Sustained Reduction in Time to Data Entry in the Cystic Fibrosis Foundation Registry.
Timely data entry into patient registries is foundational to learning health systems such as the Cystic Fibrosis Learning Network. The US Cystic Fibrosis Foundation Patient Registry (CFFPR) is an established registry that collects encounter data for clinical and research activities. Coordinators manually enter approximately 1,500 encounters annually at our institution, but there is limited evidence for interventions facilitating timely data entry. Our institution aimed to reduce the number of days between a clinical encounter and data entry into the CFFPR from an average of 43 days (range 0 to 183 days) to less than 30 days in a 3-month interval. Data coordinators tested interventions to address barriers in four themes: accountability, work burden, communication, and visibility using plan-do-study-act cycles. We used statistical process control charts to assess progress on average time of entry. Coordinators provided feedback about acceptability and satisfaction for process changes. Initial interventions standardized process and reduced average time to data entry from 42.6 to 22.5 days in 3 months, but this process was not stable in the subsequent 6 months. Subsequent changes to increase metric visibility and improve team communication increased stability and decreased the average time to data entry to 23.0 days. Coordinators reported high satisfaction with process changes and have sustained improved time for over 2 years. This quality improvement project reduced and maintained data entry time by addressing significant barriers without additional personnel. Increased access to near real-time data in CFFPR accelerates learning for clinical care, quality improvement, and research.


Cross-species queries of large gene expression databases.
Expression databases, including the Gene Expression Omnibus and ArrayExpress, have experienced significant growth over the past decade and now hold hundreds of thousands of arrays from multiple species. Since most drugs are initially tested on model organisms, the ability to compare expression experiments across species may help identify pathways that are activated in a similar way in humans and other organisms. However, while several methods exist for finding co-expressed genes in the same species as a query gene, looking at co-expression of homologs or arbitrary genes in other species is challenging. Unlike sequence, which is static, expression is dynamic and changes between tissues, conditions and time. Thus, to carry out cross-species analysis using these databases, we need methods that can match experiments in one species with experiments in another species. To facilitate queries in large databases, we developed a new method for comparing expression experiments from different species. We define a distance metric between the ranking of orthologous genes in the two species. We show how to solve an optimization problem for learning the parameters of this function using a training dataset of known similar expression experiments pairs. The function we learn outperforms previous methods and simpler rank comparison methods that have been used in the past for single species analysis. We used our method to compare millions of array pairs from mouse and human expression experiments. The resulting matches can be used to find functionally related genes, to hypothesize about biological response mechanisms and to highlight conditions and diseases that are activating similar pathways in both species. Supporting methods, results and a Matlab implementation are available from http://sb.cs.cmu.edu/ExpQ/.


Evaluation of cationic liposome suitable for gene transfer into pregnant animals.
Cationic liposome-mediated in vivo gene transfer represents a promising approach for somatic gene therapy. To assess the most suitable liposome for gene delivery into a wide range of organs and fetuses in mice, we have explored several types of cationic liposomes conjugated with plasmid DNA carrying the beta-galactosidase gene through intravenous injection into pregnant animals. Transduction efficiency was assessed by Southern blot analysis and expression of the transferred gene was evaluated by enzymatic demonstration of beta-galactosidase activity. Through the analysis of several types of recently synthesized cationic liposome/lipid formulations, DMRIE-C reagent, a liposome formulation of the cationic lipid DMRIE (1, 2-dimyristyloxypropyl-3-dimethyl-hydroxy ethyl ammonium bromide) and cholesterol in membrane-filtered water met our requirements. When the plasmid DNA/DMRIE-C complexes were administered intravenously into pregnant mice at day 11.5 post coitus (p.c.), transferred genes were observed in several organs in dams and were expressed. Furthermore, although the copy numbers transferred into embryos were low, we observed reporter gene expression in the progeny.


Prevalence of Vitamin D Deficiency Between Type 2 Diabetes Mellitus Patients and Non-Diabetics in the Arab Gulf.
The link between the risk of type 2 diabetes mellitus (T2DM) and vitamin D deficiency has perplexed the medical society due to the controversy in the data available. Saudi Arabia (SA) is a sunny region; however, ample amount of data reported the increased prevalence of vitamin D deficiency along with T2DM. Thus, this study aimed to compare vitamin D deficiency between healthy and T2DM patients in SA, alongside with the risk factors associated with that. A cross-sectional study was conducted in the Medical Unit, Taibah University in Al-Madinah Al-Munawarah, SA, from November 2017 to May 2018. The involved participants were non-diabetics and T2DM men. Measuring vitamin D for T2DM and non-diabetics group was done by trained technicians. Data analysis was done via SPSS. Sixty-four participants (T2DM group = 32; non-diabetics group = 32) were recruited, and the mean age of T2DM patients was 48.6 ± 10.4, while that of the non-diabetics was 42.4 ± 6.5. The mean of vitamin D level was found higher in the non-diabetic participants than in diabetic patients. There was statistically significant association between vitamin D deficiency and T2DM (P = 0.001). Besides, duration of diabetes was the only factor, found to be positively correlated with vitamin D deficiency in T2DM patients. Early screening for vitamin D serum-level is recommended for T2DM patients in Saudi Arabia. Therefore, early correction of vitamin D levels should be considered, and medical and scientific societies, along with other sectors such as the media, should highlight and increase the awareness of the importance of vitamin D and the seriousness of its deficiency.


Equilibration of molecules between two compartments through a nanochannel in the presence of osmolytes: a molecular dynamics simulation study.
Using molecular dynamics simulations, we study the equilibration of a system consisting of two nanoscale compartments connected by a carbon nanotube through which small mobile molecules can pass. The system is initially in a state where only one compartment is filled with molecules and the other is empty. When the molecules are allowed to move from the filled compartment to the empty one, the system starts equilibrating and finally reaches an equilibrium state where the molecules are distributed between the two compartments. In the absence of osmolytes, the equilibrium distribution of molecules is simply determined by the relative volumes of the compartments, but in the presence of osmolytes, the distribution is dependent on not only the relative compartment volumes but also the osmolyte properties. To systematically study the effect of osmolytes, we investigate how the number of osmolytes and the strength of the interaction between molecules and osmolytes affect the equilibrium state. Interestingly, we find that osmolytes strongly interacting with molecules can drain the initially filled compartment and induce the complete transfer of molecules to the initially empty compartment. We also study the kinetic and thermodynamic aspects of the equilibration processes.


Generation, validation, and utilization of a three-dimensional pharmacophore model for EP3 antagonists.
Studies reported here are aimed to investigate the important structural features that characterize the human EP(3) antagonists. Based on the knowledge of low-energy conformation of the endogenous ligand, the initial hit analogs were prepared. Subsequently, a ligand-based lead optimization approach using pharmacophore model generation was utilized. A 5-point pharmacophore using a training set of 19 compounds spanning the IC(50) data over 4-log order was constructed using the HypoGen module of Catalyst. Following pharmacophore customization, using a linear structure-activity regression equation, a six feature three-dimensional predictive pharmacophore model, P6, was built, which resulted in improved predictive power. The P6 model was validated using a test set of 11 compounds providing a correlation coefficient (R(2)) of 0.90 for predictive versus experimental EP(3) IC(50) values. This pharmacophore model has been expanded to include diverse chemotypes, and the predictive ability of the customized pharmacophore has been tested.


Cherenkov phase matched THz-wave generation with surfing configuration for bulk lithium nobate crystal.
We demonstrated a Cherenkov phase matched THz-wave generation with surfing configuration for bulk lithium niobate crystal. THz-wave output was enhanced about 50 times by suppressing phase mismatching for THz-wave propagation direction. The suppression was achieved by combining two pumping waves with dual wavelength with finite angle, and THz-frequency was controllable by changing the angle within 2.5 degrees range. Higher frequency THz-wave generation at around 4.0 THz was successfully obtained by the method.


The impact of physiological stimuli on the expression of corticotropin-releasing hormone (CRH) and other neuropeptide genes.
The article reviews some of the recent work showing how physiological stimuli act to alter neuropeptide gene expression. It describes how neural and humoral factors activated by physiological stimuli interact with the mechanisms regulating neuropeptide gene expression in neurons with either vascular (neurosecretory) or cellular (centrally directed) synapses. Although the focus will be on corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus, comparisons will be made between this neurosecretory cell group and others that express this gene. The regulation of neuropeptide genes colocalized in neurons that synthesize CRH is also considered. The review begins with a brief historical introduction, placing peptides in the overall functional perspective of neurosecretory and centrally directed neurons. It then describes studies using in vitro preparations that reveal details of the signal transduction mechanisms responsible for altering the expression of neuropeptide genes. For the CRH gene they are providing the foundations for future work on how physiological stimuli alter mRNA levels in the whole animal. Physiological stimuli provide a very broad range of signals to neuropeptide neurons commensurate with the wide variety of motor responses they initiate. One important humoral signal impacting neuropeptide neurons is plasma corticosterone, and many workers have addressed this aspect of its function. Corticosterone appears capable of interacting with at least two different neuronal mechanisms to regulate CRH mRNA levels: one is clearly seen in paraventricular neurosecretory neurons, where increasing plasma corticosteroid reduces CRH mRNA levels; the other, seen in neurons in the central nucleus of the amygdala, acts to increase them. Since physiological stimuli present a complex mixture of humoral and neural signals to the CNS, integration of these two signal types is a critical aspect of peptide metabolism that requires detailed attention. Studies that are beginning to address this important question are described. Circadian influences play an important role in organizing homeostatic processes, and their influence on CRH gene expression is considered. The viscerosensory-motor integration associated with dehydration offers a useful model for investigating the role of peptides in neuronal function and motor architecture. Much of our work has concentrated on how peptide genes are regulated by alterations to fluid homeostasis, and these studies, along with those of other investigators, are described in this integrative context. Finally, consideration is given to the many studies that have addressed the impact of nonviscerosensory stimulation on neuropeptide gene expression.


