Lung-kidney interactions and their role in chronic kidney disease-associated pulmonary diseases.
Chronic illnesses rarely present in a vacuum, devoid of other complications, and chronic kidney disease is hardly an exception. Comorbidities associated with chronic kidney disease lead to faster disease progression, expedited dialysis dependency, and a higher mortality rate. Although chronic kidney disease is most commonly accompanied by cardiovascular diseases and diabetes, there is clear cross talk between the lungs and kidneys pH balance, phosphate metabolism, and immune system regulation. Our present understanding of the exact underlying mechanisms that contribute to chronic kidney disease-related pulmonary disease is poor. This review summarizes the current research on kidney-pulmonary interorgan cross talk in the context of chronic kidney disease, highlighting various acute and chronic pulmonary diseases that lead to further complications in patient care. Treatment options for patients presenting with chronic kidney disease and lung disease are explored by assessing activated molecular pathways and the body's compensatory response mechanisms following homeostatic imbalance. Understanding the link between the lungs and kidneys will potentially improve health outcomes for patients and guide healthcare professionals to better understand how and when to treat each of the pulmonary comorbidities that can present with chronic kidney disease.


Monoplane 3D Overlay Roadmap versus Conventional Biplane 2D Roadmap Technique for Neurointervenional Procedures.
We investigated whether a 3D overlay roadmap using monoplane fluoroscopy offers advantages over a conventional 2D roadmap using biplane fluoroscopy during endovascular aneurysm treatment. A retrospective chart review was conducted for 131 consecutive cerebral aneurysm embolizations by three neurointerventionalists at a single institution. Allowing for a transition period, the periods from January 2012 to August 2012 (Time Period 1) and February 2013 to July 2013 (Time Period 2) were analyzed for radiation exposure, contrast administration, fluoroscopy time, procedure time, angiographic results, and perioperative complications. Two neurointerventionalists (Group 1) used a conventional 2D roadmap for both Time Periods, and one neurointerventionalist (Group 2) transitioned from a 2D roadmap during Time Period 1 to a 3D overlay roadmap during Time Period 2. During Time Period 2, Group 2 demonstrated reduced fluoroscopy time (p<0.001), procedure time (P=0.023), total radiation dose (p=0.001), and fluoroscopy dose (P=0.017) relative to Group 1. During Time Period 2, there was no difference of immediate angiographic results and procedure complications between the two groups. Through the transition from Time Period 1 to Time Period 2, Group 2 demonstrated decreased fluoroscopy time (p< 0.001), procedure time (p=0.022), and procedure complication rate (p=0.041) in Time Period 2 relative to Time Period 1. The monoplane 3D overlay roadmap technique reduced fluoroscopy dose and fluoroscopy time during neurointervention of cerebral aneurysms with similar angiographic occlusions and complications rate relative to biplane 2D roadmap, which implies possible compensation of limitations of monoplane fluoroscopy by 3D overlay technique.


Treatment of obsessive morbid jealousy with cognitive analytic therapy: An adjudicated hermeneutic single-case efficacy design evaluation.
The evidence base for the treatment of morbid jealousy with integrative therapies is thin. This study explored the efficacy of cognitive analytic therapy (CAT). An adjudicated hermeneutic single-case efficacy design evaluated the cognitive analytic treatment of a patient meeting diagnostic criteria for obsessive morbid jealousy. A rich case record was developed using a matrix of nomothetic and ideographic quantitative and qualitative outcomes. This record was then debated by sceptic and affirmative research teams. Experienced psychotherapy researchers acted as judges, assessed the original case record, and heard the affirmative-versus-sceptic debate. Judges pronounced an opinion regarding the efficacy of the therapy. The efficacy of CAT was supported by all three judges. Each ruled that change had occurred due to the action of the therapy, beyond any level of reasonable doubt. This research demonstrates the potential usefulness of CAT in treating morbid jealousy and suggests that CAT is conceptually well suited. Suggestions for future clinical and research directions are provided. The relational approach of CAT makes it a suitable therapy for morbid jealousy. The narrative reformulation component of CAT appears to facilitate early change in chronic jealousy patterns. It is helpful for therapists during sessions to use CAT theory to diagrammatically spell out the patterns maintaining jealousy.


The Survival of Well-Fixed Cementless Femoral Component After Isolated Acetabular Component Revision.
It remains controversial whether isolated acetabular component revision or both component revision surgeries should be performed in patients with stable femoral component. The present study aimed to evaluate the survival of patients with unrevised stable uncemented femoral stem who underwent isolated acetabular component revision. A retrospective analysis was conducted in patients who underwent isolated acetabular component revision and had stable uncemented femoral component during revision hip arthroplasty between February 1998 and December 2009. Demographic data of the patients included age, previous surgery, complications, duration between primary and revision surgery, and duration between revision and latest follow-up. Functional results were analyzed using Harris Hip Score (HHS). Fifteen hips of thirteen patients were included in the study with a mean age of 62.08 ± 12.9 years. Average time from THA to the isolated acetabular revision was 9.2 ± 3.48 years. Average follow-up time from revision to the latest follow-up was 12.39 ± 2.68 years, and femoral components had been followed for an average of 21.6 ± 4.06 years since the time of implantation. Average HHS of the patients were 53 before revision surgery and 81.9 at the last follow-up (p < 0.001). The 10-year survival rate of patients who underwent revision in the femoral component was 100%, whereas their 15-year survival rate was 93.3%. None of the acetabular components required revision. Isolated revision of acetabular component may be considered if there is stable uncemented femoral component in revision THA. Acetabular reconstruction quality, acetabular and unrevised femoral component survival are not affected by retaining well-fixed femoral component. 4, retrospective cohort study.


Comparing auditory vs visual stimuli in the tip-of-the-tongue phenomenon.
An experiment is reported comparing the effectiveness of auditory and visual stimuli in eliciting the tip-of-the-tongue phenomenon. 30 participants were asked to name the titles of 27 television shows. Half of the participants were given segments of the theme song for each show (auditory cue), and half were shown the cast photographs for each show (visual cue). Participants were asked to report whenever they experienced the tip-of-the-tongue state. There were no significant differences between the auditory and visual stimuli in terms of the incidence rate for the tip-of-the-tongue state, the amount of partial information that participants provided in their responses, or the frequency of interlopers (alternative responses that persistently come to mind). These findings suggest that the characteristics of the tip-of-the-tongue state are determined more by the nature of the response set than by the type of stimuli used as cues. The results are inconsistent with inferential theories of the tip-of-the-tongue phenomenon, such as the cue familiarity hypothesis and, instead, tend to support direct-access hypotheses.


Postprandial Metabolic Effects of Accelerometer Measured Spontaneous Low-Level Activity.
Interrupting sedentary time induces improvements in glucose metabolism; however, it is unclear how much activity is required to reduce the negative effects of prolonged sitting. Sixty-six participants sat continuously for 9 hours except for required bathroom breaks. Participants were fed meal replacement beverages at 60, 240 and 420 min. Blood samples were obtained hourly for 9 hours, with additional samples collected 30 and 45 min after each feeding. Responses were calculated as incremental area under the curve (iAUC) for plasma glucose, insulin and triglyceride. Participants wore a triaxial accelerometer and a heart rate monitor. Energy expenditure was estimated using indirect calorimetry. After controlling for age, sex and BMI, every 100 count increase in accelerometer derived total movement was associated with a 0.06 mmol·L-1·9 hours decrease in glucose iAUC (95% CI 0.004-0.1; P = .035), but not associated with changes in insulin or triglyceride iAUC. Every 1 bpm increase in mean heart rate was associated with a 0.76 mmol·L-1·9 hours increase in triglyceride iAUC (95% CI 0.13-1.38). Accelerometer measured movement during periods of prolonged sitting can result in minor improvements in postprandial glucose metabolism, but not lipid metabolism.


Evaluating sources for secondary analysis.
Secondary analysis can be extremely versatile in understanding change of phenomena and extending previous studies. However, all data are not created equal. When using secondary sources, it is important to evaluate the data, weigh potential biases, and adopt an attitude of healthy skepticism. Although the potentials of secondary analysis are enormous, certain problems can be avoided if sources are evaluated carefully. Nurse researchers should be aware of some limitations of secondary data sets. Expert knowledge of research designs and statistical techniques, in addition to an open and creative mind, will be invaluable assets in answering the preceding eight questions.


NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells.
Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.


Boronic Acid-Based Carbohydrate Sensing.
The covalent boron-diol interaction enables elaborate design of boronic acid-based saccharide sensors. Over the last decade, this research topic has been well developed thanks to the integration of boronic acid chemistry with a range of techniques, including supramolecular chemistry, materials chemistry, surface modification, and nanotechnology. New sensing strategies and platforms have been introduced and remarkable progress has been achieved to fully utilize the unique property of boron-diol interaction and to improve the binding affinity towards different targets, especially under physiological conditions. In this review, the latest progress over the past 30 months (from late 2012 to early 2015) is highlighted and discussed to shed light on this versatile and promising platform for saccharide sensing.


Clinical implications of Delphian lymph node metastasis in papillary thyroid carcinoma.
As is known, identifying risk factors precisely for lymph node metastasis (LNM) plays a vital role in initial treatment for papillary thyroid carcinoma (PTC). Nonetheless, whether Delphian lymph node (DLN) metastasis has value in predicting LNM remains an open question. This study covered a sample of 1,575 patients, which is the largest sample group so far, aiming to assess the predictive validity of DLN metastasis in PTC. This retrospective cohort study was conducted with 1,575 eligible PTC patients who underwent thyroid operation between July 2013 and December 2018 and clinicopathologic parameters of patients with DLN metastasis were compared with those without DLN metastasis. The incidence of DLN metastasis, according to our research samples, is 24.4% (384/1,575 patients). And results show that DLN positivity was closely associated with adverse prognostic factors including younger age, larger tumor size, extrathyroid extension, tumor location in the isthmus or upper lobe of the thyroid, number of LNM >5, higher recurrence. After carefully adjusting important confounding factors, we find that in multivariate logistic regression analyses, DLN metastasis is an independent predictor for both central LNM (CLNM, adjusted OR =7.81, P<0.001) and lateral LNM (LLNM, adjusted OR =3.40, P<0.001). Moreover, the stratified analyses also show convincing evidence of a positive correlation between DLN metastasis and LNM in levels II-IV in the vast majority of subgroups. The present study suggests that DLN metastasis is an independent risk factor for CLNM and LLNM of levels II-IV. The cervical lymph nodes should be meticulously evaluated to guide tailored treatment during operation in patients with DLN involvement.


