Ecophysiological consequences of non-random leaf orientation in the prairie compass plant, Silphium laciniatum.
The prairie compass plant (Silphium laciniatum L.) has vertical leaves that are characteristically oriented in a north-south plane (i.e., the flat surfaces of the lamina face east and west). We explored the consequences of this orientation by determining basic photosynthetic and water use characteristics in response to environmental factors and by determining total daily photosynthesis and water use of leaves held in different orientations. Average maximum CO2 exchange rate (CER) of leaves near Ames, IA was constant at 22 micromol m-2 s-1 from May through August and then declined. CER did not exhibit a distinct lightsaturation point. CER at photon flux densities near full sunlight was constant from 22 to 35°C leaf temperature but declined at higher temperatures. However, leaf temperatures rarely exceed 35°C during the growing season. There was no change in the pattern of response of CER to temperature over the growing season. We constrained leaves to face east-west (EW,=natural), to face north-south (NS), or to be horizontal (HOR) on eight days in 1986-1988. EW leaves had the highest light interception, leaf temperatures, CER, and transpiration early and late in the day, whereas HOR leaves had the highest values in the middle of the day. Integrations of CER and transpiration over the eight daytime periods showed EW and HOR leaves to have equivalent carbon gain, higher than that of NS leaves. HOR leaves had the highest daily transpiration. Daily water use efficiency (WUE, carbon gained/water lost) was always highest in EW leaves, with the HOR leaves having 16% lower WUE and NS leaves having 33% lower WUE. The natural orientation of compass plant leaves results in equivalent or higher carbon gain and in increased WUE when compared to leaves with other possible orientations; this is likely to have a selective advantage in a prairie environment.


Reduction of blood viscosity following plasma exchange.
The effect of plasma exchange with plasma protein fraction on blood viscosity was determined in seven hyperlipoproteinaemic patients with coronary or peripheral vascular disease. This resulted in decreases in whole blood viscosity of 83% and 30% respectively at the lowest and highest shear rates studied, and decreases of 21% and 59% in plasma viscosity and fibrinogen. Serum cholesterol and triglyceride were reduced by 66% and 48% respectively. Sequential studies in two patients showed that blood viscosity returned to near-basal values by the 6th day. These findings suggest that plasma exchange may result in short-term enhancement of blood flow in vessels where low shear rates predominate.


Wet precipitation chemistry at a high-altitude site (3,326 m a.s.l.) in the southeastern Tibetan Plateau.
This paper presents the results of wet precipitation chemistry from September 2009 to August 2010 at a high-altitude forest site in the southeastern Tibetan Plateau (TP). The alkaline wet precipitation, with pH ranging from 6.25 to 9.27, was attributed to the neutralization of dust in the atmosphere. Wet deposition levels of major ions and trace elements were generally comparable with other alpine and remote sites around the world. However, the apparently greater contents/fluxes of trace elements (V, Co, Ni, Cu, Zn, and Cd), compared to those in central and southern TP and pristine sites of the world, reflected potential anthropogenic disturbances. The almost equal mole concentrations and perfect linear relationships of Na(+) and Cl(-) suggested significant sea-salts sources, and was confirmed by calculating diverse sources. Crust mineral dust was responsible for a minor fraction of the chemical components (less than 15%) except Al and Fe, while most species (without Na(+), Cl(-), Mg(2+), Al, and Fe) arose mainly from anthropogenic activities. High values of as-K(+) (anthropogenic sources potassium), as-SO4(2-), and as-NO3(-) observed in winter and spring demonstrated the great effects of biomass burning and fossil fuel combustion in these seasons, which coincided with haze layer outburst in South Asia. Atmospheric circulation exerted significant influences on the chemical components in wet deposition. Marine air masses mainly originating from the Bay of Bengal provided a large number of sea salts to the chemical composition, while trace elements during summer monsoon seasons were greatly affected by industrial emissions from South Asia. The flux of wet deposition was 1.12 kg N ha(-1) year(-1) for NH4(+)-N and 0.29 kg N ha(-1) year(-1) for NO3(-)-N. The total atmospheric deposition of N was estimated to be 6.41 kg N ha(-1) year(-1), implying potential impacts on the alpine ecosystem in this region.


Are educational differences in U.S. self-rated health increasing?: an examination by gender and race.
Recent literature has documented changes in educational differences in health over recent time periods, across the life course, and by gender and race. We unite previous literature regarding period, age, gender, and race variations in educational health differences by examining how trends in educational differences in self-rated health have unfolded from 1982 to 2003 and whether or not such trends vary across gender and race groups. We use 22 years of pooled repeated cross-sectional data from the National Health Interview Survey to examine these trends among U.S. adults aged 35-79. Consistent with recent literature, we find a trend toward widening gaps in self-rated health by educational level in recent years for middle-aged and older adults but relatively stable or even slightly narrowing gaps in recent years for younger adults. All of these changes are in the context of generally improving health across this time period, particularly for persons with a college education. Moreover, we find that these trends differ to some degree by race and gender, with young adult black women being the only group among whom educational differences in health are converging. Our findings point to the continued need to address educational health disparities in the United States, which are increasing for most demographic subgroups despite the national goal of their elimination.


The effect of wavelength on endothermal heat-induced thrombosis incidence after endovenous laser ablation.
We hypothesized that the incidence of endothermal heat-induced thrombosis (EHIT) depends on the laser wavelength used in endovenous laser ablation (EVLA) of the saphenous veins. We identified patients undergoing EVLA in our office from 2005 to 2014 with an 810-nm (hemoglobin-specific) or 1470-nm (water-specific) laser. We reviewed the records for age, sex, body mass index, Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) class, vein diameter, vein(s) treated, adjunctive phlebectomy, energy delivered, laser pullback times, and EHIT (closure level ≥3) development. The Fisher exact test and Pearson χ(2) test were used to evaluate the association between EHIT and the categoric variables. Logistic regression was used to evaluate the relationship between EHIT and the continuous variables. There were 1439 veins ablated in 1109 patients (769 female, 340 male). The great saphenous vein (GSV) was treated in 1332, the small saphenous vein (SSV) in 78, and both in 29 (22 procedures on accessory veins were excluded). The CEAP C class for these patients was 1 in 0, 2 in 616, 3 in 522, 4 in 150, 5 in 51, and 6 in 98, and was not recorded in 2. EHIT occurred in 76 cases (5.28%), in 73 after GSV ablation and in three after SSV ablation. The 810-nm laser was used in 1144 procedures, and EHIT developed in 69 patients (6.0%). The 1470-nm laser was used in 295 procedures, with EHIT developing in seven patients (2.4%; P = .0122 by Fisher exact test). The average energy delivered to the EHIT group (3517 ± 1998.1 J) was higher than for the non-EHIT group (2825.1 ± 1491.2 J; P = .0002). The average vein diameter was larger in the EHIT group (9.3 ± 3.8 mm) than in the non-EHIT group (7.2 ± 3.3 mm; P = .0001). EHIT occurred in 59 of 837 cases (6.6%) undergoing simultaneous stab phlebectomy compared with 17 of 525 cases (3.1%) undergoing only EVLA (P = .0049). Statistical analysis confirmed the association between EHIT and CEAP class was significant (P = .0001). No differences were seen for age, body mass index, sex, combined bilateral, and multiple or simultaneous GSV and SSV ablations between the two groups. A multivariate analysis confirmed that CEAP class, vein diameter, adjunctive phlebectomy, and laser wavelength were indeed risk factors for post-EVLA EHIT and that energy delivered and pullback time were not. Water-specific laser fiber wavelength (1470 nm) reduces the risk of EHIT compared with a hemoglobin-specific wavelength (810 nm). CEAP class, simultaneous phlebectomy, and vein diameter >7.5 mm are associated with increased risk of EHIT after EVLA.


Telemedicine for veterans in the setting of the COVID-19 pandemic: Lessons learned from a virtual urgent care center.
Although telemedicine was predominantly adopted during the COVID-19 pandemic, its impact on healthcare outcomes in the veteran population in achieving first contact resolution, or the ability to safely manage patient care at home from an urgent care perspective, is yet to be determined. This study included 13,090 veteran patient episodes who presented to the Department of Veteran's Affairs Veterans Integrated Services Network 8's Clinical Contact Center, a virtual urgent care organization covering South Georgia, Florida, and U.S. Virgin Islands in providing episodic care, between March 2020 and February 2021. Multivariate logistic regression estimated the probability that veterans with COVID-19-related symptoms stayed at home compared to presenting to the emergency department (ED) or their primary care provider. Patients with COVID-related symptoms were 33% less likely to present to the ED compared to patients who presented with non-COVID-related symptoms. The virtual urgent care center enabled veterans to receive timely care and avoid public places that could potentially lead to a COVID-19 infection or infecting others.


Sagittal plane translation of the knee during stair walking. Comparison of healthy and anterior cruciate ligament--deficient subjects.
With an electrogoniometer system, we made bilateral measurements of the maximal sagittal plane anterior-posterior knee translations in 15 healthy subjects (controls) and 14 patients with arthroscopically confirmed unilateral anterior cruciate ligament deficiency during two types of ascents and descents (straight and side). In both groups, during the ascent cycle the tibia moved anteriorly in relation to the femur, whereas during the descent cycle it moved posteriorly. There was wide individual variation in maximal translation in both the control and anterior cruciate ligament-deficient groups (range, 1 to 12 mm; mean, 7 mm). The maximal translations were similar in both groups (P > 0.05), but they occurred at a significantly smaller flexion angle in the injured knees (38 degrees +/- 8 degrees) than in the control and non-injured knees (44 degrees +/- 8 degrees) (P < 0.05). The translation during step ascent and descent did not differ between the injured and control knees. These findings indicate that patients with anterior cruciate ligament injuries are able to control abnormal anterior translation during normal activity.