Resistance Training Behavior Is Enhanced With Digital Behavior Change Coaching: A Randomized Controlled Trial With Novice Adults.
Approximately a third of US adults meet the physical activity guidelines of engaging in resistance training 2 times per week, yet few studies have examined how to increase participation rates. The present randomized control trial compared a remotely delivered coaching intervention with an education only control group. Eligible participants completed 2 remotely delivered Zoom-based personal training sessions during a 1-week run-in period. Participants randomized to the intervention group received synchronous weekly behavioral video coaching sessions over Zoom, whereas the control group received no further contact. Days of resistance training completed were assessed at baseline (pre), 4 weeks (post), and 8 weeks (follow-up). Linear mixed models were used to examine group differences at each time point and within-group differences over time. There were significant between-group differences favoring the intervention, at posttest for both the previous week (b = 0.71, SE = 0.23; P = .002) and the previous 4 weeks (b = 2.54, SE = 0.87; P = .003) but not at the follow-up period for either the last week (b = 0.15, SE = 0.23; P = .520) or the last 4 weeks (b = 0.68, SE = 0.88; P = .443). The present study showed that by providing participants with equipment, skill, and in the case of the intervention group, a remote coaching intervention, resistance training participation increased.


Twenty-year follow-up: an unusual case of nephropathy of antiphospholipid syndrome.
Nephropathy of antiphospholipid antibody syndrome (NAPS) is an increasingly well-recognized aspect of antiphospholipid syndrome. The most characteristic histopathology is that of thrombotic microangiopathy, and thrombosis occurring in the renal vasculature is thought to be the initiating event. Other less common pathologies have been reported, and the mechanisms of these are unclear. Therapy has been largely empiric. We report a case of NAPS in a patient with atypical pathology, who has declined therapy with immunosuppressive agents and anticoagulants and who has maintained normal renal function in 20 years of follow-up.


[Analysis of direct results of mitral valve annuloplasty].
In the present-day cardiosurgery there is no doubt that in case of possible plastic operation on the mitral valve the latter must be preserved. In the current literature there are no investigations which could convincingly prove advantages of any single group of techniques of constriction of the fibrous ring when performing mitral reconstructions. The aim of the work was to compare the direct results of reconstructive operations on the mitral valve with the using of three different means of constriction of the fibrous ring. It was found that all the three types of plasty of the mitral valve fibrous ring gave good direct results. Nevertheless an analysis of long-term results is necessary for the assessment of effectiveness of mitral reconstructions in the long-term postoperative period.


Ursodesoxycholic acid alleviates liver fibrosis via proregeneration by activation of the ID1-WNT2/HGF signaling pathway.
The human liver possesses a remarkable capacity for self-repair. However, liver fibrosis remains a serious medical concern, potentially progressing to end-stage liver cirrhosis and even death. Liver fibrosis is characterized by excess accumulation of extracellular matrix in response to chronic injury. Liver regenerative ability, a strong indicator of liver health, is important in resisting fibrosis. In this study, we provide evidence that ursodesoxycholic acid (UDCA) can alleviate liver fibrosis by promoting liver regeneration via activation of the ID1-WNT2/hepatocyte growth factor (HGF) pathway. Bile duct ligation (BDL) and partial hepatectomy (PH) mouse models were used to verify the effects of UDCA on liver fibrosis, regeneration, and the ID1-WNT2/HGF pathway. An Id1 knockdown mouse model was also used to assess the role of Id1 in UDCA alleviation of liver fibrosis. Our results demonstrate that UDCA can alleviate liver fibrosis in the BDL mice and promote liver regeneration via the ID1-WNT2/HGF pathway in PH mice. In addition, Id1 knockdown abolished the protection afforded by UDCA in BDL mice. We conclude that UDCA protects against liver fibrosis by proregeneration via activation of the ID1-WNT2/HGF pathway.


Genetic metabolic polymorphisms and the risk of cancer: a review of the literature.
Abstract The purpose of this paper is to systematically analyse the design and results of epidemiological studies on the association between various types of cancer (lung, bladder, breast, colon, stomach) and four genetically-based metabolic polymorphisms, involved in the metabolism of several carcinogens (glutathione-S-transferase M1, debrisoquine hydroxylase, N acetyltransferase, aryl hydrocarbon hydroxylase). These inherited polymorphisms usually cause modifications in the quality or quantity of the relevant enzymes. Such enzymes are involved in the activation/inactivation of known carcinogens and seem to modify the extent to which carcinogens interact with DNA in target tissues. Two enzymes, debrisoquine hydroxylase and aryl hydrocarbon hydroxylase, activate procarcinogens to carcinogens (phase I enzymes). The other two, glutathione-S-transferase M1 and N-acetyltransferase, mainly detoxity carcinogenic substances (phase II enzymes). Because of their role as host factors (modulating the action of carcinogens), it has been hypothesized that subjects presenting a specific phenotype for such polymorphisms could be at a greater risk of developing various types of cancer. A number of epidemiological studies have investigated such associations, often with discordant results. We examine and discuss the design of the studies, and present a meta-analysis of the available data.


Confinement-induced entropic recoil of single DNA molecules in a nanofluidic structure.
The behavior of DNA molecules is observed in a nanofluidic device near the interface of two regions that produce different configuration entropies. An electric field is applied to drive the molecules partway across the interface. Upon removal of the field, the molecules recoil to the higher-entropy region with a profile characteristic of a force localized to the interface and independent of length. This is consistent with a confinement-mediated entropic force, distinct from the well-known entropic elasticity common to all polymers. An estimate of the hydrodynamic drag is used to produce a lower bound for the force. The phenomenon can be exploited to separate long-strand polyelectrolytes according to length.


Relationship between conformational changes in pol lambda's active site upon binding incorrect nucleotides and mismatch incorporation rates.
The correct replication and repair of DNA is critical for a cell's survival. Here, we investigate the fidelity of mammalian DNA polymerase lambda (pol lambda) utilizing dynamics simulation of the enzyme bound to incorrect incoming nucleotides including A:C, A:G, A(syn):G, A:A, A(syn):A, and T:G, all of which exhibit differing incorporation rates for pol lambda as compared to A:T bound to pol lambda. The wide range of DNA motion and protein residue side-chain motions observed in the mismatched systems demonstrates distinct differences when compared to the reference (correct base pair) system. Notably, Arg517's interactions with the DNA template strand bases in the active site are more limited, and Arg517 displays increased interactions with the incorrect dNTPs. This effect suggests that Arg517 helps provide a base-checking mechanism to discriminate correct from incorrect dNTPs. In addition, we find Tyr505 and Phe506 also play key roles in this base checking. A survey of the electrostatic potential landscape of the active sites and concomitant changes in electrostatic interaction energy between Arg517 and the dNTPs reveals that pol lambda binds incorrect dNTPs less tightly than the correct dNTP. These trends lead us to propose the following order for mismatch insertion by pol lambda: A:C > A:G > A(syn):G > T:G > A(syn):A > A:A. This sequence agrees with available kinetic data for incorrect nucleotide insertion opposite template adenine, with the exception of T:G, which may be more sensitive to the insertion context.


Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues.
MUC2 and MUC3 are prominent mucin genes expressed in the human intestine. Using in situ hybridization with RNA probes, we examined the cellular distribution of MUC2 and MUC3 mRNA in normal, malignant, and inflammatory human intestinal tissues. In normal small intestine and colon, MUC2 mRNA was expressed exclusively in goblet cells and occurred throughout the entire height of the mucosa. MUC3 mRNA was expressed by goblet and columnar cells but was restricted to the villous compartment of the small intestine and the surface epithelium of the colon. Expression of MUC2 and MUC3 mRNA were both markedly decreased in poorly, moderately, and well-differentiated colon cancers but were preserved in mucinous colon cancers. In ulcerative colitis and Crohn's colitis tissues, MUC2 and MUC3 mRNA expression displayed a normal pattern regardless of whether the mucosa manifested active or quiescent inflammation. These findings indicate that MUC2 is goblet cell-specific, whereas MUC3 is related to maturation of intestinal epithelial cells. In colon cancers, the genetic regulation of MUC2 and MUC3 is different depending on the histological type of tumor. The constitutive expression of MUC2 and MUC3 mRNA in inflammatory bowel diseases suggests that these genes may be necessary for maintenance of normal epithelial cell function during inflammation.


Biomechanical analysis of lumbar nonfusion dynamic stabilization using a pedicle screw-based dynamic stabilizer or an interspinous process spacer.
This study aimed to investigate and compare the effects of two widely used nonfusion posterior dynamic stabilization (NPDS) devices, pedicle screw-based dynamic stabilizer (PSDS) and interspinous process spacer (IPS), on biomechanics of the implanted lumbar spine under static and vibration loadings. The finite element model of healthy human lumbosacral segment was modified to incorporate NPDS device insertion at L4-L5 segment. Bioflex and DIAM were used as PSDS-based and IPS-based NPDS devices, respectively. As a comparison, lumbar interbody fusion with rigid stabilization was also simulated at L4-L5. For static loading, segmental range of motion (ROM) of the models under moments of four physiological motions was computed using hybrid testing protocol. For vibration loading, resonant modes and dynamic stress of the models under vertical excitation were extracted through random response analysis. The results showed that compared with the rigid fusion model, ROM of the nonfusion models was higher at L4-L5 level but lower at adjacent levels (L1- L2, L2-L3, L3-L4, L5-S1). Compared with the Bioflex model, the DIAM model produced higher ROM at L4-L5 level but lower ROM at adjacent levels, especially under lateral bending and axial rotation; resonant frequency of the DIAM model was slightly lower; dynamic response of nucleus stress at L4-L5 level was slightly higher for the DIAM model, and the dynamic stress at adjacent levels was no obvious difference between the nonfusion models. This study reveals biomechanical differences between the Bioflex and DIAM systems, which may provide references for selecting surgical approaches in clinical practice.


