Minimal changes in postoperative creatinine values and early and late mortality and cardiovascular events after coronary artery bypass grafting.
Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with adverse outcomes. This study investigated if already a minimal change of 0 to 0.3 mg/dl in postoperative serum creatinine values was associated with early death and long-term cardiovascular outcomes and death. From the SWEDEHEART registry, we included 25,686 patients who underwent elective, isolated, primary CABG in Sweden from 2000 to 2008. AKI was categorized according to increases in postoperative creatinine values: group 1, 0 to 0.3 mg/dl; group 2, 0.3 to 0.5 mg/dl; and group 3, >0.5 mg/dl. The primary outcome measure was death from any cause. During a mean follow-up of 6 years, there were 4,350 deaths (17%) and 7,095 hospitalizations (28%) for myocardial infarction, stroke, heart failure, or death (secondary outcome). The adjusted odds ratios (95% confidence interval [CI]) for early mortality in AKI groups 1 to 3 were 1.37 (0.84 to 2.21), 3.64 (2.07 to 6.38), and 15.4 (9.98 to 23.9), respectively. For long-term mortality, the corresponding hazard ratios (95% CI) were 1.07 (1.00 to 1.15), 1.33 (1.19 to 1.48), and 2.11 (1.92 to 2.32), respectively. There was a significant association between each AKI group and the composite outcome (HR 1.09, 95% CI 1.03 to 1.15; HR 1.39, 95% CI 1.27 to 1.52; and HR 1.99, 95% CI 1.84 to 2.16, respectively). In conclusion, already a minimal increase in the postoperative serum creatinine level after CABG was independently associated with long-term all-cause mortality and cardiovascular outcomes, regardless of preoperative renal function.


Evaluation of the Removal of Selected Phthalic Acid Esters (PAEs) in Municipal Wastewater Treatment Plants Supported by Constructed Wetlands.
Phthalic acid esters (PAEs) have a negative impact on living organisms in the environment, therefore, are among the group of Endocrine Disrupting Compounds (ECDs). Unfortunately, conventional methods used in municipal wastewater treatment plants (MWWTPs) are not designed to eliminate PAEs. For this reason, the development of cheap and simple but very effective techniques for the removal of such residues from wastewater is crucial. The main aim of this study was the evaluation of the removal of six selected PAEs: diethyl phthalate (DEP), di-n-octyl phthalate (DOP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP) and dimethyl phthalate (DMP), in real MWWTPs supported by constructed wetlands (MWWTP-CW system). For the first time, the possibility of using three new plants for this purpose, Cyperus papyrus (papyrus), Lysimachia nemorum (yellow pimpernel) and Euonymus europaeus (European spindle), has been presented. For determining the target PAEs in wastewater samples, a method of SPE (Solid-Phase Extraction)-GC-MS(SIM) was developed and validated, and for plant materials, a method of UAE (Ultrasound-Assisted Extraction)-SPE-GC-MS(SIM) was proposed. The obtained data showed that the application of the MWWTP-CW system allows a significant increase in the removal of DEP, DBP, BBP and DEHP from the wastewater stream. Euonymus europaeus was the most effective among the tested plant species for the uptake of analytes (8938 ng × g-1 dry weight), thus, this plant was found to be optimal for supporting conventional MWWTPs.


Synthesis and cleavage experiments of oligonucleotide conjugates with a diimidazole-derived catalytic center.
Ribonuclease mimics based on diimidazole derived constructs in combination with or without additional amino groups have been synthesized and conjugated to oligonucleotides. The imidazole moiety was used either unprotected, protected with a monomethoxytrityl group or a tert-butyloxy carbonyl group. Acylation reactions were carried out using the 3-acyl-1,3-thiazolidine-2-thione activation strategy. The peptides were coupled to the oligonucleotides with a mixture of PyBOP, DIEA an HOBt in DMF on solid support. The conjugates were purified by RP-HPLC and identified using negative ion mode mass spectrometry. Unfortunately, no cleavage of a linear RNA target under physiological conditions could be observed.


A cross-national analysis of measurement invariance of the Satisfaction With Life Scale.
Measurement invariance of the Satisfaction With Life Scale (SWLS) was examined in probability samples of adults 50-79 years of age living in the United States, England, and Japan. Confirmatory factor analysis modeling was used to test for multigroup measurement invariance of a single-factor structure of the SWLS. Results support a single-factor structure of the SWLS across the 3 countries, with tests of measurement invariance of the SWLS supporting its configural invariance and metric invariance. These results suggest that the SWLS may be used as a single-factor measure of life satisfaction in the United States, England, and Japan, and that it is appropriate to compare correlates of the SWLS in middle-aged and older adults across these 3 countries. However, results provided evidence for only partial scalar invariance, with the intercept for SWLS Item 4 varying across countries. Cross-national comparisons of means revealed a lower mean at the latent variable level for the Japanese sample than for the other 2 samples. In addition, over and above the latent mean difference, the Japanese sample also manifested a significantly lower intercept on Item 4. Implications of the findings for research on cross-national comparisons of life satisfaction in European American and East Asian countries are discussed. (PsycINFO Database Record


Effectiveness of Recombinant Human Growth Hormone Therapy for Children With Phelan-McDermid Syndrome: An Open-Label, Cross-Over, Preliminary Study.
Phelan-McDermid syndrome (PMS), also known as the 22q13. 3 deletion syndrome, is a rare neurodevelopmental syndrome with approximately 2,800 patients reported worldwide. Previous pilot study demonstrated that IGF-1 could significantly improve in both social impairment and restrictive behaviors of the patients. However, most of the patients in the developing countries like China cannot afford the high cost of using IGF-1. Our research team speculated that rhGH might serve as a low-cost and more accessible treatment for PMS. Therefore, the purpose of this open-label, cross-over, pilot study was to further investigate the safety and efficiency of rhGH in patients with PMS. A total of six children with PMS were enrolled in in this open-label, cross-over, pilot study. The children were randomly divided into two different groups. Group A received placebo followed by rhGH, while group B was treated with rhGH first. Neuropsychological and behavior assessments of the patients were performed before the stage I of study and 3 months after the intervention of stage I. After a 4-week period of washout, these assessments were conducted again before the stage II of study and 3 months after the intervention of stage II. Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding-protein (IGFBP)-3 were also evaluated monthly during the intervention phases of the pilot study. Compared with the placebo, rhGH treatment significantly decreased subscale scores of GDS (P < 0.0085) and trended to improve the total scores of GDS (P < 0.05), while the total scores and subscale scores of SC-ABC significantly decreased (P < 0.0085) following 3-months rhGH treatment. The similar results were also observed in comparison with baseline. Compared with the baseline, the level of serum IGF-1 and IGFBP-3 increased significantly (P < 0.05) following 3-months rhGH treatment, while the placebo group had no significant impact on serum IGF-1 and IGFBP-3 (P > 0.05). One child developed skin allergy the day after the first rhGH treatment, which were resolved later. In summary, this pilot study involving six PMS children patients reveals that rhGH has a positive treatment effect on PMS. These results encourage the undertaking of a large, randomized placebo-controlled trial to conclusively prove rhGH efficacy and tolerability in PMS, thereby promoting it as a low-cost, more accessible treatment for PMS, as compared to IGF-1.


Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently "orphan" viral proteins.
The genome sequences of new viruses often contain many "orphan" or "taxon-specific" proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as "genus specific" by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virions.


Evidence for a hybrid macrophage phenotype in erythrophagocytic histiocytosis.
The phenotype of the proliferating cells in two patients with erythrophagocytic histiocytosis is described. These 6- and 18-month-old female patients presented with fever, anemia, hepatosplenomegaly, and lymphadenopathy. Clinical histories were reviewed, and pathological specimens of both patients were studied by histology, and electron microscopy/immunohistochemistry using antibodies against macrophage and Langerhans cell (LC) antigens. Histology revealed prominent erythrophagocytosis of proliferating histiocytes. By immunohistochemistry, conventional macrophage (HAM-56, alpha 1-antitrypsin, alpha 1-antichymotrypsin, lisozyme, CD68, and alpha-subunit of S-100 protein) and LC (CD1a and S-100 protein) markers were positive, as well as double labeling for CD1a and alpha 1-antichymotrypsin, in a majority of proliferating cells. Ultrastructural examination revealed Birbeck granules and prominent phagolysosomes frequently in the same cell. The hybrid ultrastructural and immunohistochemical phenotype between phagocytic macrophage and LC of proliferating histiocytes supports the common origin of these different histiocyte subtypes. This unusual phenotype might be the expression of the proliferating (hybrid) precursor or be the effect of unknown stimuli. Additional cases of childhood erythrophagocytic histiocytosis should be studied with immunophenotyping and ultrastructure to determine whether the hybrid phenotype represents a specific entity or an epiphenomenon.


How does cellular contact affect differentiation mediated pattern formation?
In this paper, we present a two-population continuous integro-differential model of cell differentiation, using a non-local term to describe the influence of the local environment on differentiation. We investigate three different versions of the model, with differentiation being cell autonomous, regulated via a community effect, or weakly dependent on the local cellular environment. We consider the spatial patterns that such different modes of differentiation produce, and investigate the formation of both stripes and spots by the model. We show that pattern formation only occurs when differentiation is regulated by a strong community effect. In this case, permanent spatial patterns only occur under a precise relationship between the parameters characterising cell dynamics, although transient patterns can persist for biologically relevant timescales when this condition is relaxed. In all cases, the long-lived patterns consist only of stripes, not spots.


Intraoperative defibrillation threshold testing during implantable cardioverter-defibrillator insertion: do we really need it?
The assessment of defibrillation efficacy using a safety margin of 10 J has long been the standard of care for insertion of implantable cardioverter-defibrillator (ICD), but physicians are concerned about complications related to induction test. Therefore, the need for testing has been recently questioned. The aim of our study was to assess the impact of defibrillation threshold (DFT) testing of ICD on the efficacy of ICD therapy. We analyzed data obtained from follow-up visits of 122 consecutive patients who underwent ICD implantation at our institute from April 1996 to June 2008, with (n = 42) or without (n = 80) DFT testing. Patients in the DFT group were less likely to be men (83.3% vs 96.3%, P < .031) than those in the non-DFT group. Conversely, the 2 groups were similar in age, left ventricular ejection fraction at baseline, functional class, and underlying cardiovascular disease. Results during a 12-month follow-up, 13 (31.0%) and 30 (37.5%) ventricular tachyarrhythmic episodes were recorded in the DFT and non-DFT groups, respectively (P = .472). Antitachycardia pacing (ATP) terminated most of episodes, reducing the need of defibrillation at 7.7% in the DFT group and 3.3% in the non-DFT group (P = .533). Similar percentages of inappropriate ATP interventions (7.1% vs 3.8%, P = .413) and shock deliveries (2.4% vs 5.0%, P = .659) were recorded between DFT and non-DFT groups. At 1-year follow-up, the performance of DFT testing does not seem to add any significant efficacy advantage in patients undergoing ICD implantation. Prospective randomized trials and long-term follow-up are warranted to clarify whether routine DFT testing may be safely abandoned leading to a revision of current guidelines.


