This inflammatory environment drives the expression of a unique array of chemokine receptors on senescent T cells, most notably C-X-C motif chemokine receptor type 2. However, this increased expression of migratory markers does not translate to improved extravasation owing to a lack of glucose uptake by the T cells. Our results therefore demonstrate that the presence of senescent T cells has a detrimental impact on immune function during type 2 diabetes.


Applying Collaborative Care Model on Intensive Caregiver Burden and Resilient Family Caregivers of Patients with Mental Disorders: A Randomized Controlled Trial.
Objective: Psychological education for families in the form of a model is one of the effective approaches in managing problems caused by mental health problems. The present study aimed to determine the effect of using the participatory care model on the caregiver burden and resilience of home caregivers of patients with mental disorders. Method : In this clinical trial, 66 households with psychiatric patients hospitalized at Shahid Rajaee Psychiatric Hospital in Yasuj during 2014-2015 were selected and assigned into 2 groups of experimental and intervention based on convenience and simple random sampling. The data of this study were gathered by Novak & Guest (1989) Caregiver burden and Sixbey (2005) Resilience Questionnaire before and after intervention. Participatory care model was performed for 12 ninety-minute sessions in the intervention group. No intervention was provided to the control group during the study period. SPSS software (version 21) was used to run the descriptive and inferential statistics. Results: Chi-squared test showed that the caregiver burden was significantly lower in the experimental group than in the control group after the intervention (P = 0.0001). Following the intervention, increased resilience and all its components were observed in the experimental group compared to the control group. According to the independent t test and Mann-Whitney U, the 2 groups were considerably different (P < 0.05). Conclusion: The application of the participatory care model efficiently increased resilience and decreased the intensity of the caregiver burden on the home caregivers of patients suffering from mental disorders.


Synthesis, spectral properties, and antitumor activity of a new axially substituted phthalocyanine complex of zirconium(IV) with citric acid.
The new axially substituted phthalocyanine (pc) complex of zirconium(IV) with citric acid is reported. It has been shown that the replacement of two Cl-atoms with two citric acid fragments takes place as the result of the reaction between [ZrCl2(pc)] and citric acid. The complex [Zr(citrate)2(pc)] was formed. The spectroscopic properties of the synthesized compound in DMSO, RPMI 1640 medium with and without fetal calf serum (FCS), H2O, and buffer (Tris) solutions have been described. Antitumor activity of this compound has been studied. The cytostatic activity was observed in the concentration range of 6.1-9.0x10(9) molecules [Zr(citrate)2(pc)]/cell and occurred in 4-6 h after treatment with [Zr(citrate)2(pc)] solution.


The Process of Change in Pain During Cognitive-Behavior Therapy for Chronic Fatigue Syndrome.
Cognitive-behavior therapy (CBT) leads to a reduction of fatigue and pain in chronic fatigue syndrome. The processes underlying the reduction in pain have not been investigated. Recently, it was shown that increased self-efficacy, decreased focusing on symptoms, increased physical functioning, and a change in beliefs about activity contribute to the decrease in fatigue. The present study has 2 objectives: (1) to determine the relationship between the reduction of fatigue and pain during CBT; (2) test to what extent the model for change in fatigue is applicable to the reduction in pain. One hundred forty-two patients meeting United States centers for Disease Control and Prevention criteria for chronic fatigue syndrome, currently reporting pain, and starting CBT were included. A cross-lagged analysis was performed to study the causal direction of change between pain and fatigue. Pain and process variables were assessed before therapy, 3 times during CBT, and after therapy. Actual physical activity was also assessed. The model was tested with multiple regression analyses. The direction of change between pain and fatigue could not be determined. An increase in physical functioning and decrease in focusing on symptoms explained 4% to 14% of the change in pain. Pain and fatigue most probably decrease simultaneously during CBT. Pain reduction can partly be explained by a reduction of symptom focusing and increased physical functioning. Additional, yet unknown cognitive-behavioral factors also play a role in the reduction of pain.


Imaging findings in a neglected case of chronic otitis media.
Intracranial complications of otitis media are associated with high mortality. Persistent otalgia or otorrhea while on oral antibiotics with associated neurological symptoms are ominous signs suggestive of a complication. A high index of suspicion and early diagnosis with radioimaging are essential for better outcome in these patients. We report a neglected case of chronic otitis media and discuss the magnetic resonance imaging findings.