Unveiling the Modulating Role of Extracellular pH in Permeation and Accumulation of Small Molecules in Subcellular Compartments of Gram-negative Escherichia coli using Nonlinear Spectroscopy.
Quantitative evaluation of small molecule permeation and accumulation in Gram-negative bacteria is important for drug development against these bacteria. While these measurements are commonly performed at physiological pH, Escherichia coli and many other Enterobacteriaceae infect human gastrointestinal and urinary tracts, where they encounter different pH conditions. To understand how external pH affects permeation and accumulation of small molecules in E. coli cells, we apply second harmonic generation (SHG) spectroscopy using SHG-active antimicrobial compound malachite green as the probe molecule. Using SHG, we quantify periplasmic and cytoplasmic accumulations separately in live E. coli cells, which was never done before. Compartment-wise measurements reveal accumulation of the probe molecule in cytoplasm at physiological and alkaline pH, while entrapment in periplasm at weakly acidic pH and retention in external solution at highly acidic pH. Behind such disparity in localizations, up to 2 orders of magnitude reduction in permeability across the inner membrane at weakly acidic pH and outer membrane at highly acidic pH are found to play key roles. Our results unequivocally demonstrate the control of external pH over entry and compartment-wise distribution of small molecules in E. coli cells, which is a vital information and should be taken into account in antibiotic screening against E. coli and other Enterobacteriaceae members. In addition, our results demonstrate the ability of malachite green as an excellent SHG-indicator of changes of individual cell membrane and periplasm properties of live E. coli cells in response to external pH change from acidic to alkaline. This finding, too, has great importance, as there is barely any other molecular probe that can provide similar information.


The etiology of acute hepatitis in adults in Egypt.
The causes of acute hepatitis were prospectively studied in 141 patients admitted to Embaba Fever Hospital, Cairo, Egypt in 1983. Serologic diagnosis showed: hepatitis A (0.7%), hepatitis B (46.8%), dual infections with A and B (1.4%), acute hepatitis in HBsAg carriers (14.2%), drug induced hepatitis (5.7%), and hepatitis non-A non-B (NANB) (31.2%). Among hepatitis B patients tested for the following seromarkers, 40% had HBeAg, 8% anti-delta antibody, and 6 simultaneous presence of HBsAg and anti-HBs; in convalescence, a 9% HBsAg carrier rate was found. Clinical, epidemiological, and biochemical findings did not distinguish one cause of hepatitis from another. For 32% of NANB patients parenteral injection was a likely source of infection.


Should helicopter frequent flyers wear head protection? A study of helmet effectiveness.
Flight helmets have been recommended as aircrew head protection since 1908, yet debate continues regarding their effectiveness. Estimates of helmet use in civilian helicopter aeromedical programs range from 6.5% to 13%. The effectiveness of the Army's SPH-4 flight helmet in reducing severe head injuries sustained during helicopter accidents was evaluated using the accident data base at the US Army Safety Center, Fort Rucker, Alabama. Analysis was restricted to severe (Class A) accidents that were at least partially survivable, using US Army Safety Center criteria. Occupants not wearing a protective helmet were significantly more likely to sustain severe and fatal head injuries than were occupants wearing the SPH-4 (RR = 3.8 and 6.3, respectively; P less than .01). Unhelmeted noncockpit occupants were at higher risk of head injuries (RR = 5.3 and 7.5; P less than .01). All personnel regularly participating in helicopter flight, civilian or military, should be equipped with protective headgear.


Toad urinary bladder: intercellular spaces.
Vasopressin causes dilation of the intercellular spaces of the mucosal epithelium in toad bladder, an effect previously thought to result from enhanced net transepithelial water transport. Under conditions of zero net fluid transport, vasopressin exerted the same effect in seven tissues, which indicates that the width of the intercellular spaces cannot be taken as a reliable index of net transepithelial fluid transport.


Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA: a pilot study.
To develop and evaluate a procedure for quantifying the hepatocyte-specific uptake of Gd-BOPTA and Gd-EOB-DTPA using dynamic contrast-enhanced (DCE) MRI. Ten healthy volunteers were prospectively recruited and 21 patients with suspected hepatobiliary disease were retrospectively evaluated. All subjects were examined with DCE-MRI using 0.025 mmol/kg of Gd-EOB-DTPA. The healthy volunteers underwent an additional examination using 0.05 mmol/kg of Gd-BOPTA. The signal intensities (SI) of liver and spleen parenchyma were obtained from unenhanced and enhanced acquisitions. Using pharmacokinetic models of the liver and spleen, and an SI rescaling procedure, a hepatic uptake rate, K (Hep), estimate was derived. The K (Hep) values for Gd-EOB-DTPA were then studied in relation to those for Gd-BOPTA and to a clinical classification of the patient's hepatobiliary dysfunction. K (Hep) estimated using Gd-EOB-DTPA showed a significant Pearson correlation with K (Hep) estimated using Gd-BOPTA (r = 0.64; P < 0.05) in healthy subjects. Patients with impaired hepatobiliary function had significantly lower K (Hep) than patients with normal hepatobiliary function (K (Hep) = 0.09 ± 0.05 min(-1) versus K (Hep) = 0.24 ± 0.10 min(-1); P < 0.01). A new procedure for quantifying the hepatocyte-specific uptake of T (1)-enhancing contrast agent was demonstrated and used to show that impaired hepatobiliary function severely influences the hepatic uptake of Gd-EOB-DTPA. • The liver uptake of contrast agents may be measured with standard clinical MRI. • Calculation of liver contrast agent uptake is improved by considering splenic uptake. • Liver function affects the uptake of the liver-specific contrast agent Gd-EOB-DTPA. • Hepatic uptake of two contrast agents (Gd-EOB-DTPA, Gd-BOPTA) is correlated in healthy individuals. • This method can be useful for determining liver function, e.g. before hepatic surgery.


Prognostic value of left atrial size in hypertensive African Americans undergoing stress echocardiography.
Left atrial (LA) enlargement is a marker of increased risk in the general population undergoing stress echocardiography. African American (AA) patients with hypertension are known to have less atrial remodeling than whites with hypertension. The prognostic impact of LA enlargement in AA with hypertension undergoing stress echocardiography is uncertain. To investigate the prognostic value of LA size in hypertensive AA patients undergoing stress echocardiography. This retrospective outcomes study enrolled 583 consecutive hypertensive AA patients who underwent stress echocardiography over a 2.5-year period. Clinical characteristics including cardiovascular risk factors, stress and echocardiographic data were collected from the electronic health record of a large community hospital. Treadmill exercise and Dobutamine protocols were conducted based on standard practices. Patients were followed for all-cause mortality. The optimal cutoff value of antero-posterior LA diameter for mortality was assessed by receiver operating characteristic analysis. Cox regression was used to determine variables associated with outcome. The mean age was 57 ± 12 years. LA dilatation was present in 9% (54) of patients (LA anteroposterior ≥ 2.4 cm/m2). There were 85 deaths (15%) during 4.5 ± 1.7 years of follow-up. LA diameter indexed for body surface area had an area under the curve of 0.72 ± 0.03 (optimal cut-point of 2.05 cm/m2). Variables independently associated with mortality included age [P = 0.004, hazard ratio (HR) 1.34 (1.10-1.64)], tobacco use [P = 0.001, HR 2.59 (1.51-4.44)], left ventricular hypertrophy [P = 0.001 , HR 2.14 (1.35-3.39)], Dobutamine stress [P = 0.003, HR 2.12 (1.29-3.47)], heart failure history [P = 0.031, HR 1.76 (1.05-2.94)], LA diameter ≥ 2.05 cm/m2 [P = 0.027, HR 1.73 (1.06-2.82)], and an abnormal stress echocardiogram [P = 0.033, HR 1.67 (1.04-2.68)]. LA diameter as a continuous variable was also independently associated with mortality but LA size ≥ 2.40 cm/m2 was not. LA enlargement is infrequent in hypertensive AA patients when traditional reference values are used. LA enlargement is independently associated with mortality when a lower than "normal" threshold (≥ 2.05 cm/m2) is used.


Effect of subunit III removal on control of cytochrome c oxidase activity by pH.
Studies were undertaken to assess the postulated involvement of subunit III in the proton-linked functions of cytochrome c oxidase. The effect of pH on the steady-state kinetic [corrected] parameters of subunit III containing and subunit III depleted cytochrome oxidase was determined by using beef heart and rat liver enzymes reconstituted into phospholipid vesicles. The TNmax and Km values for the III-containing enzyme increase with decreasing pH in a manner quantitatively similar to that reported by Thornstrom et al. [(1984) Chem. Scr. 24, 230-235], giving three apparent pKa values of less than 5.0, 6.2, and 7.8. The maximal activities of the subunit III depleted enzymes (beef heart and rat liver) show a similar dependence on pH, but the Km values are consistently higher than those of the III-containing enzyme, an effect that is accentuated at low pH. The pH dependence of TNmax/Km for both forms of the enzyme (+/- subunit III) indicates that protonation of a group with an apparent pKa of 5.7 lowers the affinity for substrate (cytochrome c) independently of a continued increase in maximal velocity. N,N'-Dicyclohexylcarbodiimide (DCCD) decreases the pH responsiveness of the electron-transfer activity to the same extent in both III-containing and III-depleted enzymes, indicating that this effect is mediated by a peptide other than subunit III. Control of intramolecular electron transfer by a transmembrane pH gradient (or alkaline intravesicular pH) is shown to occur in cytochrome oxidase vesicles with cytochrome c as the electron donor, in agreement with results of Moroney et al. [(1984) Biochemistry 23, 4991-4997] using hexaammineruthenium(II) as the reductant.(ABSTRACT TRUNCATED AT 250 WORDS)


[Brain function and level of consciousness in fentanyl anesthesia in heart surgery].
The level of consciousness and the supply/demand ratio of oxygen in the brain was studied in anaesthetized patients undergoing open heart surgery. Anaesthesia was accomplished with intravenous fentanyl; 26 patients received 25 micrograms/kg and 24 patients received 50 micrograms/kg fentanyl. In addition only pancuronium bromide was administered for muscular relaxation; all patients were ventilated with 100% oxygen. The following measurements were made during induction and prior to cardiopulmonary bypass and in the first ten minutes of bypass: 1. EEG with the Klein EEG Analyzer. This instrument permits simultaneous analysis of frequency and amplitude while eliminating muscular artifacts. 2. Cerebral oxygen with the Niroscope. This instrument uses an infrared light beam through the brain to evaluate cerebral oxygen sufficiency. 3. Oxygen supply/demand ratio in the whole body, estimated from mixed venous oxygen saturation measured with a fiberoptic pulmonary artery catheter. Clinical unconsciousness occurred in all patients within about 30 s after the administration of fentanyl. Simultaneously the EEG showed a significant decrease in frequency and an increase in amplitude. With the Niroscope no change in oxygen supply and demand was seen in any patients. This is in contrast to previous studies with thiopental, where changes were seen. A slight increase in mixed venous oxygen saturation was observed. This indicates an increase in the total oxygen supply/demand ratio, probably due to decreased muscle metabolism induced by pancuronium bromide paralysis. From the end of induction until cardiopulmonary bypass a slight increase in cerebral electrical activity was observed; an additional increase occurred in the first ten minutes of bypass.(ABSTRACT TRUNCATED AT 250 WORDS)


Applications of microwave-assisted organic synthesis on the multigram scale.
This review presents a summary of reactions performed using microwave irradiation on a multigram scale. Results are described in the context of existing equipment, and equipment currently in development, for the processing of multigram to kilogram quantities of materials including single- and multimode microwave reactors and batch, batch-flow and continuous-flow systems. Although limited in number, reports found in the literature to date suggest that with appropriate controls, reproducible scale-up of microwave reactions is feasible and requires minimal re-optimization of laboratory-scale reaction conditions. This feature, along with the dramatic reductions in reaction time generally observed for microwave reactions suggests that application of this technology in process research could be beneficial.