CERKL mutation causing retinitis pigmentosa(RP) in Indian population - a genotype and phenotype correlation study.
Mutations in CERKL gene has been reported to cause Retinitis pigmentosa (RP) and clinically appears discrete from other commonly encountered phenotypes. We report 14 patients who were seen to have CERKL mutation of the 152 patients of RP from Indian population who underwent genetic testing. A retrospective analysis was performed in 28 eyes of the 14 unrelated patients to establish genotype phenotype correlation. Targeted next generation sequencing was performed using the STRAND® NGS v2.5 software. Validation was done using PCR-based bidirectional Sanger sequencing. Clinical data was collected along with imaging such as fundus photo, autofluorescence(AF), Optical coherence tomography and Electroretinogram wherever available. Three variants c.1045_1046delAT, c.847 C > T and a novel c.899-IG>A were identified. Retinal morphological features were typically bilaterally symmetrical with mild to moderate disc pallor and arteriolar attenuation in all cases, while sparse peripheral pigmentation was noted in seven patients indicating paucipigmentary character. Early macular involvement in all cases was a characteristic finding with central hypo-autofluorescence and surrounding hyper-autofluorescence. Peripheral scalloped chorioretinal atrophic patches were seen in five patients particularly in older patients. Phenotype associated with CERKL mutation appears clinically discrete from other commonly encountered phenotypes of inherited retinal dystrophies. Recognizing this typical genotype phenotype correlation will help clinicians to identify this form of RP, prognosticate the disease and segregate candidates for futures gene therapy.


[A new mutation in the connexin 32 gene of a Chinese family with Charcot-Marie-Tooth disease associated with central conduction slowing].
To report a Chinese Charcot-Marie-Tooth disease (CMT) family whose proband had abnormal brainstem auditory evoked potentials (BAEPs) and to study its relationship with connexin 32 (Cx32) gene mutation. All family members were studied through clinical examinations, out of them, the proband was subjected to electromyography and BAEPs examination. Mutation analysis of Cx32 was screened by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) combined with DNA direct sequencing in the proband, 8 family members and 50 unrelated normal individuals. The proband had highly decreased nerve conduction velocities and delayed BAEPs. Leu131Pro mutation was found in the proband and 3 family members, not found in 50 normal controls. This mutation has not been reported previously. Central nervous system can be affected in CMT patients.


Tissue oxygenation in hypovolemic shock.
Bowel mucosal ischemia may be related to the development of systemic sepsis. Traditional indices of oxygen metabolism are flow-weighted averages which do not reflect tissue-specific oxygen concentration. We undertook this study to examine the relationship between systemic oxygen delivery (DO2) and tissue oxygen tension (TPO2) in hypovolemic shock. A modified Wiggers model was used to produce hypotension in five swine. TPO2 was measured continuously with fluorescence-quenching 1-mm probes placed in the submucosa of the terminal ileum and subcutaneously in an axillary fold. Shock was maintained for 1 hr, followed by resuscitation. Cardiac output, systemic and pulmonary arterial pressures, and arterial and mixed venous blood gases were measured every 15 min. Data were analyzed by nonparametric ANOVA and rank coefficients, with logarithmic curve fitting and linear regression. DO2 decreased with phlebotomy (P < 0.003) as did skin TPO2 (P < 0.001) and bowel TPO2 (P < 0.0004). Skin and bowel TPO2 varied with DO2 and each other (P < 0.05). TPO2 remained low throughout the shock period and returned to or exceeded baseline levels with resuscitation (P < 0.05). The following were concluded: (1) Hypovolemic shock produces a significant and rapid decrease in subcutaneous and bowel TPO2 with concomitant change in DO2. (2) The degree of bowel ischemia, clinically inaccessible for quantitation, is paralleled by subcutaneous TPO2. (3) TPO2 provides information about oxygen availability in shock and resuscitation not available from traditional parameters of oxygen transport.


Pseudo third cranial nerve palsy secondary to orbital ectopic lacrimal gland cyst: management with functional endoscopic sinus surgery.
An otherwise healthy 13-month-old girl was noted by her pediatrician to have developed a left head turn. The patient was referred to a pediatric ophthalmologist, who noticed signs of incomplete third cranial nerve palsy. Magnetic resonance imaging revealed the presence of an abnormal lesion in the inferonasal orbit that was abutting the ethmoid sinus. After consultation with an ENT specialist, the decision was made to remove the lesion via functional endoscopic sinus surgery because this approach was deemed to provide adequate access while limiting morbidity. Histology of the excised lesion identified it as true ectopic lacrimal gland tissue with cysts. We recognize and comment on the fact that in many reported cases of ectopic lacrimal gland cyst, the tissue was not ectopic at all but instead represented an extension of normal lacrimal gland tissue.


Binding energy curves from nonempirical density functionals II. van der Waals bonds in rare-gas and alkaline-earth diatomics.
Binding energy curves have been calculated for the ground-state rare-gas diatomics Ne(2) and Ar(2) and for the alkaline-earth diatomic Be(2) using the nonempirical density functionals from the first three rungs of a ladder of approximations: the local spin density (LSD) approximation, the Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA), and the Tao-Perdew-Staroverov-Scuseria (TPSS) meta-GGA. Binding energy curves in reasonable agreement with those constructed from experiment are found from PBE and TPSS, which incorporate inhomogeneity corrections that satisfy the Lieb-Oxford bound and so describe the short-range part of the van der Waals interaction. At large internuclear separation, these functionals produce an exponentially decaying attraction in place of the correct long-range -C(6)/R(6). Basis-set and exchange-only effects are also discussed.


Ring-closing metathesis of chiral allylamines. Enantioselective synthesis of (2S,3R,4S)-3,4-dihydroxyproline.
The ring-closing metathesis (RCM) of two types of unsaturated chiral allylamines III, easily available from enantiomerically enriched epoxy alcohols, has been studied. Fully protected allylamines IIIa [(1)R = CH(2)-(CH(2))(n)()-CH=CH(2); (2)R = Boc; (3)R = PMB] have been prepared from unsaturated epoxy alcohols, whereas bis-allylamines IIIb ((1)R = Ph, (2)R = allyl,(3)R = Boc or PMB) have been prepared from 2,3-epoxy-3-phenylpropanol. Both types have been subjected to RCM to provide either cyclic allylamine I or II. The synthetic potential of these intermediates has been demonstrated by the enantioselective synthesis of (2S,3R,4S)-3,4-dihydroxyproline.


3D reconstruction of objects with occlusion and surface reflection using a dual monocular structured light system.
Three-dimensional (3D) vision plays an important role in industrial vision, where occlusion and reflection have made it challenging to reconstruct the entire application scene. In this paper, we present a novel 3D reconstruction framework to solve the occlusion and reflection reconstruction issues in complex scenes. A dual monocular structured light system is adopted to obtain the point cloud from different viewing angles to fill the missing points in the complex scenes. To enhance the efficiency of point cloud fusion, we create a decision map that is able to avoid the reconstruction of repeating regions of the left and right system. Additionally, a compensation method based on the decision map is proposed for reducing the reconstruction error of the dual monocular system in the fusion area. Gray-code and phase-shifting patterns are utilized to encode the complex scenes, while the phase-jumping problem at the phase boundary is avoided by designing a unique compensation function. Various experiments including accuracy evaluation, comparison with the traditional fusion algorithm, and the reconstruction of real complex scenes are conducted to validate the method's accuracy and the robustness to the shiny surface and occlusion reconstruction problem.


Synthetic biliary bypass.
A method for the bypass of high biliary strictures using a Dacron velour prosthesis is discussed. This has been employed in 24 patients with obstructive jaundice caused by malignant disease which could not be relieved by conventional means.


Generation of SARS-CoV-2 Spike Pseudotyped Virus for Viral Entry and Neutralization Assays: A 1-Week Protocol.
The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus requires reliable assays for studying viral entry mechanisms which remains poorly understood. This knowledge is important for the development of therapeutic approaches to control SARS-CoV-2 infection by permitting the screening for neutralizing antibodies and other agents that can block infection. This is particularly important for patients who are at high risk for severe outcomes related to COVID-19. The production of pseudotyped viral particles may seem like a daunting task for a non-virology laboratory without experience in the two most commonly used pseudotyping systems, namely retro/lentiviruses and vesicular stomatitis virus (VSV) which lacks the VSV envelope glycoprotein (VSVΔG). By incorporating the most up-to-date knowledge, we have developed a detailed, easy-to-follow novel protocol for producing SARS-CoV-2 spike-bearing pseudovirus using the VSV-ΔG system. We describe the infection assay which uses GFP fluorescence as a measure of infection in a 24-well live imaging system. We present results of our optimization of the system to enhance viral infection levels through the over-expression of human ACE2 receptor and the overexpression of at least one of two proteases - TMPRSS2 or Furin, as well as, supplementation with Poloxamer 407 (P407) and Prostaglandin E2 (PGE2) as adjuvants. We show that the system works efficiently in three unrelated, clinically relevant cell lines: human 293T (renal epithelial) cells, human Calu-3 (lung epithelial) cells, and the non-human primate (African Green Monkey) cell line, Vero-E6 (renal epithelial) cells. In addition, we have used this system to show infection of human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs). This system is efficient (virus generation, titration, and infection assays can be performed in 1 week), quantitative, inexpensive, and readily scalable for application in drug development and therapeutic screening approaches.


