Barotrauma susceptibility in hamster lungs following elastase exposure.
The hypothesis that reduced lung compliance increases barotrauma susceptibility was tested in isolated hamster lungs. Elastase, instilled intratracheally in some hamsters from 4 h up to 8 days prior to testing, caused a patchy distribution of acute suppurative bronchiolitis and pneumonia. Airway blockage and decreased compliance were the anticipated results. For testing, anesthetized animals were ventilated with positive end-expiratory pressure prior to opening of the chest wall; this minimum pressure was maintained throughout testing. Transpulmonary pressure and lung volume changes, determined plethysmographically, were used to calculate quasi-static (C) and dynamic compliance (Cdyn) over a 2-ml tidal volume at frequencies up to 120 breaths/min. Some lungs were exposed, airway open, to a vacuum to stimulate a rapid ascent to the surface. All lungs were eventually pressurized through the trachea to determine rupture pressure (Pr). Rupture pressure exhibited an unexpected dichotomy apparently unrelated to elastase exposure. Statistically C did not differ between the elastase-treated and nontreated animals. Compliance correlated with Pr in a well-defined group (elastase-treated, nonevacuated lungs), but compliance had no value in predicting Pr for the group as a whole.


Mycophenolate mofetil limits renal damage and prolongs life in murine lupus autoimmune disease.
Classical immunosuppressants like cyclophosphamide give excellent results in human lupus nephritis. However, they augment malignancies and viral infections. Here we investigated the effect of the new immunosuppressant agent, mycophenolate mofetil (MMF), in New Zealand Black x New Zealand White (NZBxW) F1 hybrid mice, a model of genetically determined immune complex disease that mimics systemic lupus in humans. MMF has a selective antiproliferative effect on T- and B-lymphocytes, inhibits antibody formation and blocks the glycosylation of lymphocyte glycoproteins involved in the adhesion of leukocytes to endothelial cells. Two groups of NZBxW mice were used: group 1 (N = 20) given daily MMF (60 mg/kg p.o.) and group 2 (N = 15) given daily vehicle alone. Treatment started at three months of age and lasted until the death of the animals. Results showed that percentage of proteinuric mice was significantly reduced by MMF treatment and serum BUN levels were also lower than vehicle. MMF had a suppressive effect on autoantibody production and protected animals from leukopenia and anemia. Life survival of MMF treated lupus mice was significantly improved in respect to untreated animals. Thus, MMF delayed renal function deterioration and prolonged life survival in murine lupus nephritis. MMF has been already recognized as reasonably well tolerated in renal transplant patients and despite its gastrointestinal toxicity its overall safety profile appears superior to azathioprine. Human studies are needed to establish whether MMF may function as a steroid-sparing drug in lupus nephritis.


2-Methyl-4-phenyl-3,4-dihydro-quinazoline.
The title compound, C(15)H(14)N(2), was formed during the lithia-tion of 2-methyl-quinazoline with phenyl-lithium followed by hydrolysis of the inter-mediate lithium 2-methyl-4-phenyl-4H-quinazolin-3-ide. NMR spectra as well as single-crystal X-ray structural data indicate that the reaction product to have the same structure in chloro-form solution as in the crystalline state. The phenyl substituent is twisted out of the plane of the 3,4-dihydro-quinazoline ring system by 86.47 (7)°. In the crystal, inter-molecular N-H⋯N inter-actions connect the mol-ecules into infinite chains.


The impact of changes in employment status on psychosocial well-being: a study of breast cancer survivors.
Recent developments in the treatment of cancer have resulted in an increase in the number of cancer survivors. With this increase in the survival rate comes an increase in questions as to how a diagnosis of cancer and its treatment affects survivors and their well-being. Research has emphasized the impact that medical factors related to cancer have on the well-being of cancer survivors. However, the literature also suggests that socioeconomic factors may affect cancer survivors; well-being. This study focuses on the role that employment status plays in relationship to the levels of psychosocial well-being of women diagnosed with and treated for breast cancer. This study was a cross-sectional design utilizing secondary data analysis. The sample consisted of 369 breast cancer survivors from four cancer treatment facilities in the Mid-Atlantic region. The independent variable was employment status during and after treatment and the dependent variables were psychological distress, physical and mental functioning and quality of life. Utilizing analysis of covariance, controlling for age at diagnosis and stage of cancer it was found that there was a statistically significant difference in the dependent variables by employment status. These findings are discussed in terms of clinical and policy implications.


Antagonistic compensation as a function of reduced weight bearing.
The principle of antagonistic compensation was presented by RIESENFELD in 1966 to explain the relative shortening and broadening of hypofunctional bones. Few studies have concerned themselves with this phenomenon, even though the causative agent(s) have not been delineated. In this study, RIESENFELD induced the hypofunction by complete unilateral bilateral forelimb amputation. The resulting hypofunctional condition may be attributed to the lack of muscle function or to the lack of weight bearing or both in combination. In the present study weight bearing was eliminated in such a manner as to preserve muscle functioning. This was accomplished by two techniques: (1) unilateral forearm amputation and (2) unilateral humeral resection. Statistically significant differences in interindividual scapular length and breadth as well as humeral and ulnar lengths are reported. In all cases, the bones of the operated side were shorter than those of the unoperated side and the scapular breadth of the unoperated side was relatively greater. This confirms the hypothesis that weight bearing is, at least, partially responsible for the morphological changes induced by hypofunction and described by the principle of antagonistic compensation. However, as the reduction in length was of a lesser magnitude than that reported by RIESENFELD, the input of muscle function cannot be ignored. Rather, as both muscle functioning and weight bearing induce compressive force on long bones (including the scapula), both may serve to initiate the observed morphological changes through the vehicle of reduced compression.


The coefficient of the voltage induced frequency shift measurement on a quartz tuning fork.
We have measured the coefficient of the voltage induced frequency shift (VIFS) of a 32.768 KHz quartz tuning fork. Three vibration modes were studied: one prong oscillating, two prongs oscillating in the same direction, and two prongs oscillating in opposite directions. They all showed a parabolic dependence of the eigen-frequency shift on the bias voltage applied across the fork, due to the voltage-induced internal stress, which varies as the fork oscillates. The average coefficient of the VIFS effect is as low as several hundred nano-Hz per millivolt, implying that fast-response voltage-controlled oscillators and phase-locked loops with nano-Hz resolution can be built.


Arbuscular mycorrhizal fungal propagules from tillage and no-tillage systems: possible effects on Glomeromycota diversity.
Arbuscular mycorrhizal fungi (AMF) can use different types of propagules to colonize new roots. In this work we tested different types of AMF inocula obtained from a field experiment with tilled and no-tilled soils planted with wheat as well as from nondisturbed treatments with spontaneous vegetation. AMF trap cultures were carried out with soil, mycelium, segments of roots and wheat plants from the field as sources of inocula. Then after the senescence of the trap plants Glomeromycota species that had been established from each type of propagule in the substrate from the pots were identified. In field soils the proportions of Acaulosporaceae and Gigasporaceae were relatively similar to that of Glomeraceae, mainly in conventional tillage, whereas in all trap cultures investigated the percentages of members of the Glomeraceae family were higher than 90%. Because most of the trap cultures were based on intra- and/or extraradical mycelium our results show that members of Glomeraceae have advantages in the use of these propagules over Acaulosporaceae and Gigasporaceae species. We suggest that the higher contribution of Glomeraceae previously found in no-tillage systems could be related partially to the lack of disruption of the hyphal network and the composition of the soil propagules in this system.


A Cross-Sectional Study to Evaluate the Impact of Placental Location on Maternal and Fetal Outcomes.
Background The human placenta is a critical organ for facilitating nutrient uptake, waste elimination, and gaseous exchange between the mother and the fetus. In the placenta, there are two circulations, namely, maternal and fetal. The blood supply of the placenta is not uniformly distributed as the maternal circulation, determined by uterine blood supply, depends on the implantation site. The uterine blood supply plays a significant role in placental blood flow and pregnancy success. Hence, abnormalities in the placental implantation may affect the placenta's blood supply, leading to adverse maternal and fetal outcomes. This study aims to examine the relationship between placental location and maternofetal outcomes. Methodology This cross-sectional study was conducted in the Department of Obstetrics & Gynaecology at Bijapur Lingayat District Educational Association (Deemed to be University), Shri B. M. Patil Medical College, Hospital and Research Centre, Vijayapura, from January 2021 to April 2022. A total of 1,301 patients were included in this study. Results There was a positive and significant association between fundal implantation and severe preeclampsia and premature rupture of membranes. There was a positive and significant association between left lateral implantation and severe preeclampsia. The histopathological changes seen in the histopathological report of the fetal surface of the placenta also had a positive and significant association with the fundal location of the placenta. Conclusions This study suggests that fundal left lateral placentation leads to abnormal results. Such patients can be considered high risk and should be given meticulous antenatal care, depending on placental location at the 28-week ultrasonography.


Epidemiology of adult hand injuries presenting to a tertiary hand surgery unit: a review of 4216 cases.
This study investigates the pattern of hand injuries presenting to a UK regional tertiary centre. All referrals to our Hand Surgery Unit in 2019 were reviewed. Subgroup analyses of sex, deprivation, occupational injuries and assault cases were carried out. Over the study period, 4216 cases were referred. Most were male (70%), with a median age of 36 years and from a deprived area (75.2%). Soft tissue injury was documented in 53.6% and bone injury (fracture/dislocation) in 52.4%. Surgical management was required in 2214 (52.5%) cases. Work-related injuries accounted for 16.7% of cases and were more likely to require surgery. Assault-related injuries accounted for 8% of cases, with a male preponderance. Our findings can help facilitate service provision and guide regional and national prevention policies.Level of evidence: III.