A new approach to the study of therapeutic work in the transference.
This article proposes a new method for evaluating the effects of therapist and patient work in the transference. Work in the transference is often difficult for the patient, and may show a characteristic pattern of lag between a transference interpretation and its therapeutic effect. To account for this lag, we assessed patient responses to interpretations over the course of entire sessions. The narratives patients told about others, or Relationship Episodes (REs), were used as units of study. In a sample of three consecutive sessions taken from each of three psychodynamic cases, we identified several instances when transference work appeared to have an initial inhibitory effect, but facilitated progress over the course of the entire session. We recommend that to examine the effects of interpretations future studies use longer, more clinically meaningful segments of patient speech than have been used in the past. Dieser Beitrag propagiert eine neue Methode zur Evaluierung der Effekte von Übertragungsarbeit durch Therapeut und Patient. Arbeit in der Übertragung ist für den Patienten oftmals schwierig und zeigt häufig eine charakteristisches Muster von zeitlichen Verzögerungen bzgl. Übertragungsdeutungen und deren therapeutischen Effekten. Um diese zeitliche Verzögerung zu erklären, untersuchten wir die Reaktionen von Patienten auf derartige Deutungen im Verlauf ganzer Sitzungen. Narrative, in denen die Patienten über andere berichteten, also Beziehungsepisoden, dienten in dieser Studie als Einheit. In einter Stichprobe dreier aufeinanderfolgender Sitzugnen, die sich auf drei Fälle bezogen, identifizierten wir verschiedene Umstände, unter denen Übertragungsarbeit anfänglich einen hemmenden Affekt zu haben schien, letztlich aber den Gesamtverlauf der Sitzung günstig beeinflussten. Wir empfehlen, in Zukunft die Effekte von Übertragungsdeutungen auf der Basis längerer, klinische sinnvoller Segmente von Patientenäußerungen zu untersuchen als dies in der Vergangenheit der Fall war. Cet article propose une nouvelle méthode pour évaluer les effets du travail sur le transfert entre thérapeute et patient. Ce travail est souvent difficile pour le patient, et il peut y avoir un pattern caractéristique de délai entre une înterprétation de transfert et son effet thérapeutique. Pour expliquer ce délai, nous avons évalué les réponses des patients à des interprétatios au cours de séances entières. C'est les narrations des patients sur d'autres, ou Episodes Relationnels (ERs), qui ont constitué les unités de base de cette étude. Dans un échantillon de 3 séances consécutives venant de 3 cas psychodynamiques, nous avons identifié plusieurs moments où le traail sur le transfert semblait avoir un effet inhibitoire initial, mais favorisait le progrès en regardant la séance entière. Nous recommandons pour de futures études sur l'effet des interprétations de prendre des segments plus longs et cliniquement significatifs du récit du patient que ceux utilisés dans le passé. Este artículo propone un nuevo método para evaluar los efectos del trabajo de terapeuta y paciente en la transferencia. El trabajo en la transferencia es, con frecuencia, dificil para el paciente y puede mostrar un lapso característico entre una interpretación transferencial y sus efectos terapéuticos. Para explicar este lapso, hemos evaluado las respuestas del paciente a las interpretaciones a lo largo de sesiones enteras. Como unidad de estudio se usaron las narrativas de los pacientes acerca de otros, o sea, los episodios relacionales (REs). En una muestra de tres sesiones consecutivas tomadas de tres casos psicodinámicos, identificamos varioss casos en los que la trasferencia parecía tener un efecto inicial inhibitorio, aunque se vio que a lo largo de la sesión facilitaba el progreso. Recomendamos que, para examinar los efectos de las interpretaciones, los futuros estudios usen segmentos más largos y clínicamente más significativos del habia del paciente que los que se usaron en el pasado.


Visualization of skin deformation during wound closure.
A simple technique is described which enables the accurate visualization of skin deformation following wound closure. Results obtained during two surgical procedures involving the excision of areas of skin are presented.


Screening of new bioactive materials from microbial extracts of soil microorganism (I). Antimicrobial activity from 200 samples using microdilution assay.
The microdilution assay recommended by NCCLS (National Committee for Clinical Laboratory Standards) is one of the standardized methods of antibiotic susceptibility test. This method has been widely used clinically to obtain MIC values of antibiotics on pathogenic microorganisms. It is more convenient, rapid and simple to test many samples than other test methods such as agar diffusion assay and broth macrodilution assay. The screening of antimicrobial agents from microbial extracts is too laborious in its process. Therefore, a number of screening methods having more simple procedure have been developed. In our laboratory, we applied microdilution assay for screening the antimicrobial agents. This assay showed dose-response results and was more sensitive than disc diffusion assay in our system. We tested 200 samples of microbial extracts originated from 100 microbial strains and selected several samples as potential candidates. In this report, we show that the microdilution assay is more convenient method in screening of antibiotic susceptibility than those previously reported.


Traumatic pseudoaneurysm of the supra-orbital artery associated with von Willebrand's disease: case report.
The presence of an established coagulation disorder, in conjunction with minor arterial trauma, may lead to the genesis of a pseudoaneurysm. We report a case of a traumatic pseudoaneurysm of the supraorbital artery after minor blunt trauma in a patient with von Willebrand's disease.


Influence of Different Tibial Fixation Techniques on Initial Stability in Single-Stage Anterior Cruciate Ligament Revision With Confluent Tibial Tunnels: A Biomechanical Laboratory Study.
To kinematically and biomechanically compare 4 different types of tibial tunnel management in single-stage anterior cruciate ligament (ACL) revision reconstruction with the control: primary ACL reconstruction using a robotic-based knee testing setup. Porcine knees and flexor tendons were used. One hundred specimens were randomly assigned to 5 testing groups: (1) open tibial tunnel, (2) bone plug technique, (3) biodegradable interference screw, (4) dilatation technique, and (5) primary ACL reconstruction. A robotic/universal force-moment sensor testing system was used to simulate the KT-1000 (MEDmetric, San Diego, CA) and pivot-shift tests. Cyclic loading and load-to-failure testing were performed. Anterior tibial translation increased significantly with all of the techniques compared with the intact ACL (P < .05). In the simulated KT-1000 test, groups 2 and 3 achieved results equal to those of primary ACL reconstruction (P > .05). The open tunnel and dilated tunnel techniques showed significantly greater anterior tibial translation (P < .05). The results of the simulated pivot-shift test were in accordance with those of the KT-1000 test. No significant differences could be observed regarding stiffness or maximum load to failure. However, elongation was significantly lower in the primary ACL reconstruction group compared with groups 1 and 3 (P = .02 and P = .03, respectively). Filling an incomplete and incorrect tibial tunnel with a press-fit bone plug or a biodegradable interference screw in a standardized laboratory situation provided initial biomechanical properties and knee stability comparable with those of primary ACL reconstruction. In contrast, the dilatation technique or leaving the malplaced tunnel open did not restore knee kinematics adequately in this model. Backup extracortical fixation should be considered because the load to failure depends on the extracortical fixation when an undersized interference screw is used for aperture fixation. Our biomechanical results could help orthopaedic surgeons to optimize the results of primary ACL revision with incomplete, incorrect tunnel placement.


Impact of a Rapid-Access Ambulatory Psychiatry Encounter on Subsequent Emergency Department Utilization.
The authors sought to determine whether providing a rapid-access ambulatory psychiatry encounter correlated with emergency department utilization during a 6-month follow-up period. Electronic medical records of patients who accessed ambulatory psychiatric care through an urgent care psychiatry clinic that offers treatment exclusively on a walk-in basis over a 1-year period (N = 157) were reviewed retrospectively to track emergency department encounters with and without a psychiatric chief complaint in the 6 months before and after the initial psychiatry evaluation. Among patients who had not previously received ambulatory psychiatric care (N = 88), emergency department utilization decreased from 0.68 visits per patient to 0.36, and this difference was statistically significant (p = 0.0147). No statistically significant differences were found between the average number of emergency department encounters in the 6 months before and after the rapid-access ambulatory psychiatry encounter, regardless of chief complaint, when all patients were included in the analysis. Providing a rapid-access ambulatory psychiatry encounter may reduce subsequent emergency department utilization among patients who have not previously received ambulatory psychiatric care.


L-DOPA modulates cell viability through the ERK-c-Jun system in PC12 and dopaminergic neuronal cells.
L-DOPA causes neurotoxicity by modulating the Epac-ERK system in PC12 cells. This study investigated the effects of a single treatment with L-DOPA and multiple treatments with L-DOPA (MT-LD) on ERK1/2 and JNK1/2-c-Jun systems. In PC12 cells, a toxic L-DOPA concentration (200 μM) induced sustained ERK1/2 and JNK1/2 phosphorylation that was inhibited by the Epac inhibitor brefeldin A, but not by the PKA inhibitor H89. This ERK1/2 and JNK1/2 phosphorylation was also inhibited by ERK1/2 (U0126) and JNK1/2 (SP600125) inhibitors, respectively, but sustained ERK1/2 phosphorylation was not affected by JNK1/2 phosphorylation. A non-toxic L-DOPA concentration (20 μM) induced c-Jun phosphorylation (Ser73) via transient ERK1/2 phosphorylation, whereas the toxic L-DOPA concentration induced c-Jun phosphorylation (Ser63) and c-Jun expression via Epac-sustained ERK1/2-JNK1/2 phosphorylation, which then enhanced cleaved caspase-3 expression. MT-LD (20 μM) initially enhanced c-Jun phosphorylation (Ser73) (for 1-4 days), but later (5-6 days) induced c-Jun phosphorylation (Ser63) and c-Jun expression. In the 6-hydroxydopamine-lesioned rat model of Parkinson's disease, L-DOPA administration (10 mg/kg) protected against neurotoxicity through c-Jun phosphorylation (Ser73) for 1-2 weeks. However, L-DOPA administration (10 or 30 mg/kg) showed neurotoxicity through c-Jun phosphorylation (Ser63) and c-Jun expression via ERK1/2 phosphorylation for 3-4 weeks. Thus, in PC12 cells, non-toxic L-DOPA treatment maintained cell survival through c-Jun phosphorylation (Ser73). By contrast, toxic L-DOPA treatment or MT-LD (20 μM) induced c-Jun phosphorylation (Ser63) and c-Jun expression via Epac-dependent sustained ERK1/2 and JNK1/2 phosphorylation, which subsequently led to cell death. These results were validated by those obtained after long-term L-DOPA administration in a rat model of Parkinson's disease. Our data indicate that L-DOPA causes neurotoxicity via the ERK1/2-c-Jun system in dopaminergic neuronal cells.