A comparison of dequalinium chloride vaginal tablets (Fluomizin®) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety.
To investigate if vaginal application of dequalinium chloride (DQC, Fluomizin®) is as effective as vaginal clindamycin (CLM) in the treatment of bacterial vaginosis (BV). This was a multinational, multicenter, single-blind, randomized trial in 15 centers, including 321 women. They were randomized to either vaginal DQC tablets or vaginal CLM cream. Follow-up visits were 1 week and 1 month after treatment. Clinical cure based on Amsel's criteria was the primary outcome. Secondary outcomes were rate of treatment failures and recurrences, incidence of post-treatment vulvovaginal candidosis (VVC), lactobacillary grade (LBG), total symptom score (TSC), and safety. Cure rates with DQC (C1: 81.5%, C2: 79.5%) were as high as with CLM (C1: 78.4%, C2: 77.6%). Thus, the treatment with DQC had equal efficacy as CLM cream. A trend to less common post-treatment VVC in the DQC-treated women was observed (DQC: 2.5%, CLM: 7.7%; p = 0.06). Both treatments were well tolerated with no serious adverse events occurring. Vaginal DQC has been shown to be equally effective as CLM cream, to be well tolerated with no systemic safety concerns, and is therefore a valid alternative therapy for women with BV [ClinicalTrials.gov, Med380104, NCT01125410].


HSV-1-mediated modulation of cytokine gene expression in a permissive cell line: selective upregulation of IL-6 gene expression.
Pathological effects of herpes simplex virus (HSV) can result due to a combination of direct viropathic effects and immunological reactions to viral antigens. The immunological reactions are orchestrated by a variety of cytokines and chemokines released by the host cells. Therefore, the cytokine gene expression in response to HSV-1 infection in a permissive murine cell line was investigated. The data demonstrate that HSV-1 induced a selective activation of IL-6 gene expression at the mRNA and protein levels, in the permissive cell line. The cell line used was capable of expressing IL-1, IL-7, and IL-10 in addition to IL-6, upon lipopolysaccharide stimulation. UV or heat-inactivated viruses were unable to upregulate IL-6 expression. However, mutant HSV-1 strains lacking fully functional ICP0, ICP4, ICP8, or ICP27 genes, thereby rendering them replication incompetent or impaired in in vitro cell growth (ICP0), enhanced IL-6 expression selectively. Considering the role of IL-6 in inflammation, immune response, and its known association with increased levels of MyD116 and GADD 34 mRNAs (genes involved in the prevention of apoptotic death of cells), the present data may have relevance to HSV-1-mediated diseases as well as to the prevalence of HSV-1 in the host.


Rapid and Efficient Detection of 16SrI Group Areca Palm Yellow Leaf Phytoplasma in China by Loop-Mediated Isothermal Amplification.
Areca palm yellow leaf (AYL) disease caused by the 16SrI group phytoplasma is a serious threat to the development of the Areca palm industry in China. The 16S rRNA gene sequence was utilized to establish a rapid and efficient detection system efficient for the 16SrI-B subgroup AYL phytoplasma in China by loop-mediated isothermal amplification (LAMP). The results showed that two sets of LAMP detection primers, 16SrDNA-2 and 16SrDNA-3, were efficient for 16SrIB subgroup AYL phytoplasma in China, with positive results appearing under reaction conditions of 64oC for 40 min. The lowest detection limit for the two LAMP detection assays was the same at 200 ag/μl, namely approximately 53 copies/μl of the target fragments. Phytoplasma was detected in all AYL disease samples from Baoting, Tunchang, and Wanning counties in Hainan province using the two sets of LAMP primers 16SrDNA-2 and 16SrDNA-3, whereas no phytoplasma was detected in the negative control. The LAMP method established in this study with comparatively high sensitivity and stability, provides reliable results that could be visually detected, making it suitable for application and research in rapid diagnosis of AYL disease, detection of seedlings with the pathogen and breeding of disease-resistant Areca palm varieties.


[Medicolegal considerations about rape as a reason to decriminalize abortion].
The Chilean senate is discussing a proposal to decriminalize abortion in 3 causals. One of these is when the pregnancy occurs as a result of a rape. To be legally able to perform the abortion in this circumstance, a health care team must confirm the occurrence of the facts constituting the offence. Regardless of the patient's will, the accusation will be reported to the justice. In our view, in its current status the proposed rule does not consider certain medicolegal and procedural topics. Those flaws may determine in certain scenarios critical problems, such as: a) a wrongful conviction as a consequence of a false allegation of rape; (b) some pregnant due to a rape will not have access to the abortion procedure; (c) some accusations of rape will not be accredited nor criminally sanctioned. Employing a fictional case, we illustrate how those scenarios can actually be seen in practice. We also emphasize the difficulties and limitations that the health care team will encounter if the project is approved under the current conditions. Finally, we encourage the professional societies implicated in the theme to contribute in the legislatorial debate. Therefore, we give a set of proposals aimed to improve the bill before it may be enacted as a law.


Age dependence of lung mesenchymal stromal cell dynamics following pneumonectomy.
Aging is a critical determinant of regenerative capacity in many organ systems, but it remains unresolved in the lung. This study examines murine lung cell dynamics during age-dependent lung regeneration. Proliferation of lung progenitor cells (EpCAM(neg)/Sca-1(high) lung mesenchymal stromal cells - LMSCs, EpCAM(pos)/Sca-1(low) epithelial progenitor cells, proSP-C(pos) alveolar type II epithelial cells - AECII, and CD31(pos) - endothelial cells) was tracked to day 3 or 7 after pneumonectomy (PNX) or SHAM surgery in 3, 9, and 17 month mice. In 3 month mice, post-PNX LMSC proliferation peaked early (3 days), with 50%-80% more BrdU-positive cells than the other cell types, which peaked later (4-7 days). In older mice (9 and 17 month), abundance and post-PNX proliferation of LMSCs at day 3 were reduced (40%-80%). In both young and old mice, LMSCs were isolated and compared phenotypically with whole lung non-LMSCs. Donor age had no qualitative effect on the phenotype (LMSC vs. non-LMSC), with increased expression of CD90/Thy1, CD105/Eng, CD106/Vcam, CD146/Mcam, and Pdgfrα, and up-regulation of mRNA encoding Fap, Eln, Col1a1, Col3a1, Aldh1a3, Arhgef25, Dner, Fgfr1, and Midkine. However, compared with LMSCs isolated from young mice, LMSCs from older mice exhibited reduced mRNA expression of retinoic acid (Aldh1a3, Rbp4), Fgf/Wnt (Fgfr1, Sfrp1, Wnt2, and Ctnnb1), and elastogenesis (Col1a1, Eln, Fbn1, and Sdc2) pathway genes. Isolated LMSCs from older mice also demonstrated lower colony-forming units (-67%), growth potential (-60% by day 7), ALDH activity (-49%), and telomerase activity (-47%). Therefore, age is associated with declining proliferative potential and regenerative functions of LMSCs in the lung.


Percutaneous ultrasound-guided irreversible electroporation: A goat liver study.
Irreversible electroporation (IRE) is a new tumor ablation technique. Pulsed electric fields (PEFs) with permanent duration (100 μsec) permanently permeabilize the cell membrane, causing the formation of innumerable permanent nanopores in the cell membrane and leading to cell death. In this study, percutaneous IRE was performed on 24 goat livers under the guidance of ultrasonography (US). IRE-exposed tissues were pathologically examined and glucose-6-phosphatase (G-6-P) and succinodehydrogenase (SDH) staining were used to detect the activity and function of the endoplasmic reticulum and mitochondria of liver tissues at 0 and 24 h after IRE ablation. Tissue ablation responses were monitored in real-time with US in the percutaneous IRE group; the largest diameter of the ablation zones was measured immediately (D1) and after 24 h (D2). Following D2 measurement, the animals were sacrificed and the gross sections (D3) were measured. The pathological examination results showed complete tissue necrosis after 24 h instead of immediately following IRE. The largest long diameters measured by intraprocedural US immediately after IRE (D1, 39.58±2.13 mm) were larger than those measured by US after 24 h (D2, 37.07±3.51 mm) and in gross section measurements (D3, 36.44±2.04 mm; P<0.05). D1 showed a good linear correlation with D3 (r=0.949). We conclude from these studies that IRE is not an acute ablating effect which leads to cell death. If US-guided percutaneous IRE focused on the target liver areas accurately, physicians would be able to assess the extent of necrosis through the regression equation during the IRE ablation procedure, and evaluate whether sufficient electric field energy had been applied to the desired tissue. Assisted with US guiding and monitoring, the minimally invasive IRE procedure in intraperitoneal lesions may become an important tumor ablation technique.


Principal neurons as local circuit neurons in the rat superior cervical ganglion: the synaptology of the neuronal processes revealed by intracellular injection of biocytin.
To analyze the local circuitry of the sympathetic ganglion, the synaptic relations of the neuronal processes of the principal neurons in the rat superior cervical ganglion were investigated by correlated light and electron microscopy combined with intracellular injection of biocytin. Intracellular iontophoresis of biocytin followed by avidin-biotinylated horseradish peroxidase cytochemistry allowed complete visualization of the neuronal processes of the principal neurons. The stained principal neurons have a single process (axon), which leaves the ganglion, and several intraganglionic processes (dendrites), some of which show specific terminal arborizations. Some terminals of the dendritic collaterals formed pericellular plexuses or intercellular glomerular plexuses. Electron microscopically, the dendrites and their collaterals contain numerous small vesicles. Synaptic membrane specializations were observed between the stained dendritic collaterals and unlabeled neurites. These may be both preganglionic axon terminals and processes of principal neurons. The likely direction of neurotransmission often could not be determined because of the bidirectional synaptic structures. Our findings show that the dendritic collaterals of principal neurons appear to make both post- and presynaptic contacts with both the principal neurons and the preganglionic axons. It is suggested that the principal neurons might participate in local circuits involving not only preganglionic axons but also neighboring principal neurons.