Protein kinase C activation enhances cAMP accumulation in Swiss 3T3 cells: inhibition by pertussis toxin.
Addition of phorbol 12,13-dibutyrate (PBt2) in the presence of forskolin or cholera toxin caused marked (6- to 8-fold) and rapid accumulation of cAMP in Swiss 3T3 cells. The effect of PBt2 is mediated by protein kinase C because the synthetic diacylglycerol 1-oleoyl-2 acetylglycerol substitutes for PBt2 in enhancing cAMP accumulation and because the enhancing effect of either PBt2 or 1-oleoyl-2-acetylglycerol was prevented by down-regulation of protein kinase C. Vasopressin, which activates protein kinase C but does not directly affect adenylate cyclase in 3T3 cells, also enhanced cAMP accumulation in cells treated with cholera toxin or forskolin. This effect was abolished by down-regulation of protein kinase C. Treatment with pertussis toxin blocked the enhancing effect of PBt2 in a concentration- and time-dependent manner. Pertussis toxin neither prevented protein kinase C activation by PBt2 nor other biologic responses elicited by PBt2. The results presented here suggest an unusual function for a pertussis toxin substrate--namely, coupling protein kinase C activation to cAMP production.


Full canonical information from grand-potential density-functional theory.
We present a general and formally exact method to obtain the canonical one-body density distribution and the canonical free energy from direct decomposition of classical density functional results in the grand ensemble. We test the method for confined one-dimensional hard-core particles for which the exact grand potential density functional is explicitly known. The results agree to within high accuracy with those from exact methods and our Monte Carlo many-body simulations. The method is relevant for treating finite systems and for dynamical density functional theory.


Functional outcomes in proximal humerus fractures: A prospective registry-based analysis.
The present study evaluated and compared functional outcomes of proximal humerus fractures of different categories and their management with different procedures. Data of this prospective cohort was obtained from the orthopaedic trauma registry at a tertiary care hospital for the period from June 2015 to October 2019. Sixty-eight adult patients with proximal humerus fracture were identified out of which 57 (84%) had been operated. Functional outcomes were assessed up to 12-month follow-ups and were compared with different treatment groups, fracture category, and between isolated versus proximal humerus with additional upper limb fractures. At 3-month follow-up, there was significantly better outcomes in Proximal Humeral Internal Locking System (PHILOS) treatment group as compared to PHILOS with bone graft/BMP (p=0.041). PHILOS combined with bone graft/BMP was associated with delayed recovery compared to other management methods. There was non-significant difference in functional outcomes between isolated versus proximal humerus fractures associated with other upper limb fractures, among different fracture categories and between genders.


Difficult intubation managed using standard laryngeal mask airway, flexible fibreoptic bronchoscope and wire guided enteral feeding tube.
This case report describes an alternative method of achieving trans-oral intubation in a patient with a difficult airway who was apnoeic secondary to the therapeutic administration of a non-depolarizing neuromuscular blocking drug given to aid laryngoscopy. After attempts to intubate were unsuccessful by means of direct laryngoscopy utilizing various aids including bougies, a standard laryngeal mask airway was used to ventilate the patient and subsequently, with a swivel Y-connector attached in order to maintain PEEP, to aid the passage of a bronchoscope. The flexible guide-wire from an enteral feeding tube was then passed through the suction port of the bronchoscope into the trachea, after which the laryngeal mask airway and bronchoscope were withdrawn. By passing the enteral feeding tube over the guide-wire and then using this as a guide, a cuffed endotracheal tube was inserted into the trachea. The technique described permitted the continuous application of positive airway pressure, which dramatically improved the bronchoscopic view during the crucial step of placing the guide-wire into the trachea. Passing the feeding tube over the guide-wire aided the subsequent passage of the endotracheal tube, by acting as a stiffer and larger diameter guide through the glottis.


Safety of chloral hydrate sedation in dental practice for children: an overview.
Chloral hydrate is the oldest and most common sedative drug used in moderate sedation for pediatric dental patients. Hence, the purpose of this article is to review the safety and possible adverse events of this drug when used for pediatric dental treatment. A bibliographic search in PubMed, MEDLINE, Cochrane Library and KMbase, KISS, DBpia, KoreaMed, and RISS databases was performed. Using the keywords "dental sedation," "chloral hydrate," and "children or adolescent," 512 scientific articles were found. Subsequently, 183 studies were individually assessed for their suitability for inclusion in this literature review. Altogether, 24 studies were selected. They included 12 cases of death before, during, or after chloral hydrate sedation for dental treatment, majorly due to dosing error and use of multiple sedatives. Additionally, intraoperative adverse events were mostly respiratory problems such as hypoxia and apnea, but most events were temporary. After treatment, prolonged sedation, including excessive sleep and less activity were the most common postoperative adverse events, and even death cases were reported. Despite the wide acceptance of chloral hydrate as a sedative-hypnotic agent, the risk of adverse events and adequate dose should be of great concern when using it for pediatric dental sedation.


Technique for realistic anterior crowns using the IPS Empress porcelain system.
In dentistry, the concept of realism can be applied to the creation of an artificial prosthesis that is not perfect, but real. If prosthesis are made to a flawless perfection, they will appear artificial. Ultimately, the clinician and ceramist should strive for realism. The IPS Empress System (Ivoclar Williams, Amherst, NY) is an all-ceramic restorative alternative utilizing a pressable leucite-reinforced glass ceramic for a variety of indications (e.g., crowns, inlays/onlays, veneers). The resulting tooth-colored and metal-free restorations combine strength and aesthetics approaching those of natural teeth. This article describes the technique and procedures required to achieve realistic anterior crowns with this all-ceramic system.


Inhibition of Hep G2 hepatic cancer cell growth and CCl₄ induced liver cytotoxicity in Swiss albino mice by Mahua extract.
Mahua flower extract may provide protective effects against hepatotoxicity. The effect of Mahua flower extract (ME) was investigated on Hep G2 cell line and carbon tetrachloride (CCl4)-induced liver damages in Swiss albino mice. To investigate its cytotoxic effect in liver cancer, Hep G2 cells were treated with different doses of ME, and cell proliferation as well as colony formation assays demonstrated dose-dependent cytotoxicity of ME towards Hep G2 cells in tissue culture. Further gene expression studies showed significant down-regulation of AKT1/2/3, p-AKT, and COX-2 proteins including up-regulation of active caspase-3 in ME treated Hep G2 cells. In in vivo experiments, the mice were pretreated with ME for 15 days. On the 16th day CCl4 was injected intraperitoneally and after 24 h all mice were sacrificed. The antioxidant enzyme activities were measured in liver homogenates. CCl4-induced hepatotoxicity was evidenced by significant increase in lipid peroxidation and decrease in activities of antioxidant enzymes such as GST, GSH, SOD, CAT, and GPx. Histological studies showed CCl4-induced centrilobular necrosis and formation of fatty vacuoles in cirrhotic mice liver. Treatment with ME at a dose of 2 mg and 4 mg/kg exhibited the potential to prevent significant liver toxicity. The expression of active caspase-3 protein was down-regulated in ME treated groups compared to CCl4 exposed animals. This study demonstrated ME mediated antioxidant activity and hepatoprotective effects; therefore it could be used in the future for treating hepatic disorders including liver cancer, especially in combination with chemotherapeutics.


Activation of the ATF3 gene through a co-ordinated amino acid-sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitation.
Expression of ATF3 (activating transcription factor 3) is induced by a variety of environmental stress conditions, including nutrient limitation. In the present study, we demonstrate that the increase in ATF3 mRNA content following amino acid limitation of human HepG2 hepatoma cells is dependent on transcriptional activation of the ATF3 gene, through a highly co-ordinated amino acid-responsive programme of transcription factor synthesis and action. Studies using transient over-expression and knockout fibroblasts showed that several ATF and C/EBP (CCAAT/enhancer-binding protein) family members contribute to ATF3 regulation. Promoter analysis showed that a C/EBP-ATF composite site at -23 to -15 bp relative to the transcription start site of the ATF3 gene functions as an AARE (amino acid response element). Chromatin immunoprecipitation demonstrated that amino acid limitation increased ATF4, ATF3, and C/EBPbeta binding to the ATF3 promoter, but the kinetics of each was markedly different. Immediately following histidine removal, there was a rapid increase in histone H3 acetylation prior to an enhancement in ATF4 binding and in histone H4 acetylation. These latter changes closely paralleled the initial increase in RNA pol II (RNA polymerase II) binding to the promoter and in the transcription rate from the ATF3 gene. The increase in ATF3 and C/EBPbeta binding was considerably slower and more closely correlated with a decline in transcription rate. A comparison of the recruitment patterns between ATF and C/EBP transcription factors and RNA polymerase II at the AARE of several amino acid-responsive genes revealed that a highly co-ordinated response programme controls the transcriptional activation of these genes following amino acid limitation.


Speciation analysis of arsenic by selective hydride generation-cryotrapping-atomic fluorescence spectrometry with flame-in-gas-shield atomizer: achieving extremely low detection limits with inexpensive instrumentation.
This work describes the method of a selective hydride generation-cryotrapping (HG-CT) coupled to an extremely sensitive but simple in-house assembled and designed atomic fluorescence spectrometry (AFS) instrument for determination of toxicologically important As species. Here, an advanced flame-in-gas-shield atomizer (FIGS) was interfaced to HG-CT and its performance was compared to a standard miniature diffusion flame (MDF) atomizer. A significant improvement both in sensitivity and baseline noise was found that was reflected in improved (4 times) limits of detection (LODs). The yielded LODs with the FIGS atomizer were 0.44, 0.74, 0.15, 0.17 and 0.67 ng L(-1) for arsenite, total inorganic, mono-, dimethylated As and trimethylarsine oxide, respectively. Moreover, the sensitivities with FIGS and MDF were equal for all As species, allowing for the possibility of single species standardization with arsenate standard for accurate quantification of all other As species. The accuracy of HG-CT-AFS with FIGS was verified by speciation analysis in two samples of bottled drinking water and certified reference materials, NRC CASS-5 (nearshore seawater) and SLRS-5 (river water) that contain traces of methylated As species. As speciation was in agreement with results previously reported and sums of all quantified species corresponded with the certified total As. The feasibility of HG-CT-AFS with FIGS was also demonstrated by the speciation analysis in microsamples of exfoliated bladder epithelial cells isolated from human urine. The results for the sums of trivalent and pentavalent As species corresponded well with the reference results obtained by HG-CT-ICPMS (inductively coupled plasma mass spectrometry).