Prophylactic cranial irradiation could improve overall survival in patients with extensive small cell lung cancer : A retrospective study.
To evaluate the effect of prophylactic cranial irradiation (PCI) on overall survival (OS) in patients with extensive small cell lung cancer (ESCLC). Between April 2005 and May 2014, 204 patients with ESCLC who had any response (according to RECIST 1.1) to initial chemotherapy were reviewed. All patients had undergone appropriate imaging tests to exclude brain metastases before initial chemotherapy. PCI was performed on 45 patients (22.1 %) and the remaining patients (77.9 %) received no such treatment (control group). Primary endpoint was OS. The incidence of brain metastases, brain metastases-free survival (BMFS), and adverse effects were also evaluated. Survival data of the 204 patients were analyzed statistically. PCI significantly prolonged median OS from 12.6 to 16.5 months as compared to the control group (hazard ratio, HR, 0.63; 95 % confidence interval, CI, 0.41 to 0.96; p = 0.033). PCI significantly lowered the risk of brain metastases (HR 0.48; 95 % CI 0.30 to 0.76; p = 0.001). The 1‑year incidence of brain metastases was 17.1 and 55.9 % in the PCI and control group, respectively. PCI significantly correlated with the increased median BMFS (p = 0.002). Additionally, multivariate analyses demonstrated that PCI was a favorable independent predictor of OS, BMFS, and the incidence of brain metastases. Acute and chronic adverse effects were generally low grade and well tolerated in patients receiving PCI. PCI after any response to initial chemotherapy significantly improved OS of ESCLC patients analyzed in this study.


Uncertainty evaluation of human risk analysis (HRA) of chemicals by multiple exposure routes.
The application of an ISO standard procedure (Guide to the Expression of Uncertainty in Measurement (GUM)) is here discussed to quantify uncertainty in human risk estimation under chronic exposure to hazardous chemical compounds. The procedure was previously applied to a simple model; in this article a much more complex model is used, i.e., multiple compound and multiple exposure pathways. Risk was evaluated using the usual methodologies: the deterministic reasonable maximum exposure (RME) and the statistical Monte Carlo method. In both cases, the procedures to evaluate uncertainty on risk values are detailed. Uncertainties were evaluated by different methodologies to account for the peculiarity of information about the single variable. The GUM procedure enables the ranking of variables by their contribution to uncertainty; it provides a criterion for choosing variables for deeper analysis. The obtained results show that the application of GUM procedure is easy and straightforward to quantify uncertainty and variability of risk estimation. Health risk estimation is based on literature data on a water table contaminated by three volatile organic compounds. Daily intake was considered by either ingestion of water or inhalation during showering. The results indicate one of the substances as the main contaminant, and give a criterion to identify the key component on which the treatment selection may be performed and the treatment process may be designed in order to reduce risk.


An apoplastic fluid extraction method for the characterization of grapevine leaves proteome and metabolome from a single sample.
The analysis of complex biological systems keeps challenging researchers. The main goal of systems biology is to decipher interactions within cells, by integrating datasets from large scale analytical approaches including transcriptomics, proteomics and metabolomics and more specialized 'OMICS' such as epigenomics and lipidomics. Studying different cellular compartments allows a broader understanding of cell dynamics. Plant apoplast, the cellular compartment external to the plasma membrane including the cell wall, is particularly demanding to analyze. Despite our knowledge on apoplast involvement on several processes from cell growth to stress responses, its dynamics is still poorly known due to the lack of efficient extraction processes adequate to each plant system. Analyzing woody plants such as grapevine raises even more challenges. Grapevine is among the most important fruit crops worldwide and a wider characterization of its apoplast is essential for a deeper understanding of its physiology and cellular mechanisms. Here, we describe, for the first time, a vacuum-infiltration-centrifugation method that allows a simultaneous extraction of grapevine apoplastic proteins and metabolites from leaves on a single sample, compatible with high-throughput mass spectrometry analyses. The extracted apoplast from two grapevine cultivars, Vitis vinifera cv 'Trincadeira' and 'Regent', was directly used for proteomics and metabolomics analysis. The proteome was analyzed by nanoLC-MS/MS and more than 700 common proteins were identified, with highly diverse biological functions. The metabolome profile through FT-ICR-MS allowed the identification of 514 unique putative compounds revealing a broad spectrum of molecular classes.


Effect of clonidine and atropine on rest tremor in the MPTP monkey model of parkinsonism.
The purported alpha 2-adrenergic agonist clonidine was found to inhibit rest tremor at doses of 0.023-0.1 mg/kg in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of parkinsonism. The effect was dose dependent, but sedation and reduced mobility were observed. Atropine at doses of 0.1-1 mg/kg also reduced tremor in a dose-dependent fashion, but side-effects in the form of agitation, dilated pupils, and dry mouth were seen. When the two drugs were combined, however, we saw a significant potentiation of the antitremor effect. We could even abolish tremor with doses of atropine and clonidine that by themselves were without effect. The side-effects were almost eliminated by the combination.


Well-Defined Silanols in the Structure of the Calcined High-Silica Zeolite SSZ-70: New Understanding of a Successful Catalytic Material.
The structure of the calcined form of the high-silica zeolite SSZ-70 has been elucidated by combining synchrotron X-ray powder diffraction (XRPD), high-resolution transmission electron microscopy (HRTEM), and two-dimensional (2D) dynamic nuclear polarization (DNP)-enhanced NMR techniques. The framework structure of SSZ-70 is a polytype of MWW and can be viewed as a disordered ABC-type stacking of MWW-layers. HRTEM and XRPD simulations show that the stacking sequence is almost random, with each layer being shifted by ±1/3 along the ⟨110⟩ direction with respect to the previous one. However, a small preponderance of ABAB stacking could be discerned. DNP-enhanced 2D 29Si{29Si} J-mediated NMR analyses of calcined Si-SSZ-70 at natural 29Si isotopic abundance (4.7%) establish the through-covalent-bond 29Si-O-29Si connectivities of distinct Si sites in the framework. The DNP-NMR results corroborate the presence of MWW layers and, more importantly, identify two distinct types of Q3 silanol species at the surfaces of the interlayer regions. In the first, an isolated silanol group protrudes into the interlayer space pointing toward the pocket in the adjacent layer. In the second, the surrounding topology is the same, but the isolated -SiOH group is missing, leaving a nest of three Si-O-H groups in place of the three Si-O-Si linkages. The analyses clarify the structure of this complicated material, including features that do not exhibit long-range order. With these insights, the novel catalytic behavior of SSZ-70 can be better understood and opportunities for enhancement recognized.


M(BO)k+1- Anions: Novel Superhalogens Based on Boronyl Ligands.
Superhalogens have been a subject of continuous attraction in the last four decades due to their unusual structures and interesting applications. In the quest for new superhalogens based on boronyl (BO) ligands, we investigate M(BO)k+1- anions using a high-level ab initio CCSD(T) and B3LYP density functional method for M = Li, Na, K, Be, Mg, Ca, B, and Al. Their structures are linear for M = Li, Na, K; trigonal planar for M = Be, Mg, Ca; and tetrahedral for M = B, Al. These anions are energetically and thermodynamically stable against various fragmentations. Their superhalogen property has been established due to their higher vertical detachment energy (VDE) than halogen, being in the range 4.44-7.81 eV. For a given k, the stability and VDE of M(BO)k+1- anions decrease with an increase in the size of M, which is due to the decrease in charge delocalization on BO moieties. There exists a linear correlation between frontier orbitals energy gap and VDE with coefficient R2 = 0.93888. It was also noticed that the BO ligand, due to the lower dimerization energy, can be preferably used as an inorganic analogue of CN. However, the structural relaxation in BO-based neutral species significantly affect the VDE and, hence, their superhalogen nature. We believe that these findings should be interesting for researchers working in superatomic chemistry as well as in boron chemistry.


How optimal foragers should respond to habitat changes: a reanalysis of the Marginal Value Theorem.
The Marginal Value Theorem (MVT) is a cornerstone of biological theory. It connects the quality and distribution of patches in a fragmented habitat to the optimal time an individual should spend exploiting them, and thus its optimal rate of movement. However, predictions regarding how habitat alterations should impact optimal strategies have remained elusive, with heavy reliance on graphical arguments. Here we derive the sensitivity of realized fitness and optimal residence times to general habitat attributes, for homogeneous and heterogeneous habitats, retaining the level of generality of the MVT. We provide new predictions on how altering travel times, patch qualities and/or relative abundances should affect optimal strategies, and study the consequences of habitat heterogeneity. We show that knowledge of average characteristics is in general not sufficient to predict the change in the average rate of movement. We apply our results to examine the conditions under which the optimal strategies are invariant to scaling. We prove a previously conjectured form of invariance in homogeneous habitats, but show that invariances to scaling are not generic in heterogeneous habitats. We also consider the relative exploitation of patches that differ in quality, clarifying the conditions under which it is adaptive to stay longer on poorer patches.


Dynamic behavior in diplatinum metalloreceptors.
Diplatinum metalloreceptors anti-4a and anti-4b exhibit dynamic behavior in solution that is modified by anion binding. An X-ray crystal structure determination of anti-4a supports its proposed solution structure.