Central benzodiazepine receptor distribution after subcortical hemorrhage evaluated by means of [123I]iomazenil and SPECT.
[123I]Iomazenil is a single-photon emission computed tomography (SPECT) tracer that selectively binds to central benzodiazepine receptor in the neuron membrane. With this ligand, we studied the central benzodiazepine receptor distribution in the cortex remote from subcortical hematoma in intracerebral hemorrhage patients. Four patients with unilateral putaminal hemorrhage and one patient with right thalamic hemorrhage were studied (mean +/- 1 SD age, 50.0 +/- 8.8 years). The initial volume of hematoma ranged from 4.3 to 31.0 mL (mean +/- 1 SD, 17.5 +/- 12.3 mL). SPECT images obtained 3 hours after intravenous administration of [123I]iomazenil (167 MBq/750 ng) were analyzed. In three patients, perfusion was evaluated with [123I]IMP. On SPECT images, the radioactivity ratio of the ipsilateral to the contralateral cerebral cortex (I/C ratio) or of the contralateral to the ipsilateral cerebellar hemisphere (C/I ratio) was measured. The I/C ratio for iomazenil was significantly decreased compared with unity in the temporal lobe (0.84 +/- 0.08, P < .01) and the parietal lobe (0.87 +/- 0.10, P < .05), but the C/I ratio in the cerebellum (1.00 +/- 0.03) was not. The C/I ratio for perfusion in the cerebellar cortex (0.83 +/- 0.04, P < .01) was significantly decreased compared with that in normal subjects. Central benzodiazepine receptor-[123I]iomazenil binding was decreased in the ipsilateral cerebral cortex remote from the subcortical hematoma. This preliminary result may facilitate further study of the potential damage of the cortical neurons remote from subcortical hematoma.


Intense Pulsed Light for the Treatment of Dry Eye Owing to Meibomian Gland Dysfunction.
Dry eye disease (DED) is an increasingly common condition and one of the most common complaints of patients. The vast majority of DED is caused by the so-called "evaporative" subtype, that is mainly caused by meibomian gland dysfunction (MGD). Intense pulsed light (IPL) devices employ high intensity pulses of polychromatic lights with a broad range of wavelength (515-1200 nm). IPL treatment has been utilized for years in the field of dermatology, and then its use was applied to ophthalmology for the treatment of MGD. Recently, a new device employing IPL was specifically designed for the periocular application. This procedure determines the thermal selective coagulation and ablation of superficial blood vessels and telangiectasias of the eyelids skin, reducing the release of inflammatory mediators and tear cytokines levels, and improving meibomian glands outflow. IPL treatment is noninvasive and easy to perform, lasts for only a few minutes and can be conducted in an office setting. In the present study, 19 patients underwent 3 sessions of IPL treatment. After treatment, both mean noninvasive break-up time and lipid layer thickness grade significantly increased, as a result of an improvement of tear film stability and quality, respectively. Conversely, no statistically significant changes were found for meibomian gland loss and tear osmolarity. Furthermore, the vast majority of the treated patients (17/19; 89.5% of the total) perceived an improvement of their ocular discomfort symptoms after IPL treatment. Although IPL treatment provides an improvement of both ocular surface parameters and ocular discomfort symptoms after one cycle of three sessions, regular repeated treatments are usually required to maintain the persistence over the time of its beneficial effects.


Human-like, population-level specialization in the manufacture of pandanus tools by New Caledonian crows Corvus moneduloides.
The main way of gaining insight into the behaviour and neurological faculties of our early ancestors is to study artefactual evidence for the making and use of tools, but this places severe constraints on what knowledge can be obtained. New Caledonian crows, however, offer a potential analogous model system for learning about these difficult-to-establish aspects of prehistoric humans. I found new evidence of human-like specialization in crows' manufacture of hook tools from pandanus leaves: functional lateralization or 'handedness' and the shaping of these tools to a rule system. These population-level features are unprecedented in the tool behaviour of free-living non-humans and provide the first demonstration that a population bias for handedness in tool-making and the shaping of tools to rule systems are not concomitant with symbolic thought and language. It is unknown how crows obtain their tool behaviour. Nevertheless, at the least they can be studied in order to learn about the neuropsychology associated with early specialized and/or advanced population features in tool-making such as hook use, handedness and the shaping of tools to rule systems.


Rapid Knockout and Reporter Mouse Line Generation and Breeding Colony Establishment Using EUCOMM Conditional-Ready Embryonic Stem Cells: A Case Study.
As little as a decade ago, generation of a single knockout mouse line was an expensive and time-consuming undertaking available to relatively few researchers. The International Knockout Mouse Consortium, established in 2007, has revolutionized the use of such models by creating an open-access repository of embryonic stem (ES) cells that, through sequential breeding with first FLP1 recombinase and then Cre recombinase transgenic mice, facilitates germline global or conditional deletion of almost every gene in the mouse genome. In this Case Study, we describe our experience using the repository to create mouse lines for a variety of experimental purposes. Specifically, we discuss the process of obtaining germline transmission of two European Conditional Mouse Mutagenesis Program (EUCOMM) "knockout-first" gene targeted constructs and the advantages and pitfalls of using this system. We then outline our breeding strategy and the outcomes of our efforts to generate global and conditional knockouts and reporter mice for the genes of interest. Line maintenance, removal of recombinase transgenes, and cryopreservation are also considered. Our approach led to the generation of heterozygous knockout mice within 6 months of commencing breeding to the founder mice. By describing our experiences with the EUCOMM ES cells and subsequent breeding steps, we hope to assist other researchers with the application of this valuable approach to generating versatile knockout mouse lines.


Arsenic induces reactive oxygen species-caused neuronal cell apoptosis through JNK/ERK-mediated mitochondria-dependent and GRP 78/CHOP-regulated pathways.
Arsenic (As), a well-known high toxic metal, is an important environmental and industrial contaminant, and it induces oxidative stress, which causes many adverse health effects and diseases in humans, particularly in inorganic As (iAs) more harmful than organic As. Recently, epidemiological studies have suggested a possible relationship between iAs exposure and neurodegenerative disease development. However, the toxicological effects and underlying mechanisms of iAs-induced neuronal cell injuries are mostly unknown. The present study demonstrated that iAs significantly decreased cell viability and induced apoptosis in Neuro-2a cells. iAs also increased oxidative stress damage (production of malondialdehyde (MDA) and ROS, and reduction of Nrf2 and thioredoxin protein expression) and induced several features of mitochondria-dependent apoptotic signals, including: mitochondrial dysfunction, the activations of PARP and caspase cascades, and the increase in caspase-3 activity. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively reversed these iAs-induced responses. iAs also increased the phosphorylation of JNK and ERK1/2, but did not that p38-MAPK, in treated Neuro-2a cells. NAC and the specific JNK inhibitor (SP600125) and ERK1/2 inhibitor (PD98059) abrogated iAs-induced cell cytotoxicity, caspase-3/-7 activity, and JNK and ERK1/2 activation. Additionally, exposure of Neuro-2a cells to iAs triggered endoplasmic reticulum (ER) stress identified through several key molecules (GRP 78, CHOP, XBP-1, and caspase-12), which was prevented by NAC. Transfection with GRP 78- and CHOP-specific si-RNA dramatically suppressed GRP 78 and CHOP expression, respectively, and attenuated the activations of caspase-12, -7, and -3 in iAs-exposed cells. Therefore, these results indicate that iAs induces ROS causing neuronal cell death via both JNK/ERK-mediated mitochondria-dependent and GRP 78/CHOP-triggered apoptosis pathways.


Multidrug-resistant Pseudomonas aeruginosa and mortality in mechanically ventilated ICU patients.
The link between bacterial resistance and prognosis remains controversial. Predominant pathogen causing ventilator-associated pneumonia (VAP) is Pseudomonas aeruginosa (Pa), which has increasingly become multidrug resistant (MDR). The aim of this study was to evaluate the relationship between MDR VAP Pa episodes and 30-day mortality. From a longitudinal prospective French multicenter database (2010-2016), Pa VAP onset and physiological data were recorded. MDR was defined as non-susceptibility to at least 1 agent in 3 or more antimicrobial categories. To analyze if MDR episodes were associated with greater in-hospital 30-day mortality, we performed a multivariate survival analysis using the multivariate nonlinear frailty model. A total of 230 patients presented 286 Pa VAP. A maximum of 3 episodes per patient was observed; 73 episodes were MDR and 213 were susceptible. In the multivariate model, factors independently associated with 30-day mortality included hospitalization in the 6 months preceding the first episode (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.50-3.60; P = .0002), chronic renal failure (HR, 2.34; 95% CI, 1.15-4.77; P = .0196), and Pa VAP recurrence (HR, 2.29; 95% CI, 1.79-4.87; P = .032). Finally, MDR Pa VAP was not associated with death (HR, 0.87; 95% CI; 0.52-1.45; P = .59). This study did not identify a relationship between the resistance profile of Pseudomonas aeruginosa and mortality.


Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis.
Hemodynamic and neurohumoral responses to acute diuretic therapy were measured in 15 patients with severe chronic heart failure given intravenous furosemide, 1.3 +/- 0.6 (SD) mg/kg body weight. Left ventricular pump function deteriorated by 20 minutes, as indicated by a fall in stroke volume index (27 +/- 8 to 24 +/- 7 mL/min X m2 body surface area, p less than 0.01) and an increase in left ventricular filling pressure (28 +/- 7 to 33 +/- 9 mm Hg, p less than 0.01). Increases occurred in heart rate (87 +/- 13 to 91 +/- 16 beats/min, p less than 0.01), mean arterial pressure (90 +/- 15 to 96 +/- 15 mm Hg, p less than 0.01), systemic vascular resistance (1454 +/- 394 to 1676 +/- 415 dynes X s X cm-5, p less than 0.01), plasma renin activity (9.9 +/- 8.5 to 17.8 +/- 16 ng/mL X h, p less than 0.05), plasma norepinephrine level (667 +/- 390 to 839 +/- 368 pg/mL, p less than 0.01), and plasma arginine vasopressin level (6.2 +/- 1.3 to 8.3 +/- 2.0 pg/mL, p less than 0.01). During the next 3.5 hours the patients had diuresis (2085 +/- 1035 mL) and the expected fall in filling pressure (28 +/- 7 to 22 +/- 10 mm Hg, p less than 0.01). Neurohumoral indicators also returned toward the control levels. Intravenous furosemide, in patients with severe chronic heart failure, is associated with acute pump dysfunction temporally related to activation of the neurohumoral axis.


Hyperthermal effects in phototherapy with hematoporphyrin derivative sensitization.
Although the photochemical reaction of hematoporphyrin derivative (HpD) appears to play a major role in cytotoxic activity, the hyperthermal contribution to tumor destruction has not yet been clarified. We investigated its role in the effectiveness of laser photoradiation therapy using MS-2 sarcoma transplanted into the hind pad of BALB/c mice as the experimental model. Mice received HpD i.v., 25 mg/kg - 24 h before exposure to light delivered from a dye laser or Nd-YAG laser, or before warming in a thermostated bath. Since our aim was not to cure the tumor, the treatment response was evaluated only as inhibition of tumor growth at different days after treatment. Our results support the view that in laser photochemotherapy the hyperthermia produced by irradiation and the photodynamic effect mediated by HpD could contribute to tumor destruction. Moreover, a synergistic interaction between the photodynamic effect and heat was observed in this experimental model.