Harmonizing controls for chemicals and radionuclides.
Risk harmonization means more than harmonizing the way that the risk from ionizing radiation is managed by regulatory agencies. It also means bringing a common language and approach to the management of all environmental carcinogens. If this goal is accomplished, it can result in better communication between radiation and chemical risk managers and a better informed public. If the public understands that there is consistency and coherence in how risks are managed, they are more likely to accept risk management decisions.


Effects of Tyroserleutide on phosphatidylinositol 3'-kinase/AKT pathway in human hepatocellular carcinoma cell.
Tyroserleutide (YSL) is an active, low-molecular-weight polypeptide with in vitro and in vivo anticancer effects on human hepatocellular carcinoma BEL-7402 cells. In this study, we studied the effects of YSL on PI3K/AKT in the BEL-7402 cells to explore its anti-tumor mechanism. Results showed that YSL could up-regulate the mRNA and protein expression of tumor suppressor PTEN and increase their activities, meanwhile inhibited the mRNA and protein expression of oncogene AKT and decreased the kinase activities of AKT and PDK1. The resuming balance effect of YSL between PTEN and AKT could prevent the transmission of tumor cell proliferation signals in the PI3K/AKT pathway. Inhibition of AKT would change the status of downstream effectors in the PI3K/AKT pathway: (1) inhibition of AKT up-regulated expression of cell cycle regulatory factors of downstream - P21 and P27 which repressed cell cycle and inhibited proliferation of tumor cells. (2) Inhibition of AKT decreased the phosphorylation level of MDM2, and then increased the protein level of P53 which would accelerate death proceeding of tumor cells. (3) Inactivation of AKT removed its inhibition effect on phosphorylation of Bad, which might decrease protein level of apoptosis inhibitor Bcl-2 and Bcl-XL, damaging mitochondria of tumor cells and inducing apoptosis.


Plasmonic photothermal properties of silver nanoparticle grating films.
The plasmon-induced photothermal effect offers effective light-to-heat conversion systems. In this study, we fabricate plasmonic photothermal silver nanoparticle (AgNP) grating films to produce highly effective plasmon-induced heat generation films. AgNP films provide effective heat generation by localized surface plasmon excitation in the void of the AgNP films. The heat generated at a AgNP film by irradiation of solar light is 3.4 times higher than that generated at the reference flat evaporated-Ag film. Furthermore, simultaneous excitation of localized surface plasmons and propagating surface plasmons is confirmed to be obtained on AgNP grating films by finite-difference time-domain simulation and reflectivity measurements. The AgNP grating film is created by the nanoimprinting technique. The grating structure on AgNPs further enhances electric field intensity in the large area of the film, which results in higher heat generation. Thus, 5.4 times higher heat generation is achieved compared with that of the reference flat evaporated-Ag film.


Markers of inflammation and immune activation are associated with lung function in a multi-center cohort of persons with HIV.
Studies have shown that people with HIV (PWH) may be at increased risk for chronic lung diseases and lung function abnormalities, which may be associated with immune activation. We tested the association of a panel of 12 immune activation and inflammation biomarkers with spirometry and single-breath diffusing capacity for carbon monoxide (DLco). Cross-sectional, observational study. Participants were enrolled from the Inflammation, Aging, Microbes and Obstructive Lung Disease cohort of PWH at two US sites. Biomarkers were examined and standardized spirometry and DLco testing were performed. We tested associations between each biomarker and lung function, examined individually and in combination, using multi-variable linear and logistic regression. Among 199 participants, median forced expiratory volume in 1 s (FEV1) was normal (90% predicted) and median DLco was abnormal (69% predicted). The most common lung function abnormality (57%) was a normal FEV1 to forced vital capacity ratio with an abnormal DLco of 80% or less predicted (iso↓DLco). Two markers (IL-6, high-sensitivity C-reactive protein) were associated with FEV1% predicted, whereas eight markers (soluble CD14, soluble CD163, inducible protein-10, soluble CD27, IL-6, soluble tumor necrosis factor receptors 1 and 2, D-dimer) were associated with DLco% predicted. Compared with those participants with normal spirometry and DLco, five markers (soluble CD14, soluble CD163, interferon gamma inducible protein-10, soluble tumor necrosis factor receptors 1 and 2) were associated with iso↓DLco. Among PWH, different markers of immune activation and inflammation are associated with FEV1% predicted than with DLco% predicted and with an iso↓DLco, representing possible unique pathways of chronic lung disease. Identifying plausible drivers of these inflammatory pathways may clarify mechanisms underlying impaired lung function in HIV infection and may identify therapeutic avenues.


VIP induces in HT-29 cells 2'5'oligoadenylate synthetase and antiviral state via interferon beta/alpha synthesis.
Vasoactive intestinal peptide (VIP), composed of 28 amino acids, is a multifunctional neurotransmitter. We have demonstrated here that its action on human transformed colonic epithelial (HT-29) cells is mediated through the induction of interferon (IFN) synthesis. We have found that these cells have a functional receptor for IFN alpha 2; binding was specific to either IFN alpha 2 or IFN beta but not to IFN gamma. VIP induced the 2'5'oligoadenylate synthetase (2'5'A synthetase) and the antiviral state with the same efficiency as poly (I).poly (C). The induction of 2'5'A synthetase activity required cellular RNA and protein synthesis, and the maximum induction occurred with 10(-7) M VIP at 24 h. VIP, like some IFN inducers, induced the synthesis of the 70 hsp which, however, preceded the expression of 2'5'A synthetase. VIP treatment caused the induction and secretion of IFN, having a titer value of 32 international units/ml. This IFN has been identified as type beta/alpha, because both 2'5'A synthetase and the antiviral activities were abolished by anti-human IFN beta/alpha antibodies, but not by anti-IFN gamma antibodies. Thus the pathway of VIP action on HT-29 cells may be outlined as 1) binding of VIP, 2) synthesis of 70 hsp, 3) induction of IFN synthesis and its secretion, 4) binding of the secreted IFN to cell surface receptors and 5) turning on the induction of 2'5'A synthetase and antiviral activities.


Value of free-run electromyographic monitoring of lower cranial nerves in endoscopic endonasal approach to skull base surgeries.
Objective The main objective of this study was to evaluate the value of free-run electromyography (f-EMG) monitoring of cranial nerves (CNs) VII, IX, X, XI, and XII in skull base surgeries performed using endoscopic endonasal approach (EEA) to reduce iatrogenic CN deficits. Design We retrospectively identified 73 patients out of 990 patients who had EEA in our institution who had at least one CN monitored. In each CN group, we classified patients who had significant (SG) f-EMG activity as group I and those who did not as group II. Results We monitored a total of 342 CNs. A total of 62 nerves had SG f-EMG activity including CN VII = 18, CN IX = 16, CN X = 13, CN XI = 5, and CN XII = 10. No nerve deficit was found in the nerves that had significant activity during procedure. A total of five nerve deficits including (CN IX = 1, CN X = 2, CN XII = 2) were observed in the group that did not display SG f-EMG activity during surgery. Conclusions f-EMG seems highly sensitive to surgical manipulations and in locating CNs. It seems to have limited value in predicting postoperative neurological deficits. Future studies to evaluate the EMG of lower CNs during EEA procedures need to be done with both f-EMG and triggered EMG.


Perspectives of elder abuse in Lebanon.
Elder abuse is a preventable problem. Presently, little is known about this phenomenon in Middle Eastern settings. The purpose of this study was to explore elder abuse in Beirut, Lebanon from different stakeholders' points of view with a focus on identifying behaviors that are considered to be abusive to older adults and predisposing factors. Focus group discussions were carried out with 88 home- and institution-based older adults, their family members and caregivers, and with 49 stakeholders (medical professionals, institution directors, government officials). Results showed that behaviors considered abusive among Lebanese participants were comparable to reports from international studies. The most commonly mentioned risk factors were history of abuse in a seemingly dysfunctional family followed by caregivers' lack of acceptance of the physical changes that accompany aging. The response to elder abuse requires a multidimensional approach that spans protective policies to increase care providers' awareness about the physiologic changes of aging as well as concerted efforts to correct misinformation about the hidden problem of elder abuse.


Liver sinusoidal endothelial and biliary cell repopulation following irradiation and partial hepatectomy.
To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for non-parenchymal cell (NPC) transplantation. Livers of dipeptidyl peptidase IV (DPPIV)-deficient rats were pre-conditioned with external beam IR (25 Gy) delivered to two-thirds of the right liver lobules followed by a one-third PH of the untreated lobule. DPPIV-positive liver cells (NPC preparations enriched for liver sinusoidal endothelial cells (LSECs) and hepatocytes) were transplanted via the spleen into the recipient livers. The extent and quality of donor cell engraftment and growth was studied over a long-term interval of 16 wk after transplantation. Host liver staining demonstrated 3 different repopulation types. Well defined clusters of donor-derived hepatocytes with canalicular expression of DPPIV were detectable either adjacent to or in between large areas of donor cells (covering up to 90% of the section plane) co-expressing the endothelial marker platelet endothelial cell adhesion molecule. The third type consisted of formations of DPPIV-positive duct-like structures which co-localized with biliary epithelial CD49f. Liver IR and PH as a preconditioning stimulus enables multiple cell liver repopulation by donor hepatocytes, LSECs, and bile duct cells.