Structure of an acidic exopolysaccharide produced by the diazotrophic endophytic bacterium Burkholderia brasiliensis.
The structure of an exopolysaccharide (EPS) produced by Burkholderia brasiliensis, a diazotrophic endophytic organism originally isolated from rice roots, has been determined. The bacterium was grown in a synthetic medium, containing mannitol and glutamate, which favours the expression of two anionic EPSs, which were separated by anion-exchange chromatography. The structure of the repeat unit of EPS A, eluted at higher ionic strength, was determined by a combination of methylation analysis, partial hydrolysis, chemical degradations, and NMR spectroscopic studies, and shown to be the linear O-acetylated pentasaccharide: -->4)-alpha-D-Glcp-(1-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GlcpA-(1-->3)-beta-L-Rhap[2OAc]-(1-->4)-beta-D-Glcp-(1-->.


Air quality during demolition and recovery activities in post-Katrina New Orleans.
Air samples were collected during demolition and cleanup operations in the Lakeview district of New Orleans, Louisiana, USA, in late 2005 during the period immediately after Hurricane Katrina. Three different high-volume air samples were collected around waste collection areas that were created to temporarily hold the debris from the cleanup of residential properties in the area. Particulate concentrations were elevated and included crystalline fibers associated with asbestos. Metal concentrations on particulate matter resembled those measured in sediments deposited by floodwaters with the exception of Ba, which was elevated at all three locations. The highest organic contaminant concentration measured on particulates was the pesticide Ziram (Zinc, bis[diethylcarbamodithioato-S,S']-, [T-4]-) at 2,200 microg/g of particulate matter during sampling period 2. Ziram is used in latex paint, adhesives, caulking, and wallboard as a preservative. Fungal isolates developed from particulate air samples included species associated with disease including Aspergillus and Penicillium species. These data represent the most comprehensive assessment of demolition activities during the period immediately after Hurricane Katrina.


Comparison of Ligament Isometry and Patellofemoral Contact Pressures for Medial Patellofemoral Ligament Reconstruction Techniques in Skeletally Immature Patients.
Adult medial patellofemoral ligament (MPFL) reconstruction techniques are not appropriate for the skeletally immature patient given the proximity of the distal femoral physis. Biomechanical consequences of reconstructions aimed at avoiding the physis have not been adequately studied. To quantify the biomechanical effects of MPFL reconstruction techniques intended for skeletally immature patients. Controlled laboratory study. Four MPFL reconstruction techniques were evaluated using a computationally augmented cadaveric model: (1) Schoettle point: adult-type reconstruction; (2) epiphyseal: socket distal to the femoral physis; (3) adductor sling: graft wrapped around the adductor tendon; (4) adductor transfer: adductor tendon transferred to patella. A custom testing frame was used to cycle 8 knees for each technique from 10° to 110° of flexion. Patellofemoral kinematics were recorded using a motion camera system, contact stresses were recorded using Tekscan pressure sensors, and MPFL length was computed using an inverse kinematics computational model. Change in MPFL length, patellar facet forces, and patellar kinematics were compared using generalized estimating equation modeling. Schoettle point reconstruction was the most isometric, demonstrating isometry from 10° to 100°. The epiphyseal technique was isometric until 60°, after which the graft loosened with increasing flexion. The adductor sling and adductor transfer techniques were significantly more anisometric from 40° to 110°. Both grafts tightened with knee flexion and resulted in significantly more lateral patellar tilt versus the intact state in early flexion and significantly higher contact forces on the medial facet versus the epiphyseal technique in late flexion. In this cadaveric simulation, the epiphyseal technique allowed for a more isometric ligament until midflexion, when the patella engaged within the trochlear groove. The adductor sling and adductor transfer grafts became tighter in flexion, resulting in potential loss of motion, pain, graft stretching, and failure. Marginal between-condition differences in patellofemoral contact mechanics and patellar kinematics were observed in late flexion. In the skeletally immature patient, using an epiphyseal type MPFL reconstruction with the femoral attachment site distal to the physis results in a more isometric graft compared with techniques with attachment sites proximal to the physis.


[Dynamic features of tumefactive demyelinating lesions in different clinical stages by contrast-enhanced magnetic resonance imaging].
Objective: To explore the dynamic features of tumefactive demyelinating lesions (TDLs) in different clinical stages by contrast-enhanced magnetic resonance imaging (MRI). Methods: Thirty-five patients with TDLs proven by pathological studies were prospectively recruited from January 2015 to January 2017.Brain contrast-enhanced MRI of the patients in different clinical stages including acute phase, subacute phase and chronic phase were completed after enrollment.The characteristics of contrast-enhanced MRI in different clinical stages were compared and the evolutional characteristics were summarized. Results: (1) Acute phase (35/35): the patterns of enhancement were patchy (74.3%, n=26), nodule (34.3%, n=12), closed ring (14.3%, n=5) and open ring (11.4%, n=4). (2) Subacute phase (32/35): the patterns of enhancement were open ring (40.6%, n=13), closed ring (31.3%, n=10), patchy (25.0%, n=8) and irregular edge of enhancement (21.9%, n=7). (3) Chronic phase (15/35): the patterns of enhancement were pale patchy (10/15), open ring (5/15) and closed ring (2/15). (4) The proportions of enhancement patterns including patchy, nodule, edge enhancement and pale patchy were significantly different among different clinical stages: ① The patchy and nodule were the more common enhancement patterns in acute phase. ② The edge enhancement was found mostly in subacute phase. ③ The pale patchy was found mostly in chronic phase. Conclusions: The manifestation of the lesions on contrast-enhanced MRI may have some characteristics of dynamic evolution according to different clinical stages.The dynamic observation may be helpful for the diagnosis and differential diagnosis of TDLs.


Diagnostic value of T2-weighted imaging for the detection of superficial cranial artery inflammation in giant cell arteritis.
To evaluate the diagnostic value of T2-weighted radial MR imaging for the detection of superficial cranial arteries' inflammatory involvement in patients with giant cell arteritis (GCA). Forty-three patients with suspected giant cell arteritis underwent 3 Tesla (T) high-field MRI. T2-weighted inversion recovery (IR) fast spin echo images with radial sampling (BLADE-technique) were acquired and compared with postcontrast T1-weighted spin echo images. T2-weighted images revealed mural edema in the superficial cranial arteries in 11 patients in concordance with severe inflammatory contrast enhancement in T1-weighted images (grade 4 in a 4-point ranking scale). Excellent correlation (r = 0.82; P < 0.001) of measured wall thickness in T1- and T2-weighted images was achieved. The results of this study indicate the potential of radial T2 weighted imaging for a first detection of inflammatory changes in the small superficial cranial arteries without the need for contrast medium. Future studies are needed to evaluate the influence of spatial resolution of the T2 images and to improve the detection of moderate GCA related changes in vessel inflammation.


Mobilization of arachidonyl moieties from triacylglycerols into chloroplastic lipids following recovery from nitrogen starvation of the microalga Parietochloris incisa.
The microalga Parietochloris incisa (Trebouxiophyceae, Chlorophyta) was isolated from an alpine environment. It was found to accumulate unusually high amounts of arachidonic acid (AA)-rich TAG. We have hypothesized that microalgal PUFA-rich TAG might have a role as a depot of PUFA, which could be mobilized for the construction of chloroplastic membranes under sudden changes in environmental conditions. We have thus studied the changes in lipid and fatty acid composition during recovery from nitrogen starvation at 24 and 12 degrees C. At both temperatures, TAG was mainly consumed to support growth, however, there was a significant increase in the content of AA in the chloroplastic lipids, predominantly, monogalactosyldiacylglycerol (MGDG) at 24 degrees C, but much less so at 12 degrees C. Similar results were obtained using radiolabeled precursors. These and other findings point to the existence of three modes of operation for the construction of chloroplastic lipids that the alga can utilize to support growth under changing environmental conditions. When environmental conditions do not support growth, the prokaryotic pathway predominates. When sudden changes occur, the eukaryotic pathway is enhanced and can be even further augmented by influx of acyl moieties from TAG to maximize the exploitation of growth conditions that may possibly be transitory.


Management of intracardiac bullet embolisation and review of literature.
Vascular injury is a common complication in firearm injuries; however, intravascular missile embolism is relatively rare. There are only 38 documented cases of intravascular missile embolisation to the heart. Bullet embolisms are difficult to diagnose even with multiple diagnostic modalities and even once identified, the most optimal choice of surgical management is debated. Our patient presented with a gunshot wound to the right posterior shoulder. Cardiac focused assessment with sonography for trauma, chest X-ray, CT and echocardiogram were performed, showing missile location adjacent to the right ventricle with inconclusive evidence of pericardial injury. Exploratory median sternotomy was performed, revealing intact pericardium and injury to the superior vena cava (SVC) with bullet embolisation to the right ventricle. The patient became temporarily asystolic secondary to haemorrhage from the SVC injury. Cardiac massage was performed, dislodging the missile into the inferior vena cava. A venotomy was performed to retrieve the bullet and vascular injuries were primarily repaired.


Evolution of the mitochondrial DNA control region in the Anopheles gambiae complex.
We have sequenced the AT-rich control region of the mitochondrial DNA (mtDNA) of six species in the Afrotropical Anopheles gambiae complex and the closely related A. christyi. Contrary to expectations, the AT-rich region in this group is evolving rather slowly, more slowly than the third position of mtDNA protein-coding genes. Despite being relatively conserved between species, we detected intraspecific and intra-individual (heteroplasmy) variation in this region. Phylogenetically, we found we could place the rare endemic A. bwambae as a sister taxon to A. melas, the same evolutionary position as indicated by chromosomal inversions. The outgroup, A. christyi, gave evidence of the root of the tree. In comparing the molecular trees with that deduced by chromosomal inversions, they are completely congruent with the exception of the placement of A. arabiensis. The anomalous position of this species can be explained by introgression with A. gambiae. From the phylogenetic position, we could infer mtDNA gene flow from A. gambiae to A. arabiensis.