The identification and localization of a human gene with sequence similarity to Polycomblike of Drosophila melanogaster.
The Drosophila Polycomb group (PcG) of genes is required for the epigenetic regulation of a number of important developmental genes, including the homeotic (Hox) genes. The members of this gene family encode proteins that do not share sequence similarity, implying that each plays a unique role in this epigenetic repression mechanism. Polycomblike (Pcl) was the second PcG gene to be identified. We report here the isolation and characterization of a human cDNA, termed PHF1, which encodes a protein with significant sequence similarity to Drosophila Polycomblike (PCL). The region of similarity between PHF1 and PCL includes the two PHD fingers (C4-H-C3 motif), the region between them, and sequences C-terminal to the PHD fingers. PHF1 and PCL are 34% identical over this 258-residue region. PHF1 was mapped to 6p21.3 by fluorescence in situ hybridization. While several genetic diseases that are likely to result from developmental abnormalities map to this region, PHF1 is not a clear candidate gene for any of them.


Impact of concurrent medication use on statin adherence and refill persistence.
Effective therapy for chronic illness requires daily medication adherence (DMA) for prolonged periods. Overall medical regimen complexity may represent one barrier to successful adherence. To assess the relationship between the number of concurrently prescribed medicines and adherence to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), we analyzed a cohort of 5488 patients in a single health insurance plan who began statin therapy between July 1, 1999, and June 30, 2002. We assessed 2 parameters of statin adherence: (1) DMA ([total number of pills dispensed/total number of days between first and last prescription] x100) and (2) refill persistence (RP) (consecutive months of refills after initial prescription). The cohort was 61.6% male, with a mean +/- SD age of 52.7 +/- 9.3 years. Patients were prescribed a mean +/- SD of 2.9 +/- 2 total medicines (range, 1-13), with a mean +/- SD statin DMA of 82.1% +/- 26.5%. By 12 months, only 68% of patients continued filling statin prescriptions. After controlling for age, income level, and treatment for hypertension or ischemic heart disease, a greater number of concurrently prescribed medicines was significantly associated with better DMA (P = .005) and longer RP (P = .03). In this cohort, statin DMA was generally adequate, but RP was suboptimal. Patients with more concurrently prescribed medicines had higher DMA and better RP, even after adjusting for demographic factors and cardiovascular comorbidity. Physicians should not be deterred from initiating statin therapy by a patient's medical regimen complexity but should be alert for lack of therapy persistence, particularly in younger and healthier patients.


Effect of bilateral upper extremity exercise on trunk performance in patients with stroke.
[Purpose] The aim of this study was to investigate the effect of bilateral upper extremity exercises on trunk performance in patients with stroke. [Subjects and Methods] Twenty in-patients with chronic stroke of at least 6 month's duration participated in this study. Patients in the experimental and control groups received neurological rehabilitation treatment for stroke. In addition to the neurological rehabilitation treatment, patients in the experimental group received 30 minutes of bilateral upper extremity exercises 3 times weekly for 4 weeks. Outcomes were measured using the Trunk Impairment Scale before and after the 4-week training period. [Results] Significant intragroup differences in all items of Trunk Impairment Scale were observed after intervention. In particular, significant intergroup differences were observed for dynamic sitting balance, trunk coordination, and between total scores of the Trunk Impairment Scale. [Conclusion] The results of this study suggest bilateral upper extremity exercises could be used in addition to trunk exercises to improve trunk performance in patients with stroke.


Regulation of Cancer Stem Cell Metabolism by Secreted Frizzled-Related Protein 4 (sFRP4).
Tumours contain a small number of treatment-resistant cancer stem cells (CSCs), and it is through these that tumour regrowth originates at secondary sites, thus rendering CSCs an attractive target for treatment. Cancer cells adapt cellular metabolism for aggressive proliferation. Tumour cells use less efficient glycolysis for the production of ATP and increasing tumour mass, instead of oxidative phosphorylation (OXPHOS). CSCs show distinct metabolic shift and, depending on the cancer type, can be highly glycolytic or OXPHOS dependent. Since Wnt signalling promotes glycolysis and tumour growth, we investigated the effect of the Wnt antagonist secreted frizzled-related protein 4 (sFRP4) on CSC metabolism. We demonstrate that sFRP4 has a prominent role in basal glucose uptake in CSCs derived from breast and prostate tumour cell lines. We show that sFRP4 treatment on CSCs isolated with variable glucose content induces metabolic reprogramming by relocating metabolic flux to glycolysis or OXPHOS. Altogether, sFRP4 treatment compromises cell proliferation and critically affects cell survival mechanisms such as viability, glucose transporters, pyruvate conversion, mammalian target of rapamycin, and induces CSC apoptosis under conditions of variable glucose content. Our findings provide the feasibility of using sFRP4 to inhibit CSC survival in order to induce metabolic reprogramming in vivo.


Automated, continuous, and dynamic speciation of urinary arsenic in the bladder of living organisms using microdialysis sampling coupled on-line with high performance liquid chromatography and hydride generation atomic absorption spectrometry.
An on-line and fully automated method was developed for the continuous and dynamic in vivo monitoring of four arsenic species [arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] in urine of living organisms. In this method a microdialysis sampling technique was employed to couple on-line with high performance liquid chromatography (HPLC) and hydride generation atomic absorption spectrometry (HGAAS). Dialysates perfused through implanted microdialysis probes were collected with a sample loop of an on-line injector for direct and automated injection into HPLC system hyphenated with HGAAS. The saline (0.9% NaCl) solution was perfused at the rate of 1 microl min(-1) through the microdialysis probe and the dialysate was loaded into 50 microl of sample loop. The separation conditions were optimally selected to be in phosphate buffer solution at a pH 5.2 with a flow rate of 1.2 ml min(-1). The effluent from the HPLC was first mixed on-line at the exit of the column with HCl (1 M) solution and then mixed with a NaBH4 (0.2% m/v) solution. Based on the optimal conditions obtained, linear ranges of 2.5-50 ng ml(-1) for AsIII and 6.75-100 ng ml(-1) for the other three arsenic species were obtained. Detection limits of 1.00, 2.18, 1.03 and 2.17 ng ml(-1) were obtained for AsIII, DMA, MMA and AsV, respectively. Typical precision values of 3.4% (AsIII), 5.4% (DMA), 3.6% (MMA) and 7.5% (AsV) were obtained, respectively, at a 25 ng ml(-1) level. Recoveries close to 100%, relative to an aqueous standard, were observed for each species. The average in vivo recoveries of AsIII, DMA, MMA and AsV in rat bladder urine were 56+/-5%, 60+/-9%, 49+/-3% and 55+/-7%, respectively. The use of an on-line microdialysis-HPLC-HGAAS system permitted the determination of four urinary arsenic species in the bladder of an anesthetized rat with a temporal resolution of 50 min sampling.


Haplodeficiency of Ataxia Telangiectasia Mutated Accelerates Heart Failure After Myocardial Infarction.
Cell senescence is involved in the process of organ damage and repair; however, the underlying molecular mechanism needs to be further explored. Senescence-related genes (ie, p21, p53, and ataxia telangiectasia mutated [ATM]) were shown to be elevated after myocardial infarction (MI) in both mouse and human hearts. Ten- to 12-week-old male wild-type littermates (ATM+/+) and ATM heterozygous mice (ATM+/-) were subjected to MI. Cardiac echography showed that ATM haplodeficiency did not affect the survival rate but aggravated heart failure at day 28 post MI. Histologic analysis showed increased fibrosis in the noninfarct area of ATM+/- mice compared with that in ATM+/+ mice. Senescence-associated β-galactosidase staining showed that the number of senescent fibroblasts was decreased when ATM was haplodeficient both in vivo and in vitro. Costaining of α-smooth muscle actin with p53 or p19 showed fewer senescent myofibroblasts in ATM+/- mouse hearts. Moreover, angiogenesis was also examined using the endothelial markers CD31 both at early (day 7) and late stages (day 28) after MI, and ATM haplodeficiency reduced angiogenesis after MI. Finally, cardiac fibroblasts were isolated from infarcted mouse heart and the medium were tested for its capacity of endothelial tubing formation, revealing that ATM haplodeficiency led to lower vascular endothelial growth factor production from cardiac fibroblast and reduced capacity of endothelial tube formation in vitro. The present study shows that ATM haplodeficiency decreases fibroblast senescence and vascular endothelial growth factor production and impaired angiogenesis in response to MI, leading to accelerated heart failure.


Ginsenoside Rg3 attenuates cisplatin-induced kidney injury through inhibition of apoptosis and autophagy-inhibited NLRP3.
The NOD-like receptor family pyrin domain-containing (NLRP3) inflammasomes is centrally implicated in cisplatin (CP)-induced kidney injury. Autophagy is critical for inhibiting production of NLRP3 protein that effectively reduces the inflammatory response. Ginsenoside Rg3 (SY), an active component extracted from ginseng, is reported to protect against CP-induced nephrotoxicity. However, the mechanisms underlying renoprotection by SY have not been established to date. Our results indicate that SY attenuated CP-induced apoptosis and damage in vivo and in vitro, as evidenced by increased cell viability, decreased the proportion of late apoptotic cells, elevated mitochondrial membrane potential, and ameliorated histopathological damage of the kidney. SY ameliorated CP-induced human renal tubular (HK-2) cells and kidney injury through upregulation of LC3II/I and beclin-1, inhibition of p62, NLRP3, ASC, caspase-1, and interleukin-1β. However, blockade of autophagy by 3-methyladenine reversed the suppression of SY on NLRP3 inflammasome activation and the protection of SY on HK-2 cells. Our collective results support the utility of SY as a therapeutic agent that effectively protects against CP-induced kidney injury by activating the autophagy-mediated NLRP3 inhibition pathway.