Biofilms in Chronic Wounds: Pathogenesis and Diagnosis.
Chronic non-healing wounds have become a major worldwide healthcare burden. The impact of biofilms on chronic wound infection is well established. Despite increasing understanding of the underlying mechanism of biofilm formation in chronic wounds, current strategies for biofilm diagnosis in chronic wounds are still far from ideal. In this review, we briefly summarize the mechanism of biofilm formation and focus on current diagnostic approaches of chronic wound biofilms based on morphology, microbiology, and molecular assays. Innovative biotechnological approaches, such as wound blotting and transcriptomic analysis, may further shed light on this unmet clinical need. The continuous development of these sophisticated diagnostic approaches can markedly contribute to the future implementation of point-of-care biofilm detection in chronic wound care.


Progestins for contraception: modern delivery systems and novel formulations.
Since the development of combined oral contraceptives over 50 years ago, significant innovations have occurred in the domain of the progestin. Evolving knowledge of progestin mechanism of action and physiology has allowed for development of novel progestins with limited steroid receptor cross-reactivity, decreased side effect profiles, and pharmacokinetics optimized for modern delivery systems. This review summarizes current knowledge of progestin physiology, modern delivery systems, and developments of progestin agonists and antagonists for contraception.


Separation of the Hageman factor fragment from human serum albumin by chromatography on blue sepharose CL-6B.
The separation of the Hageman factor fragment (HFf) activity from human serum albumin by chromatography on Blue Sepharose CL-6B is described. The complete separation cannot be achieved in a single chromatography step due to complex formation between HFf and albumin.


A review of neovascular glaucoma. Etiopathogenesis and treatment.
Neovascular glaucoma (NVG) is a type of secondary glaucoma, refractory to treatment, often incurable, with very poor visual prognosis. It is characterized by the appearance of new vessels over the iris and iridocorneal angle and frequently associates the presence of a fibrovascular membrane which limits the aqueous humor outflow from the anterior chamber. The most common causes of NVG are: central retinal vein occlusion, proliferative diabetic retinopathy, and ocular ischemic syndrome. Once the gonioscopy developed as a part of clinical examination, it became possible to visualize the new vessels of the anterior segment of the eye in early stages and to understand the mechanisms of increased intraocular pressure (IOP), including narrowing and closing of the iridocorneal angle. Also, the modern imaging techniques, such as optical coherence tomography angiography and fluorescein angiography became indispensable for the clinician. Thus, an early diagnosis, followed by starting an appropriate therapy: panretinal photocoagulation or administration of anti-VEGF drugs, with or without hypotensive ocular therapy, allows the preservation of visual functions for patient's better quality of life. However, one or more surgeries will often be required, especially in the advanced stages of the disease, which do not respond to drug therapy. Managing the NVG we should aim to: 1) reduce ocular ischemia and treat its underlying cause, 2) reduce elevated IOP, once installed and 3) control the inflammatory process. Anyway, the best treatment is prevention, so we must be very attentive at patients with risk factors for developing the NVG. Abbreviations: NVG = neovascular glaucoma, ICA = iridocorneal angle, IOP = intraocular pressure, TM = trabecular meshwork, AH = aqueous humor, AC = anterior chamber, PRP = panretinal photocoagulation, VEGF = vascular endothelial growing factor, Anti-VEGF = anti- vascular endothelial growing factor, PAS = peripheral anterior synechiae, CRVO = central retinal vein occlusion, PDR = proliferative diabetic retinopathy, DR = diabetic retinopathy, OIS = ocular ischemic syndrome, CRAO = central retinal artery occlusion, ROP = retinopathy of prematurity, FEVR = familial exudative vitreoretinopathy, PVR = proliferative vitreoretinopathy, MMPs = matrix metalloproteinases, VEGFR = vascular endothelial growing factor receptor, PDGF = platelet-derived growth factor, PIGF = placental growth factor, NRP = neuropilins, HIF = hypoxia-inducible factor, SDF1 = stromal cell-derived factor 1, DDL4 = delta like ligand 4, NICD = Notch intracellular domain, TIMMPs = tissue inhibitors of matrix metalloproteinases, ANGPT = angiopoietin, Tie 2 = tyrosine-protein kinase receptor for angiopoietins, IGF-1 = insulin-like growth factor 1, RPE = retinal pigment epithelium, IL = interleukin, TNF = tumor necrosis factor, bFGF = basic fibroblast growth factor, TGF = transforming growth factor, HGF = hepatocyte growth factor, TNFR 2 = tumor necrosis factor receptor 2, OIR = oxygen induced retinopathy, NVI = neovascularization of the iris, NVA = neovascularization of the iridocorneal angle, FA = fluorescein angiography, RAPD = relative afferent pupillary defect, CNP = capillary non-perfusion, NVE = neovascularization elsewhere in the retina, NVD = neovascularization of the optic disc, FFA = fundus fluorescein angiography, OCTA = optical coherence tomography angiography, B-scan US = B-scan ocular ultrasound, AS-OCT = anterior segment optical coherence tomography, ARC = anterior retinal cryotherapy, FDA = food and drug administration, United States of America, BVZ = bevacizumab, RBZ = ranibizumab, AFB = aflibercept, AMD/ ARMD = age related macular degeneration, DME = diabetic macular edema, GDDs = glaucoma drainage devices, MMC = mitomycin C, 5-FU = 5-fluorouracil, AGV = Ahmed glaucoma valve, AADI = Aurolab aqueous drainage implant, MIGS = minimally invasive glaucoma surgery, BCVA = best corrected visual acuity, TVT = Tube versus Trabeculectomy study, MPC = micro-pulse cyclophotocoagulation.


Tamoxifen-inducible Cre-mediated recombination in adipocytes.
To generate a mouse line which allows inducible, Cre/loxP-dependent recombination in adipocytes, we used RedE/RedT-mediated recombineering to insert the CreER(T)²-transgene, which encodes a fusion protein of Cre and a mutated tamoxifen-responsive estrogen receptor, into the start codon of the adipocyte-specific Adipoq gene. Adipoq encodes adiponectin, an adipokine specifically expressed in differentiated adipocytes. Tamoxifen treatment induced almost complete recombination in white adipose tissue of the AdipoqCreER(T)² mouse line (97%-99%), while no recombination was seen in vehicle-treated animals. Recombination in brown adipose tissue was about 15%, whereas other organs and tissues did not undergo recombination. In addition, mice expressing CreER(T)² in adipocytes did not show any alterations of metabolic functions like glucose tolerance, lipolysis, or energy expenditure compared to control mice. Therefore the AdipoqCreER(T)² mouse line will be a valuable tool for studying the consequences of a temporally controlled deletion of floxed genes in white adipose tissue.


The characterisation of the in vitro metabolism and transport of 6-hydroxykynurenic acid, an important constituent of Ginkgo biloba extracts.
6-Hydroxykynurenic acid (6-HKA) is a nitrogen-containing phenolic acid compound in Ginkgo biloba leaves. The pharmacological activities of 6-HKA have been reported and shown that 6-HKA has the potential to become a therapeutic drug and may play an important role in the treatment of nervous system diseases. However, there are few studies on the drug metabolism and transport of 6-HKA. The aim of this study is to investigate the in vitro metabolism of 6-HKA and its interaction with multiple important drug transporters.The in vitro metabolism experiments in the present study demonstrate that 6-HKA might not undergo phase-I or phase-II metabolism in hepatic microsomes/S9 of rats. In addition, some drug transporters, including OAT1/3, OCT2, MDR1, OATP1B1, MATE1/2K and OCTN2, were investigated. The cellular uptake assays indicate that 6-HKA exhibits inhibition to the transport of classical substrates mediated by OAT3, OCT2, MATE2K and OCTN2 but has no significant effect on the transport of substrates mediated by MDR1, OAT1, OATP1B1 or MATE1. Further investigation of cellular accumulation assays shows that 6-HKA might be the substrate of OAT3, but not OCT2 or OCTN2. The bidirectional transport study suggests that 6-HKA is not a substrate of MDR1.The information about the in vitro metabolism of 6-HKA and the interaction between 6-HKA and some transporters will help us to better understand the pharmacokinetic properties of 6-HKA and provide reference for its pharmacodynamics, DDIs and drug-food interactions studies.


Methods for a Nonuniform Bose Gas.
We review mathematical methods for the treatment of a system of Bose particles with nonuniform density. The use of the pseudopotential is explained, especially with respect to negative scattering lengths. It is emphasized that the delta-function potential produces no scattering in three dimensions, and should not be used in the Bogoliubov self-consistent field method, which is variational in nature. A common misuse of the Bogoliubov method at finite temperatures is pointed out. A Gaussian variational method is proposed.


Urodynamic assessment and quantification of prostatic obstruction before and after transurethral resection of the prostate: standardization with the aid of the computer program CLIM.
The clinical manifestations of benign prostatic hypertrophy (BPH) are ascribed entirely to the infravesical obstruction. Therefore relief of symptoms is pursued by surgical removal of obstruction, i.e. prostatectomy. On the other hand, it is generally accepted that the conventional clinical signs and symptoms do not correlate with obstruction as urodynamically defined. In the present study, objective obstruction and detrusor contractility parameters were calculated from detrusor pressure and flow rate measurements in 22 patients before and after transurethral resection of the prostate (TURP) using the computer program CLIM. The results indicate: (1) that CLIM supplies reliable obstruction and contractility parameters for preoperative assessment and follow-up in patients with BPH and (2) that greater than 25% of the patients, who underwent TURP, were objectively not obstructed. These findings form strong arguments for including CLIM parameters in the preoperative assessment to perform a TURP.