Rewarding actions of phencyclidine and related drugs in nucleus accumbens shell and frontal cortex.
Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens, indicating that the drug has direct rewarding actions in that region. Separate groups of rats learned to lever-press when reinforced with microinjections of dizoclipine (MK-801) or 3-((+/-)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP), drugs known to block NMDA receptor function but not dopamine uptake, into the same region. Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens. Self-administration of PCP, MK-801, or CPP directly into nucleus accumbens was not altered by co-infusion of a dose of the dopamine antagonist sulpiride that effectively blocked intracranial self-administration of the dopamine uptake inhibitor nomifensine, suggesting that the rewarding actions of the NMDA receptor antagonists are not dopamine-dependent. Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine. Thus nucleus accumbens and frontal cortex are each potential substrates for the rewarding properties of PCP and related drugs, and the ability of these drugs to disrupt NMDA receptor function seems sufficient to account for their rewarding actions. When considered with independent evidence, the present results suggest a model of drug reward within which the critical event is inhibition of medium spiny neurons in nucleus accumbens.


Traditional Herbal Medicine in Mesoamerica: Toward Its Evidence Base for Improving Universal Health Coverage.
The quality of health care in Mesoamerica is influenced by its rich cultural diversity and characterized by social inequalities. Especially indigenous and rural communities confront diverse barriers to accessing formal health services, leading to often conflicting plurimedical systems. Fostering integrative medicine is a fundamental pillar for achieving universal health coverage (UHC) for marginalized populations. Recent developments toward health sovereignty in the region are concerned with assessing the role of traditional medicines, and particularly herbal medicines, to foster accessible and culturally pertinent healthcare provision models. In Mesoamerica, as in most regions of the world, a wealth of information on traditional and complementary medicine has been recorded. Yet these data are often scattered, making it difficult for policy makers to regulate and integrate traditionally used botanical products into primary health care. This critical review is based on a quantitative analysis of 28 survey papers focusing on the traditional use of botanical drugs in Mesoamerica used for the compilation of the "Mesoamerican Medicinal Plant Database" (MAMPDB), which includes a total of 12,537 use-records for 2188 plant taxa. Our approach presents a fundamental step toward UHC by presenting a pharmacological and toxicological review of the cross-culturally salient plant taxa and associated botanical drugs used in traditional medicine in Mesoamerica. Especially for native herbal drugs, data about safety and effectiveness are limited. Commonly used cross-culturally salient botanical drugs, which are considered safe but for which data on effectiveness is lacking constitute ideal candidates for treatment outcome studies.


Antinociception from a stereospecific action of morphine microinjected into the brainstem: a local or distant site of action?
Morphine (1 microgram) was microinjected into rats in the midline medullary nucleus raphe magnus (NRM); 1 mm lateral into nucleus reticularis paragigantocellularis (NRPG); 2 mm lateral into the VIIth nerve nucleus and 3 mm lateral into the Vth nerve nucleus. The time course of changes in the sensitivity to noxious heat was followed by the tail flick test. Significant and prolonged antinociception was seen following microinjection into NRPG. At sites 1 mm from NRPG very weak effects were seen and at 2 mm from NRPG no antinociception occurred. It is concluded that 1 microgram of morphine microinjected into the brainstem is unlikely to cause antinociception by entering the circulation and having effects at remote sites. The distance diffused by morphine to cause significant antinociception after microinjection of 1 microgram is less than 1 mm. Levorphanol (1 microgram) had very similar effects to morphine but dextrorphan and saline were ineffective. It is concluded that although the concentrations achieved following microinjections may be high, they are not excessive as the effects show stereospecificity. The concentrations of endogenous substances released into the synaptic cleft may also be high.


Risk and protective factors for severe COVID-19 infection in a cohort of patients with sickle cell disease.
Continued investigation of comorbid conditions that increase the mortality rate of COVID-19 is necessary to provide the best care for those affected. This continued push to find answers is even more important for populations with COVID-19 comorbidities that are historically under-researched. We performed a retrospective analysis of 30 patients with sickle cell disease (SCD) who tested positive for the COVID-19 virus. An analysis of each patient's history of SCD complications, hydroxyurea usage, comorbidities, and several other factors was performed to identify the trends that will allow the practitioners to better predict the outcomes of patients with SCD before and during hospitalization for COVID-19. Through these analyses, we found that patients receiving hydroxyurea before COVID-19 infection and patients with SCD-type HbSC had significantly milder COVID-19 disease courses than those not receiving hydroxyurea or with SCD-type HbSS. A history of acute chest syndrome (ACS), a complication seen in patients with SCD, appeared to be associated with a more severe COVID-19 disease course. By creating systems to better interpret what makes a patient with SCD at high risk for a poor prognosis, practitioners are better equipped to make data-supported recommendations for prevention, risk, and treatment. These recommendations should include beginning or maintaining hydroxyurea usage in all qualifying patients with SCD, advising patients with a history of ACS to take extra precautions to prevent initial COVID-19 infection, and initiating close monitoring in the hospital for patients with HbSS and a history of ACS.


Thylakoid polypeptides of light and dark aged chloroplasts.
Spinach (Spinacia oleracea) chloroplasts were aged at 4 degrees C under red light and in the dark. The electron transport activity was monitored together with the thylakoid polypeptide patterns in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The light-induced decay of photosystem II (PSII) activity (half-life, about 4 hours) was correlated with a decrease in polypeptides with apparent molecular weights of 36, 48, and 50 kilodaltons. There was very little decay of photosystem I (PSI) activity until after 8 hours illumination. Prior freezing of the chloroplasts enhanced the decrease in PSI activity which was correlated with chlorophyll-protein complex I (CPI) disappearance and an increase in a polypeptide with apparent molecular weight of 60 kilodalton. No variations were detected in the light-harvesting chlorophyll a/b protein. In the dark, the decay of PSII started at 4 to 6 hours and showed a half life of about 30 hours. PSI activity decay (half life about 6 days) occurred simultaneously with the disappearance of CPI. The use of bovine serum albumin (30 mg/mg of chlorophyll) in the light-induced decay experiments increased the stability of PSII more than 2-fold; in the dark experiments, the stability of both photosystems was also more than doubled and the stability of the CPI complex was considerably improved. Comparative electrophoresis of the purified proteins indicated no changes in the cytochrome f band or in the subunits of the ATPase coupling factor during the light-induced decay experiments. Heating of purified PSI particles prior to electrophoresis showed that the 60 kilodaltons polypeptide increased with the disappearance of CPI.


Survival Training Effects on Oxidative Stress and Muscle Damage Biomarkers of Naval Cadets.
INTRODUCTION: It is important for military commanders to know the extent of fatigue experienced by soldiers undergoing a long-term military training. This knowledge can enable them to determine the level of physical capabilities of soldiers. The present study aimed to evaluate changes in the level of chosen biochemical parameters in blood during the survival training of Polish Naval Academy cadets.METHODS: Participating voluntarily in the research study were 14 cadets. All subjects were men, ages 23.1 2.0 yr. During the 36-h survival training, the subjects were deprived of sleep. The following biochemical parameters were assessed in venous blood collected from the cadets: creatine kinase (CK) activity, concentration of lipid hydroperoxides (LOOHs), superoxide dismutase activity (SOD), and glutathione peroxidase activity (GPx).RESULTS: After 36 h of training a significant increase was observed in CK (from 183.1 up to 530.2 U L1), LOOHs (from 1.72 up to 3.74 mol L1), and GPx (from 27.4 up to 36.4 U gHb1). After 12 h of rest, the level of LOOHs returned to the initial level, GPx activity did not change significantly, and CK activity was significantly higher than those at baseline (422.3 U L1).DISCUSSION: The 36-h survival training increased oxidative stress, which contributed to the damage to muscle cells in the group of cadets of the Polish Naval Academy. The intensity of postexercise changes in the level of oxidative damage indicators is dependent on the initial level of enzymatic antioxidant defense. The 12-h recovery proved to be too short to regenerate the damaged muscle tissue.Tomczak A, Jwko E, Raski P. Survival training effects on oxidative stress and muscle damage biomarkers of naval cadets. Aerosp Med Hum Perform. 2020; 91(9):720724.


Disordered Eating among People with Schizophrenia Spectrum Disorders: A Systematic Review.
Disordered eating, or abnormal eating behaviours that do not meet the criteria for an independent eating disorder, have been reported among people with schizophrenia. We aimed to systemati-cally review literature on disordered eating among people with schizophrenia spectrum disorder (SSD). Seven databases were systematically searched for studies that described the prevalence and correlates of disordered eating among patients with SSD from January 1984 to 15 February 2021. Qualitative analysis was performed using the National Institutes of Health scales. Of 5504 records identified, 31 studies involving 471,159 subjects were included in the systematic review. The ma-jority of studies (17) rated fair on qualitative analysis and included more men, and participants in their 30s and 40s, on antipsychotics. The commonest limitations include lack of sample size or power calculations, poor sample description, not using valid tools, or not adjusting for con-founders. The reported rates were 4.4% to 45% for binge eating, 16.1% to 64%, for food craving, 27% to 60.6% for food addiction, and 4% to 30% for night eating. Positive associations were re-ported for binge eating with antipsychotic use and female gender, between food craving and weight gain, between food addiction and increased dietary intake, and between disordered eating and female gender, mood and psychotic symptoms. Reported rates for disordered eating among people with SSD are higher than those in the general population. We will discuss the clinical, treatment and research implications of our findings.


Purification, properties, and distribution of ascorbate peroxidase in legume root nodules.
All aerobic biological systems, including N(2)-fixing root nodules, are subject to O(2) toxicity that results from the formation of reactive intermediates such as H(2)O(2) and free radicals of O(2). H(2)O(2) may be removed from root nodules in a series of enzymic reactions involving ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. We confirm here the presence of these enzymes in root nodules from nine species of legumes and from Alnus rubra. Ascorbate peroxidase from soybean nodules was purified to near homogeneity. This enzyme was found to be a hemeprotein with a molecular weight of 30,000 as determined by sodium dodecyl sulfate gel electrophoresis. KCN, NaN(3), CO, and C(2)H(2) were potent inhibitors of activity. Nonphysiological reductants such as guaiacol, o-dianisidine, and pyrogallol functioned as substrates for the enzyme. No activity was detected with NAD(P)H, reduced glutathione, or urate. Ascorbate peroxidation did not follow Michaelis-Menten kinetics. The substrate concentration which resulted in a reaction rate of (1/2) V(max) was 70 micromolar for ascorbate and 3 micromolar for H(2)O(2). The high affinity of ascorbate peroxidase for H(2)O(2) indicates that this enzyme, rather than catalase, is responsible for most H(2)O(2) removal outside of peroxisomes in root nodules.