Applying rapid 'de-facto' HTA in resource-limited settings: experience from Romania.
In attempting to constrain healthcare expenditure growth, health technology assessment (HTA) can enable policy-makers to look beyond budget impact and facilitate more rational decision-making. However lack of technical capacity and poor governance can limit use in some countries. Undertaking de facto HTA by adapting decisions taken in countries with established processes is a method that may be applied while building domestic HTA capacity. We explored the potential for applying this approach in Romania. As part of a review of the basic health benefits available to insured Romanians we examined the listing process and content of the Romanian drug reimbursement formulary. We assessed value for money indirectly by drawing on appraisals by UK's NICE, and for products considered cost effective in the UK, adjusting prices by the ratio of Romanian per capita GDP to UK per capita GDP. We found more than 30 of the top 50 medicines on the Romanian formulary unlikely to be cost-effective, suggesting that existing external reference pricing mechanisms may not be delivering good value for money. While not taking into account local costs or treatment patterns, absent local considerations of value for money, this method offers a guide for both drug selection and pricing. Until robust local HTA processes are established this approach could support further analysis of existing prices and pricing mechanisms. Applied more generally, it is arguably preferable to external reference pricing, product delisting or arbitrary price cuts, and may support the future development of more rigorous, evidence-based decision-making.


Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.
Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls. Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue. Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.


Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results.
To prove the long-term dampening effect of riboflavin- and ultraviolet-A-induced collagen crosslinking on progressive keratoconus. Department of Ophthalmology, C.G. Carus University Hospital, Dresden, Germany. Four hundred eighty eyes of 272 patients with progressive keratoconus were included in this long-term retrospective study. The maximum follow-up was 6 years. At the first and all follow-up examinations, refraction, best corrected visual acuity (BCVA), corneal topography, corneal thickness, and intraocular pressure were recorded. The analysis included 241 eyes with a minimum follow-up of 6 months. The steepening decreased significantly by 2.68 diopters (D) in the first year, 2.21 D in the second year, and 4.84 D in the third year. The BCVA improved significantly (> or = 1 line) in 53% of 142 eyes in the first year, 57% of 66 eyes in the second year, and 58% of 33 eyes in the first year or remained stable (no lines lost) in 20%, 24%, and 29%, respectively. Two patients had continuous progression of keratoconus and had repeat crosslinking procedures. Despite the low number of patients with a follow-up longer than 3 years, results indicate long-term stabilization and improvement after collagen crosslinking. Thus, collagen crosslinking is an effective therapeutical option for progressive keratoconus.


Multilayer hydrogel coatings to combine hemocompatibility and antimicrobial activity.
While silver-loaded catheters are widely used to prevent early-onset catheter-related infections [1], long term antimicrobial protection of indwelling catheters remains to be achieved [2] and antiseptic functionalization of coatings often impairs their hemocompatibility characteristics. Therefore, this work aimed to capitalize on the antimicrobial properties of silver nanoparticles, incorporated in anticoagulant poly(ethylene glycol) (PEG)-heparin hydrogel coatings [3] on thermoplastic polyurethane materials. For prolonged antimicrobial activity, the silver-containing starPEG-heparin hydrogel layers were shielded with silver-free hydrogel layers of otherwise similar composition. The resulting multi-layered gel coatings showed long term antiseptic efficacy against Escherichia coli and Staphylococcus epidermidis strains in vitro, and similarly performed well when incubated with freshly drawn human whole blood with respect to hemolysis, platelet activation and plasmatic coagulation. The introduced hydrogel multilayer system thus offers a promising combination of hemocompatibility and long-term antiseptic capacity to meet an important clinical need.


Will the presence of the patient at multidisciplinary meetings influence the decision in head and neck oncology management?
Multidisciplinary team meetings (MTM) are essential in the choice of a therapeutic strategy in head and neck cancer. In many centres patients attend MTMs and are examined by the team. The aim of this study was to assess the influence of the patient's presence on therapeutic decisions. Prospective study of 119 consecutive patients. Two therapeutic situations were compared: the therapeutic decision taken following discussion of the patient's file in the MTM (D1) and the therapeutic decision taken after examination of the patient during MTMs (D2). Concordance between the two situations was measured. Concordance between D1 and D2 was 97%. No factors likely to decrease concordance were identified. Decisions taken during MTMs were acted upon for 97% of the patients. The presence of the patient during MTMs is not essential if the files are thoroughly presented and discussed.


A randomized prospective study of the use-effectiveness of two methods of natural family planning: an interim report.
Data accumulated to date from the Los Angeles study indicate that the total termination rate for 12 months from the beginning of the training period and from formal entry into the study was high for the ovulation method (OM), and symptothermal method (STM). Voluntary withdrawal was the highest single reason for termination in both methods. The 12 month voluntary withdrawal rate, measured from formal entry into the study, was significantly higher for OM users. Pregnancy rates measured from both the beginning of training and formal entry into the study were significantly higher for OM users than for STM users. Complete analysis of the data collected during the study is currently in progress. It is anticipated that some of the causes for the differences in pregnancy rates and withdrawal rates between the two methods can be identified.


Two new compounds from Paeonia lactiflora.
Two new compounds, namely 5-methyl-4,2',3',5'-tetrahydroxy-4'-methoxy-2-aldehyde biphenyl (1) and 1,8-dioxo-1,8-dihydropyrano[3,4-c]pyran-3,6- dicarboxyl acid, diethyl ester (2), were isolated from the 95% ethanol extract of the roots of Paeonia lactiflora Pall. The structures of 1 and 2 were elucidated by spectroscopic methods, including UV, IR, HR-ESI-MS and extensive 1D and 2D NMR techniques.


Severe combined immunodeficiency disease: a pathological analysis of 26 cases.
Autopsy material and clinical information were analyzed in 25 cases of untreated or unsuccessfully treated severe combined immunodeficiency disease and one case successfully treated by bone marrow grafting. Two cases were adenosine deaminase deficient and one was nucleoside phosphorylase deficient. The histological appearance of the thymus fell into four clearly recognizable patterns: simple dysplasia, dysplasia with corticomedullary differentiation, dysplasia with pseudoglandular appearance, and atrophic pattern. Three cases lacked lymph nodes and belonged to the category of thymic dysplasia with pseudoglandular appearance. From the data, the following conclusions can be made: (i) The thymic atrophic pattern is a phase in a dynamic process of which the end result is simple dysplasia or dysplasia with corticomedullary differentiation. (ii) The pseudoglandular pattern represents a disease process of early intrauterine onset. (iii) At least a proportion of the cases represent a T-cell defect rather than a lymphoid stem-cell defect. (iv) The lymphoid germinal centers are not the source of plasma cells. (v) The graft-versus-host reaction probably causes lymphoid cells depletion in lymph nodes and spleen.


Long-term angiogenic activity of free grafts and pedicle flap in a rabbit urethroplasty model.
We studied the late angiogenic activity of free grafts and a pedicle flap in a rabbit urethroplasty model to determine whether angiogenic activity plays a role in late outcomes of urethral reconstruction in rabbits. Twenty-eight rabbits were randomly divided into five groups according to the method used to bridge a urethral defect as an onlay patch: Control, simple closure of urethral defect (Group O1); free penile skin graft (FPSG, Group A1); buccal mucosal graft (BuMG, Group B1); bladder mucosal graft (BlMG, Group C1); and pedicle penile skin flap (PPSF, Group D1). Angiogenic activity of the patch on postoperative day 84 was assessed by immunohistochemistry. The angiogenic activity in Groups O1, A1, B1, C1, and D1 was 23.33 ± 4.92 (means ± SD), 42.89 ± 6.52, 55.78 ± 3.46, 53.61 ± 6.17, and 24.11 ± 9.07 vessels per optical field, respectively. There were statistically significant differences (p < .001) between Group O1 and A1 B1, C1, Group A1 and B1, C1, D1, Groups B1 and D1 and Groups C1 and D1, but not between Groups O1 and D1 (p = 1.000) and Groups B1 and C1 (p = .872). The long-term angiogenic activity of all the groups was significantly lower (p < .001) than in the corresponding early groups. Although the angiogenic activity of all the groups decreased in the late assessment, the buccal mucosal graft continued to exhibit elevated angiogenesis above bladder or skin (free or pedicle) graft. Therefore, buccal mucosal patch graft might be preferable because of its easier harvesting.


Immunohistologic study of epiretinal membranes in proliferative vitreoretinopathy.
We performed an immunohistologic study on 11 specimens of epiretinal membranes surgically obtained from patients who had rhegmatogenous retinal detachment with proliferative vitreoretinopathy. Immunostaining procedures were used to identify immunoglobulin and complement deposits, to visualize class II antigen expression by proliferating cells, and to determine eventual infiltration by cells of the immune system. Diffuse deposits of IgG, IgA, IgE, C1q, C3c, and C3d were found in epiretinal membranes, whereas numerous cells, including glial or pigmented epithelial cells, expressed HLA-DR and HLA-DQ antigens. Some macrophages and B or T8 lymphocytes were identified. These results suggest activation of the immune system during the course of proliferative vitreoretinopathy. Class II antigen expression could be dependent upon growth-promoting factors and interferon gamma and could play a crucial role in this immune reaction, which resulted in immunoglobulin deposition and activation of complement. However, the eventual role of immune phenomena in the extension of proliferative processes remains to be determined.


[Echocardiography findings before and following beta-irradiation (106Ru/106Rh) of choroid melanoma].
Echographic follow-up examinations were performed in 72 patients in whom a choroidal melanoma was treated with (106Ru/106Rh) applicators. The observation period was between 6 and 15 months. Echographic measurement of tumor prominence and assessment of the degree of reflection proved to be important indicators for judging the success of beta radiation therapy. If the prominence diminishes and the degree of reflection increases after treatment, regression of the tumor may safely be assumed to have occurred. Apart from an increase in the prominence of the tumor, a constantly low or even falling level of reflection are signs of a less favorable prognosis.


Management's response to the union phenomenon.
While management must be allowed to assert its right to govern, it must not neglect the dignity of the employee in the process. If management can satisfactorily handle employeees' grievances about poor upward communication and poor and unfair treatment, it might also prevent unionization in its institution.