"Just Throw It Behind You and Just Keep Going": Emotional Labor when Ethnic Minority Healthcare Staff Encounter Racism in Healthcare.
Encountering racism is burdensome and meeting it in a healthcare setting is no exception. This paper is part of a larger study that focused on understanding and addressing racism in healthcare in Sweden. In the paper, we draw on interviews with 12 ethnic minority healthcare staff who described how they managed emotional labor in their encounters with racism at their workplace. Data were analyzed using thematic analysis. The analysis revealed that experienced emotional labor arises from two main reasons. The first is the concern and fear that ethnic minority healthcare staff have of adverse consequences for their employment should they be seen engaged in discussing racism. The second concerns the ethical dilemmas when taking care of racist patients since healthcare staff are bound by a duty of providing equal care for all patients as expressed in healthcare institutional regulations. Strategies to manage emotional labor described by the staff include working harder to prove their competence and faking, blocking or hiding their emotions when they encounter racism. The emotional labor implied by these strategies could be intense or traumatizing as indicated by some staff members, and can therefore have negative effects on health. Given that discussions around racism are silenced, it is paramount to create space where racism can be safely discussed and to develop a safe healthcare environment for the benefit of staff and patients.


Sensor systems for prognostics and health management.
Prognostics and health management (PHM) is an enabling discipline consisting of technologies and methods to assess the reliability of a product in its actual life cycle conditions to determine the advent of failure and mitigate system risk. Sensor systems are needed for PHM to monitor environmental, operational, and performance-related characteristics. The gathered data can be analyzed to assess product health and predict remaining life. In this paper, the considerations for sensor system selection for PHM applications, including the parameters to be measured, the performance needs, the electrical and physical attributes, reliability, and cost of the sensor system, are discussed. The state-of-the-art sensor systems for PHM and the emerging trends in technologies of sensor systems for PHM are presented.


Stimulation of anaerobic digestion of thickened sewage sludge by iron-rich sludge produced by the fenton method.
In batch mesophilic anaerobic digestion of a mixture of iron-rich sludge collected from Fenton treatment of molasses wastewater (MWW) and thickened sewage sludge from a municipal wastewater treatment plant, the methane content in the gas from the mixture was significantly higher than that from thickened sewage sludge only. When minerals in iron-rich sludge obtained by incineration were fed to thickened sewage sludge in semi-continuous experiments, the methane content obtained by digestion of thickened sewage sludge only increased approximately from 53% to 64%. These results suggest that iron-rich sludge can enhance methane production for thickened sewage sludge.


A Primer on Usability Assessment Approaches for Health-Related Applications of Virtual Reality.
Health-related virtual reality (VR) applications for patient treatment, rehabilitation, and medical professional training are on the rise. However, there is little guidance on how to select and perform usability evaluations for VR health interventions compared to the supports that exist for other digital health technologies. The purpose of this viewpoint paper is to present an introductory summary of various usability testing approaches or methods that can be used for VR applications. Along with an overview of each, a list of resources is provided for readers to obtain additionally relevant information. Six categories of VR usability evaluations are described using a previously developed classification taxonomy specific to VR environments: (1) cognitive or task walkthrough, (2) graphical evaluation, (3) post hoc questionnaires or interviews, (4) physical performance evaluation, (5) user interface evaluation, and (6) heuristic evaluation. Given the growth of VR in health care, rigorous evaluation and usability testing is crucial in the development and implementation of novel VR interventions. The approaches outlined in this paper provide a starting point for conducting usability assessments for health-related VR applications; however, there is a need to also move beyond these to adopt those from the gaming industry, where assessments for both usability and user experience are routinely conducted.


Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen.
The absence of readily manipulable experimental systems to study the cytotoxic T lymphocyte (CTL) response against hepatitis B virus (HBV) antigens has thus far precluded a definitive demonstration of the role played by this response in the pathogenesis of liver cell injury and viral clearance during HBV infection. To circumvent the problem that HBV infection of human cells in vitro for production of stimulator/target systems for CTL analysis is not feasible, a panel of 22 overlapping synthetic peptides covering the entire amino acid sequence of the HBV core (HBcAg) and e (HBeAg) antigens were used to induce and to analyze the HBV nucleocapsid-specific CTL response in nine patients with acute hepatitis B, six patients with chronic active hepatitis B, and eight normal controls. By using this approach, we have identified an HLA-A2-restricted CTL epitope, located within the NH2-terminal region of the HBV core molecule, which is shared with the e antigen and is readily recognized by peripheral blood mononuclear cells from patients with self-limited acute hepatitis B but less efficiently in chronic HBV infection. Our study provides the first direct evidence of HLA class I-restricted T cell cytotoxicity against HBV in humans. Furthermore, the different response in HBV-infected subjects who successfully clear the virus (acute patients) in comparison with patients who do not succeed (chronic patients) suggests a pathogenetic role for this CTL activity in the clearance of HBV infection.


Monitoring of heavy metal contaminants using feathers of shorebirds, Korea.
This study presents concentrations of iron, zinc, copper, lead and cadmium in the feathers of 3 shorebird species (n = 29) from Okgu Mudflat, Korea in the East Asian-Australian Migration Flyways. Lead concentrations (ANOVA, p < 0.001) in Red-necked Stints (geomean = 9.61 μg g(-1) dry weight) were higher than in Terek Sandpipers (geomean = 5.56 μg g(-1) dry weight) which in turn were higher than in Great Knots (geomean = 2.78 μg g(-1) wet weight). Cadmium concentrations (ANOVA, p < 0.001) were higher in Great Knots (geomean = 2.97 μg g(-1) wet weight) and in Red-necked Stints (geomean = 2.70 μg g(-1) dry weight) than in Terek Sandpipers (geomean = 0.33 μg g(-1) dry weight). Lead (r = 0.574, p < 0.01) and cadmium (r = 0.380, p < 0.05) concentrations between feathers and livers of shorebirds were significantly correlated. Lead concentrations in 65.5% (19 individuals) of shorebirds exceeded a toxicity threshold for feathers (4 μg g(-1) dry weight). Iron, zinc, copper, lead and cadmium concentrations in feathers were within the range of earlier studies for wild birds, but lead concentrations in Red-necked Stints were higher than those reported in other studies. Because lead concentrations in feathers and livers of Red-necked Stints were markedly higher than in other shorebirds, we suggest that Red-necked Stints were exposed to higher lead concentrations than the other shorebirds on their breeding or wintering grounds.


Submandibular and sublingual salivary gland function in familial dysautonomia.
Drooling in familial dysautonomia (FD) has been attributed to denervation supersensitivity. The aim of this study was to investigate submandibular and sublingual (SM/SL) gland function in FD. SM/SL saliva was collected from 15 children with FD and from 31 healthy control subjects. The protein and electrolyte content and the salivary flow rate were determined in each subject. Children with FD displayed significantly elevated outputs of chloride, potassium, calcium, phosphorous, magnesium, and total protein. Salivary flow rates were significantly increased. Phosphorous concentration was statistically low. These results imply SM/SL hyperfunction at the acinar and ductal levels. The concentration of lysozyme, the activity of amylase, and the output of both were similar in patients and control subjects. SM/SL gland hyperactivity is a newly described abnormality in FD. At the acinar level, this hyperactivity is expressed with increased fluid, electrolyte, and protein output, and at the ductal level, with increased ion secretion and absorption rate. These changes may be the result of ongoing parasympathetic denervation characteristic in FD.


Climacteric modifications in body weight and fat tissue distribution.
To estimate the effects of climacteric modifications on body weight and fat distribution. From 8764 women attending the authors' Menopause Clinic, 1075 untreated, normal healthy women were selected and divided into three groups: premenopausal (n = 380), perimenopausal (n = 263) and postmenopausal (n = 432). The total body fat tissue mass and distribution were analyzed using the dual energy X-ray method. Body weight and body mass index (BMI) were significantly higher in perimenopausal and postmenopausal than in premenopausal women. The mean total body fat and the percentage of fat with respect to soft tissue were significantly (p < 0.05) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. The amount of fat tissue and the regional fat percentage with respect to total fat tissue were higher in the trunk (p < 0.05) and arm (p < 0.05) regions in perimenopausal and postmenopausal than in premenopausal women. In the postmenopausal group, the leg fat tissue was significantly (p < 0.05) less than in the premenopausal and perimenopausal groups. Total body and leg lean tissue was significantly (p < 0.01) less in postmenopausal than in premenopausal and perimenopausal women. In the premenopausal group, body weight and BMI were positively correlated with age (r = 0.37 and r = 0.54, respectively). No significant correlations were observed in the perimenopausal group. In postmenopausal women, body weight and BMI were loosely correlated with age (r = 0.13 and r = 0.11, respectively). In three groups of 63 age-matched women, with similar BMI, the percentage of total body fat with respect to soft tissue was significantly (p < 0.001) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. Regarding body fat distribution, the percentage of fat with respect to total fat tissue was significantly higher in the trunk (p < 0.001) region in perimenopausal and postmenopausal women than in premenopausal women. In the leg region, the percentage of fat with respect to total fat tissue was significantly (p < 0.05) higher in the premenopausal group than in the postmenopausal group. In the arm region, a slight but not significant (p < 0.08) difference was shown in fat distribution among the three groups. Climacteric changes rather than the aging process are relevant for prediction of body weight and fat distribution, especially for perimenopausal and postmenopausal women, who show a shift to a central, android fat distribution.


A clinical trial of intradermal and intramuscular seasonal influenza vaccination in patients with atopic dermatitis.
Antibody responses to the inactivated seasonal influenza vaccine in patients with atopic dermatitis (AD) have not been carefully characterized. The primary objective of this study was to compare antibody responses to intradermal vaccination in participants with moderate/severe AD with those in nonatopic participants. Secondary objectives were to evaluate the effect of route of administration, Staphylococcus aureus skin colonization, and disease severity on vaccine response. This was an open-label study conducted in the 2012-2013 influenza season at 5 US clinical sites. A total of 360 participants with moderate/severe AD or nonatopic subjects were assessed for eligibility, 347 of whom received intradermal or intramuscular vaccination per label and were followed for 28 days after vaccination. The primary outcome was the difference in the proportion of participants achieving seroprotection (hemagglutination-inhibition antibody titer ≥1:40 on day 28 after vaccination). Seroprotection rates for influenza B, H1N1, and H3N2 were not different (1) between participants with AD and nonatopic participants receiving intradermal vaccination and (2) between AD participants receiving intradermal and intramuscular vaccination. After intradermal, but not intramuscular, vaccination, participants with AD with S aureus colonization experienced (1) lower seroprotection and seroconversion rates and lower hemagglutination-inhibition antibody titer geometric mean fold increase against influenza B and (2) lower seroconversion rates against influenza H1N1 than noncolonized participants with AD. Participants with AD colonized with S aureus exhibited a reduced immune response to influenza vaccination compared with noncolonized participants after intradermal but not intramuscular vaccination. Because most patients with AD are colonized with S aureus, intramuscular influenza vaccination should be given preference in these patients.