Extracellular Vesicles from Bovine Follicular Fluid Support Cumulus Expansion.
Expansion of the cumulus complex surrounding the oocyte is critical for ovulation of a fertilizable egg. The ovulation-inducing surge of luteinizing hormone leads to an increased expression of genes such as prostaglandin-endoperoxide synthase 2 (Ptgs2), pentraxin-related protein 3 (Ptx3), and tumor necrosis factor alpha-induced protein 6 (Tnfaip6) that support cumulus expansion. Factors released by mural granulosa and cumulus granulosa cells into the follicular fluid induce paracrine signaling within the follicular compartment. The follicular fluid that separates these distinct granulosa cell types is an enriched fluid containing numerous proteins, nucleic acids, and other macromolecules. Extracellular vesicles (EVs) are also present; however, no physiologically relevant functions of follicular EVs have yet been demonstrated. In our study, the effect of follicular EVs on cumulus-oocyte complex (COC) expansion and relevant gene expression was assayed. Follicular EVs were isolated using ultracentrifugation from follicular fluid of small (3-5 mm) and large (>9 mm) antral bovine follicles, then characterized by nanoparticle tracking analysis, electron microscopy, and Western blot analysis. To test for bioactivity, mouse and bovine COCs were cultured with follicular EVs. Cumulus expansion and Ptgs2, Ptx3, and Tnfaip6 gene expression were measured following COC maturation culture. The results demonstrated that follicular EVs can support both measurable cumulus expansion and increased gene expression.


African American Clergy Recommendations to Enhance the Federal Plan to End the HIV Epidemic: A Qualitative Study.
African Americans in the southern United States continue to be disproportionately affected by HIV. Although faith-based organizations (FBOs) play important roles in the social fabric of African American communities, few HIV screening, care, and PrEP promotion efforts harness the power of FBOs. We conducted 11 focus groups among 57 prominent African American clergy from Arkansas, Mississippi, and Alabama. We explored clergy knowledge about the Ending the HIV Epidemic: A Plan for America (EHE); normative recommendations for how clergy can contribute to EHE; and how clergy can enhance the HIV care continua and PrEP. We explored how clergy have responded to the COVID-19 crisis, and lessons learned from pandemic experiences that are relevant for HIV programs. Clergy reported a moral obligation to participate in the response to the HIV epidemic and were willing to support efforts to expand HIV screening, treatment, PrEP and HIV care. Few clergy were familiar with EHE, U = U and TasP. Many suggested developing culturally tailored messages and were willing to lend their voices to social marketing efforts to destigmatize HIV and promote uptake of biomedical interventions. Nearly all clergy believed technical assistance with biomedical HIV prevention and care interventions would enhance their ability to create partnerships with local community health centers. Partnering with FBOs presents important and unique opportunities to reduce HIV disparities. Clergy want to participate in the EHE movement and need federal resources and technical assistance to support their efforts to bridge community activities with biomedical prevention and care programs related to HIV. The COVID-19 pandemic presents opportunities to build important infrastructure related to these goals.


Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1α signaling contributing to increased vulnerability in diabetic heart.
Impaired mitochondrial biogenesis causes skeletal muscle damage in diabetes. However, whether and how mitochondrial biogenesis is impaired in the diabetic heart remains largely unknown. Whether adiponectin (APN), a potent cardioprotective molecule, regulates cardiac mitochondrial function has also not been previously investigated. In this study, electron microscopy revealed significant mitochondrial disorders in ob/ob cardiomyocytes, including mitochondrial swelling and cristae disorientation and breakage. Moreover, mitochondrial biogenesis of ob/ob cardiomyocytes is significantly impaired, as evidenced by reduced Ppargc-1a/Nrf-1/Tfam mRNA levels, mitochondrial DNA content, ATP content, citrate synthase activity, complexes I/III/V activity, AMPK phosphorylation, and increased PGC-1α acetylation. Since APN is an upstream activator of AMPK and APN plasma levels are significantly reduced in ob/ob mice, we further tested the hypothesis that reduced APN in ob/ob mice is causatively related to mitochondrial biogenesis impairment. One week of APN treatment of ob/ob mice activated AMPK, reduced PGC-1α acetylation, increased mitochondrial biogenesis, and attenuated mitochondrial disorders. In contrast, knocking out APN inhibited AMPK-PGC-1α signaling and impaired both mitochondrial biogenesis and function. The ob/ob mice exhibited lower survival rates and exacerbated myocardial injury after MI, when compared to controls. APN supplementation improved mitochondrial biogenesis and attenuated MI injury, an effect that was almost completely abrogated by the AMPK inhibitor compound C. In high glucose/high fat treated neonatal rat ventricular myocytes, siRNA-mediated knockdown of PGC-1α blocked gAd-enhanced mitochondrial biogenesis and function and attenuated protection against hypoxia/reoxygenation injury. In conclusion, hypoadiponectinemia impaired AMPK-PGC-1α signaling, resulting in dysfunctional mitochondrial biogenesis that constitutes a novel mechanism for rendering diabetic hearts more vulnerable to enhanced MI injury.


A UK validation of the Stages of Recovery Instrument.
There is considerable interest in the concept of recovery from psychosis. Consumers describe recovery as a process as opposed to a clinical outcome. However, measures of recovery have an important role in the development of recovery-based mental health services. This study sought to investigate the validity and reliability of the Stages of Recovery Instrument (STORI) (Andresen et al., 2006). This is an Australian instrument chosen as a promising measure of recovery developed from the perspectives of consumer accounts. A questionnaire design was used to investigate the following aspects of validity: face validity and feasibility; concurrent validity; construct validity; and test-retest reliability. Fifty (50) people from the caseloads of three specialist mental health teams in a London borough completed the STORI, the Recovery Assessment Scale (RAS) (Corrigan et al., 1999) and a feedback questionnaire. Twenty two (22) people completed the STORI a second time for the purposes of test-retest reliability exploration. Participants' responses to the feedback questionnaire were mainly positive. This was seen as evidence of face validity and feasibility. Correlations between the STORI and the RAS provided evidence of concurrent validity. Cluster analysis revealed that the STORI items formed three clusters rather than five. Strong correlations between the first and second STORI administrations provided initial evidence for the test-retest reliability. The STORI can be used to measure recovery concepts in the UK. However, it does not measure the five-stage model on which it was based. A three-stage model of recovery might best form the basis of future recovery research.


Counselling users of hearing technology: a comprehensive literature review.
The purpose of this review is to determine the scope of peer-reviewed empirical research related to counselling in audiology with patients using hearing technology and to identify limitations and gaps to guide recommendations for future research. A rapid evidence assessment was used to identify relevant articles for the review. Eighteen articles met the inclusion criteria. Three themes were identified: (1) audiologist counselling perspectives, (2) counselling communication trends in practice and (3) audiologist experiences with professional training and reported patient outcomes. Findings revealed audiologists are more confident providing information than counselling that addresses adjustment aspects, and other communication gaps have been observed. There is limited research related to counselling in audiology. Audiologists continue to report a need for more training in counselling in their graduate programmes. Additional research is needed to determine effective ways to implement counselling in practice and to improve graduate student supervision for the development of counselling competencies and confidence in using skills in practice.


Optimization of a Decoction Process for an Herbal Formula Using a Response Surface Methodology.
An herbal formula, Huang-Qi-Liu-Yi Tang, is a prescription medicine that has been commonly used for the treatment of prostatitis and condyloma acuminatum over the last thousand years. In this study, response surface methodology, with a Box-Behnken design (BBD), was used to optimize the decoction conditions of an herbal formula. Astragaloside, calycosin-7-glucoside, glycyrrhizic acid, liquiritin, polysaccharide, and extractum were used as multiple evaluation markers. Soak time, water-to-medicinal herb ratio, and extraction time were determined as the three main variables by single-factor experiments and further optimized to obtain the maximum yields for the six marker compounds. Data from well-designed experiments were fitted to obtain second-order polynomial equations using multiple regression analysis, and the accuracies of these equations were evaluated and verified using statistical methods. By solving the regression equations and analyzing the three-dimensional response surfaces, optimum conditions were obtained and are summarized as follows: soak time of 57 min, water-to-medicinal herb ratio of 9:1 (mL/g), and extraction time of 48 min. Under optimized conditions, the experimental yields of astragaloside, calycosin-7-glucoside, glycyrrhizic acid, liquiritin, polysaccharide, and extractum were 0.13, 0.085, 1.64, 1.56, 72.19, and 25.64%, respectively, which was in good agreement with the values predicted by the BBD.


Safety of operation in biliary pancreatitis during the same hospitalization.
Over the past 4 years, 61 patients with biliary pancreatitis were managed, 48 of whom had operation on the biliary tree within the same hospital admission. Initial therapy was medical and operation was performed at a median of 6 days from admission (range: 3-14 days). Two patients required surgery for non-resolution of the pancreatitis, but the other 44 patients had clinical and biochemical resolution prior to surgery. At operation, oedematous-interstitial pancreatitis was found in 18 patients, necrotizing pancreatitis in two and a normal pancreas in 28 patients. Common duct exploration in 15 patients resulted in 10 positive explorations. One death occurred in a patient with necrotizing pancreatitis and an impacted stone, but overall morbidity was low and total hospitalization in the operated group averaged 12 days. There was a statistically significant difference in the incidence of bile duct stones (five of 10 versus seven of 38, P = 0.019) and operative findings of pancreatitis (seven of 10 versus 11 of 38, P = 0.038) in patients having surgery before or after 4 days of hospitalization. Initial conservative management for 4 days allows resolution of pancreatitis in most patients, minimizing the need for and potential risk from common duct exploration.


A survey to describe common practices on antifungal monitoring among Spanish clinicians.
We developed a survey to obtain information on the monitoring practices of major systemic antifungals for treatment and prevention of serious fungal infection. The survey included questions relating to methodology and practice and was distributed among 137 colleagues of the Study Group of Medical Mycology (GEMICOMED) from July to December 2019. Monitoring was routinely carried out by most respondents, mainly for voriconazole, and was more likely used to determine the efficacy of the dose administered and less for minimizing drug toxicity. Most responders did not follow the strategies of voriconazole dosage based on CYP2C19 genotyping. Monitoring of posaconazole, itraconazole, or other azole metabolites was not carried out or scarcely demanded. Most responders rarely used flucytosine in their clinical practice nor did they monitor it. According to the answers given by some responders, monitoring isavuconazole, amphotericin B, caspofungin and fluconazole exposure would be also interesting in daily clinical practice in selected patient populations. The survey reveals common practices and attitudes towards antifungal monitoring, sometimes not performed as per best recommendations, offering an opportunity for education and research. Appropriate use of therapeutic drug monitoring may be an objective of antifungal stewardship programmes.