Effects of patient-specific treatment planning on eligibility for photodynamic therapy of deep tissue abscess cavities: retrospective Monte Carlo simulation study.
Antimicrobial photodynamic therapy (PDT) effectively kills bacterial strains found in deep tissue abscess cavities. PDT response hinges on multiple factors, including light dose, which depends on patient optical properties. Computed tomography images for 60 abscess drainage subjects were segmented and used for Monte Carlo (MC) simulation. We evaluated effects of optical properties and abscess morphology on PDT eligibility and generated treatment plans. A range of abscess wall absorptions (μa , wall) and intra-cavity Intralipid concentrations were simulated. At each combination, the threshold optical power and optimal Intralipid concentration were found for a fluence rate target, with subjects being eligible for PDT if the target was attainable with <2000 mW of source light. Further simulations were performed with absorption within the cavity (μa , cavity). Patient-specific treatment planning substantially increased the number of subjects expected to achieve an efficacious light dose for antimicrobial PDT, especially with Intralipid modification. The threshold optical power and optimal Intralipid concentration increased with increasing μa , wall (p < 0.001). PDT eligibility improved with patient-specific treatment planning (p < 0.0001). With μa , wall = 0.2 cm - 1, eligibility increased from 42% to 92%. Increasing μa , cavity reduced PDT eligibility (p < 0.0001); modifying the delivered optical power had the greatest impact in this case. MC-based treatment planning greatly increases eligibility for PDT of abscess cavities.


A cis-regulatory site downregulates PTHLH in translocation t(8;12)(q13;p11.2) and leads to Brachydactyly Type E.
Parathyroid hormone-like hormone (PTHLH) is an important chondrogenic regulator; however, the gene has not been directly linked to human disease. We studied a family with autosomal-dominant Brachydactyly Type E (BDE) and identified a t(8;12)(q13;p11.2) translocation with breakpoints (BPs) upstream of PTHLH on chromosome 12p11.2 and a disrupted KCNB2 on 8q13. We sequenced the BPs and identified a highly conserved Activator protein 1 (AP-1) motif on 12p11.2, together with a C-ets-1 motif translocated from 8q13. AP-1 and C-ets-1 bound in vitro and in vivo at the derivative chromosome 8 breakpoint [der(8) BP], but were differently enriched between the wild-type and BP allele. We differentiated fibroblasts from BDE patients into chondrogenic cells and found that PTHLH and its targets, ADAMTS-7 and ADAMTS-12 were downregulated along with impaired chondrogenic differentiation. We next used human and murine chondrocytes and observed that the AP-1 motif stimulated, whereas der(8) BP or C-ets-1 decreased, PTHLH promoter activity. These results are the first to identify a cis-directed PTHLH downregulation as primary cause of human chondrodysplasia.


A method of estimating inspiratory flow rate and volume from an inhaler using acoustic measurements.
Inhalers are devices employed to deliver medication to the airways in the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease. A dry powder inhaler (DPI) is a breath actuated inhaler that delivers medication in dry powder form. When used correctly, DPIs improve patients' clinical outcomes. However, some patients are unable to reach the peak inspiratory flow rate (PIFR) necessary to fully extract the medication. Presently clinicians have no reliable method of objectively measuring PIFR in inhalers. In this study, we propose a novel method of estimating PIFR and also the inspiratory capacity (IC) of patients' inhalations from a commonly used DPI, using acoustic measurements. With a recording device, the acoustic signal of 15 healthy subjects using a DPI over a range of varying PIFR and IC values was obtained. Temporal and spectral signal analysis revealed that the inhalation signal contains sufficient information that can be employed to estimate PIFR and IC. It was found that the average power (Pave) in the frequency band 300-600 Hz had the strongest correlation with PIFR (R(2) = 0.9079), while the power in the same frequency band was also highly correlated with IC (R(2) = 0.9245). This study has several clinical implications as it demonstrates the feasibility of using acoustics to objectively monitor inhaler use.


Continuous infusion of amphotericin B deoxycholate in the treatment of cryptococcal meningoencephalitis: analysis of safety and fungicidal activity.
We measured fungicidal activity of continuous infusion of amphotericin B deoxycholate plus 5'flucytosine using quantitative cultures of cerebrospinal fluid (CSF) obtained from lumbar punctures of human immunodeficiency virus (HIV)-infected patients with neurocryptococcosis during 14 days of treatment. Glomerular renal function was preserved in all patients. Mycological efficacy with progressive reduction in CSF cryptococcal colony-forming units was comparable to standard 4-h infusion of amphotericin B.


[Three-dimensional reconstruction research on Mingmen (GV 4)].
To show the space structures of Mingmen (GV 4) area and its adjacent tissues. A frozen female corpse was cut into about 0.5 mm thick sections with a high-speed steel plane machine and photographed with digital and optical camera. Two 2-D transverse phase picture data sets were obtained and then were sequenced, matched, modified and divided. The 3-D reconstruction software was used to reconstruct the outline form of the lumbar part containing Mingmen (GV 4) to attain transverse phase picture data sets (3 022 sheets, 0.57 mm in thickness). The sagittal, coronal and different oblique plane were cut and the tissue structures in these pictures were analyzed. Thus, the reconstruction data sets were obtained. After the structures of Mingmen (GV 4) were reconstructed with computer, the form of Mingmen (GV 4) can be dynamically observed from any angle and the space construction law of gross form of Mingmen (GV 4) can be proved.


Diverse patterns of anti-TNF-α-induced lupus: case series and review of the literature.
The induction of autoantibodies is common following therapy with anti-TNF-α agents. However, anti-TNF-α-induced lupus (ATIL) is rare. We assessed the clinical characteristics of three patients with inflammatory bowel disease (IBD) who were treated with infliximab and developed distinct subsets of ATIL. Also, we searched for similar cases in the published literature. We describe three patients with ATIL. The first patient had a classical drug-induced lupus (DIL) presented by thrombocytopenia that resolved after infliximab discontinuation. The second case experienced symmetric polyarthritis of 14 joints in rheumatoid arthritis (RA)-like distribution accompanied by lymphopenia. The third one had a severe serositis including ascites and pleural and pericardial effusions along with pancytopenia. In this patient, ATIL coexisted with anti-TNF-α-induced hepatitis. The second and third patients met the American College of Rheumatology classification criteria for SLE. Nevertheless, all three cases exhibited ANA and anti-dsDNA positivity, and only the second patient had anticardiolipin (aCL IgG) and anti-histone antibodies. The coexistence of both lupus-like syndrome and hepatitis following anti-TNF-α therapy in the same patient is very rare, and to the best of our knowledge, only four such case reports are mentioned in literature. Patients with mild ATIL may tolerate another anti-TNF-α agent without recurrence of the disease. Rheumatologists should be aware of the distinct clinical presentations of ATIL and its coexistence with other rare anti-TNF-alpha complications such as hepatitis.


Use of YouTube to watch health-related videos and participation in online support groups among US adults with heart disease, diabetes, and hypertension.
Social media use has grown over time. However, it is unclear how people with a self-reported history of cardiovascular disease or cardiovascular disease-related risk factors such as diabetes and hypertension use social media. Data from the 2020 Health Information National Trends Survey (HINTS 5, Cycle 4) were analyzed (N = 3865). Only respondents with complete data for all variables of interest were included in the analyses, resulting in 306 respondents with a heart condition, 1291 with hypertension, and 608 with diabetes. We explored associations between two dependent variables: (1) participated in an online forum or support group and (2) watched a health-related video on YouTube, and sociodemographic factors and patient-provider communication. Analyses were conducted separately by medical condition. Odds ratios, 95% confidence intervals, and p-values were calculated. In respondents with a heart condition, hypertension, or diabetes, 5.4%, 8.4%, and 10.3% had participated in an online support group and 29.6%, 40.4%, and 36.6% had watched health-related videos on YouTube, respectively. Univariately, the odds of using online support groups was associated with younger age (vs. > = 65) in people with a heart condition and hypertension, but not diabetes. Regarding YouTube, younger age was associated with watching health-related videos across all three medical conditions, with additional gender and education associations observed in those with hypertension. There were no associations between social media use and patient-provider communication. These findings may inform the selection of social media platforms for behavioral interventions depending on the intended patient population and goals (e.g. social support vs. video-based health education).


Management of hypertension and its sequelae with ACE inhibitors: biochemical, pharmacological and clinical aspects.
ACE inhibitors are a widely prescribed class of drug for the management of hypertension. Their therapeutic role in the treatment of heart failure, diabetic nephropathy and post myocardial infarction with left ventricular dysfunction is steadily increasing. Although ACE inhibitors have a similar mechanism of action--namely, inhibition of circulatory ACE, thereby decreasing the formation of angiotensin II--individual members differ in their physicochemical properties, enzyme-binding kinetics, pharmacokinetic profile, organ-specific affinity and selectivity, as well as in their bradykinin potentiating effect. These factors play an important part in influencing the pharmacological profile of an agent and its clinical efficacy, especially in the treatment of hypertension. It is therefore prudent to take into account the existing pharmacological and clinically relevant differences between the individual members of this drug class before making the decision to select a particular ACE inhibitor for the long-term management of arterial hypertension.