Bartholin's gland carcinoma: epidemiology and therapeutic management.
Primary carcinoma of the Bartholin's gland is a very rare malignancy of the vulva. Of the utmost importance in the management of these tumors is the management by specialized gynecological oncologist at referral centres. Gynecologists should always consider these unusual neoplasms as a differential diagnosis of potentially benigns lesions of Bartholin's gland. Treatment modality must be tailored to each patient: each histological type of these unusual neoplasms has their natural history and may require a different level of operative aggressiveness to obtain the optimal outcome. Given the rarity of this disease, there have been no prospective randomized trials to evaluate optimal treatment. Therapeutic principles in the management of median vulvar cancer are applicable for Bartholin's gland carcinoma. In this review, we aim to update the current knowledge on the treatment of Bartholin's gland carcinoma.


Giant prolactinomas, a detailed analysis of 196 adult cases.
Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the clinical, biochemical and radiological characteristics, management and therapeutic outcomes in men versus women is made. A structured search was conducted using the term 'giant prolactinoma'. Following inclusion criteria were used: diameter ≥ 40 mm, prolactin levels > 1000 ng/ml and no concomitant GH/ ACTH secretion. 196 cases were included [age: 38 (28-50) years, F/M ratio: 1/3.6]. Median tumor diameter was 53 (43-69) mm. Pituitary deficiency was present in 91% of cases, with hypogonadotropic hypogonadism being the most frequent. Most common presenting symptoms were visual impairment (73%) and headache (50%) in men and amenorrhea (58%) in women. 82% of cases were treated with a dopamine agonist (DA) as first-line treatment which led to normoprolactinemia, tumor shrinkage and visual improvement in 51%, 88% and 85% of cases, respectively. Surgery was performed in 29% of cases and all showed tumor remnant and persistent hyperprolactinemia. Women had a lower prolactin level and a smaller tumor diameter at diagnosis but pituitary deficiencies were more frequent and outcome was worse. Giant prolactinomas are rare and have a male predominance. Visual impairment is the most frequent presenting symptom in men and amenorrhea in women. The gender-related difference in tumor size and level of prolactin was confirmed in this analysis where men had a larger diameter and a higher baseline prolactin level. DAs are the treatment of choice, irrespective of tumor size and presence of visual impairment. As only half of the cases achieved normoprolactinemia we do not, in contrast to previous literature, state giant prolactinomas to be exquisitely sensitive to DAs. Patient characteristics associated with persistent hyperprolactinemia after treatment with a DA were female gender, higher baseline prolactin and larger tumor size . This analysis did show TSH- and ACTH-deficiency to be more frequent after surgery which was not seen for LH/FSH deficiency.


Influence of physical activity on vertebral strength during late adolescence.
Reduced vertebral strength is a clear risk factor for vertebral fractures. Men and women with vertebral fractures often have reduced vertebral size and bone mineral density (BMD). Vertebral strength is controlled by both genetic and developmental factors. Malnutrition and low levels of physical activity are commonly considered to result in reduced bone size during growth. Several studies have also demonstrated the general relationship between BMD and physical activity in the appendicular skeleton. In this study, we wanted to clarify the role of physical activity on vertebral bodies. Vertebral dimensions appear to generally be less pliant than long bones when lifetime changes occur. We wanted to explore the association between physical activity during late adolescence and vertebral strength parameters such as cross-sectional size and BMD. The association between physical activity and vertebral strength was explored by measuring vertebral strength parameters and defining the level of physical activity during adolescence. The study population consisted of 6,928 males and females who, at 15 to 16 and 19 years of age, responded to a mailed questionnaire inquiring about their physical activity. A total of 558 individuals at the mean age of 21 years underwent magnetic resonance imaging (MRI) scans. We measured the dimensions of the fourth lumbar vertebra from the MRI scans of the Northern Finland Birth Cohort 1986 and performed T2* relaxation time mapping, reflective of BMD. Vertebral strength was based on these two parameters. We analyzed the association of physical activity on vertebral strength using the analysis of variance. We observed no association between the level of physical activity during late adolescence and vertebral strength at 21 years.


Effects of IVIg treatment on autoantibody testing in neurological patients: marked reduction in sensitivity but reliable specificity.
Therapy of autoimmune diseases of the central and peripheral nervous system with intravenous IgG immunoglobulin (IVIg) is well established. Since IVIg is produced from pooled human plasma, autoantibodies can be found in IVIg products and, accordingly, in patient sera after transfusion. The de novo evidence or disappearance of anti-neural autoantibodies after IVIg treatment has so far not been systematically examined. We screened 50 neurological patients before and after IVIg treatment for classical onconeural and the most common neurological surface autoantibodies as well as for ganglioside autoantibodies and 23 different antinuclear autoantibodies using immunoblot or cell-based indirect immunofluorescence assays. Furthermore, we screened 31 neurological patients with previously known seropositivity for disappearance of the corresponding antibody after treatment. After IVIg treatment, 90% of all sera were de novo positive for antinuclear antibodies, especially for Ro-52. In contrast, 94% of all sera did not show any de novo-positive anti-neural antibodies. In the remaining three cases, titers were very low. Importantly, 12.9% of all tested sera of patients with known antibody positivity turned false negative after IVIg treatment and titers were falsely low in 37% of the remaining sera. Here, we present for the first time results of a broad screening for clinically relevant autoantibodies before and after IVIg treatment in neurological patients. We identified a high specificity but reduced sensitivity for anti-neural antibody testing after IVIg transfusion. In contrast, antinuclear antibody testing is not reliable after IVIg treatment. These results are of high practical importance for diagnostic of neuroimmunological diseases.


Generation of a novel CD8+ cytotoxic T lymphocyte that requires soluble factor to lyse autologous antigen-presenting cells.
We reported the existence of high and low responders to the streptococcal cell wall antigen (SCW) in the human population. To analyze the mechanism of the low responsiveness to SCW at the cellular level, we established SCW-specific CD4+ T cell lines. During the course of generation of a SCW-specific CD4+ T cell line restricted by HLA-DQ from a low responder, we obtained autoreactive CD8+ cytotoxic T lymphocytes as a cell line (HYCD8). They proliferated in the presence of autologous monocytes and IL-2, without SCW. HYCD8 lysed autologous monocytes and Epstein-Barr virus-transformed B lymphoblastoid cell line (BLCL). This cytotoxic activity was specifically inhibited by an anti-HLA class I framework monoclonal antibody and restricted by HLA-B52 or B54 specificity, as judged by killing activity against panel cells and HLA class I-transfected BLCL. It was unique to HYCD8 that the HLA class I-restricted cytotoxicity was observed only in the presence of soluble factor with low molecular mass (< 10(4) Da) produced mainly by B cells, which could not be replaced by known cytokines and their mixtures. We thus describe novel HLA class I-restricted cytotoxic CD8+ T cells that kill antigen-presenting cells in a soluble factor-dependent manner.


Development and validation of an indirect competitive enzyme-linked immunosorbent assay for monitoring organoarsenic compounds in edible chicken and pork and feed.
For the first time in this study, we used molecular modelling to design a suitable hapten (arsanilic acid, ASA) and produced a broad-specificity monoclonal antibody (mAb). This mAb exhibited the IC50 for ASA was 913.7 μg L(-1) and showed the cross-reactivity to ASA (100%), carbarsone (849.2%), and nitarsone (1159.5%), respectively. Based on this mAb, an optimised indirect competitive enzyme linked immunosorbent assay (ic-ELISA) protocol was developed to monitor organoarsenic compounds (OAs) in edible chicken and pork and feed, which the detection limit for OAs in a muscle matrix ranged from 74.2 μg kg(-1) to 143.3 μg kg(-1) and in a feed matrix ranged from 7.4 mg kg(-1) to 11.8 mg kg(-1), the recoveries were 61.3-109.6% with a coefficient of variation of less than 10.8%. These data demonstrated that the developed ic-ELISA is a reliable and useful tool for screening OAs in edible chicken and pork and feed.


Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines.
In anticipation of developing gene therapy against thyroid carcinoma we created an expression vector using the thyroglobulin (Tg) gene promoter. The inhibition of both Tg and thyroid-specific transcription factor (TTF-1 and PAX-8) gene expression, however, has been well documented in thyroid carcinomas. We therefore examined the effects of overexpression of TTF-1 and PAX-8 on Tg gene promoter activity in the human thyroid carcinoma cell lines, ARO (anaplastic) and WRO (follicular). ARO, WRO, and nonthyroid cells were transfected with an expression vector in which beta-galactosidase (beta-gal) is driven by the Tg gene promoter (beta-gal). Tg, TTF-1, and PAX-8 gene expression were also examined by reverse transcriptase-polymerase chain reaction (RT-PCR). ARO and WRO exhibited decreased gene expression of Tg, TTF-1, and PAX-8. Transfection with TG--gal alone exhibited minimal beta-gal expression, whereas cotransfection with TTF-1 and PAX-8 resulted in markedly increased expression. There was no evidence of beta-gal expression with or without TTF-1 and PAX-8 in nonthyroid cells. Weak Tg gene promoter activity in ARO and WRO is associated with decreased expression of transcription factors TTF-1 and PAX-8 but can be restored with their overexpression. This model may serve as a template on which to further develop cell-specific gene therapy against thyroid carcinoma.


Supralevator anorectal abscess presenting as acute low back pain and sciatica.
Anorectal abscess is a suppurative process that begins in the anal glands. Clinical presentation is variable and depends on the direction and tissue plane along which the infection tracks. All cases require urgent incision and drainage. We report an unusual case of a supralevator abscess in a man who presented to the emergency department on two occasions with acute low back pain and sciatica. The case demonstrates the importance and difficulty of identifying the exceptional case among the numerous routine cases of mechanical low back pain. Attentiveness to atypical features should direct the clinician to a more extensive evaluation for serious illness. The case also illustrates that sciatica is not a diagnostic end-point but rather a label for a pain syndrome that encompasses a long differential diagnosis.