Experience in patent foramen ovale closure with the CERA Lifetech occluder in patients with cryptogenic stroke.
Nowadays, percutaneous closure of patent foramen ovale (PFO) in patients after cryptogenic stroke is becoming a dominating strategy. The most commonly used and investigated device is the Amplatzer occluder. However, several other devices have been designed for transcatheter closure of PFO, which are not so well examined. To assess the effectiveness and safety of PFO closure with the Lifetech CERA occluder. A prospective, single-arm registry of patients with PFO treated with CERA occluder (Lifetech Scientific, Shenzhen, China) implantation was conducted. We assessed peri-procedural and 12-month follow-up. Patients were screened for the residual shunt in transcranial Doppler/transesophageal echocardiography. Ninety-six patients entered the registry. Most patients were women (76%) and the analyzed group was relatively young (mean age of 42.3 ±13.6 years). Before closure, most patients had a large shunt through the PFO. Procedures of PFO closure were performed under TEE guidance. All procedures were made under local anesthesia and all patients had the PFO successfully closed. No device-related complications were reported in the peri-procedural period or during follow-up. No recurrent neurological ischemic events were reported at 12 months. During follow-up we observed a 9% rate of residual shunts, which were mostly small. The study confirmed excellent immediate and 12-month results of CERA occluder implantation in patients with PFO.


A readability analysis of patient education materials about chronic venous disease provided by professional vascular societies.
Professional vascular societies and forums have disseminated patient information on education materials about chronic venous disease (CVD) via their official websites. While online patient education material is readily available with an Internet connection, its practical utility may be limited for patients with low health literacy. Six readability measures were used to evaluate the patient education materials regarding CVD published by 12 professional medical societies. Patient education materials on CVD vary considerably in length among medical societies, and their comprehensibility points toward a difficult level. The mean readability score was 11.20, prominently above the National Institutes of Health (NIH) and American Medical Association (AMA) recommendations. Our analysis of patient education materials produced by 12 professional vascular societies and forums found that all materials exceeded the recommended readability levels. The innovative section "Information for patients'' in the ESVS CVD guidelines also exceeded these levels. Improving the readability of patient education materials is essential to meet patient health literacy standards and might improve patient outcomes in managing CVD.


Metastasis to the ovaries from transitional cell carcinoma of the bladder and renal pelvis: a report of two cases.
Ovarian metastases from a primary urinary tract carcinoma are extremely rare. This can be difficult to distinguish from transitional cell carcinomas (TCC) of ovarian origin because of histologic similarity. A 65-year-old woman who was diagnosed with renal pelvis TCC 4 months prior was referred for evaluation of a left ovarian mass. A 47-year-old woman who underwent radical cystectomy due to bladder TCC 1 year ago was referred because of a right ovarian mass. Both patients underwent a bilateral salpingo-oophorectomy. The tumor cells had morphology identical to those of the primary urinary tract tumors. Gynecologic oncologists should consider metastatic TCC of the ovary from urinary tract origin, as well as breast, and gastrointestinal tract origins.


[Rupture of the descending thoracic aortic aneurysm in the lung: report of a case].
A 65-year-old man underwent a prosthetic graft replacement for a rupture of the saccular descending thoracic aneurysm in the lung. Chest computed tomography (CT) performed on the day of admission was suggestive of a thrombosed localized aortic dissection. However, sagittal plane CT performed on the following day indicated the rupture of a penetrating atherosclerotic ulcer. The operation was performed approximately 36h after the onset of the symptom since diagnosis was difficult due to the following reasons. First, the size of the saccular aortic aneurysm was not sufficiently large, i.e., it was 4.5 cm diameter and 3.0 cm in length. Second, the aneurysm was completely filled with thrombus: therefore, it could not be enhanced on CT scanning. Third, since the aneurysm was present on the side of the greater curvature of the descending aorta, the protrusion of the aneurysm was very indistinct. Fourth, the amount of bleeding was not significant because the rupture was extremely small, approximately 2 mm in width. Fifth, only an interlobar hematoma was observed due to the tight adhesion of the lung with the aorta.


Academic resilience in education: the role of achievement goal orientations.
In the past 2 decades, research findings established achievement goal theory as a powerful framework for conceptualizing difference in the quality of student's engagement, persistence on task, and academic resilience. So the present study examined the relationship between achievement goal orientations and academic resilience. Participants were 606 students (307 girls and 297 boys) selected from Shiraz high schools. They completed the Achievement Goals Questionnaire and Youth development Module Scale (RYDM). To analyze the data, the relationships between variables were examined, using Pearson product-moment correlations. Also simulanteous multiple regression was performed to investigate the prediction of academic resilience by achievement goal orientations. To examine the reliability and the validity of measures Cronbach alpha coefficient and factor analysis method were applied, respectively. Simultaneous multiple regression of achievement goal orientations on academic resilience showed that "mastery-approach" was a significant positive predictor of the "home care/high" and "peer care" subscales. Also, "performance-approach" was a significant, positive predictor of "home care/high", and "school/community meaningful" was predicted by "performance-avoidance" positively. According to the findings, it seems that achievement goal orientation has a critical role in students' academic achievement. Implications of the results are discussed in more details.


Are COVID-19 lockdowns associated with a change in sexual desire? Results from an online survey of Australian women.
In early 2020, the Australian government implemented lockdown restrictions to prevent the spread of COVID-19. Our study aims to investigate the impact of lockdowns on sexual desire and enjoyment of sex among Australian women. We conducted an online survey in August 2020 when Victoria was in strict lockdown, but all other states/territories had minimal restrictions. Here, we report on responses from female participants aged ≥18 years. Respondents were asked whether COVID-19 had impacted their desire and/or enjoyment of sex (yes/no). Those who responded "yes" were asked to elaborate in a free-text question. Factors associated with desire were investigated using the chi-square test. Conventional content analysis was used to explore free-text responses. Of the 622 participants, 44.1% reported COVID-19 related impacts on their sexual desire. Women living in Victoria, who were not heterosexual, and whose employment was negatively affected by lockdown were all more likely to report an impact on their sexual desire. Free-text comments revealed that mental health, living arrangements, and a reduced ability to meet with sexual partners were key reasons behind these impacts. The COVID-19 pandemic and lockdown measures clearly impacted the desire and enjoyment of sex for many women, important factors of people's relationships, health, and wellbeing.


Detection of metastatic vulvar and cervical squamous carcinoma in regional lymph nodes by use of a polyclonal keratin antibody.
A polyclonal keratin antibody (pK), a marker for epithelial cells, was used to evaluate lymph nodes (LNs) from patients with invasive squamous carcinomas of the cervix (CxCa) or vulva (VCa) to determine whether this technique could increase the detection of metastases (mets) over that obtained by light microscopy using a routine hematoxylin and eosin (H&E)-stained slide. The LN status of 15 cases of stage 1B CxCa and 14 cases of VCa was determined using a routine H&E slide. Subsequently, all LNs were resectioned and examined using a pK immunoperoxidase stain. In 329 lymph nodes from 14 cases of CxCa and 9 cases of VCa originally classified as LN-negative, only a single met was detected by the pK technique. In five cases of VCa and one case of CxCa (121 LNs), with LN mets or LN tumor emboli on the original H&E, three additional microscopic foci of mets were detected by pK. Of the four foci of mets discovered by pK, one was visible in retrospect on the original H&E section, and all four were easily identified on examination of a serial H&E section adjacent to the pK section. These results suggest that pK stains are unlikely to significantly increase our sensitivity in detecting mets in CxCa and VCa, beyond merely further sectioning and H&E staining of nodes.


Recording Risk Factors of Physical Abuse in Children Younger Than 36 Months With Bone Fractures: A 12-Years Retrospective Study in an Italian General Hospital Emergency Room.
Skeletal fractures (SFs) are very common in pediatrics. In some cases, they are secondary to child abuse. Differentiation of accidental from non-accidental fractures (NAFs) is essential as in abused children risk of further injuries leading to severe clinical problems and death is significant. Main objectives of this study were to evaluate the characteristics of SFs of children ≤3 years of age presenting to the Emergency Room (ER) of a Children's Teaching Hospital over a 12-year period and the attention paid by ER physicians to the identification of the indicators that increase suspicion of NAF and that suggest referring of the patient to the child protection agencies. This is a descriptive, retrospective study of the medical records of all the pediatric patients ≤ 36 months of age admitted to the ER of the Azienda Ospedaliera Santa Maria della Misericordia, University of Perugia, Perugia, Italy, for radiological documented SFs between January 1, 2004, and March 31, 2016. Available information was used to evaluate whether indicators of possible child abuse were documented by the ER staff and whether diagnosis of potential abuse was followed by further screening or referral to child protection agencies. During the study period, 11,136 accesses of the ER by children younger than 36 months were documented, among whom 417 presented long bone or skull fractures. Skull fractures were significantly more common among children <12 months of age (p = 0.001), whereas radius/ulna and humerus fractures were diagnosed significantly more frequently in children 12-36 months of age (p = 0.036 and p = 0.022, respectively). Recorded medical history was considered inadequate in 255 (61.2%) cases with no difference related to patient's age. Our study showed that the majority of charts in case of SFs were found to contain inadequate documentation to explain causes at the heart of the fractures and, therefore, to rule out any inflicted trauma. The development of specific referral guidelines, along with the continuous education and training of health professionals, as well as the preparation of structured medical forms, are essential measures to activate in order to improve the referral of children from the ER to child protection agencies.