[Propranolol for prophylaxis of first hemorrhage in cirrhotic patients with esophageal varices--a controlled study comparing with sclerotherapy].
To compare the efficacy of oral propranolol and sclerotherapy in the prevention of first hemorrhage from esophageal varices, 65 cirrhotic patients with moderate to large esophageal varices and no history of bleeding were included in the prospective controlled trial. After randomization, 33 patients received propranolol at a does reducing the heart rate by 25%; 32 patients were treated with intra-variceal and extra-variceal injection of ethanolamine oleate. On entry to the trial, the two groups were comparable in terms of clinical and biological parameters. The patients were observed for up to 60 months, with an average of 31 months. Nine patients bled (5 in propranolol and 4 in sclerotherapy) during follow-up. No significant difference were observed between propranolol and sclerotherapy in the cumulative bleeding rate and survival. The multivariate Cox model indicated that drug compliance in the propranolol group and high portal pressure in the sclerotherapy group were factors predictive of the first hemorrhage. These data support that propranolol and sclerotherapy are of comparable value in preventing the first hemorrhage in cirrhotic patients with esophageal varices.


Synthesis, structures and reactions of acylsulfenyl iodides with theoretical investigations.
A series of acylsulfenyl iodides (RCOSI) were synthesized by the reactions of carbothioic acid group 11-16 element derivatives with iodine or N-iodosuccinimides in moderate to good yields. The structure of the PhCOSI was nearly square planar based on the X-ray analysis, where the C[double bond, length as m-dash]O⋯I distance (3.153(5) Å) was significantly shorter than the sum of the van der Waals radii of the atoms (Σr vdW), indicating close contact within the molecule. The distances between an iodine atom and the neighbouring two iodine atoms were also less than Σr vdW, perhaps due to the energy lowering effect of the interactions. The acylsulfenyl iodides readily reacted with alkenes and alkynes to give the expected addition products in moderate to good yields at approximately 0 °C. A new synthesis of acylated sulfines, sulfenamides and sulfenochalcogenides using acylsulfenyl iodides is also described. Theoretical calculations were performed on PhCOSI with the Sapporo-TZP(+1s1p) basis sets at the MP2 level, which perfectly reproduced the observed structures. Similar calculations were performed on the reactions, exemplified by those of MeCOSI and CH2[double bond, length as m-dash]CH2, together with those of MeSI and CH2[double bond, length as m-dash]CH2. Mechanisms for both reactions were proposed, which were very similar. The proposed mechanism for the former was understood based on that of the latter. For both mechanisms, the episulfuranes and episulfonium ions played an important role. The dynamic and static nature of the bonds in the COSI group of PhCOSI and MeCOSI were elucidated based on QTAIM dual functional analysis.


Eco-Friendly Procedure for Rendering the Antibacterial and Antioxidant of Cotton Fabrics via Phyto-Synthesized AgNPs With Malva sylvestris (MS) Natural Colorant.
There is a growing interest for producing multifunctional cellulose fabrics using green and sustainable technology. In this study, we explored an eco-friendly procedure for dyeing cotton fabrics with Malva sylvestris (MS) as a natural colorant and rendering antibacterial cotton fabric by the silver nanoparticles. MS colorants were extracted from dried petals in water using the ultrasound technique, cotton fabrics were dyed with the extracted MS colorant at 100°C for 90 min. The colorimetric data and colorfastness properties were investigated in the absence and presence of tannic acid (TA) as a bio-mordant. Results indicated that MS dye had a high potential for reducing the silver nitrate, so that the silver particle size distribution on cotton fabric was obtained 50-80 nm, and TA had a positive effect on the MS extract and reduced Ag on the cotton. Furthermore, the reduction of bacterial growth of the dyed cotton considerably (up to 99%) improved by AgNPs. The wash-, and light-fastness properties of samples dyed with MS were enhanced from moderate to good-very good by mordanting.


Multifarious Indigenous Diazotrophic Rhizobacteria of Rice (Oryza sativa L.) Rhizosphere and Their Effect on Plant Growth Promotion.
A diverse group of rhizobacteria persists in the rhizospheric soil, on the surface of roots, or in association with rice plants. These bacteria colonize plant root systems, enhance plant growth and crop yield. Indigenous rhizobacteria are known to promote soil health, grain production quality and serve as sustainable bioinoculant. The present study was aimed to isolate, identify and characterize indigenous plant growth promoting (PGP) diazotrophic bacteria associated with the rhizosphere of rice fields from different areas of Jammu and Kashmir, India. A total of 15 bacteria were isolated and evaluated for various PGP traits, antagonistic activity against phytopathogens, production of hydrolytic enzymes and biofilm formation under in-vitro conditions. The majority of the isolated bacteria were Gram-negative. Out of 15 bacterial isolates, nine isolates produced IAA (12.24 ± 2.86 to 250.3 ± 1.15 μg/ml), 6 isolates exhibited phosphate solubilization activity (36.69 ± 1.63 to 312.4 ± 1.15 μg/ml), 7 isolates exhibited rock phosphate solubilization while 5 isolates solubilized zinc (10-18 mm), 7 isolates showed siderophore production, 8 isolates exhibited HCN production, 6 isolates exhibited aminocyclopropane-1-carboxylate (ACC) deaminase activity, 13 isolates exhibited cellulase activity, nine isolates exhibited amylase and lipase activity and six isolates exhibited chitinase activity. In addition, 5 isolates showed amplification with the nifH gene and showed a significant amount of nitrogenase activity in a range of 0.127-4.39 μmol C2H4/mg protein/h. Five isolates viz., IHK-1, IHK-3, IHK-13, IHK-15 and IHK-25 exhibited most PGP attributes and successfully limited the mycelial growth of Rhizoctonia solani and Fusarium oxysporum in-vitro. All the five bacterial isolates were identified based on morphological, biochemical and 16S rDNA gene sequencing study, as Stenotrophomonas maltophilia, Enterobacter sp., Bacillus sp., Ochrobactrum haematophilum and Pseudomonas aeruginosa. Rice plants developed from seeds inoculated with these PGP strains individually had considerably higher germination percentage, seed vigor index and total dry biomass when compared to control. These findings strongly imply that the PGP diazotrophic bacteria identified in this work could be employed as plant growth stimulators in rice.


Metabolic reprogramming in glioblastoma: the influence of cancer metabolism on epigenetics and unanswered questions.
A defining hallmark of glioblastoma is altered tumor metabolism. The metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation, regardless of oxygen availability, is a phenomenon known as the Warburg effect. In addition to the Warburg effect, glioblastoma tumor cells also utilize the tricarboxylic acid cycle/oxidative phosphorylation in a different capacity than normal tissue. Altered metabolic enzymes and their metabolites are oncogenic and not simply a product of tumor proliferation. Here we highlight the advantages of why tumor cells, including glioblastoma cells, require metabolic reprogramming and how tumor metabolism can converge on tumor epigenetics and unanswered questions in the field.


Ionizable lipid nanoparticles for in utero mRNA delivery.
Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)-mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.


The Microbiota of Grana Padano Cheese. A Review.
Grana Padano (GP) is the most appreciated and marketed cheese with Protected Designation of Origin in the world. The use of raw milk, the addition of undefined cultures (defined as 'sieroinnesto naturale'), the peculiar manufacturing proces, and the long ripening make the cheese microbiota play a decisive role in defining the quality and the organoleptic properties of the product. The knowledge on the microbial diversity associated with GP has been the subject, in recent years, of several studies aimed at understanding its composition and characteristics in order, on the one hand, to improve its technological performances and, on the other hand, to indirectly enhance the nutritional quality of the product. This review aims to briefly illustrate the main available knowledge on the composition and properties of the GP microbiota, inferred from dozens of studies carried out by both classical microbiology techniques and metagenomic analysis. The paper will essentially, but not exclusively, be focused on the lactic acid bacteria (LAB) derived from starter (SLAB) and the non-starter bacteria, both lactic (NSLAB) and non-lactic, of milk origin.


Hemostatic function of packed red blood cells: an in-vitro study.
Clinical observations suggest that red blood cells (RBCs) participate directly in hemostasis. We designed an in-vitro system aimed at evaluating the hemostatic function of RBCs. Blood samples were collected from 20 healthy volunteers and packed RBCs (PRBCs) were supplied by the Shaanxi Province Blood Center. We investigated the effect of RBCs and hemoglobin concentration on the hemostatic function in vitro by thromboelastography. The activation of platelets was evaluated by detecting their active markers through flow cytometry. PRBCs ameliorated the coagulation disorders induced by dilution of the blood in vitro. However, addition of hemoglobin did not increase the blood coagulation, as the level of hemoglobin was negatively correlated to the clot index. Furthermore, washing PRBCs to remove contaminating residual clotting factors and platelets excluded that the coagulation effect of the PRBCs transfusion was because of the RBCs itself. Platelet activity in PRBCs exposed to storage greater than 3 weeks was not significantly reduced consistent with it being a possible contributor. Therefore, we postulate that the suspected coagulation effects ascribed to the PRBCs at transfusion may simply be because of residual clotting factors and active platelets incompletely removed in the preparation of PRBCs rather than because of the red cell membrane or its contents.


Angina: current approaches to diagnosis, drug therapy, and surgical referral.
An abnormal resting ST segment renders the stress ECG impossible to interpret. Therefore, one must substitute a radionuclide stress evaluation in the presence of digitalis, left bundle-branch block, left ventricular hypertrophy, a paced rhythm, or any other condition that would cause abnormal baseline ST segments. All these are more common in the elderly. Beta-blocker therapy is useful in patients with demand-related ischemia because it decreases two of the major determinants of myocardial oxygen demand: heart rate and contractility. Propranolol, timolol, and metoprolol have been shown to decrease the reinfarction and mortality rates in patients who have had an infarction.