Contribution of chemical changes in membrane lipids to the osmoadaptation of the halophilic bacterium Chromohalobacter salexigens.
The long-term response of the broad-salt growing halophile Chromohalobacter salexigens DSM 3043T to salt stress has been investigated with respect to adaptive changes in membrane lipid composition. This study included the wild-type and three salt-sensitive, ectoine-deficient strains: CHR62 (ectA::Tn1732, unable to grow above 0.75 M NaCl), CHR63 (ectC::Tn1732, unable to grow above 1.5 M NaCl), and CHR64, which was able to grow in minimal medium M63 up to 2.5 M NaCl, but its growth was slower than the wild-type strain at salinities above 1.5 M NaCl. This mutant accumulated ectoine and hydroxyectoine as major compatible solutes, but also the ectoine precursor, N-gamma-acetyldiaminobutyric acid, and was found to be affected in the ectoine synthase gene ectC. The main phospholipids of the wild-type strain were phosphatidylethanolamine, phosphatidylglycerol (PG), and cardiolipin (CL). Major fatty acids were detected as 16:0, 18:1, and 16:1, including significant amounts of cyc-19:0, and cyc-17:0. CL and cyclopropane fatty acids (CFA) levels were elevated when the wild-type strain was grown at high salinity (2.5 M NaCl). Membranes of the most salt-sensitive trains CHR62 and CHR63, but not of the less salt-sensitive strain CHR64, contained lower levels of CL. The proportion of cyc-19:0 in CHR64 was three-fold (at 2.0M NaCl) and 2.5-fold (at 2.5 M NaCl) lower than that of the wild type, suggesting that this mutant has a limited capacity to incorporate CFA into phospholipids at high salt. The addition of 1 mM ectoine to cultures of the wild-type strain increased the ratio PG/CL from 1.8 to 3.3 at 0.75 M NaCl, and from 1 to 6.5 at 2.5 M NaCl, and led to a slight decrease in CFA content. Addition of 1 mM ectoine to the mutants restored the steady-state levels of CL and CFA found in the wild-type strain supplemented with ectoine. These findings suggest that exogenous ectoine might attenuate the osmostress response involving changes in membrane lipids.


Construction of tissue-engineered lymphatic vessel using human adipose derived stem cells differentiated lymphatic endothelial like cells and decellularized arterial scaffold: A preliminary study.
We have previously demonstrated that human adipose-derived stem cells (hADSCs) can be differentiated into lymphatic endothelial like cells. The purpose of this study was to investigate the feasibility of utilizing the induced lymphatic endothelial like cells and decellularized arterial scaffold to construct the tissue-engineered lymphatic vessel. The hADSCs were isolated from adipose tissue in healthy adults and were characterized the multilineage differentiation potential. Decellularized arterial scaffold was prepared using the Triton x-100 method. ADSCs were differentiated into lymphatic-like endothelial cells, and the induced cells were then seeded onto the decellularized arterial scaffold to engineer the lymphatic vessel. The histological analyses were performed to examine the endothelialized construct. The decellularized arterial scaffold was successfully obtained and was able to maintain its vessel morphology. The isolated ADSCs can be differentiated into osteocytes and adipocytes. After seeding onto the scaffold, the seeded cells attached and grew well on the decellularized arterial scaffold. Our preliminary results demonstrated that the induced lymphatic endothelial like cells combined with decellularized arterial scaffold could be utilized to successfully engineer the lymphatic vessel. Our findings may be helpful for the development of tissue-engineering of the lymphatic graft.


Glomerular permeability to neutral and anionic dextrans in experimental diabetes.
Renal clearances of polydispersed neutral and anionic dextrans were measured in diabetic rats. In addition, urinary protein and albumin excretion rates were determined. Measurements were performed 3 months after the induction of diabetes (i.v. alloxan 50 to 55 mg/kg of body wt) in rats which were either untreated or which received supplemental insulin (6 U of NPH daily) and were compared to those in age-matched SHAM-treated rats. Fractional clearances (relative to inulin) of neutral dextrans remained unchanged in insulin-supplemented rats and were slightly but significantly increased in untreated rats. The application of an isoporous model of the glomerular filtration barrier permitted the conclusion that the size-selective characteristics of the barrier were unaltered in diabetic rats. Fractional clearances of anionic dextrans were significantly reduced 50 to 60% in both diabetic groups suggesting an increase in the negative charge density of the filtration barrier and potentially an increase in restriction to the glomerular filtration of anionic proteins. However, urinary and albumin excretions tended to increase in both groups of diabetic rats, including a 164% increase in albumin excretion in untreated rats. This apparent discrepancy between reduced dextran sulfate clearances and increased protein excretions suggests that factors other than charge-selectivity may be of major importance in determining the filtration of proteins. The marked increase in albumin excretion observed in our diabetic rats appears to be a result of decreased tubular reabsorption rather than increased filtration of albumin.


Brain Death/Death by Neurological Criteria: International Standardization and the World Brain Death Project.
This article reviews the criteria for determination of brain death, discusses the importance of protocol development, and reviews the international efforts to standardize clinical testing.


Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals.
A novel peptide, islet amyloid polypeptide (IAPP), with structural resemblance to calcitonin gene-related peptide has recently been purified from amyloid deposits in an insulinoma and from islets of Langerhans. By immunohistochemical methods, using antisera to a synthetic undecapeptide of IAPP and to insulin, we show that freshly fixed islet B cells in man, guinea pig, rat, mouse and hamster exhibit strong IAPP-immunoreactivity while A cells are unreactive. In human autopsy material, all of 11 non-diabetic individuals had IAPP immunoreactivity of the islets. In comparison 8 of the 13 patients with Type 2 (non-insulin-dependent) diabetes had no IAPP immunoreactive cells. The proportion of islet cells having IAPP immunoreactivity exceeded 10% in only 1 of the 5 remaining diabetic patients while in all 13 patients substantially more than 10% of the islet cells contained immunoreactive insulin. IAPP-positive amyloid deposits were found in 20-99% of the islets in 12 of the Type 2 diabetic patients while 6 of 11 non-diabetic subjects had amyloid in 3-11% of their islets. In islets with IAPP-immunoreactive amyloid, very few IAPP-cells were seen despite a strong reaction of the B cells with antiserum to insulin. This study shows that IAPP is a normal islet B cell component and that IAPP immunoreactivity in B cells is diminished in Type 2 diabetes while IAPP is deposited as amyloid fibrils in the islets of Langerhans. Although the function of IAPP is unknown, its occurrence in the islet B cells and its structural relation to calcitonin gene-related peptide makes a hormonal nature probable.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of antimicrobial-resistant Staphylococcus aureus from retail foods in Beijing, China.
Staphylococcus aureus is an opportunistic pathogen leading to food poisoning as well as human infections. The present study examined the prevalence and characterization of antimicrobial-resistant S. aureus in sushi from 42 outlets and in pork products from eight outlets in Beijing, China. The total bacterial counts were between 3.0 and 8.9 log CFU/g (mean 5.5 ± 1.5 log CFU/g) in sushi products and 4.8 to 7.4 log CFU/g (mean 5.6 ± 0.8 log CFU/g) in pork products. The mean counts of coliforms were 2.7 and 2.9 log CFU/g in sushi and pork, respectively. Staphylococcus aureus was isolated from seven sushi outlets (13 isolates) and two pork outlets (2 isolates) with average counts below 2 log CFU/g in all cases. A total of 15 S. aureus isolates were further characterized. Six lineages of S. aureus were present, including ST398 (n = 5), ST25 (n = 4), ST15 (n = 2), ST59 (n = 2), ST8 (n = 1) and ST2631 (n = 1). Thirteen isolates contained the scn virulence marker, whereas four and eight isolates contained the virulence marker edinB and enterotoxin genes, respectively. Characterization of antimicrobial resistance profiles documented resistances to ampicillin (n = 15), penicillin (n = 14), ceftazidime (n = 6), erythromycin (n = 4), tetracycline (n = 3), clindamycin (n = 3), and gentamicin (n = 1). Three MRSA isolates were obtained, one from pork (ST398) and two from one sushi outlet (ST59). They were all resistant to at least three classes of antimicrobials and two of them contained the scn gene and enterotoxin genes. Twelve sushi isolates and one of the pork isolates contained the scn gene, indicating that they were of human origin. This emphasizes the potential importance of transmission through foods of antimicrobial-resistant S. aureus including MRSA. We also showed that S. aureus exhibited geographical variation with regards to ST profiles, antimicrobial-resistance and virulence genes when comparing isolates from sushi products sold in Beijing and Copenhagen, Denmark. Whereas food safety is not compromised by the presence of low amounts of S. aureus in sushi, this study shows that with regards to public health such foods may serve as vehicles for transmission of multidrug-resistant S. aureus and MRSA lineages.


Introducing a highly dispersed reduced graphene oxide nano-biohybrid employing chitosan/hydroxyethyl cellulose for controlled drug delivery.
In this research, an attempt was made to stabilize reduced graphene oxide (rGO) in all pH ranges, incorporating both chitosan (CS) and hydroxyethyl cellulose (HEC) to make a proper drug carrier with suitable stability and drug release behaviour. The stability of rGO-CS-HEC nanohybrid was assessed using field emission scanning electron microscopy (FE-SEM), ultraviolet-visible spectroscopy (UV-Vis) and Zeta potential measurements. Results depicted that the novel synthesized nanohybrid was stable in all pH ranges, due to the utilization of HEC, while without incorporation of this material, the rGO-CS nanohybrid aggregated at neutral and alkaline media, due to the ionic nature of chitosan. In addition, drug loading and release behaviour of folic acid (FA), as a model drug, was investigated to assess the role of chitosan on the release behaviour of FA from the rGO-CS-HEC nanohybrid in comparison with rGO-HEC and rGO-CS nanohybrids. It was proved that the resultant nanohybrid could release nearly 27% more FA than the rGO-HEC nanohybrid and only 9% lower than the rGO-CS nanohybrid during 120h. Moreover, the biocompatibility of the resultant nanohybrid was also checked to introduce the novel rGO-CS-HEC nanohybrid as a suitable candidate for drug delivery application.


A C. elegans sperm TRP protein required for sperm-egg interactions during fertilization.
Fertilization, a critical step in animal reproduction, is triggered by a series of specialized sperm-egg interactions. However, the molecular mechanisms underlying fertilization are not well understood. Here, we identify a sperm-enriched C. elegans TRPC homolog, TRP-3. Mutations in trp-3 lead to sterility in both hermaphrodites and males due to a defect in their sperm. trp-3 mutant sperm are motile, but fail to fertilize oocytes after gamete contact. TRP-3 is initially localized in intracellular vesicles, and then translocates to the plasma membrane during sperm activation. This translocation coincides with a marked increase in store-operated calcium entry, providing an in vivo mechanism for the regulation of TRP-3 activity. As C. elegans oocytes lack egg coats, our data suggest that some TRPC family channels might function to mediate calcium influx during sperm-egg plasma membrane interactions leading to fertilization.