Analysis of food taints and off-flavours: a review.
Taints and off-flavours in foods are a major concern to the food industry. Identification of the compound(s) causing a taint or off-flavour in food and accurate quantification are critical in assessing the potential safety risks of a product or ingredient. Even when the tainting compound(s) are not at a level that would cause a safety concern, taints and off-flavours can have a significant impact on the quality and consumers' acceptability of products. The analysis of taints and off-flavour compounds presents an analytical challenge especially in an industrial laboratory environment because of the low levels, often complex matrices and potential for contamination from external laboratory sources. This review gives an outline of the origins of chemical taints and off-flavours and looks at the methods used for analysis and the merits and drawbacks of each technique. Extraction methods and instrumentation are covered along with possible future developments. Generic screening methods currently lack the sensitivity required to detect the low levels required for some tainting compounds and a more targeted approach is often required. This review highlights the need for a rapid but sensitive universal method of extraction for the unequivocal determination of tainting compounds in food.


Effect of different administration paradigms on cholinesterase inhibition following repeated chlorpyrifos exposure in late preweanling rats.
Chlorpyrifos (CPS) is widely used in agricultural settings and residue analysis has suggested that children in agricultural communities are at risk of exposure. This has resulted in a large amount of literature investigating the potential for CPS-induced developmental neurotoxic effects. Two developmental routes of administration of CPS are orally in corn oil at a rate of 0.5 ml/kg and subcutaneously in dimethyl sulfoxide (DMSO) at a rate of 1.0 ml/kg. For comparison between these methods, rat pups were exposed daily from days 10 to 16 to CPS (5 mg/kg) either orally dissolved in corn oil or subcutaneously dissolved in DMSO, both at rates of either 0.5 or 1.0 ml/kg. A representative vehicle/route group was present for each treatment. Both the low and high volume CPS in DMSO subcutaneous groups were lower than that of the low and high volume CPS in oil oral groups. At 4 h following the final administration, serum carboxylesterase was inhibited > 90% with all treatments. For cholinesterase activity in the cerebellum, medulla-pons, forebrain, and hindbrain, and serum, inhibition in the CPS-oil groups was similar and inhibition in the CPS-DMSO groups was similar. However, significantly greater inhibition was present in the high volume CPS-DMSO group as compared to the CPS-oil groups. Inhibition in the low volume CPS-DMSO group was generally between that in the CPS-oil groups and the high volume CPS-DMSO group. These data suggest that using DMSO as a vehicle for CPS may alter the level of brain ChE inhibition.


Disability due to gouty arthritis.
Disability, or activity limitation, is a common problem in patients with gout. This study explores recent studies examining the nature and extent of disability in gout and addresses the merits and limitations of current self-reported measures of disability. Gout has a significant impact on patients' ability to perform normal self-care activities, recreational and social activities, and work. Comparative studies indicate that gout patients' physical functioning is strongly reduced and comparable to those with other severe rheumatic conditions. Moreover, gout has been shown to result in substantial work absence and reduced productivity. However, few studies have thoroughly examined the concept of disability in gout. Additionally, assessment of disability due to gout still seems particularly challenging and it is unclear whether current measurement instruments are sufficiently valid and accurate. Gout-related disability is an underestimated and understudied problem. More qualitative and quantitative studies are needed that examine the concept of disability in gout and its impact on patients' lives, both during and between disease flares. Moreover, future studies should try to identify gout-specific disability issues and examine the relevance and comprehensiveness of existing measures to further improve the assessment of disability in gout.


Plasmablastic lymphoma of the retroperitoneum in an HIV-negative patient.
Herein is reported a case of plasmablastic lymphoma (PBL) of the retroperitoneum in an HIV-negative patient. This is the first reported case of PBL at this location and of PBL from Japan in the English-language literature. A 76-year-old Japanese man was admitted to hospital with a chief complaint of right inguinal lymph node swelling. Lymph node biopsy indicated large tumor cells with both diffuse and cohesive growth patterns, and conspicuous tumor cell proliferation in lymph node sinuses. The initial pathological diagnosis was metastatic carcinoma. The patient died approximately 1 month after admission, and autopsy showed that the main lesion was a very large retroperitoneal mass. On histology diffusely proliferated plasmablast-like or immunoblast-like tumor cells were identified, which were positive on immunohistochemistry for CD138 and negative for B-cell and epithelial markers. Approximately 90% of the tumor cells were positive for Ki-67. Tumor cells were diffusely positive for EBV-encoded small RNA on in situ hybridization. The autopsy findings suggested a diagnosis of PBL. Accordingly, PBL should be considered as a differential diagnosis when lymph node biopsy findings resemble those of the present patient.


The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and 'hard-to-reach' patients.
Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60-75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led 'lung health check' hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number: ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015.


Fibular Hemimelia: More Than Just An Absent Bone.
Fibular hemimelia is a congenital deficiency or absence of the fibula. There is a spectrum of disease from mild fibular hypoplasia to fibular aplasia. The ipsilateral tibia may be hypoplastic, bowed or normal. Fibular hemimelia can be an isolated deformity of the lower leg but frequently it is associated with proximal focal femoral deficiency, deficiencies of the lateral aspect of the foot, or is part of a malformation syndrome. In this article, we review the embryology of the extremities, discuss proposed etiologies for fibular hemimelia, highlight associated abnormalities, and present the radiographic and imaging findings. Surgical treatment options and long-term outcomes are discussed.


Response to Puts and Dawood's 'the evolution of female orgasm: adaptation or byproduct?'--Been there.
David Puts and Khytam Dawood's recent critique of my book, The Case of the Female Orgasm: Bias in the Science of Evolution, attempts to make plausible an adaptive account of female orgasm based on a hypothesized mechanism of uterine upsuck and sperm competition. Yet the authors fail to respond to the criticisms of such accounts that I detailed previously in my book. They raise a further concern about my definition of adaptation--a red herring--and manufacture a conceptual error regarding heritability that they then attribute to me. Most seriously, they fail to address the glaring failure of sperm competition accounts to accord with evidence from sexology. Specifically, the distribution curve of orgasm-with-intercourse--according to Dawood et al.'s own data, as well as others'--is relatively flat across the various classes. This curve needs to be tested against a well-formed multistrategy adaptive hypothesis; it cannot be explained by the adaptive account defended by Puts and Dawood in their critique.


Antimalarial activity of natural product extracts from Papua New Guinean and Australian plants against Plasmodium falciparum.
In the search for new antimalarial compounds, a subset of a natural product extract library prepared from plant samples collected from Papua New Guinea and Australia was screened for in vitro activity against the chloroquine-sensitive 3D7 and chloroquine-resistant Dd2 strains of Plasmodium falciparum. Using the incorporation of ((3)H)-hypoxanthine into parasite nucleic acid as a marker of growth, 93 of the 794 extracts screened displayed >40% inhibition against 3D7 infected erythrocytes at 312 microge/mL. Antimalarial activity was confirmed in 48 of these extracts against both 3D7 and Dd2 infected erythrocytes at concentrations between 78 and 390 microge/mL, 14 of which caused >90% growth inhibition of 3D7 at the lowest concentration screened. Extracts were also tested for mammalian cell cytotoxicity to evaluate selectivity of action.


Exercise echocardiography in asymptomatic survivors of childhood cancer treated with anthracyclines: a prospective follow-up study.
Exercise echocardiography reveals abnormalities in asymptomatic childhood cancer survivors who previously have been treated with anthracyclines. We determined the added value of monitoring childhood cancer survivors with exercise echocardiography compared to monitoring with resting echocardiography alone to predict anthracycline-induced cardiotoxicity. Secondary aims were to evaluate change in resting cardiac function over 10 years and to determine risk factors for late cardiotoxicity. We invited a cohort of 110 originally asymptomatic anthracycline-treated childhood cancer survivors, who had undergone cardiac tests including exercise echocardiography 10.5 years earlier, for new cardiac evaluation. Each subject underwent a resting echocardiogram at both evaluations. At first evaluation a repeat echocardiogram was performed following peak exercise. Resting echocardiographic parameters were converted to z-character. Ninety-two of 110 survivors (mean anthracycline dose 307 mg/m(2), mean follow-up time from start of treatment 8.2 years at first and 18.8 years at second evaluation) were evaluated prospectively. Mean resting fractional shortening z-character (RFSz) decreased from -0.18 to -0.93. Higher cumulative anthracycline dose was a risk factor for a lower RFSz at late follow-up (P = 0.0002). Adding exercise fractional shortening (XFS) to a model containing RFSz did not improve prediction of abnormal RFSz at late follow-up. Monitoring with exercise echocardiography has no added value to monitoring with resting echocardiography alone in predicting late anthracycline-induced cardiotoxicity in childhood cancer survivors. RFSz deteriorates over time, even in originally asymptomatic patients. Previous treatment with higher cumulative anthracycline dose is the main risk factor for a lower RFSz at late follow-up.


Diffusive Adhesives for Water-Rich Materials: Strong and Tunable Adhesion Beyond the Interface.
It is notoriously difficult to adhere water-rich materials, such as hydrogels and biological tissues. Existing adhesives usually suffer from weak and nonadjustable adhesion strength, in part because the contact between the adhesive and substrate is largely restrained to the adhesive/substrate interface. In this study, we have attempted to overcome this shortcoming by developing a class of diffusive adhesives (DAs) that can extend adhesion deep into the substrate to maximize the adhesive/substrate contact. The DAs consist of hydrogel matrices and preloaded water-soluble monomers and crosslinkers that can diffuse extensively into the water-rich substrates after adhesive/substrate contact. Polymerization and crosslinking of the monomers are then triggered leading to a bridging network that interpenetrates the DA and substrate skeletons and topologically binds them together. This kind of adhesion, in the absence of adhesive/substrate covalent bonding, is of high strength and toughness, comparable to those of the best-performing natural and artificial adhesives. More importantly, we can precisely tune the adhesion strength on demand by manipulating the diffusion profile. It is envisioned that the DA family could be extended to include a large pool of hydrogel matrices and monomers, and that they could be particularly useful in biological and medical applications.