Nephritogenicity of anti-Engelbreth-Holm-Swarm sarcoma antibody.
We have examined the antibody activity and nephritogenicity of anti-Engelbreth-Holm-Swarm (EHS) sarcoma antiserum in order to analyze the pathogenesis of the EHS nephropathy which has already been reported by us. An increased amount of urine protein was not recognized in rats injected with a large quantity of anti-EHS sarcoma antiserum. In addition, rats immunized with rabbit IgG before anti-EHS sarcoma antiserum injection developed no abnormal proteinuria, despite positive fluorescent staining for rat IgG as well as rabbit IgG in the glomeruli. From these results we concluded that nephritogenic antibodies could not be produced in rabbits by immunization with EHS sarcoma, which could induce the EHS nephropathy in an active model.


Variable clinical spectrum of the myocilin Gln368X mutation in a Dutch family with primary open angle glaucoma.
To describe the clinical phenotype in a family with primary open angle glaucoma harboring a p.Gln368X mutation in MYOC. We identified a proband with primary open angle glaucoma and the p.Gln368X MYOC mutation. She and her six siblings were examined clinically, including Heidelberg Retina Tomography II, and venous blood samples were screened for other variants in MYOC, WDR36, OPTN, and CYP1B1. Four individuals showed the p.Gln368X MYOC mutation, no other genetic variations were assessed. Two of these four siblings had glaucomatous optic disc changes with corresponding visual field losses and abnormal Heidelberg Retina Tomography results by the Moorfields regression analysis, one had abnormal results by the Moorfields regression analysis but no visual field loss, and one showed no glaucomatous signs or symptoms at all. These findings did not correlate with the age of the affected individuals. In the primary open angle glaucoma family described here, we documented a wide range in clinical symptoms, demonstrating a highly variable penetrance of the MYOC p.Gln368X mutation.


The Other Obesity Epidemic-Of Drugs and Bugs.
Chronic psychiatric patients with schizophrenia and related disorders are frequently treatment-resistant and may require higher doses of psychotropic drugs to remain stable. Prolonged exposure to these agents increases the risk of weight gain and cardiometabolic disorders, leading to poorer outcomes and higher medical cost. It is well-established that obesity has reached epidemic proportions throughout the world, however it is less known that its rates are two to three times higher in mentally ill patients compared to the general population. Psychotropic drugs have emerged as a major cause of weight gain, pointing to an urgent need for novel interventions to attenuate this unintended consequence. Recently, the gut microbial community has been linked to psychotropic drugs-induced obesity as these agents were found to possess antimicrobial properties and trigger intestinal dysbiosis, depleting Bacteroidetes phylum. Since germ-free animals exposed to psychotropics have not demonstrated weight gain, altered commensal flora composition is believed to be necessary and sufficient to induce dysmetabolism. Conversely, not only do psychotropics disrupt the composition of gut microbiota but the later alter the metabolism of the former. Here we review the role of gut bacterial community in psychotropic drugs metabolism and dysbiosis. We discuss potential biomarkers reflecting the status of Bacteroidetes phylum and take a closer look at nutritional interventions, fecal microbiota transplantation, and transcranial magnetic stimulation, strategies that may lower obesity rates in chronic psychiatric patients.


The effect of tensile strength on the clinical effectiveness and patient acceptance of dental floss.
This study compared the clinical effectiveness and subjective approval of 2 waxed dental flosses that differed significantly in tensile strength and wax content. At the initial appointment, subjects (20 1st-year dental students) were instructed to stop interproximal cleaning on 2 contralateral quadrants in order to allow plaque to accumulate on these surfaces for 1 week. 1 week later, subjects were instructed to begin flossing these 2 contralateral quadrants with 1 of the 2 types of floss for the next 1-week period, while withdrawing interproximal cleaning on the opposite 2 contralateral quadrants. After flossing these 2 quadrants for 1 week, the subjects began flossing the opposite 2 contralateral quadrants with the same floss. After 2 weeks of flossing contralateral quadrants, the 1st floss was withdrawn and replaced with the alternative floss for another similar 2-week trial period. At the end of each 2-week trial period, subjects completed subjective questionnaires concerning the floss they had used during the previous 2-week period. Pre- and post-flossing plaque indices were calculated for each week for both flosses, and compared statistically by a repeated measures analysis of variance. The results showed that both flosses significantly reduced interproximal plaque deposits, and had equal subjective approval. However, neither the greater-strength nor the lower-wax content of the experimental floss was associated with an increase in clinical effectiveness or with a change in subjective approval.


In search of optimal long-term female hormone replacement: the potential of selective estrogen receptor modulators.
Selective estrogen receptor modulators (SERMs) comprise a group of structurally diverse compounds which are distinguished from estrogens by their ability to interact with the estrogen receptor but to act as either an estrogen agonist or antagonist depending on the target tissue and hormonal milieu. The mechanisms by which SERMs elicit tissue-specific responses are being intensively investigated, and recently a novel pathway for estrogen receptor-mediated gene activation by the SERM raloxifene has been demonstrated. The tissue-specific activity of SERMs suggests that they may be clinically useful as, for example, potential substitutes for long-term female hormone replacement therapy. Large-scale clinical testing currently in progress for raloxifene, and soon to begin for other SERMs, will evaluate this important potential.


Electromyographic findings in patients with low back pain due to unsuspected primary and metastatic spinal or paraspinal muscle disease.
Electromyographic studies were performed on 16 patients with intractable low back pain and no antecedent history of malignancy or metastatic disease. In each case, electromyographic evidence of severe segmental denervation limited to the paraspinal muscles innervated by the posterior primary rami was found. Subsequent diagnostic studies in each patient revealed a primary neoplasm or tumor metastasis as the source of pain. Applying current knowledge of neuromuscular physiology, the electromyograph may prove to be a valuable aid to the early detection of remote metastasis to the spine and paraspinal muscle structures.


Frontobasal skull fracture patterns.
30 cases of frontobasal skull fractures are studied. The fracture lines are registered and shown to make patterns characteristic for this type of lesion. The patterns depend on the architecture of the anterior skull fossa, deflecting the energy of the trauma.


Neuroinflammation in neurodegeneration via microbial infections.
Recent epidemiological studies show a noticeable correlation between chronic microbial infections and neurological disorders. However, the underlying mechanisms are still not clear due to the biological complexity of multicellular and multiorgan interactions upon microbial infections. In this review, we show the infection leading to neurodegeneration mediated by multiorgan interconnections and neuroinflammation. Firstly, we highlight three inter-organ communications as possible routes from infection sites to the brain: nose-brain axis, lung-brain axis, and gut-brain axis. Next, we described the biological crosstalk between microglia and astrocytes upon pathogenic infection. Finally, our study indicates how neuroinflammation is a critical player in pathogen-mediated neurodegeneration. Taken together, we envision that antibiotics targeting neuro-pathogens could be a potential therapeutic strategy for neurodegeneration.


'The marvellous harmony of the nervous parts': the origins of multiple sclerosis.
Working in the 1660s, William Croone wrote on the nature of connections between nerve and muscle. A previously unknown copy of his essay, wrongly attributed to Thomas Willis, has recently come to light. Croone left the challenges of clinical neurology to his successors. The story of multiple sclerosis begins early in the nineteenth century. Despite much information on the aetiology and pathogenesis, the origins of that disease remain obscure. Here, the hypothesis is advanced--based on the epidemiology, clinical neurology, immunology and genetics of demyelinating disease, linked to European history and population genetics--that multiple sclerosis evolved from a related disorder, neuromyelitis optica (or Devic's disease). Genetic drift and stratification altered the immune response to a common pathogen and changed the disease phenotype. Against this background, the sustained epidemic of multiple sclerosis arose when cultural changes led to a subtle but crucial alteration in the age at which genetically vulnerable individuals are exposed to Epstein Barr infection.


Challenges Experienced by Italian Nursing Home Staff in End-of-Life Conversations with Family Caregivers during COVID-19 Pandemic: A Qualitative Descriptive Study.
End-of-life conversations are among the most challenging of all communication scenarios and on the agenda of several healthcare settings, including nursing homes (NHs). They may be also difficult for experienced healthcare professionals (HCPs). This study explores the difficulties experienced by Italian NH staff in end-of-life conversations with family caregivers (FCs) during COVID-19 pandemic to uncover their educational needs. A qualitative descriptive study based on inductive thematic analysis was performed. Twenty-one HCPs across six Italian NHs were interviewed. Four themes described their experiences of end-of-life conversations: (1) communicating with FCs over the overall disease trajectory; (2) managing challenging emotions and situations; (3) establishing a partnership between HCPs and FCs; (4) addressing HCPs' communication skills needs. HCPs had to face multiple challenging situations that varied across the care period as well as complex emotions such as anxiety, guilt, uncertainty, fear, anger, or suffering, which required tailored answers. COVID-19 pandemic increased FCs' aggressive behaviors, their distrust, and uncertainty due to visitation restrictions. HCPs had to overcome this by developing a set of strategies, including adoption of an active-listening approach, supportive communication, and explicit acknowledgement of FCs' emotions. Since communication needs were mostly practical in nature, HCPs valued practical communication training.


Differential Localization of Fraction I Protein between Chloroplast Types.
The soluble proteins of C(3) and C(4) mesophyll chloroplasts and C(4) bundle sheath extracts have been analyzed by gel electrophoresis for fraction I protein. Gel scans of soluble protein from C(4) bundle sheath extracts and C(3) mesophyll chloroplasts showed typical fraction I protein peaks that could be identified by ribulose diphosphate carboxylase activity. No such peak was observed for C(4) mesophyll chloroplasts, which also lacked both large and small subunits of ribulose diphosphate carboxylase on sodium dodecyl sulfate gels. The absence of fraction I protein in these chloroplasts was reflected in the soluble protein to chlorophyll ratios, which were roughly 3-fold lower than the ratio obtained for C(3) chloroplasts. The carboxylating enzyme in C(4) mesophyll cells, phosphoenolpyruvate carboxylase, was found to be a major protein in the cytoplasm of C(4) mesophyll protoplasts, and had higher mobility than fraction I protein.