Assessing the effects of maternal HIV infection on pregnancy outcomes using cross-sectional data in Malawi.
Several studies have shown that maternal HIV infection is associated with adverse pregnancy outcomes such as low birth weight and perinatal mortality. However, the association is conflicted with the effect of antiretroviral therapy (ART) on the pregnancy outcomes and it remains unexamined. If the association is confirmed then it would guide policy makers towards more effective prevention of mother to child HIV transmission interventions. Using methods for matching possible confounders, the objectives of the study were to assess the effect of maternal HIV infection on birth weight and perinatal mortality and to investigate the effect of ART on these two pregnancy outcomes in HIV-infected women. Data on 4111 and 4759 children, born within five years of the 2010 and 2015-16 Malawi Demographic and Health Surveys (MDHS) respectively, whose mothers had an HIV test result, were analysed. A best balancing method was chosen from a set of covariate balance methods namely, the 1:1 nearest neighbour (NN) matching, matching on the propensity score (PS) and inverse weighting on the PS. HIV and ART data were only available in the MDHS 2010, permitting an assessment of the moderating effect of ART on the association between maternal HIV infection and birth weight and perinatal mortality. The overall average birth weight was 3227.9g (95% CI: 3206.4, 3249.5) in 2010 and 3226.4g (95%: 3205.6, 3247.2) in 2015-16 and perinatal mortality was 3.8% (95%: 3.2, 4.3) in 2010 and 3.5% (95%: 2.8, 3.8) in 2015-16. The prevalence of HIV among the mothers was 11.1% (95%: 10.1, 12.0) and 9.2% (95% CI: 8.4, 10.1) in 2010 and 2015-16, respectively. In 2010, maternal HIV infection was negatively associated with birth weight (mean= -25.3g, 95% CI:(-95.5, -7.4)) and in 2015-16 it was positively associated with birth weight (mean= 116.3g, 95% CI:(27.8, 204.7)). Perinatal mortality was higher in infants of HIV-infected mothers compared to infants of HIV-uninfected mothers (OR = 1.5, 95% CI:(1.1 - 3.1)) in 2010, while there was no difference in the rate in 2015-16 (OR = 1.0, 95% CI:(0.4, 1.6)). ART was not associated with birth weight, however, it was associated with perinatal mortality (OR=3.9, 95% CI:(1.1, 14.8)). The study has found that maternal HIV infection had an adverse effect on birth weight and perinatal mortality in 2010. Birth weight was not dependent on ART uptake but perinatal mortality was higher among infants of HIV-infected mothers who were not on ART. The higher birth weight among HIV-infected mothers and similarity in perinatal mortality with HIV-uninfected mothers in 2015-16 may be indicative of successes of interventions within the PMTCT program in Malawi.


Screening of inhibitors of glycogen synthase kinase-3β from traditional Chinese medicines using enzyme-immobilized magnetic beads combined with high-performance liquid chromatography.
Glycogen synthase kinase-3β (GSK-3β) was immobilized on magnetic beads (MBs) by affinity method for the first time. The enzyme-immobilized MBs were coupled with high-performance liquid chromatography-ultraviolet (HPLC-UV) technique to establish a cost-effective and reliable method for screening of inhibitors of GSK-3β. A peptide substrate of GSK-3β containing a tyrosine residue was employed since it can be sensitively detected by UV detector at 214nm. The substrate and its phosphorylated product were separated by baseline within 10min. The enzyme activity was determined by the quantification of peak area of the product. Parameters including enzyme immobilization, enzyme reaction and the performance of immobilized-enzyme were investigated. The immobilized enzyme can be reused for 10 times and remain stable for 4 days at 4°C. The inhibitory activities of extracts of 15 traditional Chinese medicines (TCMs) were screened. As a result, three of them including Euonymus fortunei, Amygdalus communis and Garcinia xanthochymus were found possessing high inhibitory activities (inhibition rate >90%). From G. xanthochymus, a new inhibitor of GSK-3β, fukugetin, was discovered with an IC50 value of 3.18±0.07μM. Enzyme kinetics and molecular docking experiments further revealed the inhibitory mechanism, indicating fukugetin was a non-ATP competitive inhibitor interacting with the phosphate recognizing substrate binding site of GSK-3β.


Inhibition of the adenosinergic pathway: the indispensable part of oncological therapy in the future.
In recent years, immunotherapy has produced many unexpected breakthroughs in oncological therapy; however, it still has many deficiencies. For example, the number of patients who are unresponsive to anti-programmed death-ligand 1 (PD-L1), anti-cytotoxic T-like antigen-4 (CTLA4), and anti-programmed death-1 (PD1) therapies cannot be ignored, and the search for an undiscovered immunosuppressive pathway is imminent. Five decades ago, researchers found that activation of the adenosinergic pathway was negatively correlated with prognosis in many cancers. This review describes the entire process of the adenosinergic pathway in the tumor microenvironment and the mechanism of immunosuppression, which promotes tumor metastasis and drug resistance. Additionally, the review explores factors that regulate this pathway, including signaling factors secreted by the tumor microenvironment and certain anti-tumor drugs. Additionally, the combination of adenosinergic pathway inhibitors with chemotherapy, checkpoint blockade therapy, and immune cell-based therapy is summarized. Finally, certain issues regarding treatment via inhibition of this pathway and the use of targeted nanoparticles to reduce adverse reactions in patients are put forward in this review. Graphical Abstract The inhibitors of adenosinergic pathway loaded nanoparticles enter tumor tissue through EPR effect, and inhibit adenosinergic pathway to enhance or restore the effect of immune checkpoint blockade therapy, chemotherapies and immune cell-based therapy. Note: EPR means enhanced penetration and retention, × means blockade.


Reactive blue 2, an antagonist of rat P2Y4, increases K+ secretion in rat cochlea strial marginal cells.
Extracellular ATP decreases K+ secretion in strial marginal cells via apical P2Y4 receptors. We investigated the effect of reactive blue 2 (RB-2), an antagonist of rat P2Y4, on rat strial marginal cells using a voltage-sensitive vibrating probe. The application of RB-2 increased K+ secretion in a dose-dependent manner, and this increase was characterized as a peak followed by a partial relaxation to a steady-state. Moreover, this response was similar to that caused by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Suramin had no similar effect, except at high concentration. Thus, we tested the effects of these chemicals on P2Y4 receptors in strial marginal cells. Both RB-2 and DIDS had antagonistic activities at P2Y4, and the antagonist potency at P2Y4 paralleled the potency of K+ secretion. Interestingly, 2'- and 3'-O-(4-benzoyl-benzoyl)adenosine 5'-triphosphate (BzATP) exhibited an agonistic effect at P2Y4 receptor, which was blocked by RB-2, but not by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Based on these results, we speculate that direct and/or indirect inhibitory mechanisms between P2Y4 and KENQ1/KCNE1 K+ channels exist in strial marginal cell.


Active leukocyte detachment and apoptosis/necrosis on PEG hydrogels and the implication in the host inflammatory response.
Monocytes/Macrophages have long been recognized as key players in inflammation and wound healing and are often employed in vitro to gain an understanding of the inflammatory response to biomaterials. Previous work has demonstrated a drastic decrease in primary monocyte adherent density on biomaterial surfaces coupled with a change in monocyte behavior over time. However, the mechanism responsible for this decrease remains unclear. In this study, we explored active detachment and cellular death as possible regulating factors. Specifically, extracellular TNF-α and ROS production were analyzed as potential endogenous stimulators of cell death. MMPs, but not calpains, were found to play a key role in active monocyte detachment. Monocyte death was found to peak at 24 h and occur by both apoptosis and necrosis as opposed to polymorphonuclear leukocyte death which mainly occurred through apoptosis. Finally, TNF-α and ROS production were not found to have a causal relationship with monocyte death on TCPS or PEG surfaces. The occurrence of primary monocyte apoptosis/necrosis as well as active detachment from a material surface has implications not only in in vitro study, but also in the translation of the in vitro inflammatory response of these cells to in vivo applications.


Detection of human papillomavirus DNA on the external genitalia of healthy men and male patients with urethritis.
Only a few studies have been done involving detection of human papillomavirus (HPV) DNA on the external genitalia of men without genital warts, although many have been done for women. We conducted HPV DNA detection among healthy male volunteers and men with urethritis, both having no visible lesions on their external genitalia. The goal of the study was to determine the detection rate of HPV DNA in volunteers and patients with urethritis and to determine risk factor(s) for positive DNA. This was a prospective clinical study. HPV DNA was found in 1.3% of 75 volunteers and in 18.5% of 130 patients with urethritis. DNA of a high-intermediate oncogenic risk was more predominant than the low-risk type. Among various risk factors, only a history of STD was a significant factor for the positive detection of HPV DNA in multiple regression analysis. HPV DNA was found in patients with urethritis more frequently than in volunteers, probably because the former had higher sexual activity.


A comparative study of Western, high-carbohydrate, and standard lab diet consumption throughout adolescence on metabolic and anxiety-related outcomes in young adult male and female Long-Evans rats.
Anxiety and obesity are prevalent health concerns that are affected by diet in rodents and humans. How diet influences the development and maintenance of anxiety and obesity has been challenging to characterize, in part, due to methodological differences in chosen experimental and control diets. Within the same experiment, anxiety- and obesity-related effects were characterized in rats fed a Western diet (WD) relative to two control diets. Sixty Long-Evans rats split equally by sex were given standard diet (SD), control (i.e., high-carbohydrate) diet (HCD), or WD from weaning until sacrifice in early adulthood. Anxiety-related behavior was characterized in a modified open field test (mOFT) that allowed for the measurement of defensive behaviors (e.g., hiding within a refuge area), in addition to traditional OF measures (e.g., time in center). Both anxiety-related behaviors and hippocampal CA3 BDNF revealed specific sex differences. Neither adolescent weight gain of male and female rats, nor total body weight in early adulthood, were dependent on administration of HCD or WD, although the WD group consumed the most calories. In males only, administration of either WD or HCD resulted in elevated leptin levels relative to administration of the SD. Results indicate that SDs and HCDs are two distinct types of control diets that can affect comparability of studies and that using an SD might reveal more subtle metabolic changes. Control diet choice should be strongly considered during study design and interpretation, depending on specific research goals. Such studies should include both males and females as these effects are sex-specific.