In-Vitro Selection of Ceftazidime/Avibactam Resistance in OXA-48-Like-Expressing Klebsiella pneumoniae: In-Vitro and In-Vivo Fitness, Genetic Basis and Activities of β-Lactam Plus Novel β-Lactamase Inhibitor or β-Lactam Enhancer Combinations.
Ceftazidime/avibactam uniquely demonstrates activity against both KPC and OXA-48-like carbapenemase-expressing Enterobacterales. Clinical resistance to ceftazidime/avibactam in KPC-producers was foreseen in in-vitro resistance studies. Herein, we assessed the resistance selection propensity of ceftazidime/avibactam in K. pneumoniae expressing OXA-48-like β-lactamases (n = 10), employing serial transfer approach. Ceftazidime/avibactam MICs (0.25-4 mg/L) increased to 16-256 mg/L after 15 daily-sequential transfers. The whole genome sequence analysis of terminal mutants showed modifications in proteins linked to efflux (AcrB/AcrD/EmrA/Mdt), outer membrane permeability (OmpK36) and/or stress response pathways (CpxA/EnvZ/RpoE). In-vitro growth properties of all the ceftazidime/avibactam-selected mutants were comparable to their respective parents and they retained the ability to cause pulmonary infection in neutropenic mice. Against these mutants, we explored the activities of various combinations of β-lactams (ceftazidime or cefepime) with structurally diverse β-lactamase inhibitors or a β-lactam enhancer, zidebactam. Zidebactam, in combination with either cefepime or ceftazidime, overcame ceftazidime/avibactam resistance (MIC range 0.5-8 mg/L), while cefepime/avibactam was the second best (MIC: 0.5-16 mg/L) in yielding lower MICs. The present work revealed the possibility of ceftazidime/avibactam resistance in OXA-48-like K. pneumoniae through mutations in proteins involved in efflux and/or porins without concomitant fitness cost mandating astute monitoring of ceftazidime/avibactam resistance among OXA-48 genotypes.


Ensemble recordings in awake rats: achieving behavioral regularity during multimodal stimulus processing and discriminative learning.
To meet an increasing need to examine the neurophysiological underpinnings of behavior in rats, we developed a behavioral system for studying sensory processing, attention and discrimination learning in rats while recording firing patterns of neurons in one or more brain areas of interest. Because neuronal activity is sensitive to variations in behavior which may confound the identification of neural correlates, a specific aim of the study was to allow rats to sample sensory stimuli under conditions of strong behavioral regularity. Our behavioral system allows multimodal stimulus presentation and is coupled to modules for delivering reinforcement, simultaneous monitoring of behavior and recording of ensembles of well isolated single neurons. Using training protocols for simple and compound discrimination, we validated the behavioral system with a group of 4 rats. Within these tasks, a majority of medial prefrontal neurons showed significant firing-rate changes correlated to one or more trial events that could not be explained from significant variation in head position. Thus, ensemble recordings can be combined with discriminative learning tasks under conditions of strong behavioral regularity.


In situ crosslinking of a biomimetic peptide-PEG hydrogel via thermally triggered activation of factor XIII.
There is a medical need for robust, biocompatible hydrogels that can be rapidly crosslinked in situ through the use of gentle and non-toxic triggers, which could be used as a surgical adhesive, a bone-inductive material, or for drug and gene delivery. The complete gelation system described here includes calcium-loaded liposomes, hrFactor XIII. thrombin, and an enzymatic substrate based on a four-armed PEG in which each arm terminates with a 20mer peptide sequence derived from the gamma-chain of fibrin. Controlled release of calcium ions for efficient hrFXIII activation was accomplished by thermal triggering of a tailored liposome phase transition at 37 degrees C, which allowed the entire gelation system to be stored in aqueous solution at room temperature without premature gelation. When the system temperature was raised to 37 degrees C (body temperature), the released calcium activates the hrFactor XIII, and gelation was observed to occur within 9 min. Rheological studies performed to quantitatively determine the storage modulus (G') of the gel during oscillatory shear show that it behaves as a robust, elastic solid. Scanning electron microscopy studies revealed the hydrogel to have a very dense morphology overall, however spherical voids are observed in regions where calcium-loaded liposomes were entrapped during gelation.


[African sleeping sickness in The Netherlands].
Of the four most dangerous protozoal infections acquired in (sub)tropical regions, falciparum malaria, amoebic abscess of the liver, visceral leishmaniasis (kala azar) and African trypanosomiasis (sleeping sickness) only the fourth was up to now unreported in the Dutch medical literature. Two case histories are presented: a Cameroonian woman, resident in the Netherlands for two years, suffering from West African type sleeping sickness, and a Dutch tourist who acquired East African trypanosomiasis while travelling through Zimbabwe. Although the parasites are morphologically identical, clinical and epidemiological characteristics are distinctly different. The West African type, rarely if ever observed in Europeans, has an insidious chronic course leading to the features of classical sleeping sickness. Differential diagnosis is difficult. The East African variety runs an acute course in Europeans leading to death within days due to myocarditis. It is therefore mandatory for the diagnosis to be made as soon as possible in order to initiate specific therapy. Both patients recovered after specific therapy.


Report from the International Bone Marrow Transplant Registry and Autologous Blood and Marrow Transplant Registry - North America.
Allogeneic and autologous bone marrow and blood cell transplants are increasingly used treatments for cancer and disorders of bone marrow and immune function. This is largely due to use of autotransplants to treat common diseases such as breast cancer. The use of blood cells alone for autotransplants was also a significant change in the past 5 years. The IBMTR and ABMTR continue to provide a unique resource for studying outcomes and trends in allogeneic and autologous bone marrow and blood cell transplants.


Resveratrol given intraperitoneally does not inhibit the growth of high-risk t(4;11) acute lymphoblastic leukemia cells in a NOD/SCID mouse model.
The efficacy of resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL SEM cell line. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, mice were injected intraperitoneally with resveratrol (10 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). Comparisons of the percent of human leukemia cells in blood and survival curves showed resveratrol did not inhibit progression of the disease. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed resveratrol was rapidly metabolized to glucuronidated and sulfated forms 1 h post-injection, with low to no resveratrol or metabolites observed in sera by 24-48 h. These data indicate that in contrast to findings in in vitro models, parenterally administered resveratrol does not have potential as a preventive agent against high risk t(4;11) ALL.


Protein oxidation enhances hydration but suppresses water-holding capacity in porcine longissimus muscle.
Pork longissimus muscle was oxidized at 4 °C by mixed 10 μM FeCl(3)/100 μM ascorbate with 1, 5, 10, 20, 30, 40, or 50 mM H(2)O(2) (pH 6.2). Oxidation with >1 mM H(2)O(2) for 40 min significantly (P < 0.05) enhanced hydration of muscle samples, whereas oxidation with 40 and 50 mM H(2)O(2) for 2 min or with 20 mM H(2)O(2) for 40 min caused pronounced declines in water-holding capacity and product yield. The changes coincided with marked increases in the protein carbonyl content, TBARS formation, and cross-linking of both myofibrillar and sarcoplasmic proteins. Dye-tracing tests showed that the enhanced hydration at >1 mM H(2)O(2) was due to facilitated water diffusion into muscle tissue. This result was strongly corroborated by microscopic images that illustrated enlargements of intercellular spacing, that is, gaps, in oxidized muscle tissue, which served as canals for water diffusion.


Three-dimensional orientation sensors by defocused imaging of gold nanorods through an ordinary wide-field microscope.
Gold (Au) nanoparticles, particularly nanorods, are actively employed as imaging probes because of their special nonblinking and nonbleaching absorption, scattering, and emitting properties that arise from the excitation of surface plasmons. Herein, we report a novel sensing method that detects feature orientation at the nanoscale via the defocused imaging of individual Au nanorods (AuNRs) with an ordinary wide-field optical microscope. By simultaneously recording defocused images and two-photon luminescence intensities for a large number of individual AuNRs, we correlate their defocused images with their three-dimensional spatial orientations. The spatial orientation of many individual AuNRs can be monitored in situ and in real-time within a single frame, enabling its use as a technique for high-throughput sensing. The probe size can be as small as several nanometers, which is highly desirable for minimization of any potential interference from the probe itself. Furthermore, the sensing property is insensitive to the excitation polarization and the distribution of the probe aspect ratio, which allows AuNRs of any length within a proper regime to be used as orientation sensors without changing the laser frequency and polarization. These unique features make the orientation probes proposed here outstanding candidates for optical imaging and sensing in materials science and biological applications.


Digestive Disease Week.
We review key sessions on pharmacological treatment, including four on irritable bowel syndrome and others on pancreatitis and Helicobacter pylori infection.


Learning to generalize.
Electric fish are able to take what they have learnt about sensory processing in certain situations and apply it in other situations.


E-mail Use among a sample of intimate partner violence shelter residents.
Although it is estimated that approximately 75% of U.S. adults have e-mail access, the proportion of battered women's shelter residents who use e-mail is currently unknown. Remaining in contact with residents following shelter stays is challenging. E-mail might hold promise for follow-up contact if a sufficient number of survivors use e-mail and safety concerns can be addressed. Among a convenience sample of residents of 11 Massachusetts shelters (N = 57), the authors find that 47% had a current e-mail account. Among those with e-mail accounts, 89% used e-mail in locations other than their own homes; 81% reported that, to their knowledge, their e-mail accounts had never been accessed by unauthorized dating partners; and 88% reported that they thought it would be safe for the shelter to e-mail them following their departure. Additional research assessing the feasibility (i.e., safety, acceptability, and cost benefit) of remaining in contact with shelter residents via the Internet would be beneficial.