Lipophilic Polycation Vehicles Display High Plasmid DNA Delivery to Multiple Cell Types.
A class of cationic poly(alkylamidoamine)s (PAAAs) containing lipophilic methylene linkers were designed and examined as in vitro plasmid DNA (pDNA) delivery agents. The PAAAs were synthesized via step-growth polymerization between a diamine monomer and each of four different diacid chloride monomers with varying methylene linker lengths, including glutaryl chloride, adipoyl chloride, pimeloyl chloride, and suberoyl chloride, which served to systematically increase the lipophilicity of the polymers. The synthesized polymers successfully complexed with pDNA in reduced serum medium at N/P ratios of 5 and greater, resulting in polyplexes with hydrodynamic diameters of approximately 1 μm. These polyplexes were tested for in vitro transgene expression and cytotoxicity using HDFa (human dermal fibroblast), HeLa (human cervical carcinoma), HMEC (human mammary epithelial), and HUVEC (human umbilical vein endothelial) cells. Interestingly, select PAAA polyplex formulations were found to be more effective than Lipofectamine 2000 at promoting transgene expression (GFP) while maintaining comparable or higher cell viability. Transgene expression was highest in HeLa cells (∼90% for most formulations) and lowest in HDFa cells (up to ∼20%) as measured by GFP fluorescence. In addition, the cytotoxicity of PAAA polyplex formulations was significantly increased as the molecular weight, N/P ratio, and methylene linker length were increased. The PAAA vehicles developed herein provide a new delivery vehicle design strategy of displaying attributes of both polycations and lipids, which show promise as a tunable scaffold for refining the structure-activity-toxicity profiles for future genome editing studies.


The phage 434 OR2/R1-69 complex at 2.5 A resolution.
The crystal structure of the DNA-binding domain of bacteriophage 434 repressor (R1-69) in complex with a 20 base-pair DNA fragment has been determined to 2.5 A resolution. The DNA fragment contains the sequence of the OR2 operator site, which differs from the previously studied OR1 site at three of the variable six central base-pairs. Comparison of the two structures shows that the overall bent conformation of the DNA backbone as well as the pattern of DNA-protein interactions seen in the OR1/R1-69 complex are maintained in the OR2 complex. However, the conformations of the DNA base-pairs are different in the two structures. In particular, the central base-pairs of OR2/R1-69 structure are more co-planar than in OR1/R1-69, and there are no cross-strand "bifurcated" hydrogen bonds. These results show that binding of the protein causes operator DNA to adopt a particular, well-defined backbone conformation, and they reinforce the notion that the energetic cost of achieving this conformation, most likely different for different sequences, can determine, at least in part, the relative affinity of the repressor for different operator sites.


The therapeutic and working alliances.
The concepts of the "therapeutic alliance" (Zetzel, 1956) and "working alliance" (Greeson, 1965) are traced in their antecedents to Freud and other analysts and compared especially with Freud's "analytic pact." Differences both in theory and practice are elucidated with the aid of case material. While the therapeutic and working alliances are often used interchangeably, they are found to take up their positions at diametrically opposite points along a continuum defined by the analytic pact and show a marked tendency to depart from the guidance offered the traditional analysis by the fundamental rule. They should be regarded more as exercises in analytically oriented psychotherapy than parameters of the traditional technique. Nevertheless, as a basis for comparisons, it should be recognized that the latter technique: (1) does not formulate in theory many of the measures left for pragmatic fulfillment; (2) does not include genetic, structural and adaptive viewpoints that later developments require. Current tendencies to include the analyst's self-observations in relation to the total analytic process point up the growing influence of these more recent considerations.


Biological pretreatment of rice straw with Streptomyces griseorubens JSD-1 and its optimized production of cellulase and xylanase for improved enzymatic saccharification efficiency.
Biological pretreatment of rice straw and production of reducing sugars by hydrolysis of bio-pretreated material with Streptomyces griseorubens JSD-1 was investigated. After 10 days of incubation, various chemical compositions of inoculated rice straw were degraded and used for further enzymatic hydrolysis studies. The production of cellulolytic enzyme by S. griseorubens JSD-1 favored the conversion of cellulose to reducing sugars. The culture medium for cellulolytic enzyme production by using agro-industrial wastes was optimized through response surface methodology. According to the response surface analysis, the concentrations of 11.13, 20.34, 4.61, and 2.85 g L(-1) for rice straw, wheat bran, peptone, and CaCO3, respectively, were found to be optimum for cellulase and xylanase production. Then the hydrolyzed spent Streptomyces cells were used as a nitrogen source and the maximum filter paper cellulase, carboxymethylcellulase, and xylanase activities of 25.79, 78.91, and 269.53 U mL(-1) were achieved. The crude cellulase produced by S. griseorubens JSD-1 was subsequently used for the hydrolysis of bio-pretreated rice straw, and the optimum saccharification efficiency of 88.13% was obtained, indicating that the crude enzyme might be used instead of commercial cellulase during a saccharification process. These results give a basis for further study of bioethanol production from agricultural cellulosic waste.


A new type of antimicrobial phenolics produced by plant peroxidase and its possible role in the chemical defense systems against plant pathogens.
Syringaldehyde readily reacted in the horse-radish peroxidase (HRPOD) system. The ethyl acetate extract of the reaction mixture showed a marked antimicrobial activity against bacteria and fungi. After repeated column chromatography three potential antimicrobial compounds were obtained from the extract. The structural elucidation of active compounds was achieved by a combination of spectroscopic techniques and chemical modification.


Quantitative nuclear magnetic resonance (QNMR) spectroscopy for assessing the purity of technical grade agrochemicals: 2,4-dichlorophenoxyacetic acid (2,4-D) and sodium 2,2-dichloropropionate (Dalapon sodium).
Comparison of quantitative NMR spectroscopy (QNMR) with chromatographic methods such as gas chromatography (GC) or high-pressure liquid chromatography (HPLC) for the determination of the purity of and impurities in technical grade agrochemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), 1, and Dalapon sodium (sodium 2,2-dichloropropionate), 10, has revealed that QNMR is more precise and accurate than the chromatographic methods. Quantitative impurity profiling of technical grade 1 is rapid and accurate using 600 MHz (1)H NMR. Extra dispersion at the relatively high frequency allowed full assignment of the NMR spectrum of 1 and its related organic impurities in technical samples. The percentage purity of 1 was measured by the difference QNMR method, which involves summing the amounts of impurities and subtracting from 100%. Results are superior in consistency to those obtained by chromatographic methods. The percentage purity of Dalapon sodium, 10, in technical grade batches is readily obtained by (1)H QNMR, using either the difference method or the internal standard method, using dimethyl sulfone (DMSO2) internally as a reference material, that is chemically unrelated to the analyte. The latter method also allows the simultaneous identification and quantification of impurities, many of which are either not accessible to or detectable by the chromatographic methods. Uncertainty budgets for the QNMR method are presented and demonstrate that the major contributors to uncertainty lie in the weighing of the chemicals and in purity of the standard reference material prior to the QNMR experiment.


Environmentally benign sol-gel antifouling and foul-releasing coatings.
Biofouling on ships and boats, characterized by aquatic bacteria and small organisms attaching to the hull, is an important global issue, since over 80000 tons of antifouling paint is used annually. This biofilm, which can form in as little as 48 hours depending on water temperature, increases drag on watercraft, which greatly reduces their fuel efficiency. In addition, biofouling can lead to microbially induced corrosion (MIC) due to H2S formed by the bacteria, especially sulfate-reducing bacteria. When the International Maritime Organization (IMO) international convention banned the use of effective but environmentally damaging coatings containing tributyl tin in 2008, the development of clean and effective antifouling systems became more important than ever. New nonbiocidal coatings are now in high demand. Scientists have developed new polymers, materials, and biocides, including new elastomeric coatings that they have obtained by improving the original silicone (polydimethylsiloxane) formulation patented in 1975. However, the high cost of silicones, especially of fluoropolymer-modified silicones, has generally prevented their large-scale diffusion. In 2009, traditional antifouling coatings using cuprous oxide formulated in copolymer paints still represented 95% of the global market volume of anti-fouling paints. The sol-gel nanochemistry approach to functional materials has emerged as an attractive candidate for creating low fouling surfaces due to the unique structure and properties of silica-based coatings and of hybrid inorganic-organic silicas in particular. Sol-gel formulations easily bind to all types of surfaces, such as steel, fiberglass, aluminum, and wood. In addition, they can cure at room temperature and form thin glassy coatings that are markedly different from thick silicone elastomeric foul-releasing coatings. Good to excellent performance against biofouling, low cure temperatures, enhanced and prolonged chemical and physical stability, ease of application, and the waterborne nature of sol-gel coatings all support the diffusion of these paints to efficiently reduce the accumulation of fouling layers on valued surfaces immersed in marine or fluvial waters. Furthermore, sol-gel glassy coatings are transparent and can be effectively applied to optical devices, windows, and solar panels used in lake, fluvial, or marine environments. Sol-gel technology is eminently versatile, and the first generation sol-gel paints have already shown good performance. Even so, vast opportunities still exist for chemists to develop novel sol-gel derived coatings to both prevent biofouling and enhance the hydrodynamic properties of boat and ship hulls. Moreover, researchers have prepared and applied multifunctional sol-gel coatings providing protection against both biofouling and corrosion. They have tested these in the marine environment with good preliminary results. In this Account, we discuss some of our new strategies for the controlled functionalization of surfaces for the development of efficient antifouling and foul-releasing systems and summarize the main achievements with biocidal and nonbiocidal sol-gel coatings. We conclude by giving insight into the marine coatings and sol-gel products markets, providing arguments to justify our conclusion that the sol-gel coatings technology is now a mature platform for the development of economically viable and environmentally friendly antifouling and foul-release formulations of enhanced performance.


Comparison of Hourly PM2.5 Observations Between Urban and Suburban Areas in Beijing, China.
Hourly PM2.5 observations collected at 12 stations over a 1-year period are used to identify variations between urban and suburban areas in Beijing. The data demonstrates a unique monthly variation form, as compared with other major cities. Urban areas suffer higher PM2.5 concentration (about 92 μg/m³) than suburban areas (about 77 μg/m³), and the average PM2.5 concentration in cold season (about 105 μg/m³) is higher than warm season (about 78 μg/m³). Hourly PM2.5 observations exhibit distinct seasonal, diurnal and day-of-week variations. The diurnal variation of PM2.5 is observed with higher concentration at night and lower value at daytime, and the cumulative growth of nighttime (22:00 p.m. in winter) PM2.5 concentration maybe due to the atmospheric stability. Moreover, annual average PM2.5 concentrations are about 18 μg/m³ higher on weekends than weekdays, consistent with driving restrictions on weekdays. Additionally, the nighttime peak in weekdays (21:00 p.m.) is one hour later than weekends (20:00 p.m.) which also shows the evidence of human activity. These observed facts indicate that the variations of PM2.5 concentration between urban and suburban areas in Beijing are influenced by complex meteorological factors and human activities.