Robust Treatment Planning in Intrafraction Motion Using TomoDirect™ Intensity-modulated Radiotherapy for Breast Cancer.
To evaluate the robustness of radiotherapy treatment planning optimization for respiratory-moving breast cancer using fixed-angle beams planning TomoDirect™ intensity-modulated radiotherapy (IMRT). A minimax optimisation algorithm was applied to 10 breast cancer patients. Two sets of treatment plans with or without robust techniques were prepared considering anterior-posterior and head-tail movements due to respiration. Parameters were compared between treatment plans: 95% planned target volume (PTV) dose, conformal index and homogeneity index (HI), and organs at risk (OAR) parameters including the lung volume receiving 20 Gy or more (V20) and 5 Gy (V5). Robust planning significantly improved parameters of 95% PTV dose and HI, without deteriorating V20 or V5 in the anterior-posterior movement, while it slightly improved 95% PTV and slightly deteriorated V20 in the head-tail movement. Robust treatment planning improves coverage of targets moving because of respiration in the treatment of breast cancer using TomoDirect; however, normal lung doses should be cautiously evaluated on a case-by-case basis.


Enteropathogenic Escherichia coli infection triggers host phospholipid metabolism perturbations.
Enteropathogenic Escherichia coli (EPEC) specifically recognizes phosphatidylethanolamine (PE) on the outer leaflet of host epithelial cells. EPEC also induces apoptosis in epithelial cells, which results in increased levels of outer leaflet PE and increased bacterial binding. Consequently, it is of interest to investigate whether EPEC infection perturbs host cell phospholipid metabolism and whether the changes play a role in the apoptotic signaling. Our findings indicate that EPEC infection results in a significant increase in the epithelial cell PE level and a corresponding decrease in the phosphatidylcholine (PC) level. PE synthesis via both the de novo pathway and the serine decarboxylation pathway was enhanced, and de novo synthesis of phosphatidylcholine via CDP-choline was reduced. The changes were transitory, and the maximum change was noted after 4 to 5 h of infection. Addition of exogenous PC or CDP-choline to epithelial cells prior to infection abrogated EPEC-induced apoptosis, suggesting that EPEC infection inhibits the CTP-phosphocholine cytidylyltransferase step in PC synthesis, which is reportedly inhibited during nonmicrobially induced apoptosis. On the other hand, incorporation of exogenous PE by the host cells enhanced EPEC-induced apoptosis and necrosis without increasing bacterial adhesion. This is the first report that pathogen-induced apoptosis is associated with significant changes in PE and PC metabolism, and the results suggest that EPEC adhesion to a host membrane phospholipid plays a role in disruption of host phospholipid metabolism.


Cognitive function in patients undergoing cystectomy for bladder cancer - results from a prospective observational study.
Impaired cognitive function of bladder cancer patients plays a role in coping with the kind of urinary diversion and may impact perioperative morbidity. In this study we therefore aimed to assess the prevalence of mild cognitive impairment in patients undergoing radical cystectomy. Secondary objectives included correlation of common cognition tests, assessment of the admitting physician, and perioperative complication rates. Patients undergoing radical cystectomy for bladder cancer were prospectively screened by neuropsychological tests including cognition tests [DemTect (Dementia Detection test), MMSE (Mini-Mental State Examination), clock drawing test] prior to surgery. Besides, clinical characteristics and perioperative outcomes were documented. Frequency of mild cognitive impairment as assessed by DemTect was correlated with the results of MMSE and clock drawing test, the occurrence of anxiety and depression, the assessment of the admitting physician, and perioperative complication rates as calculated by Spearman rank correlation coefficient. Comparative analysis (parametric and nonparametric) of patient characteristics (nonpathological versus pathological DemTect suggestive of mild cognitive impairment) was performed. A total of 51 patients (80% male, median age 69 years) were analyzed. DemTect was suspicious of mild cognitive impairment in 27% (14/51) of patients, whereas MMSE and clock drawing test showed pathological results only in 10/51 and 6/51 patients, respectively. We found no correlation between mild cognitive impairment and anxiety/depression status. In all, 5/20 patients (25%) with suspicious DemTect results were considered suitable for a continent diversion neobladder by the admitting physician. Suspicious DemTect results were predictive for higher perioperative complication rates (29% versus 5%). Study limitations include small sample size and missing long-term follow-up. Mild cognitive impairment was observed in more than a quarter of radical cystectomy patients prior to surgery. Preoperative assessment should be supplemented by neuropsychological testing such as the DemTect as mild cognitive impairment is often underestimated and associated with significantly higher perioperative complication rates.