Lipid peroxidation and covalent binding in the early functional impairment of liver Golgi apparatus by carbon tetrachloride.
The onset of the lipoprotein secretory block provoked by CCl4 in the whole animal was monitored after purification of liver Golgi membranes. Both lipid transit through the apparatus and hexosylation of the lipoprotein are markedly inhibited 5-15 min after poisoning. Pre-treating the animal with alpha-tocopherol, shown to prevent lipid peroxidation without modifying the covalent binding due to CCl4 metabolites, affords little protection against lipid accumulation in the Golgi, but total preservation of galactosyl transferase activity. While haloalkylation therefore appears to be the major mechanism of damage in the early phases of CCl4-induced derangement of lipid secretion, lipid peroxidation is probably more involved later; this is indicated by the marked, though never complete, protection against fatty liver afforded at 24 h after CCl4 poisoning by supplementation of the membrane with alpha-tocopherol.


Verification of combustion rate of recovery and counting efficiency in the analysis of organically bound tritium in biota samples.
The analysis procedure of five biota samples's organically bound tritium (OBT) based on oxidation combustion and liquid scintillation counter (LSC) measurement was established. The combustion experiment under one atmospheric pressure in the presence of Pt-Al2O3 catalyst were carried out. The experiment results shown that the combustion recovery of five samples ranged from 86.4 % to 91.1 %, the combustion recovery of glucose monohydrate is about 93.7 %, which indicate that combustion recovery of biota samples differed from one species to another. Meanwhile, The counting efficiency of quenching agents CH3NO2 and CCl4 decreases from 20.3 % to 0 and from 19.3 % to 0 respectively as the quench agent mass increases from 10 μL to 500 μL. The counting efficiency of quenching agent HNO3 decreases from 22.4 % to 14.6 % as the quench agent mass increases from 10 μL to 500 μL. The SQP (E) value of CH3NO2 and CCl4 decreases as the mass of quenching agents increases, while the SQP (E) value of HNO3 increases as the quench agent mass increases. The SQP(E) of three tested quench agents ranges from 401.8 to 738.4, which covers the SQP(E) range of all the monitored biota samples in recent years. Therefore, the mapped curves and fixed equations are applicable. In addition, comparison experiment of four biota samples between two laboratories shown a relative deviation from 1.2 % to 12.8 %.


Atomic-level investigation on significance of photoreduced Pt nanoparticles over g-C3 N4 /bimetallic oxide composites.
Designing an effective photocatalyst for solar-to-chemical fuel conversion presents significant challenges. Herein, g-C3 N4 nanotubes/CuCo2 O4 (CN-NT-CCO) composites decorated with platinum nanoparticles (Pt NPs) were successfully synthesized by chemical and photochemical reductions. The size distribution and location of Pt NPs on the surface of CN-NT-CCO composites were directly observed by TEM. Extended X-ray absorption fine structure (EXAFS) spectra of Pt L3-edge for the above composite confirmed establishment of Pt-N bonds at an atomic distance of 2.09 Å in the photoreduced Pt-bearing composite, which was shorter than in chemically reduced Pt-bearing composites. This proved the stronger interaction of photoreduced Pt NPs with the CN-NT-CCO composite than chemical reduced one. The H2 evolution performance of the photoreduced (PR) Pt@CN-NT-CCO (2079 μmol h-1 g-1 ) was greater than that of the chemically reduced (CR) Pt@CN-NT-CCO composite (1481 μmol h-1 g-1 ). The abundance of catalytically active sites and transfer of electrons from CN-NT to the Pt NPs to participate in the hydrogen evolution are the primary reasons for the improved performance. Furthermore, electrochemical investigations and band edge locations validated the presence of a Z-scheme heterojunction at the Pt@CN-NT-CCO interface. This work offers unique perspectives on the structure and interface design at the atomic level to fabricate high-performance heterojunction photocatalysts.


Relationship between cognition and age at onset of first-episode psychosis: comparative study between adolescents, young adults, and adults.
Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of ≤ 18 years (N = 61), 19-24 years (N = 121), and ≥ 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings.


Linear atrophoderma of Moulin: a disease related to immunity or a kind of connective tissue disease?
We describe a 28-year-old man with linear atrophoderma of Moulin (LAM), whose serum immunological markers were abnormal (including antinuclear antibody, ribonucleoprotein, immunoglobulin M and anti-SM antibody). In addition, however, a histological analysis identified unexpected connective tissue disease changes in this patient. We speculate that the pathogenesis of LAM is associated with immunity or that LAM itself is a kind of connective tissue disease.


External cephalic version for a malpresenting first twin before labor: a prospective case series.
In twin pregnancies where the presenting twin is not cephalic, cesarean delivery is the standard of care. External cephalic version (ECV) has been used for malpresenting singleton pregnancies with low risk of complications. ECV in twin pregnancies is poorly studied. To assess feasibility and report any complications of ECV of a malpresenting twin before labor. This is a prospective cohort of twin pregnancies with malpresenting first twin. Inclusion criteria included English or Spanish speaking women. Exclusions included cases where there was a contraindication to vaginal delivery. ECV was performed according to the institutional singleton protocol. Fetal testing of both twins was performed before and after procedure. A vaginal hand was used during ECV as needed. The primary outcome was success of the procedure. Secondary outcomes included delivery characteristics and neonatal outcomes. Five patients were enrolled in this study. Four patients underwent successful ECV and vaginal delivery occurred in 2 of the 4 patients. ECV procedure was performed at a mean gestational age of 36+0 weeks in the successful ECV group and 36+6/7 weeks for the unsuccessful group. Latency to delivery was 4.5 days in the successful ECV group and 1 day in the unsuccessful ECV group. No maternal or neonatal complications occurred in any participating women. ECV in twin pregnancies where the first twin is malpresenting was feasible in our cohort. More research is needed to better characterizer the safety and efficacy of this procedure in this patient population.


Assessment of frequency, transmission, and genitourinary complications of enterobiasis (pinworms).
Pinworms are the most common helminth infection in the USA and Western Europe, with prevalence rates in some communities of as high as 30-50%. Pinworms generally live in the gastrointestinal tract, and helminth infestations have been noted in over one-quarter of acute appendectomies on histologic examination. Although transmission is often attributed to the ingestion of infective eggs by nail biting and inadequate hand washing, inhalation and ingestion of airborne eggs also occur. The female Enterobius vermicularis migrates nightly to the perianal area to deposit her eggs, but some worms find their way into adjacent orifices, most commonly the female genitourinary tract, producing an array of symptoms. More consideration of this entity is justified in patients presenting with genitourinary complaints not responding to normal therapies. In the treatment of pinworms affecting genitourinary organs, treatment with possibly two oral agents, namely mebendazole and ivermectin, and a topical therapy for the eggs may be warranted.


A fluorescent probe based on tetrahydro[5]helicene derivative with large Stokes shift for rapid and highly selective recognition of hydrogen sulfide.
In this work, we have designed and synthesized a dinitrobenzene-sulfonate tetrahydro[5]helicene (H-DNP) as an effective fluorescent probe for detection of hydrogen sulfide (H2S). Upon the addition of H2S, a significant fluorescence enhancement (75-fold) at 495 nm can be observed with a distinct color change from colorless to yellow. Additionally, H-DNP shows low background spectroscopic signal, large Stokes Shift up to ~140 nm, good sensitivity, rapid response time less than 2 min, low detection limit (48 nM) and high selectivity toward common bio-thiols (Cysteine, Homocysteine and Glutathione). Compared with the previous dinitrophenoxy tetrahydro[5]helicene, this probe has shorter response time and lower detection limit. Most importantly, this probe H-DNP has low toxicity to cells and excellent cell permeability, which can be applied to visualize H2S in living cells.


Microvasculature of crotaline snake pit organs: possible function as a heat exchange mechanism.
The infrared sensory membranes of the pit organs of pit vipers have an extremely rich capillary vasculature, which has been noted passim in the literature, but never illustrated or studied in detail. We rendered the pit vasculature visible in various ways, namely, by microinjection of India ink, by a combination of ink and succinate dehydrogenase staining, and by making resin casts for scanning electron microscope study. We also used transmission electron microscopy for identifying the types (arterioles, venules, capillaries) of blood vessels. Then we compared the pit vasculature with that of the retina and the dermis. Good visualization of the vasculature was obtained with both ink and resin injection. Arterioles, venules, and capillaries could be distinguished with all methods used. The monolayer vasculature was denser in the pit membrane than in the retina or skin. Each loop of the network enclosed a small number of infrared receptors so that all receptors were in contact with a capillary on at least one side. The forward-looking areas of the pit had a denser network than side-looking areas. Since infrared rays cause nerve impulses by raising the temperature of individual receptors, the capillary network functions not only as a supplier of energy but also as a cooling mechanism to reduce afterimages. Thus the denser network in the forward-looking areas causes these areas to be more sensitive and have better image resolution than the rest of the membrane.


Mammographic localization and biopsy: the experience of a gynecologic oncology group.
From 1976 through 1986, two hundred eighty or 9% of all breast biopsies performed by a private gynecologic oncology group were for mammographically suspicious but occult breast lesions. Sixteen percent were found to be malignant. There has been improvement in mammographic techniques, and localization procedures have evolved to the current use of hooked-wire needles, which allow for the excision of smaller amounts of tissue and use of outpatient surgery facilities. Recently, the cancers encountered have been more often carcinoma in situ rather than invasive lesions. With the current increase in mammographic screening, there needs to be a continuing evolution in diagnostic modalities.