Treatment of Pediatric Sternotomy Wound Complications: A Minimally Invasive Approach.
Pediatric sternal wound complications (SWCs) include sterile wound dehiscence (SWD) and superficial/deep sternal wound infections (SSWI/DSWI), and are generally managed by repetitive debridement and surgical wound approximation. Here, we report a novel nonsurgical management strategy of pediatric sternotomy wound complications, using serial noninvasive wound approximation technique combined with single-use negative pressure wound therapy (PICO) device. Nine children with SWCs were managed by serial approximation with adhesive skin tapes and serial PICO device application. Thorough surgical debridement or surgical approximations were not performed. Three patients were clinically diagnosed as SWD, two patients as SSWI, and four patients as DSWI. None of the wounds demonstrated apparent mediastinitis or bone destructions. PICO device was applied at 16.1 days (range: 6-26 days) postoperatively, together with serial wound approximation by skin tapes. The average duration of PICO use was 16.9 days (range: 11-29 days) and the wound approximation was achieved in all patients. None of the patients underwent aggressive surgical debridement or invasive surgical approximation by sutures. We report our successful management of selected pediatric SWCs, using serial noninvasive wound approximation technique combined with PICO device.


The edge wave on an elastically supported Kirchhoff plate.
This Letter deals with an analysis of bending edge waves propagating along the free edge of a Kirchhoff plate supported by a Winkler foundation. The presence of a foundation leads to a non-zero cut-off frequency for this wave, along with a local minimum of the associated phase velocity. This minimum phase velocity corresponds to a critical speed of an edge moving load and is analogous to that in the classical 1D moving load problem for an elastically supported beam.


Isotopic composition of sulfates: similarities - differences - misleadings.
Abstract In the hydrosphere sulfates of the following origin may exist: (1) evaporitic; they come from the leaching of sulfate rocks, (2) biological, formed by sulfur-oxidizing bacteria and (3) anthropogenic, which get into water with wastes, fertilizers or acid rains. Chemical analyses may reveal sulfates in water, but their origin cannot be assessed by means of chemical analysis. The sulfates of various origin may differ in their isotopic compositions. However, sometimes we can observe the similarity of δ(34)S of sulfates whose origin was entirely different. This similarity may be so suggestive that it could be misleading. This paper presents patterns of completely different sulfates whose δ(34)S are similar, though they have nothing in common. Other tables present patterns of sulfates whose origin is similar or even the same but their δ(34)S are characterized by great variety. All of the isotopic data presented in the tables were specially chosen from some of the results of the studies of the sulfates in waters in Poland. Isotopes techniques are becoming more popular and are useful for studies in many fields. These patterns may be a warning against drawing hasty conclusions from the results of δ-measuring.


Identification and expression of GABAC receptor in rat testis and spermatozoa.
Our previous studies showed that gamma-aminobutyric acid (GABA)A and GABAB receptors are involved in rat sperm acrosome reaction induced by progesterone or GABA. Here, we report the presence of GABAC receptor in rat testis and spermatozoa. Full-length complementary DNA encoding the rho1, rho2 and rho3 subunits of GABAC receptor were cloned from rat testis; their sequences are identical to those of rat GABAC receptor in retina. Reverse transcription-polymerase chain reaction analysis showed that during the development of rat testis, the transcript levels of the rho1 and rho2 subunits showed little change, while the expression of rho3 was gradually up-regulated. Immunofluorescence analysis using an anti-rho1 antibody revealed that GABAC receptor exists on the elongated spermatid and sperm. Using a chlortetracycline assay, we found that N(4)-chloroacetylcytosine arabinoside, a GABAC receptor agonist, triggered rat sperm acrosome reaction; whereas (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid, a GABAC receptor antagonist, inhibited the ability of N(4)-chloroacetylcytosine arabinoside to induce acrosome reaction. These results suggested that GABAC receptors are also involved in rat sperm acrosome reaction.


The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel NaV1.8 to Enhance Activation.
Venoms from cone snails and arachnids are a rich source of peptide modulators of voltage-gated sodium (NaV) channels, however relatively few venom-derived peptides with activity at the mammalian NaV1.8 subtype have been isolated. Here, we describe the discovery and functional characterisation of β-theraphotoxin-Eo1a, a peptide from the venom of the Tanzanian black and olive baboon tarantula Encyocratella olivacea that modulates NaV1.8. Eo1a is a 37-residue peptide that increases NaV1.8 peak current (EC50 894 ± 146 nM) and causes a large hyperpolarising shift in both the voltage-dependence of activation (ΔV50-20.5 ± 1.2 mV) and steady-state fast inactivation (ΔV50-15.5 ± 1.8 mV). At a concentration of 10 μM, Eo1a has varying effects on the peak current and channel gating of NaV1.1-NaV1.7, although its activity is most pronounced at NaV1.8. Investigations into the binding site of Eo1a using NaV1.7/NaV1.8 chimeras revealed a critical contribution of the DII S3-S4 extracellular loop of NaV1.8 to toxin activity. Results from this work may form the basis for future studies that lead to the rational design of spider venom-derived peptides with improved potency and selectivity at NaV1.8.


Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions.
Telomeres are essential in maintaining chromosome integrity and in controlling cellular replication. Attrition of telomere length in peripheral blood mononuclear cells (PBMCs) with age is well documented from cross-sectional studies. But the actual in vivo changes in telomere lengths and its relationship with the contributing factors within the individuals with age have not been fully addressed. In the present paper, we report a longitudinal analysis of telomere length in the PBMCs, lymphocytes and monocytes of 216 human subjects aged from 20-90 years assessed at 0-, 5- and 12-year follow-up. For the 5- and 12-year follow-up, telomere length in the PBMCs decreased in 34% and 46%, exhibited no detectable change in 56% and 47% and increased in 10% and 7% of the subjects respectively. The rate of telomere change was distinct for T-cells, B-cells and monocytes for any given subject. Telomerase activity declined with age in the resting T-cells and B-cells and the activated T-cells. Finally, a significant portion of telomere attrition in T-cells with age was explained by a decline in the telomerase activity, decreased naïve cells and the change in physiological conditions such as elevated blood glucose and interleukin (IL)-6 levels. These findings show that changes in the telomere length of the PBMCs with age in vivo occur at different rates in different individuals and cell types and reveal that changes in the telomere length in the T-cells with age is influenced by the telomerase activity, naïve T-cell percentage and changes in health conditions.


[Conventional radiology in the choice of surgical treatment of gonarthrosis].
Gonarthrosis is a pathologic condition the incident of which is high in people over 50. Its etiologic factors are varus-valgus deformities, traumatic lesions, meniscal tears, osteochondritis, and metabolic diseases. The authors report their experience with the setting of a radiographic protocol for the study of 100 patients over 50. The protocol allowed both detection and quantification of: varus and valgus deformities studied in weight-bearing (teleradiography in weight-bearing) and extensor mechanism malalignment (tangential views); chondral wear of femoral and tibial joints (varus and valgus radiographs); varus and valgus knees instability (varus and valgus radiographs). The results are extremely satisfactory: this protocol allowed correct gonarthrosis grading and the evaluation of such associated lesions as lateral instability. The surgeon is thus provided with the essential elements for the choice of the correct treatment.


Improving care coordination in primary care.
Although coordinating care is a defining characteristic of primary care, evidence suggests that both patients and providers perceive failures in communication and care when care is received from multiple sources. To examine the utility of a newly developed Care Coordination Model in improving care coordination among participating practices in the Safety Net Medical Home Initiative (SNMHI). In this paper, we used correlation analysis to evaluate whether application of the elements of the Care Coordination Model by SNMHI sites, as measured by the Key Activities Checklist (KAC), was associated with more effective care coordination as measured by another instrument, the PCMH-A. SNMHI measures are practice self-assessments based on the 8 change concepts that define a PCMH, one of which is Care Coordination. For this study, we correlated 12 KAC items that describe activities felt to improve coordination of care with 5 PCMH-A items that indicate the extent to which a practice has developed the capability to effectively coordinate care. Practice staff indicated whether any of the KAC activities were being test, implemented, sustained, or not on 4 occasions. The Care Coordination Model elements-assume accountability, build relationships with care partners, support patients through the referral or transition process, and create connections to support information exchange-were positively correlated with some PCMH-A care coordination items but not others. Activities related to the model were most strongly correlated with following up patients seen in the Emergency Department or discharged from hospital. The analysis provides suggestive evidence that activities consistent with the 4 elements of the Care Coordination Model may enable safety net primary care to better coordinate care for its patients, but further study is clearly needed.


Antibodies that selectively inhibit leukocyte function-associated antigen 1 binding to intercellular adhesion molecule-3 recognize a unique epitope within the CD11a I domain.
Several studies indicate that the I domain located in the alpha chain (CD11a) of leukocyte function-associated antigen-1 (LFA-1; CD11a/CD18) plays an essential role in ligand recognition. We recently identified three distinct epitopes (IdeA, IdeB, and IdeC) within the CD11a I domain, recognized by antibodies that block binding of LFA-1 to intercellular adhesion molecules (ICAM) 1, 2, and 3. In the present study, we used a series of human/murine CD11a I domain chimeras, to localize a fourth I domain epitope (IdeD), recognized by three independently derived anti-CD11a antibodies that selectively block the binding of LFA-1 to ICAM-3, but not to ICAM-1. The IdeD epitope depended on human CD11a residues Asp182 and Ser184 and was not present in CD11b or CD11c. Although mutation of Asp182 and Ser184 failed to abolish ICAM-3 adhesion of LFA-1 transfectants, alignment of these residues with the crystal structure of the CD11a I domain suggested that the IdeD epitope is located in close proximity to residues (Ile126 and Asn129) recently implicated in the ICAM-3 binding site. Interestingly, the IdeB and IdeC epitopes appeared to be in close proximity of a divalent cation binding pocket within the CD11a I domain that regulates both ICAM-1 and ICAM-3 adhesion. Taken together, these data indicate that distinct regions of the CD11a I domain contain epitopes for antibodies that either selectively inhibit binding of LFA-1 to ICAM-3, or interfere with both ICAM-1 and ICAM-3 binding of LFA-1.


Primitive breast localisation of Buruli ulcer in an endemic zone: a rare case.
A case of Buruli ulcer with primitive breast localisation with evident epidemiological and clinical aspects is reported. This localisation is exceptional; the differential diagnosis with breast cancer is essential. If diagnosed early, it can be cured with surgery, broad-spectrum antibiotherapy and thermotherapy.