Structural and conformational stability of horseradish peroxidase: effect of temperature and pH.
Detailed circular dichroism and fluorescence studies at different pHs have been carried out to monitor thermal unfolding of horseradish peroxidase isoenzyme c (HRPc). The change in CD in the 222 nm region corresponds to changes in the overall secondary structure of the enzyme, while that in the 400 nm region (Soret region) corresponds to changes in the tertiary structure around the heme in the enzyme. The temperature dependence of the tertiary structure around the heme also affected the intrinsic tryptophan fluorescence emission spectrum of the enzyme. The results suggested that melting of the tertiary structure to a pre-molten globule form takes place at 45 degrees C, which is much lower than the temperature (T(m) = 74 degrees C) at which depletion of heme from the heme cavity takes place. The melting of the tertiary structure was found to be associated with a pK(a) of approximately 5, indicating that this phase possibly involves breaking of the hydrogen-bonding network of the heme pocket, keeping the heme moiety still inside it. The stability of the secondary structure of the enzyme was also found to decrease at pH below 4.5. A 'high temperature' unfolding phase was observed which was, however, independent of pH. The stability of the secondary structure was found to drastically decrease in the presence of DTT (dithiothreitol), indicating that the 'high temperature' form is possibly stabilized due to interhelical disulfide bonds. Depletion of Ca(2+) ions resulted in a marked decrease in the stability of the secondary structure of the enzyme.


Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense.
The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6-RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1-infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism.


Organellar DNA Polymerases in Complex Plastid-Bearing Algae.
DNA replication in plastids and mitochondria is generally regulated by nucleus-encoded proteins. In plants and red algae, a nucleus-encoded enzyme called POP (plant and protist organellar DNA polymerase) is involved in DNA replication in both organelles by virtue of its dual localization. POPs are family A DNA polymerases, which include bacterial DNA polymerase I (PolI). POP homologs have been found in a wide range of eukaryotes, including plants, algae, and non-photosynthetic protists. However, the phylogeny and subcellular localizations of POPs remain unclear in many algae, especially in secondary and tertiary plastid-bearing groups. In this study, we report that chlorarachniophytes possess two evolutionarily distinct POPs, and fluorescent protein-tagging experiments demonstrate that they are targeted to the secondary plastids and mitochondria, respectively. The timing of DNA replication is different between the two organelles in the chlorarachniophyte Bigelowiella natans, and this seems to be correlated to the transcription of respective POP genes. Dinoflagellates also carry two distinct POP genes, possibly for their plastids and mitochondria, whereas haptophytes and ochrophytes have only one. Therefore, unlike plants, some algal groups are likely to have evolved multiple DNA polymerases for various organelles. This study provides a new insight into the evolution of organellar DNA replication in complex plastid-bearing organisms.


Lean body mass, gastric acid, and peptic ulcer.
Peak acid outputs in normal subjects and patients with duodenal and gastric ulcer were significantly (and similarly) correlated with body weight and calculated lean body mass. Expression of measurements of peak acid output as a function of body weight or lean body mass lessened but did not abolish the significance of the situation that men with no dyspepsia or gastric ulcer secreted more acid than women; the significant sex difference in duodenal ulcer was, however, abolished. Data for peak acid output have been tabulated, not only as m-equiv/hr but also as mu-equiv/kg body weight/hr and mu-equiv/kg lean body mass/hr. On the basis of the present data no change is suggested in the current expression of peak acid output as m-equiv/hr since expression of acid output as a function of body weight or lean body mass improves neither the variability nor the diagnostic discrimination of measurement of peak acid output.


Surgical creation of lymphocutaneous fistulas for the management of infants with central lymphatic obstruction.
Central lymphatic obstructions are associated with anasarca and high mortality. We hypothesized that opening dilated cutaneous lymphatic channels by creating a lymphocutaneous fistula (LCF) would decompress the lymphatic circulation and improve anasarca. We reviewed all patients that had at least one LCF created between 9/2019 and 12/2022. LCF efficacy was determined by changes in weight, urine/diuresis, ventilation, and clinical status. We created eleven LCFs in four infants. LCFs initially drained 108 cc/kg/d (IQR68-265 cc/kg/d). Weights significantly decreased after LCF creation (6.9 [IQR6.1-8.1] kg vs. 6.1 [IQR 4.9-7.6] kg, P = 0.042). Ventilatory support decreased significantly in all patients after at least one LCF was created, and 3/4 patients (75%) had significantly lower peak inspiratory pressures (28 [IQR 25-31] cmH2O vs. 22 [IQR 22-24] cmH2O, P = 0.005; 36 [IQR36-38] cmH2O vs. 33 [IQR 33-35] cmH2O, P = 0.002; 36 [IQR 34-47] cmH2O vs. 28 [28-31] cmH2O, P = 0.002). LCFs remained patent for 29d (IQR 16-49d). LCFs contracted over time, and 6/11 (54.5%) were eventually revised. There were no complications. Two patients died from overwhelming disease, one died from unrelated causes, and one remains alive 29 months after their initial LCF. LCFs provide safe and effective temporary lymphatic decompression in patients with central lymphatic obstruction. While LCFs are not a cure, they can serve as a bridge to more definitive therapies or spontaneous lymphatic remodeling. IV.


Molecular profiling of chronic myeloid leukemia in eastern India.
Molecular breakpoint of the BCR-ABL fusion gene has been characterized for 122 chronic myeloid leukemia patients. Out of 122 cases, 33 b2a2, 69 b3a2, 2 e1a2, and 2 e19a2 cases have been detected. Six coexpressed both b2a2 and b3a2 transcripts. All the coexpressing samples had an A>G polymorphism at the putative splice branchpoint in intron 13. The T>C polymorphism in exon 13, reported to be linked to coexpression, was not present in all the coexpressing patients. No correlation of transcript type with platelet count was detected. Those expressing b2a2 transcript were diagnosed at relatively younger age and with higher white blood cell count, in agreement with other reports. However, the correlation was not statistically significant.


Meningoencephalitis caused by Mycoplasma edwardii in a dog.
A 6-week-old, female, mixed-breed dog with a clinical history of sudden onset of neurologic signs was presented for necropsy. The dog was diagnosed with suppurative and histiocytic meningoencephalitis based on necropsy findings and histopathology. Mycoplasma sp. was isolated in pure culture from the brain and meninges and was identified as Mycoplasma edwardii using DNA sequencing.


Glutamine synthetase facilitates cancer cells to recover from irradiation-induced G2/M arrest.
Resistance to radiation of cancer cells can be either intrinsic or acquired, leading to treatment failure. In response to DNA damage caused by IR, cancer cells are arrested in cell cycle showing limited proliferation and increased apoptosis. However, radiation-resistant cells are able to overcome the cell cycle block and proceed to proliferation, for which the detailed mechanism remains to be elucidated. In the present study, we showed that radioresistant cells exhibited a recoverable G2/M phase during prolonged cell cycle and manifested lower apoptosis rate and more colony formation. RNA-seq analysis revealed that glutamine synthetase (GS, GLUL) gene was highly expressed in radioresistant cancer cells in comparison with the parental cells, which was in accordance with the G2/M arrest after ionizing radiation. Knocking out of GS in radioresistant cells resulted in a delayed G2/M recovery and lowered proliferation rate after ionizing radiation treatment, which was accompanied with increased inhibitory phosphorylation of CDK1 at Y15 and downregulated Cdc25B, a dual specific phosphatase of CDK1. Moreover, there was an enhanced complex formation of CDK1 and Cyclin B1 when the cells were rescued by re-introducing GS. In vivo, knocking down of GS significantly sensitized CNE2-R xenografts to RT in mice. In this study, we demonstrate a novel role of glutamine synthetase independent of metabolic function in promoting recovery from G2/M arrest caused by ionizing radiation, thus, causing cancer cell resistance to radiotherapy.


Effect of existing practices on reducing Aedes aegypti pre-adults in key breeding containers in Ho Chi Minh City, Vietnam.
This study aimed to evaluate the effects of existing practices of residents in reducing pre-adult Aedes aegypti (L.) infestation and to assess the effect of dengue-related knowledge on the practices. A house-to-house survey was conducted in two areas with different socioeconomic status in Ho Chi Minh City between October and November 2007. Some residents in both the areas used covers on the productive containers such as the jars and plastic buckets (i.e., 58% and 81% in the two study areas), and it was effective in reducing Ae. aegypti infestation: odds ratio (OR) of 4.0 and 4.9 (95% confidence interval [CI]: 1.49-10.76 and 1.2-19.57, respectively) for the containers with inappropriate covers compared with those with appropriate covers in the two areas, respectively. Appropriate cover use was an effective practice; however, no beneficial role of the knowledge related to dengue in promoting the practice was identified.


Interpreting the correlation coefficient when one of the variables is discrete.
The effect on the correlation coefficient of discretizing data was investigated in two ways. First, the theoretical effect of dichotomizing data was calculated, and it was shown that the resulting correlation coefficient is considerably less than that between the underlying bivariate normally distributed variables. Second, computer simulations were performed of a model in which a continuous variable (measured with some error) gives rise to a counting variable through a mechanism in which the count is zero below a certain threshold value for the continuous variable and then increases linearly as the continuous variable increases. It was shown that the correlation coefficient between the observed values of the continuous and counting variables decreased as (a) the measurement error increased, (b) the slope of the relationship decreased, and (c) the number of counts decreased. It is concluded that caution is required when interpreting correlation coefficients when one or both of the variables consist of a few (say only four or five) discrete scores.


Mapping of QTLS for ferrous iron toxicity tolerance in rice (Oryza sativa L.).
Ferrous iron toxicity is the main factor limiting the productivity of rice in gleyic paddy soils. In this study, an F2 and an equivalent F3 populations derived from a japonica/indica cross of rice, Longza8503/IR64, were raised under iron-enriched solution cultures, and used to map QTLs controlling ferrous iron toxicity tolerance. A genetic linkage map consisting of 101 SSR markers was constructed to determine the position and nature of quantitative trait loci (QTLs) affecting Fe2+ toxicity tolerance. Three characters, i.e., leaf bronzing index (LBI), plant height (PH) and maximum root length (MRL) were evaluated for the F2 plants and F3 lines and the parents at the seedling stage in nutrient solution. A total of 20 QTLs for LBI, PH and MRL under the Fe2+ stress were detected over 10 of the 12 rice chromosomes, reflecting multigenic control of these traits. QTLs controlling LBI were located at the region of RM315-RM212 on chromosome 1, RM6-RM240 on chromosome 2 and RM252-RM451 on chromosome 4. Compared with other mapping results: (1) the QTL for LBI located at the region of RM252-RM451 on chromosome 4 was identical with the QTL for decreased chlorophyll content on a rice function map. Another QTL for LBI located at the region of RM315-RM212 on chromosome 1 was linked with the QTL for chlorophyll content which located at the region of C178-R2635 on a rice function map. (2) The third QTL for LBI located at the region of RM6-RM240 on choromosome 2 was linked with the QTL for potassium uptake located at the region of RZ58-CDO686 under potassium deficiency stress.