Femoral specializations to locomotor habits in early archosauriforms.
The evolutionary history of archosaurs and their closest relatives is characterized by a wide diversity of locomotor modes, which has even been suggested as a pivotal aspect underlying the evolutionary success of dinosaurs vs. pseudosuchians across the Triassic-Jurassic transition. This locomotor diversity (e.g., more sprawling/erect; crouched/upright; quadrupedal/bipedal) led to several morphofunctional specializations of archosauriform limb bones that have been studied qualitatively as well as quantitatively through various linear morphometric studies. However, differences in locomotor habits have never been studied across the Triassic-Jurassic transition using 3D geometric morphometrics, which can relate how morphological features vary according to biological factors such as locomotor habit and body mass. Herein, we investigate morphological variation across a dataset of 72 femora from 36 different species of archosauriforms. First, we identify femoral head rotation, distal slope of the fourth trochanter, femoral curvature, and the angle between the lateral condyle and crista tibiofibularis as the main features varying between bipedal and quadrupedal taxa, all of these traits having a stronger locomotor signal than the lesser trochanter's proximal extent. We show a significant association between locomotor mode and phylogeny, but with the locomotor signal being stronger than the phylogenetic signal. This enables us to predict locomotor modes of some of the more ambiguous early archosauriforms without relying on the relationships between hindlimb and forelimb linear bone dimensions as in prior studies. Second, we highlight that the most important morphological variation is linked to the increase of body size, which impacts the width of the epiphyses and the roundness and proximodistal position of the fourth trochanter. Furthermore, we show that bipedal and quadrupedal archosauriforms have different allometric trajectories along the morphological variation in relation to body size. Finally, we demonstrate a covariation between locomotor mode and body size, with variations in femoral bowing (anteroposterior curvature) being more distinct among robust femora than gracile ones. We also identify a decoupling in fourth trochanter variation between locomotor mode (symmetrical to semi-pendant) and body size (sharp to rounded). Our results indicate a similar level of morphological disparity linked to a clear convergence in femoral robusticity between the two clades of archosauriforms (Pseudosuchia and Avemetatarsalia), emphasizing the importance of accounting for body size when studying their evolutionary history, as well as when studying the functional morphology of appendicular features. Determining how early archosauriform skeletal features were impacted by locomotor habits and body size also enables us to discuss the potential homoplasy of some phylogenetic characters used previously in cladistic analyses as well as when bipedalism evolved in the avemetatarsalian lineage. This study illuminates how the evolution of femoral morphology in early archosauriforms was functionally constrained by locomotor habit and body size, which should aid ongoing discussions about the early evolution of dinosaurs and the nature of their evolutionary "success" over pseudosuchians.


A Quantification of Scalp Thickness before and after Posterior Vault Distraction Osteogenesis.
Previous literature has documented craniometric changes of the bony calvaria, increases in intracranial volume, and resolution of Chiari malformations following posterior vault distraction osteogenesis. No studies have analyzed changes to the soft-tissue envelope after posterior vault distraction osteogenesis. In this study, the authors aimed to provide objective measurements of scalp thickness in patients undergoing posterior vault distraction osteogenesis, utilizing facial soft-tissue thickness as a proxy to control for growth. The authors hypothesized that the soft tissues of the scalp are not made thinner by the distraction process, either in the region of distraction or in neighboring areas. Subjects who underwent posterior vault distraction osteogenesis for a craniosynostosis diagnosis who had high-resolution predistraction and post-distractor removal computed tomographic scans within 100 days of each operation were included. The scans were analyzed on Materialise Mimics version 21 software (Materialise, Ghent, Belgium). Six key craniometric landmarks (glabella, pogonion, zygion, vertex, euryon, and opisthocranium) were identified on the three-dimensional bone masks in the Frankfort horizontal plane. The points were overlaid onto soft-tissue thickness masks and thicknesses were recorded. Percent change in postoperative facial soft-tissue thickness was used to control for growth of the craniofacial soft-tissue envelope during the study interval. The preoperative and postoperative posterior vault distraction osteogenesis cohorts did not differ significantly at the glabella, pogonion, opisthocranium, vertex, and zygion. The corrected median thickness at the euryon was significantly increased in the post-posterior vault distraction osteogenesis cohort [2.67 mm (IQR, 2.49 mm to 4.02 mm) versus 5.26 mm (IQR, 3.83 mm to 7.82 mm), p = 0.002]. This is the first study to quantify changes in soft-tissue thicknesses preoperatively and postoperatively in patients undergoing posterior vault distraction osteogenesis, demonstrating maintenance of scalp thickness. . Therapeutic, IV.


Detecting the effects of toxic agents on spermatogenesis using DNA probes.
Advances in the molecular biology of spermatogenesis suggest that DNA probes can be used to monitor the effects of toxic agents in male germ cells of mammals. Molecular hybridization analyses with DNA probes can provide a reproducible methodology capable of detecting changes ranging from massive deletions to single base pair substitutions in the genome of exposed individuals. A constantly increasing number of DNA probes that can be used to detect such alterations in human sperm DNA exist for both ubiquitously expressed proteins and for genes solely expressed in the testis. In this chapter, the currently available testicular stage-specific and/or cell type-specific DNA probes and the techniques by which they can be utilized in reproductive toxicology studies are discussed. The advantages, limitations, and future technological advances of this novel biological marker system for the human male reproductive system are also considered.


Inkjet Printing of Liquid Silicon.
A precursor solution for semiconducting Si called liquid Si (liq-Si) is synthesized, and semiconducting Si is inkjet-printed. Satisfactory inkjet discharge is achieved using liq-Si consisting of liquid-phase polysilane with an average molecular weight of 2500 g mol-1 . The printed liq-Si is converted into amorphous Si by heating at 400 °C. The resulting Si film has a flat surface with a root-mean-square roughness of 0.8 nm. These results are extended to n- and p-type Si films by synthesizing liq-Si chemically doped with P and B compounds, respectively. Liq-Si inkjet printing produces Si patterns without using traditional photolithography processes, opening up the field of printed Si electronics.


Direct evidence of the role of ATPγS in the binding of single-stranded binding protein (Escherichia coli) and RecA to single-stranded DNA.
To gain insight into the influence of ATPγS on the competitive binding of RecA and single-stranded binding protein (SSB) on single-stranded DNA (ssDNA), AFM imaging was used to examine the three-dimensional structures of the different complexes formed by the binding of the two proteins on ssDNA in the presence and absence of ATPγS. In the presence of ATPγS, RecA attaches to ssDNA, displacing SSB, to form continuous binding regions that caused considerable elongation of the strand. When ATPγS is absent, RecA could not compete with SSB and only binds at a few sites that correspond to the vacancy in ssDNA left when SSB unbinds. These results provide direct evidence that, while SSB binding affinity to DNA is substantially higher than that of RecA, the presence of ATPγS is sufficient to alter the events and enable RecA coating of DNA.


The meaning of component analysis: decomposition of the free energy in terms of specific interactions.
Free energy simulations are of particular interest for the interpretation of macroscopic data in terms of microscopic interactions. This can be done by expressing calculated free energies as a sum of components that correspond to the contributions of different energy terms or different parts of the system. Since the resulting components depend on the integration path, care is required for their use. We show that a linear coupling scheme for the alchemical creation of a chemical identity corresponds to a particularly useful path because it leads to a symmetric decoupling of the free energy components. The path dependence also provides an additional degree of freedom that can be used to study different processes. This latter point is illustrated by a reinterpretation of a recent simulation on wild-type and mutant azurin by Mark and van Gunsteren.


The Epidermal Microbiome Within an Aggregation of Leopard Sharks (Triakis semifasciata) Has Taxonomic Flexibility with Gene Functional Stability Across Three Time-points.
The epidermis of Chondrichthyan fishes consists of dermal denticles with production of minimal but protein-rich mucus that collectively, influence the attachment and biofilm development of microbes, facilitating a unique epidermal microbiome. Here, we use metagenomics to provide the taxonomic and functional characterization of the epidermal microbiome of the Triakis semifasciata (leopard shark) at three time-points collected across 4 years to identify links between microbial groups and host metabolism. Our aims include (1) describing the variation of microbiome taxa over time and identifying recurrent microbiome members (present across all time-points); (2) investigating the relationship between the recurrent and flexible taxa (those which are not found consistently across time-points); (3) describing the functional compositions of the microbiome which may suggest links with the host metabolism; and (4) identifying whether metabolic processes are shared across microbial genera or are unique to specific taxa. Microbial members of the microbiome showed high similarity between all individuals (Bray-Curtis similarity index = 82.7, where 0 = no overlap, 100 = total overlap) with the relative abundance of those members varying across sampling time-points, suggesting flexibility of taxa in the microbiome. One hundred and eighty-eight genera were identified as recurrent, including Pseudomonas, Erythrobacter, Alcanivorax, Marinobacter, and Sphingopxis being consistently abundant across time-points, while Limnobacter and Xyella exhibited switching patterns with high relative abundance in 2013, Sphingobium and Sphingomona in 2015, and Altermonas, Leeuwenhoekiella, Gramella, and Maribacter in 2017. Of the 188 genera identified as recurrent, the top 19 relatively abundant genera formed three recurrent groups. The microbiome also displayed high functional similarity between individuals (Bray-Curtis similarity index = 97.6) with gene function composition remaining consistent across all time-points. These results show that while the presence of microbial genera exhibits consistency across time-points, their abundances do fluctuate. Microbial functions however remain stable across time-points; thus, we suggest the leopard shark microbiomes exhibit functional redundancy. We show coexistence of microbes hosted in elasmobranch microbiomes that encode genes involved in utilizing nitrogen, but not fixing nitrogen, degrading urea, and resistant to heavy metal.