A New Approach to Predict Tributary Phosphorus Loads Using Machine Learning- and Physics-Based Modeling Systems.
Tributary phosphorus (P) loads are one of the main drivers of eutrophication problems in freshwater lakes. Being able to predict P loads can aid in understanding subsequent load patterns and elucidate potential degraded water quality conditions in downstream surface waters. We demonstrate the development and performance of an integrated multimedia modeling system that uses machine learning (ML) to assess and predict monthly total P (TP) and dissolved reactive P (DRP) loads. Meteorological variables from the Weather Research and Forecasting (WRF) Model, hydrologic variables from the Variable Infiltration Capacity model, and agricultural management practice variables from the Environmental Policy Integrated Climate agroecosystem model are utilized to train the ML models to predict P loads. Our study presents a new modeling methodology using as testbeds the Maumee, Sandusky, Portage, and Raisin watersheds, which discharge into Lake Erie and contribute to significant P loads to the lake. Two models were built, one for TP loads using 10 environmental variables and one for DRP loads using nine environmental variables. Both models ranked streamflow as the most important predictive variable. In comparison with observations, TP and DRP loads were predicted very well temporally and spatially. Modeling results of TP loads are within the ranges of those obtained from other studies and on some occasions more accurate. Modeling results of DRP loads exceed performance measures from other studies. We explore the ability of both ML-based models to further improve as more data become available over time. This integrated multimedia approach is recommended for studying other freshwater systems and water quality variables using available decadal data from physics-based model simulations.


[Successful treatment of locally advanced squamous cell carcinoma of the esophagus by combination chemotherapy with 5-fluorouracil plus nedaplatin following tracheal stent tube placement-a case report].
The patient was a 68-year-old man who complained of hoarseness and dyspnea. Upper gastrointestinal endoscopy revealed a type 3 tumor located in the middle thoracic esophagus at 30 cm from the incisor tooth that involved one-fourth of the circumference of the esophagus. Histopathological examination revealed moderately differentiated squamous cell carcinoma. Chest computed tomography( CT) revealed severe tracheal stenosis due to compression by a metastatic lymph node along the left recurrent laryngeal nerve. The patient was diagnosed as having cT4( 106recL-trachea), N2( 101L, 106recL, 106recR), M0, Stage IVa unresectable esophageal carcinoma. After insertion of a tracheal stent tube( spiral Z stent: diameter, 18 mm; length, 80 mm) to improve dyspnea, combination chemotherapy with 5-fluorouracil( 5-FU) plus nedaplatin was administered. Subsequent CT and endoscopy showed that the main tumor and the metastatic lymph node had significantly reduced in size and that complete response (CR) had been achieved. Thirty months after the initial treatment, the patient showed no sign of disease recurrence, after completion of 19 cycles of chemotherapy. The patient did not experience any severe adverse events. We report a case of a patient with locally advanced squamous cell carcinoma of the esophagus successfully treated with 5-FU/nedaplatin combination chemotherapy following tracheal stent tube placement.


Coronary Computed Tomographic Angiography in the Evaluation of Liver Transplant Candidates.
The feasibility, safety, and value of coronary computed tomographic angiography (CCTA) in evaluating orthotopic liver transplant (OLT) candidates are unknown. We studied a cohort of consecutive OLT candidates with intermediate-to-high risk of coronary artery disease (CAD). Intermediate risk candidates received CCTA, and those at high risk or with abnormal noninvasive testing underwent invasive coronary angiography (ICA). One hundred consecutive patients were evaluated. Fifty patients underwent a CCTA, 71.4% were β-blocked, the image quality was "good" or "excellent" in 71.4% of cases, and there was no event of significant contrast-induced nephropathy. Twenty (20%) patients were found to have severe CAD (≥70% stenosis) by CCTA and/or ICA. Independent predictors of severe CAD were age (odds ratio [OR] = 5.4 per 10-year increment, 95% confidence interval [CI] = 1.7-17.0; P = .004), dyslipidemia (OR = 12.3, 95% CI = 2.6-57.6; P = .001), and chest pain (OR = 6.0, 95% CI = 1.2-29.1; P = .03). Implementing CCTA in the evaluation of intermediate/high CAD risk OLT candidates is challenging but feasible and seems safe.


[PERIOPERATIVE MANAGEMENT IN PATIENTS WITH DISEASES OF THE CARDIOVASGULAR Yb I am IN NON-CARDIAC SURGERY (Commentary on the new European guidelines "Non-cardiac surgery: evaluation and management of cardiovascular system")].
New guidelines for the perioperative management of patients with concomitant diseases of the cardiovascular system (CVS) have been published in the beginning of 2014. The guidelines were the result of joint work of the Board of experts of the European society of cardiology (ESC) and European society of anaesthesiology (ESA). Recommendations ESC/ESA-2014 thoroughly and accurately determine the algorithm of actions of the anaesthesiologist in the process of preparation and conduct of anesthesia and intensive therapy in the early postoperative period in accordance with the modern level of development of our specialty. No doubt they will be useful to all professionals involved in the process of providing medical care to patients in non-cardiac surgery with concomitant diseases of the cardiovascular system. This article, however, does not purport to be a complete summary of the cited document; it only contains, its own commentary on those provisions which are in the author's opinion the most significant and interesting.