New concepts on treatment of the upper limb in the tetraplegic. Surgical restoration and functional neuromuscular stimulation.
Today, many tetraplegics benefit from surgical restoration of hand function. New concepts of functional neuromuscular stimulation are impacting the care of those patients who are more severely paralyzed and are unable to benefit from surgery alone. Grasp, pinch, wrist extension, and elbow extension restoration are now possible.


A model of graded ischemia in the isolated perfused rat heart.
Insertion of a flow pump into the Langendorff retrograde perfusion apparatus has permitted the production of stable, graded ischemia in hearts whose hemodynamic and metabolic response may be evaluated. Ventricular pressures were monitored with a modified balloon and catheter-tip manometer system, and oxygen consumption , lactate and glucose metabolism, and tissue high-energy phosphate stores measured. A 15-min stabilization period in 56 paced hearts was followed by 15 min of either full, 40, 30, 20, or 10% coronary flow, after which the ventricular tissue was freeze-clamped for tissue assay. Tissue creatine phosphate fell progressively from 23.7 in full flow hearts to 9.9 mumol/g dry wt after 90% reduction in flow. This was accompanied by a graded reduction in ATP from 20.3 to 14.0 mumol/g dry wt and a rise in AMP from 1.1 to 2.6 mumol/g dry wt. Tissue lactate rose progressively from 22.3 to 60.1 mumol/g dry wt. Hemodynamic function correlated with coronary flow. This preparation offers an opportunity to study pharmacological and metabolic interventions in ischemic heart disease.


Comparing cognitive-behavioural psychotherapy and psychoeducation for non-specific symptoms associated with indoor air: a randomised control trial protocol.
Indoor air-related conditions share similarities with other conditions that are characterised by medically unexplained symptoms (MUS)-a combination of non-specific symptoms that cannot be fully explained by structural bodily pathology. In cases of indoor air-related conditions, these symptoms are not fully explained by either medical conditions or the immunological-toxicological effects of environmental factors. The condition may be disabling, including a non-adaptive health behaviour. In this multifaceted phenomenon, psychosocial factors influence the experienced symptoms. Currently, there is no evidence of clinical management of symptoms, which are associated with the indoor environment and cannot be resolved by removing the triggering environmental factors. The aim of this study is to compare the effect of treatment-as-usual (TAU) and two psychosocial interventions on the quality of life, and the work ability of employees with non-specific indoor air-related symptomatology. The aim of this ongoing randomised controlled trial is to recruit 60 participants, in collaboration with 5 occupational health service units. The main inclusion criterion is the presence of indoor air-related recurrent symptoms in ≥2 organ systems, which have no pathophysiological explanation. After baseline clinical investigations, participants are randomised into interventions, which all include TAU: cognitive-behavioural psychotherapy, psychoeducation and TAU (control condition). Health-related quality of life, measured using the 15D-scale, is the primary outcome. Secondary outcomes include somatic and psychiatric symptoms, occupational factors, and related underlying mechanisms (ie, cognitive functioning). Questionnaires are completed at baseline, at 3, 6 and 12-month follow-ups. Data collection will continue until 2017. The study will provide new information on the individual factors related to indoor air-associated symptoms, and on ways in which to support work ability. The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, has granted approval for the study. The results will be published in peer-reviewed journals. NCT02069002; Pre-results.


Balancing bilinguals II: lexical comprehension and cognitive processing in children learning Spanish and English.
The present study investigated developmental changes in lexical comprehension skills in early sequential bilinguals, in both Spanish (L1) and English (L2), exploring the effects of age, years of experience, and basic-level cognitive processing (specifically the ability to maintain performance during mixed vs. single-language processing) within a timed picture-word verification task. Participants were 100 individuals, 20 at each of five different age levels (ages in years, 5-7, 8-10, 11-13, 14-16, and adults). All had learned Spanish as a first language in the home, with formal English experience beginning at 5 years. Gains (as indexed by increased response speed) were made in both languages across age, although these gains were greater in English than in Spanish. The youngest participants were relatively "balanced" in their crosslinguistic performance. By middle childhood, performance was better in English. There were no response decrements at any age between the mixed and single-language processing conditions. These results are compared to those from a previous study that investigated basic-level lexical production in developing Spanish-English bilinguals. Both studies show a move toward English dominance in middle childhood, but the transition occurs earlier in comprehension. The production study showed differences between mixed and single-language processing (reflecting potential interlanguage interference) that are not evident in comprehension.


Associations between variants in IL-33/ST2 signaling pathway genes and coronary heart disease risk.
The IL-33/ST2 signaling pathway plays an important role in coronary artery disease (CHD); however, few studies have explored how variants in IL-33/ST2 genes influence CHD risk. Here, we examined the association between genetic variants in IL-33, ST2, and IL-1RAcP of the IL-33/ST2 axis and the risk of CHD. We conducted a case-controlled study with 1146 CHD cases and 1146 age- and sex-frequency-matched controls. Twenty-eight single nucleotide polymorphisms (SNPs) in IL-33, ST2, and IL-1RAcP were genotyped by Sequenom MassArray and TaqMan assay. Logistic regression was used to analyze these associations. The SNP rs4624606 in IL-1RAcP was nominally associated with CHD risk. The AA genotype was associated with a 1.85-fold increased risk of CHD (95% confidence interval (CI) = 1.01-3.36; p = 0.045) compared to the TT genotype. Further analysis showed that AA carriers also had a higher risk of CHD than TT + TA carriers (odds ratio (OR) = 1.85; 95% CI = 1.85-3.35; p = 0.043). However, no significant association was observed between variants in IL-33/ST2 genes and CHD risk. Further studies are needed to replicate our results in other ethnic groups with larger sample size.


A Multifunctional Characterization Test Bench for Shape Memory Alloy Micro-Wires-Design, Implementation and Validation.
Most relevant to predicting the behavior of shape-memory-alloy (SMA)-based actuator-sensor applications activated by Joule heating are the electro-mechanical characteristics of the material under consideration. For a comprehensive characterization, a single setup that is able to provide all relevant data and information is desirable. This work covers the design, implementation and validation of such a high-end test bench for the holistic characterization of SMA micro-wires. In addition, the setup provides the possibility of application simulation experiments. Key elements of the design are the clamping mechanism guided on air bearings, a linear direct drive, a high-resolution load cell, a high-precision constant current source and a stress-controlled in-line wire sample installation. All measurements take place inside an isolated, temperature-controlled chamber. With the presented setup, the electro-mechanical and thermal characteristics of SMA wire samples with diameters from 20 µm to 100 µm can be determined. Via hardware-in-the-loop (HiL) implementation, the outputs with different biasing mechanisms and additional end-stops can be simulated even at high ambient temperatures. The generated results facilitate the prediction of the exact characteristics of SMA-driven actuator-sensor systems in a variety of applications and lead to a better general understanding of the alloy's properties. All functionalities and features of the setup are presented by discussing the results of exemplary experiments.


Familial insulin-dependent diabetes mellitus in Samoyed dogs.
Five adult Samoyed dogs from two unrelated litters were diagnosed with diabetes mellitus. Two full-sibling male dogs (Family A) were raised in the same household. The other three dogs, two female and one male, were also full siblings (Family B) raised in different households. All five dogs developed polyuria and polydipsia and demonstrated fasting hyperglycemia and glucosuria. Diabetes mellitus was diagnosed in all five dogs and responded to appropriate therapy with insulin. The occurrence of insulin-dependent diabetes mellitus in multiple, closely related Samoyed dogs suggests a familial predisposition in this breed.


A randomized controlled trial of league tables and control charts as aids to health service decision-making.
Health service managers and other decision-makers are required to act on the basis of data. Little attention has been paid to the effects of data presentation on the decisions taken. This study uses a randomized controlled trial design to investigate the effects of two forms of data presentation--league tables and control charts--on health service decision-makers. Directors of public health in 122 health authorities in the UK were mailed three case studies and a questionnaire. The case studies showed data on variations in mortality by health service provider. The questionnaire asked them to indicate whether they would take action as a result of the data and to identify the health service providers on whom they would take action. Participants were randomly allocated to receive the same data in the form of ranked histograms (league tables) or control charts. The percentage of participants who would take action on health service providers. Fifty-seven questionnaires were returned. For each case study, respondents receiving data as league tables stated they would take action on significantly more health service providers than those receiving data as control charts: for the first case study, the percentages were 3.3% versus 1.8% (P < 0.001) for league tables and control charts, respectively; for the second case study, 15.9% versus 6.7% (P = 0.029), respectively; and for the third, 5.9% versus 0.7% (P = 0.002), respectively. Respondents receiving data as league tables were significantly more likely to request further information on case mix. Compared with league tables, health service decision-makers identify fewer outliers for further action when performance data are presented as control charts. They also reduce the tendency to request further information. Using control charts rather than league tables for the routine presentation of comparative data would reduce over-investigation of unusual performance.


Binding of thymus- and bone marrow-derived lymphoid cells to antigen-derivatized fibers.
Thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) from mouse spleens bind specifically to antigen-derivatized nylon fibers. The fiber-bound population consisted of about 60%-70% B cells and 30% T cells as determined by cytotoxicity, fluorescence, and antibody-complement binding assays. Essentially all fiber-bound cells were viable and could be accounted for as T or B cells. Enriched populations of T or B cells could be isolated on the fibers by destruction of one or the other cell type with the appropriate antiserum plus complement. T or B cells could also be fractionated according to their relative affinity (or avidity) for a given antigen.


Long-Term Follow-Up of Patients With Isolated Side Branch Coronary Artery Disease.
The data with respect to stable coronary artery disease (SCAD) are mainly confined to main vessel disease. However, there is a lack of information and long-term outcomes regarding isolated side branch disease. This study aimed to evaluate long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients with isolated side branch coronary artery disease (CAD). A total of 437 patients with isolated side branch SCAD were included. After a median follow-up of 38 months, the overall MACCE and all-cause mortality rates were 14.6% and 5.9%, respectively. Among angiographic features, 68.2% of patients had diagonal artery and 82.2% had ostial lesions. In 28.8% of patients, the vessel diameter was ≥2.75 mm. According to the American College of Cardiology lesion classification, 84.2% of patients had either class B or C lesions. Age, ostial lesions, glycated hemoglobin A1c, and neutrophil levels were independent predictors of MACCE. On the other hand, side branch location, vessel diameter, and lesion complexity did not affect outcomes. Clinical risk factors seem to have a greater impact on MACCE rather than lesion morphology. Therefore, the treatment of clinical risk factors is of paramount importance in these patients.