Acute coronary syndrome - a frequent clinical manifestation of bare metal in-stent restenosis.
In-stent restenosis (ISR) complicates 20-30% of percutaneous coronary interventions (PCI) with bare metal stent (BMS) implantation. Although the widespread use of drug eluting stents (DES) across Europe caused a considerable reduction of BMS implantations, their number is still lower than the number of BMS implantations in several countries. The clinical presentation of ISR has not been well characterissed. Thus, we attempted to analyze this condition and assess the treatment of ISR in everyday clinical practice. We searched our database for all cases of bare metal ISR between 1999 and 2007. Follow-up angiography after PCI was not a routine procedure but a clinically driven examination. Clinical presentations of ISR were divided into: stable angina, and acute coronary syndromes (ACS), i.e. unstable angina (UA) and myocardial infarction (MI) (further subdivided into NSTEMI and STEMI). Analysis included variables associated with different clinical manifestations, methods of ISR treatment and in-hospital complications of ISR. In-stent restenosis was identified in 432 (3%) of 15,910 patients who underwent PCI. The mean age was 61.6 + or - 15.6 (27-86) years, and 295 (68.3%) patients were men. Risk factor distribution was typical for a Caucasian population. Recurrent clinical episode occurred at a mean of 7 (1-108) months after PCI. Exertional angina was present in 245 (56.7%) patients, UA in 128 (29.6%) patients and MI in 59 (13.7%) patients, including STEMI in 28 (6.5%) and NSTEMI in 31 (7.2%) patients. Overall, ACS was diagnosed in 187 patients or 43.3% of all cases of ISR. Multivariate analysis showed a positive correlation between previous MI and younger age and ACS as the clinical manifestation of ISR, and a negative correlation between more severe restenosis and ACS manifestation. The incidence of clinical complications (MI or death) was higher in patients with ACS as the clinical manifestation of ISR (6.9% vs 1.6%). In-stent restenosis after BMS implantation is a serious clinical problem. More than 40% of patients with ISR present with ACS, including 13.7% patients with MI, more frequently among younger patients and patients with previous MI. Most patients with ISR are treated with repeated PCI with high success rate (97.7%), although the risk of clinical complications is considerably higher in patients presenting with ACS.


Mechanical models for living cells--a review.
As physical entities, living cells possess structural and physical properties that enable them to withstand the physiological environment as well as mechanical stimuli occurring within and outside the body. Any deviation from these properties will not only undermine the physical integrity of the cells, but also their biological functions. As such, a quantitative study in single cell mechanics needs to be conducted. In this review, we will examine some mechanical models that have been developed to characterize mechanical responses of living cells when subjected to both transient and dynamic loads. The mechanical models include the cortical shell-liquid core (or liquid drop) models which are widely applied to suspended cells; the solid model which is generally used for adherent cells; the power-law structural damping model which is more suited for studying the dynamic behavior of adherent cells; and finally, the biphasic model which has been widely used to study musculoskeletal cell mechanics. Based upon these models, future attempts can be made to develop even more detailed and accurate mechanical models of living cells once these three factors are adequately addressed: structural heterogeneity, appropriate constitutive relations for each of the distinct subcellular regions and components, and active forces acting within the cell. More realistic mechanical models of living cells can further contribute towards the study of mechanotransduction in cells.


New paradigms in sepsis: from prevention to protection of failing microcirculation.
Sepsis, also known as septicemia, is one of the 10 leading causes of death worldwide. The rising tide of sepsis due to bacterial, fungal and viral infections cannot be stemmed by current antimicrobial therapies and supportive measures. New paradigms for the mechanism and resolution of sepsis and consequences for sepsis survivors are emerging. Consistent with Benjamin Franklin's dictum 'an ounce of prevention is worth a pound of cure', sepsis can be prevented by vaccinations against pneumococci and meningococci. Recently, the NIH NHLBI Panel redefined sepsis as 'severe endothelial dysfunction syndrome in response to intravascular and extravascular infections causing reversible or irreversible injury to the microcirculation responsible for multiple organ failure'. Microvascular endothelial injury underlies sepsis-associated hypotension, edema, disseminated intravascular coagulation, acute respiratory distress syndrome and acute kidney injury. Microbial genome products trigger 'genome wars' in sepsis that reprogram the human genome and culminate in a 'genomic storm' in blood and vascular cells. Sepsis can be averted experimentally by endothelial cytoprotection through targeting nuclear signaling that mediates inflammation and deranged metabolism. Endothelial 'rheostats' (e.g. inhibitors of NF-κB, A20 protein, CRADD/RAIDD protein and microRNAs) regulate endothelial signaling. Physiologic 'extinguishers' (e.g. suppressor of cytokine signaling 3) can be replenished through intracellular protein therapy. Lipid mediators (e.g. resolvin D1) hasten sepsis resolution. As sepsis cases rose from 387 330 in 1996 to 1.1 million in 2011, and are estimated to reach 2 million by 2020 in the US, mortality due to sepsis approaches that of heart attacks and exceeds deaths from stroke. More preventive vaccines and therapeutic measures are urgently needed.


Investigation of helium ion production in constricted direct current plasma ion source with layered-glows.
Generation of helium ions is experimentally investigated with a constricted direct current (DC) plasma ion source operated at layered-glow mode, in which electrons could be accelerated through multiple potential structures so as to generate helium ions including He(2+) by successive ionization collisions in front of an extraction aperture. The helium discharge is sustained with the formation of a couple of stable layers and the plasma ball with high density is created near the extraction aperture at the operational pressure down to 0.6 Torr with concave cathodes. The ion beam current extracted with an extraction voltage of 5 kV is observed to be proportional to the discharge current and inversely proportional to the operating pressure, showing high current density of 130 mA/cm(2) and power density of 0.52 mA/cm(2)/W. He(2+) ions, which were predicted to be able to exist due to multiple-layer potential structure, are not observed. Simple calculation on production of He(2+) ions inside the plasma ball reveals that reduced operating pressure and increased cathode area will help to generate He(2+) ions with the layered-glow DC discharge.


Efficacy of tuberculin immunotherapy in verruca vulgaris: Our experience from single center from North-West India and review of literature.
Verruca vulgaris (VV) acquired through direct contact or autoinoculation of human papilloma virus (HPV). Treatment of VV are challenging as destructive modalities have variable efficacy and recurrence rates. Various immunotherapies attempt to stimulate the cell-mediated host immune response against HPV. We have assessed efficacy of intralesional tuberculin in patients with verruca vulgaris and to see the long term follow-up at 12 months. Forty patients were enrolled in the study. All patients received intralesional tuberculin injections (5 Tuberculin U/mL) in a dose of 0.1 mL/lesion every fortnightly. Patients were followed up for 12 months duration, and response to treatment assessed. Thirty patients (75%) showed complete resolution, 5 (12.5%) patients showed partial response, 3 (7.5%) showed minimal response and 2 (5%) were non-responders. Irrespective of tuberculin sensitivity test response the majority of patients showed grade 3 response. Five (12.5%) patients had a recurrence of lesions. Two had a recurrence on the same site, and three had recurrences over distant sites. Intralesional tuberculin immunotherapy is an effective modality for VV. Immunotherapy of warts is a potential area of research, and exact method and agents are still under investigation.


Collaborative care models for the treatment of depression. Based on a presentation by Wayne Katon, MD.
The quality of treatment of depression in the primary care setting is limited by inadequate patient education, lack of adherence to treatment regimens, poor patient follow-up, and the absence of close collaboration between medical and mental health systems. Integrated models of care may help overcome some of these barriers and improve adherence, satisfaction with care, and outcomes. The health and economic outcomes of randomized controlled trials in which 2 models of collaborative care--psychiatrist and psychiatrist/psychologist plus primary care--were compared with usual primary care. Interventions were delivered at multiple levels and included enhanced patient education and monitoring, physician training, patient-physician interaction, and integration of a psychiatrist or psychologist into the primary care setting. After the interventions, patients with major depression showed significant improvements in adherence, satisfaction with care, and depressive outcomes, whereas, in patients with minor depression, outcomes were not significantly affected by the intervention. An analysis revealed that the cost of the interventions was higher than usual care, and that there was little evidence of any cost offset. However, in terms of cost effectiveness, the cost of successfully treating one patient with major depression was lower with the interventions, and the incremental costs of collaborative intervention were substantially lower than the usual primary care costs.


Antiphospholipid antibodies (aPL) increase the potential monocyte procoagulant activity in patients with systemic lupus erythematosus.
Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are frequently detected in sera from patients affected by systemic lupus erythematosus (SLE). However, the role of antiphospholipid antibodies (aPL) in thrombus formation has not been defined as yet. Twenty-two patients affected by SLE, all fulfilling the 1982 ARA revised criteria, and twenty healthy subjects were investigated for the presence of LA, aCL and other aPLs. Monocyte procoagulant activity-PCA (Tissue Factor production) was evaluated by one stage plasma recalcification time. In all patients the plasma levels of F1 + 2 and of plasminogen activator inhibitor (PAI) were also determined. Monocyte PCA was significantly higher in SLE patients with LA and/or aCL in comparison to SLE patients without LA and/or aCL (p < 0.01) and to controls (p < 0.05). However, no connection was observed between PCA expression by mononuclear cells and LA or aCL levels. No differences in F1 + 2 and PAI plasma levels were found between SLE patients with or without aPL and controls. In our SLE patients LA and/or aCL positivity appears strictly related to an increased monocyte activation that could play an important role in the occurrence of thrombotic events.


ATP Levels and their Effects on Plasmalemma Influxes of Potassium Chloride in Red Beet.
Tissue ATP concentrations in slices of red beet increase progressively with time for up to 7 days after cutting the root. ATP levels are higher in slices taken from stored roots than in slices from fresh roots. ATP is reduced during incubation in salt solutions.Plasmalemma influxes were measured by 6 minutes incubation with (42)K and/or (36)C1 under conditions in which cation and anion influxes are independent. Both fluxes showed an approximately linear correlation with ATP level when the latter was varied by addition of CN(-), carbonyl cyanide m-chlorophenylhydrazone, or oligomycin, except for Cl influx with oligomycin, where oligomycin had a greater effect on Cl influx than could be accounted for by the reduction in ATP alone.These results support the view that K(+) and Cl(-) influxes are both energized directly or indirectly by ATP, and in addition that the Cl pump may be directly inhibited by oligomycin.