Stabilized record base for implant treatment.
It is important to obtain an accurate interocclusal record for the restoration of patients undergoing implant treatment. Atrophic alveolar bone in the mandible not only limits the placement of implants, but also contributes to deficient ridge morphology resulting in unstable record bases. Securing the record base to the implants is a useful way to obtain an accurate registration. The technique presented in this article uses two widely spaced implants as the optimal number of implants to stabilize record bases.


MetalPDB in 2018: a database of metal sites in biological macromolecular structures.
MetalPDB (http://metalweb.cerm.unifi.it/) is a database providing information on metal-binding sites detected in the three-dimensional (3D) structures of biological macromolecules. MetalPDB represents such sites as 3D templates, called Minimal Functional Sites (MFSs), which describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. The 2018 update of MetalPDB includes new contents and tools. A major extension is the inclusion of proteins whose structures do not contain metal ions although their sequences potentially contain a known MFS. In addition, MetalPDB now provides extensive statistical analyses addressing several aspects of general metal usage within the PDB, across protein families and in catalysis. Users can also query MetalPDB to extract statistical information on structural aspects associated with individual metals, such as preferred coordination geometries or aminoacidic environment. A further major improvement is the functional annotation of MFSs; the annotation is manually performed via a password-protected annotator interface. At present, ∼50% of all MFSs have such a functional annotation. Other noteworthy improvements are bulk query functionality, through the upload of a list of PDB identifiers, and ftp access to MetalPDB contents, allowing users to carry out in-depth analyses on their own computational infrastructure.


Fetal heart rate, arterial pressure, and blood volume responses to cortisol infusion.
The purpose of this study was to determine whether physiological amounts of cortisol affect the fetal cardiovascular system. Cortisol (4 micrograms/min) or the vehicle was infused intravenously for 5 h into six chronically catheterized sheep fetuses at 127-143 days gestation (term = 145-150 days). In the cortisol-infused animals, plasma cortisol concentration increased from 2.0 +/- 0.6 (SE) to 8.3 +/- 0.9 ng/ml. There was a concomitant decrease in fetal heart rate of 38 beats/min (P less than 1 X 10(-6)) and an increase in arterial pressure. Estimated blood volume decreased by 6% in the cortisol-infused fetuses compared with the vehicle-infused animals (P less than 1 X 10(-4]. In addition, plasma norepinephrine and epinephrine concentrations decreased to 70% of control at the end of the 5-h cortisol infusion, whereas plasma renin concentration decreased to 34% of control. The simultaneous increase in fetal arterial pressure and decrease in estimated blood volume suggest that fetal vascular resistance increased, whereas vascular compliance and/or nonstressed vascular volume decreased. However, this does not appear to be mediated by increases in circulating vasoconstrictor hormone concentrations or increased sympathetic tone. Thus the present study shows that physiological amounts of cortisol have significant effects on the fetal cardiovascular system but the mechanisms are unknown.


Establishing an NP-staffed minor emergency area.
A nurse practitioner-staffed minor emergency area provides high quality care for approximately 21% of their adult emergency department population. Patients are triaged based on set criteria, allowing for short treatment times. The physical layout, triage criteria and the NPs' scope of practice in the Level I trauma center's ED are detailed.


Protection against Oxidative Stress-Induced Apoptosis by Fermented Sea Tangle (Laminaria japonica Aresch) in Osteoblastic MC3T3-E1 Cells through Activation of Nrf2 Signaling Pathway.
The purpose of the present study was to explore the efficacy of fermented extract of sea tangle (Laminaria japonica Aresch, FST) with Lactobacillus brevis on DNA damage and apoptosis in hydrogen peroxide (H2O2)-stimulated osteoblastic MC3T3-E1 cells and clarify related signaling pathways. Our results showed that exposure to FST significantly improved cell viability, inhibited apoptosis, and suppressed the generation of reactive oxygen species (ROS) in H2O2-stimulated cells. In addition, H2O2 triggered DNA damage in MC3T3-E1 cells was markedly attenuated by FST pretreatment. Moreover, H2O2-induced mitochondrial dysfunctions associated with apoptotic events, including loss of mitochondrial membrane potential (MMP), decreased Bcl-2/Bcl-2 associated x-protein (Bax) ratio, and cytosolic release of cytochrome c, were reduced in the presence of FST. FST also diminished H2O2-induced activation of caspase-3, which was associated with the ability of FST to protect the degradation of poly (ADP-ribose) polymerase. Furthermore, FST notably enhanced nuclear translocation and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence of H2O2 with concomitant upregulation of heme oxygenase-1 (HO-1) expression. However, artificial blockade of this pathway by the HO-1 inhibitor, zinc protoporphyrin IX, greatly abolished the protective effect of FST against H2O2-induced MC3T3-E1 cell injury. Taken together, these results demonstrate that FST could protect MC3T3-E1 cells from H2O2-induced damage by maintaining mitochondrial function while eliminating ROS along with activation of the Nrf2/HO-1 antioxidant pathway.


Incidental findings in patients with multiple injuries: how to proceed?
Multislice computed tomography (MSCT) is the diagnostic criterion standard for the initial evaluation of patients with suspected multiple injuries. Besides scanning for injuries directly related to the initial trauma, MSCT scans can reveal pathologies unrelated to the trauma of clinical relevance.The aim of the present study was to determine the frequency and follow-up course of incidental findings in patients with multiple injuries. This is a retrospective analysis of prospectively collected data on 2,242 patients with suspected multiple injuries at a Level I trauma center from 2006 to 2010.The MSCT reports were retrospectively reviewed regarding abnormal findings not related to trauma. These incidental findings were classified on a four-point level scoring system with respect to clinical importance and urgency for further diagnostic and therapeutic procedures. During initial trauma center evaluation in the emergency department, 2,246 patients met our inclusion criteria. A total of 2,036 patients (90.7%) underwent MSCT; 1,142 (50.9%) of the patients had one or more incidental findings. A total of 2,844 incidental findings were detected. Overall, 349 tumor findings were noted (12.3% of all incidental findings); 113 findings were suspicious for malignant processes or metastasis. According to our classification, 168 (5.9%) of the incidental findings required urgent follow-up (Level 4), and 527 (18.5%) of the incidental findings required a follow-up before discharge (Level 3). MSCT in patients with multiple injuries reveals one or more incidental findings in more than one of two patients. A scoring system classifying for relevance of incidental findings was introduced and could be applied in routine trauma care in the future. Epidemiologic study, level III.


Multichannel, direct-reading spectrograph attachment.
An instrument is described which provides a multichannel direct-reading capability for photoelectric spectrographic detection. The important feature of the instrument is the ability of the user to select at will any combination of channels for position adjustment and to move these while preserving the optical integrity of the enclosure. Photomultipliers are used and the results of performance tests are described.


Extraction and partial characterization of surfactant-soluble antigens from adult female Dirofilaria immitis.
Antigens were solubilized from aqueous-insoluble material of adult female Dirofilaria immitis with Triton X-100 and sodium dodecyl sulfate (SDS) and partially characterized. Concentrations of 2.1-8.3 mg Triton X-100/mg total protein and 1.06-4.26 mg SDS/mg total protein were used to solubilize antigens. Triton X-100 was more efficient in solubilizing protein than SDS; Triton X-100 and SDS released 75% and 26% of the available protein, respectively. Protein mixtures solubilized with different levels of Triton X-100 appeared to be identical in immunodiffusion. Crossed immunoelectrophoresis revealed six antigen systems. Triton X-100 solubilized antigens did not react in immunodiffusion with sera from 7 D. immitis-infected, microfilaremic dogs, but did react with sera from 4 of 5 dogs with occult D. immitis infections.


Extending Effective Dynamic Range of Hyperspectral Line Cameras for Short Wave Infrared Imaging.
In this work, a multi-exposure method is proposed to increase the dynamic range (DR) of hyperspectral imaging using an InGaAs-based short-wave infrared (SWIR) hyperspectral line camera. Spectral signatures of materials were captured for scenarios in which the DR of a scene was greater than the DR of a line camera. To demonstrate the problem and test the proposed multi-exposure method, plastic detection in food waste and polymer sorting were chosen as the test application cases. The DR of the hyperspectral camera and the test samples were calculated experimentally. A multi-exposure method is proposed to create high-dynamic-range (HDR) images of food waste and plastic samples. Using the proposed method, the DR of SWIR imaging was increased from 43 dB to 73 dB, with the lowest allowable signal-to-noise ratio (SNR) set to 20 dB. Principal Component Analysis (PCA) was performed on both HDR and non-HDR image data from each test case to prepare the training and testing data sets. Finally, two support vector machine (SVM) classifiers were trained for each test case to compare the classification performance of the proposed multi-exposure HDR method against the single-exposure non-HDR method. The HDR method was found to outperform the non-HDR method in both test cases, with the classification accuracies of 98% and 90% respectively, for the food waste classification, and with 95% and 35% for the polymer classification.


Molecular analysis of a patient with neurofibromatosis 1 and achondroplasia.
The gene for von Recklinghausen neurofibromatosis (NF1) is on proximal 17q; the location of the gene for achondroplasia (ACH) is unknown. We have begun a molecular analysis of a patient with mental retardation, NF1 and ACH, a clinical presentation suggestive of a contiguous gene syndrome. In addition, this individual has a 47,XYY chromosome constitution. To define a possible chromosome 17 deletion, we investigated the copy number of DNA sequences linked to NF1 with conventional and pulsed-field gel electrophoresis (PFGE). We found no evidence for a deletion on chromosome 17. These results make it unlikely that this patient harbors a single deletion in the NF1 region causing both NF1 and ACH and suggest different mechanisms for the de novo occurrence of 2 autosomal dominant disorders in this individual.