Cyclic nucleotide phosphodiesterase 1 regulates lysosome-dependent type I collagen protein degradation in vascular smooth muscle cells.
The phenotypic modulation of vascular smooth muscle cells (VSMCs) to a synthetic phenotype is vital during pathological vascular remodeling and the development of various vascular diseases. An increase in type I collagen (collagen I) has been implicated in synthetic VSMCs, and cyclic nucleotide signaling is critical in collagen I regulation. Herein, we investigate the role and underlying mechanism of cyclic nucleotide phosphodiesterase 1 (PDE1) in regulating collagen I in synthetic VSMCs. The PDE1 inhibitor IC86340 significantly reduced collagen I in human saphenous vein explants undergoing spontaneous remodeling via ex vivo culture. In synthetic VSMCs, high basal levels of intracellular and extracellular collagen I protein were markedly decreased by IC86340. This attenuation was due to diminished protein but not mRNA. Inhibition of lysosome function abolished the effect of IC86340 on collagen I protein expression. PDE1C but not PDE1A is the major isoform responsible for mediating the effects of IC86340. Bicarbonate-sensitive soluble adenylyl cyclase/cAMP signaling was modulated by PDE1C, which is critical in collagen I degradation in VSMCs. These data demonstrate that PDE1C regulates soluble adenylyl cyclase/cAMP signaling and lysosome-mediated collagen I protein degradation, and they suggest that PDE1C plays a critical role in regulating collagen homeostasis during pathological vascular remodeling.


Patients Who Reviewed a Decision Aid Prior to Major Orthopaedic Surgery Reported Higher Trust in Their Surgeon.
Decision aids (DAs) are utilized to ensure that patients are informed and involved in the decision-making process. Although DAs improve decision quality, other aspects of the decision-making process, such as trust and regret, are seldom measured. The objective of the present study was to determine whether patients given a DA prior to orthopaedic surgery had greater trust and lower regret at 6 months postoperatively. Consecutive patients were identified who underwent a hip or knee replacement or spine surgery from October 2018 to January 2020 and were subsequently surveyed at 6 months postoperatively. Outcomes included the Trust in the Surgical Decision and Decision Regret Scales. The primary analysis compared scores of patients who reviewed at least some of the DA to those who had not received or reviewed it. A sensitivity analysis compared patients with a DA order who reported reviewing it to those who did not. Multivariable models analyzed whether DA exposure predicted trust or regret. An exploratory mediation analysis examined the direct and indirect effects of DA exposure, including through the Shared Decision Making Process score. The response rate was 56% (700 of 1,253). In the primary analysis, the proportion of patients who reported complete trust was 50.9% among those with no DA review and 63.8% among those with DA review (adjusted odds ratio, 1.62; 95% confidence interval, 1.11 to 2.36). A nonsignificant effect was observed comparing a DA order (59.9%) versus no DA order (51.4%; adjusted odds ratio, 1.30; 95% confidence interval, 0.80 to 2.11). Regret was unrelated to DA exposure. In the mediation analysis, 19.3% (95% confidence interval, 3.1% to 35.4%) of the effect of DA review on trust could be attributed to increased shared decision making. Patients who reviewed a DA prior to orthopaedic surgery reported higher trust in their surgeons. Providing patients with a DA prior to orthopaedic surgery can improve trust in the surgeon. Improving trust between patients and surgeons may improve communication and help patients make better health decisions.


Lysine acetylation in mitochondria: From inventory to function.
Cellular signaling pathways are regulated in a highly dynamic fashion in order to quickly adapt to distinct environmental conditions. Acetylation of lysine residues represents a central process that orchestrates cellular metabolism and signaling. In mitochondria, acetylation seems to be the most prevalent post-translational modification, presumably linked to the compartmentation and high turnover of acetyl-CoA in this organelle. Similarly, the elevated pH and the higher concentration of metabolites in mitochondria seem to favor non-enzymatic lysine modifications, as well as other acylations. Hence, elucidating the mechanisms for metabolic control of protein acetylation is crucial for our understanding of cellular processes. Recent advances in mass spectrometry-based proteomics have considerably increased our knowledge of the regulatory scope of acetylation. Here, we review the current knowledge and functional impact of mitochondrial protein acetylation across species. We first cover the experimental approaches to identify and analyze lysine acetylation on a global scale, we then explore both commonalities and specific differences of plant and animal acetylomes and the evolutionary conservation of protein acetylation, as well as its particular impact on metabolism and diseases. Important future directions and technical challenges are discussed, and it is pointed out that the transfer of knowledge between species and diseases, both in technology and biology, is of particular importance for further advancements in this field.


Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events.
We investigated in patients with ongoing myocardial infarction (MI) whether coagulation factor VII (FVII) and tissue factor (TF) levels are affected at admission by genetic components and whether they may predict subsequent cardiovascular events. 256 patients admitted for MI were evaluated for FVII and TF antigen levels before any treatment at entry, and were genotyped for FVII and TF polymorphisms. FVII gene insertions at -323, 11293 and the -402G/A change predicted FVII levels and explained 14% of variance. The -603 TF gene polymorphism failed to affect significantly TF levels (P=0.07). These variables were correlated with the incidence of death (36 patients) and reinfarction (9 patients) after a median follow-up of 397 days. Events were independently predicted by FVII (HR 2.1, 95% CI 1.2 to 5.7) and TF (HR 4.1, 95% CI 2 to 11) levels. Composite end point was significantly worse when both parameters were above the receiver-operating characteristics (ROC) values (HR 8.3, 95% CI 5 to 18, compared with FVII and TF below), and above the ROC value of TF (>630 pg/mL) it differed among FVII genotype groups. Admission FVII and TF antigen levels, partially predicted by polymorphisms, are independent predictors of mortality and reinfarction in patients with acute MI.


Delayed reaction to "lead" pencil simulating melanoma.
A 74-year-old man had sustained a penetrating lead pencil injury to his right lower leg at the age of fifteen. A dark gray macule occurred that remained unchanged for fifty-eight years. An enlarging black nodule appeared in this area, simulating a melanoma, when the patient was seventy-three years old. Histologic examination revealed exogenous pigment and a foreign body reaction.


FUNCTIONAL STATE OF MULTIPOTENT MESENCHYMAL STROMAL CELLS DURING MODELING THE EFFECTS OF MICROGRAVITY.
Multipotent mesenchymal stromal cells (MMSCs) are essential for regeneration and tissue homeostasis. The investigation was focused on the functional state of MMSCs isolated from human adipose tissue and exposed to simulated microgravity in vitro by RPM (random position machine). The results point to an increase of proliferative potential, decrease of the lisosomal compartment activity, and reductions in cell size and granularity. Evaluation of the paracrine activity in relatively static control revealed increased IL-8 production and decreased IL-6 production. *Our .data supplement previous findings and allow conclude about universality of the mesenchymal cell reaction to simulated microgravity. The investigation did not detect signs of cell stress in this environment.


Preparing Nurse Leaders for Value-Based Care: A Toolkit to Guide Practice Transformation.
Organizations across the country are redesigning care delivery to improve quality and outcomes, enhance the patient experience, reduce costs, and, ultimately, produce better population health. Leaders from the American Organization for Nursing Leadership engaged key stakeholders to discuss the role nursing can play and the toolkit that will be introduced this year to guide nurse leaders in striving for value.


Prevalence and transmission of haemolytic Gallibacterium species in chicken production systems with different biosecurity levels.
A stratified cross-sectional study consisting of four strata of biosecurity based on production system type, including organic/free-range layer, battery-cage layer, layer parent, broiler parent and broiler grandparent flocks, was performed to estimate the prevalence of haemolytic Gallibacterium spp. Thirty birds were sampled by tracheal and cloacal swabs in each flock. A flock was considered infected when just one bird tested positive. A total of 27 flocks was included in the study. All chickens from the broiler grandparent flocks sampled negative, whereas 28% of the broiler parents, 40% of the layer parents, 67% of the battery-cage layers and 96% of the organic/free-range chickens sampled positive. A total of 95.9% (standard deviation +/- 7.6%) of birds from infected flocks was colonized by haemolytic Gallibacterium species. A significantly higher number of tracheal swabs was positive compared with cloacal swabs. The probability of vertical transfer was investigated by sampling offspring from an infected as well as a non-infected parent flock. None of the samples were found positive. In conclusion, we showed that haemolytic Gallibacterium spp. were widely distributed within the Danish commercial chicken production systems. However, prevalence proportions were highly influenced by the production system and found to be significantly associated with the biosecurity level observed in the flocks. In general, flock infections resembled an 'all or none' type of colonization as practically all of the chickens in infected flocks sampled positive. There was no evidence of vertical transmission of Gallibacterium.


Immunization with polyamine transport protein PotD protects mice against systemic infection with Streptococcus pneumoniae.
The human pathogen Streptococcus pneumoniae contains genes for a putative polyamine ABC transporter which are organized in an operon and designated potABCD. Polyamine transport protein D (PotD) is an extracellular protein which binds polyamines and possibly other structurally related molecules. PotD has been shown to contribute to virulence in both a murine sepsis model and a pneumonia model with capsular type 3 pneumococci. The protective efficacy of recombinant PotD was evaluated by active immunization and intravenous challenge with capsular type 3 pneumococci in CBA/N mice. Immunized mice had 91.7% survival following lethal pneumococcal challenge, compared with 100% mortality in the control group. Immunized animals had high-titer anti-PotD antibodies following three immunizations with alum. Protection in a sepsis model was also seen after passive administration of rabbit antiserum raised against PotD (P < 0.004). These results suggest that antibodies to PotD confer protection against invasive pneumococcal disease and that this protein should be studied further as a potential vaccine candidate for protection against invasive pneumococcal infections.