Puerarin prevents cadmium-induced mitochondrial fission in AML-12 cells via Sirt1-dependent pathway.
Recent investigations have revealed that puerarin (PU) alleviates cadmium (Cd)-caused hepatic damage via inhibiting oxidative stress. Mitochondria are dynamic organelles and play a critical part in regulating the occurrence of oxidative stress, but the role of mitochondria in the protection of PU against hepatocellular damage caused by Cd exposure remains unknown. Thus, this study was aimed to clarify this issue using mouse hepatocyte AML-12 cell line. Transmission electron microscopy analysis firstly showed that PU prevents Cd-induced mitochondrial ultrastructure damage. Mitochondrial network image analysis by confocal microscopy revealed that PU exerts the protection against Cd-induced cytotoxicity via restoring mitochondrial network fragmentation. Also, mitochondrial dynamic protein expression profiles showed that enhanced fission protein levels and inhibited fusion protein levels in Cd-treated cells were significantly reversed by PU, suggesting the protective effect of PU against Cd-induced mitochondrial fission. Moreover, changes of intracellular ATP level and protein levels of key regulators involving in mitochondrial biogenesis indicated that Sirtuin-1(Sirt1) pathway may be involved in the protection of Cd-impaired mitochondrial function by PU. Next, Sirt1 protein levels in treated cells were effectively regulated by genetic knockdown or chemical agonist SRT1720. Accordingly, alleviation of Cd-induced mitochondrial fission assays and cell viability by PU was markedly regulated by SRT1720 or Sirt1 knockdown, suggesting the indispensable role of Sirt1 in this process. Collectively, these findings highlight that PU prevents Cd-induced mitochondrial fission to alleviate cytotoxicity via Sirt1-dependent pathway, which provide novel evidences to fully understand the hepatoprotective action of PU against heavy metal toxicity.


Vascular segmentation of head phase-contrast magnetic resonance angiograms using grayscale and shape features.
In neurosurgery planning, vascular structures must be predetermined, which can guarantee the security of the operation carried out in the case of avoiding blood vessels. In this paper, an automatic algorithm of vascular segmentation, which combined the grayscale and shape features of the blood vessels, is proposed to extract 3D vascular structures from head phase-contrast magnetic resonance angiography dataset. First, a cost function of mis-segmentation is introduced on the basis of traditional Bayesian statistical classification, and the blood vessel of weak grayscale that tended to be misclassified into background will be preserved. Second, enhanced vesselness image is obtained according to the shape-based multiscale vascular enhancement filter. Third, a new reconstructed vascular image is established according to the fusion of vascular grayscale and shape features using Dempster-Shafer evidence theory; subsequently, the corresponding segmentation structures are obtained. Finally, according to the noise distribution characteristic of the data, segmentation ratio coefficient, which increased linearly from top to bottom, is proposed to control the segmentation result, thereby preventing over-segmentation. Experiment results show that, through the proposed method, vascular structures can be detected not only when both grayscale and shape features are strong, but also when either of them is strong. Compared with traditional grayscale feature- and shape feature-based methods, it is better in the evaluation of testing in segmentation accuracy, and over-segmentation and under-segmentation ratios. The proposed grayscale and shape features combined vascular segmentation is not only effective but also accurate. It may be used for diagnosis of vascular diseases and planning of neurosurgery.


Synthesis of a nitrogen analogue of sphingomyelin as a sphingomyelinase inhibitor.
[structure: see text] Sphingomyelin nitrogen analogue 1 was designed and synthesized as a sphingomyelinase inhibitor. The synthesis was established by continuous Hofmann rearrangement and Crutius rearrangement as key steps in constructing the 3-hydroxy-1,2-diamine structure in the backbone of 1. This analogue showed moderate inhibitory activity toward SMase isolated from B. cereus.


[Pharmacokinetic Study on Brucine in Different Administration Methods of Liposome in Rats].
To compare the pharmacokinetic differences of brucine in rats after different administration methods of brucine liposome. To determine brucine in rat plasma at different points in time by HPLC after oral administration, intramuscular injection, subcutaneous injection and intravenous injection of brucine liposome, respectively. The pharmacokinetic parameters were calculated and analyzed by DAS 3.0. Compared with other groups, AUC(0 --> t) of subcutaneous injection were higher, C(max) were lower and MRT(0 --> 1), were significantly improved. The pharmacokinetics parameters and absolute bioavailability of brucine show that bioavailability in rats after different administration methods of brucine liposome is subcutaneous injection > intramuscular injection > oral administration.


Transcriptome analysis of the early stage ifnlr1-mutant zebrafish indicates the immune response to auditory dysfunction.
IFNLR1 has been recently identified to be related to autosomal dominant nonsyndromic sensorineural hearing loss (ADNSHL). It is reported to be expressed in the inner ear of mice and the lateral line of zebrafish. However, it remains unclear how defects in this gene lead to hearing loss. To elucidate the global gene expression changes in zebrafish when the expression of ifnlr1 is downregulated. Transcriptome analysis was performed on ifnlr1 morpholino knockdown zebrafish and the control zebrafish using RNA-seq technology. The results show that 262 differentially expressed genes (DEGs) were up-regulated while 146 DEGs were down-regulated in the E4I4-Mo zebrafish larvae compared to the control-Mo. Six pathways were significantly enriched, including steroid biosynthesis pathway, adipocytokine signaling pathway, cytokine-cytokine receptor interaction pathway, p53 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and terpenoid backbone biosynthesis pathway. Among them, three pathways (steroid biosynthesis pathway, cytokine-cytokine receptor interaction pathway and p53 signaling pathway) are immune-associated. The transcriptome analysis results contribute to the groundwork for future research on the pathogenesis of IFNLR1-associated hearing loss.


Insight of low-abundance proteins in rice leaves under Cd stress using combinatorial peptide ligand library technology.
Low-abundance proteins (LAPs) play a very important role in interaction, regulation, and metabolism of plant biological processes. A combinatorial peptide ligand library (CPLL) can solve the problem of high-abundance proteins (HAPs) masking LAPs and enlarging the dynamic range of protein concentrations perfectly and be considered as one of the most advanced approaches for plant proteomics research. In this paper, a proper CPLL method to rice leaf proteins was established for the first time and 1056 proteins were identified in rice leaf extracts, and 624 (59.1%) LAPs were newly detected after CPLL. Based on this technology, we detected the response of rice to Cd stress and analyzed the differential LAPs and the biological significance of misexpressed proteins before and after Cd stress by bioinformatics analysis. An important contribution has also been made to a better understanding of the complex mechanisms by which rice adapts to Cd stress. Graphical abstract.


Primary pulmonary lymphoma in a patient with the acquired immune deficiency syndrome.
A case of primary pulmonary lymphoma presenting as a nodular lesion on the chest radiograph in a patient with the acquired immune deficiency syndrome is described.


Isoniazid could be used for antibiotic-loaded bone cement for musculoskeletal tuberculosis: an in vitro study.
Antibiotic-loaded bone cement (ALBC) has been used in serious cases of musculoskeletal tuberculosis, but the type and amount of antibiotic that should be used in ALBC have not been determined. We therefore determined the (1) elution characteristics and (2) antimycobacterial activity of isoniazid- and rifampicin-loaded bone cement. A total of 240 elution samples of each of three discs from 40 g bone cement mixed with one of eight dosages: 1 g, 2 g, and 4 g isoniazid, 1 g, 2 g, and 4 g rifampicin, and a combination of 1 + 1 g or 2 + 2 g of isoniazid and rifampicin. The polymerization of rifampicin-loaded bone cement was delayed to mean 122.5 ± 31.1 minutes. We measured the quantity of isoniazid and rifampicin and the antimycobacterial activity on Days 1, 3, 7, 14, and 30. Isoniazid eluted in almost all the samples while rifampicin was detected only on Day 1 with 2 g (0.7 ± 0.4 ug/mL/day), and until Day 14 with 4 g (0.1 ± 0.0 ug/mL/day). Most of the samples containing isoniazid showed antimycobacterial activity while the samples containing rifampicin showed antimycobacterial activity only on Day 1 with 1 g (0.52 ± 0.18 ug/mL), until Day 14 with 2 g (0.03 ± 0.00 ug/mL), and until Day 30 with 4 g (1.84 ± 1.90 ug/mL). Rifampicin was unsuitable for ALBC because of its delayed polymerization. Isoniazid eluted and showed antimycobacterial activity for 30 days. The data suggest isoniazid could be considered for use in ALBC for musculoskeletal tuberculosis if used with systemic treatment. For preventing resistance and systemic toxicity, a combination with a second-line drug and an in vivo study would be needed.


Otomastoid cholesteatoma in children: histopathological findings.
Clinical experience has shown that the otomastoid cholesteatoma is more aggressive and has a less favourable prognosis in the child than in the adult. In an attempt to verify whether, in children, the clinical behaviour of the cholesteatoma depends on the histomorphological characteristics of the perimatrix, we carried out a study of samples taken from 30 subjects under 16 years of age and from 30 adults (control group) during surgery for otomastoid cholesteatoma. The study took into account the number of plasmacytes, lymphocytes, macrophages, granulocytes and giant cells per high potency field (X 630). The results showed that in young subjects the perimatrix of the cholesteatoma is richer in mononuclear inflammatory elements with evidence of enzyme-collagenase activity. On the basis of this behaviour the authors conclude that the histomorphological characteristics of the surrounding matrix can play an important role in the pathogenesis of cholesteatoma and may explain the clinical differences that can be seen between cholesteatoma in children and in adults.


Major ion chemistry and weathering processes in the Midyan Basin, northwestern Saudi Arabia.
Chemical characteristics of 72 groundwater samples collected from Midyan Basin have been studied to evaluate major ion chemistry together with the geochemical and weathering processes controlling the water composition. Water chemistry of the study area is mainly dominated by Na, Ca, SO4, and Cl. The molar ratios of (Ca + Mg)/total cations, (Na + K)/total cations, (Ca + Mg)/(Na + K), (Ca + Mg)/(HCO3 + SO4), (Ca + Mg)/HCO3, and Na/Cl reveal that water chemistry of the Midyan Basin is controlled by evaporite dissolution (gypsum and/or anhydrite, and halite), silicate weathering, and minor contribution of carbonate weathering. The studied groundwater samples are largely undersaturated with respect to dolomite, gypsum, and anhydrite. These waters are capable of dissolving more of these minerals under suitable physicochemical conditions.


Rational design of high-yield and superior-quality rice.
Rice (Oryza sativa L.) is a staple food for more than half of the world's population. To meet the ever-increasing demand for food, because of population growth and improved living standards, world rice production needs to double by 20301. The development of new elite rice varieties with high yield and superior quality is challenging for traditional breeding approaches, and new strategies need to be developed. Here, we report the successful development of new elite varieties by pyramiding major genes that significantly contribute to grain quality and yield from three parents over five years. The new varieties exhibit higher yield potential and better grain quality than their parental varieties and the China's leading super-hybrid rice, Liang-you-pai-jiu (LYP9 or Pei-ai 64S/93-11). Our results demonstrate that rational design is a powerful strategy for meeting the challenges of future crop breeding, particularly in pyramiding multiple complex traits.