Additional seizure reduction by replacement with Vagus Nerve Stimulation Model 106 (AspireSR).
AspireSR is a novel vagus nerve stimulation (VNS) device which detects ictal heart rate changes and automatically apply additional stimulus. We investigated the difference of the efficacy between AspireSR and preceding VNS models in patients with device replacement. We retrospectively reviewed the clinical data of 17 patients whose VNS devices were changed because of battery discharge. The rates of seizure reduction, the number of antiepileptic drugs (AEDs) used and device parameters between the two devices were evaluated. AspireSR improved significantly the rates of seizure reduction of the patients. Four patients out of 11 patients with low response to the preceding VNS models (no change or <50 % reduction) achieved>50 % seizure reduction. The AEDs used were not different in the observed periods. The device parameters were low setting in AspireSR compared to preceding VNS models. AspireSR decrease significantly seizure frequencies compared to the preceding VNS models. Change of the devices to AspireSR at the time of battery empty could be recommendable.


Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model.
This study investigates whether (99m)Tc pyrophosphate (PYP) imaging provides a quantitative non-invasive assessment of the extent of electroporation injury, and of the effect of poloxamer in vivo on electroporated skeletal muscle. High-voltage electrical shock was used to produce electroporation injury in an anesthetized rat's hind limb. In each experiment, the injured limb was treated intravenously by either poloxamer-188, dextran, or saline, and subsequently imaged with (99m)Tc PYP. The radiotracer's temporal behavior among the experimental groups was compared using curve fitting of time-activity curves from the dynamic image data. The washout kinetics of (99m)Tc PYP changed in proportion to the electric current magnitude that produced electroporation. Also, (99m)Tc PYP washout from electroporated muscle differed between poloxamer-188 treatment and saline treatment. Finally, 10-kDa dextran treatment of electroporated muscle altered (99m)Tc PYP washout less than poloxamer-188 treatment. Behavior of (99m)Tc PYP in electroporated muscle appears to be an indicator of the amount of electroporation injury. Compared to saline, intravenous polaxamer-188 treatment reduced the amount of (99m)Tc PYP uptake. Coupled to results showing poloxamer-188 seals ruptured cellular membranes, lessens the extent of electroporation injury and improves cell viability, (99m)Tc PYP imaging appears to be a useful in vivo monitoring tool for the extent of electroporation injury.


[Did Georges Bizet die of a acute articular rheumatism?].
As perhaps in the case of Mozart (1) or Malher (2), Georges Bizet may have died of an acute articular rheumatism or of its consequences.


Management of sarcomatoid salivary duct carcinoma of the submandibular gland duct with coexisting seropositive human immunodeficiency virus.
Sarcomatoid salivary duct carcinoma of the submandibular gland is extremely rare. This paper highlights the impact of surgery and adjuvant radiation therapy on the outcome of this disease. A 59-year-old man with human immunodeficiency virus presented with a painless, rapidly growing left neck mass. Biopsy followed by surgical excision of the left submandibular gland revealed sarcomatoid salivary duct carcinoma of the submandibular gland duct with perineural invasion and close margins, for which he underwent adjuvant radiotherapy. Post-operative positron emission tomography and computed tomography revealed no residual or metastatic disease. Pathological analysis of tumour-node-metastasis staging revealed a T2 N0 M0 (stage II) tumour. The patient tolerated his treatment without serious acute or long-term side effects. There was no evidence of disease on comprehensive examination or on positron emission tomography or computed tomography scans at the 4.6-year follow up. Surgery followed by adjuvant radiotherapy provided practical locoregional control with acceptable toxicity. Further detailed case reports are warranted to optimise the management of this rare malignancy.


Monolithic cobalt-doped carbon aerogel for efficient catalytic activation of peroxymonosulfate in water.
As an emerging carbonaceous material, carbon aerogels (CAs) display a great potential in environmental cleanup. In this study, a macroscopic three-dimensional monolithic cobalt-doped carbon aerogel was developed by co-condensation of graphene oxide sheets and resorcinol-formaldehyde resin in the presence of cobalt ions, followed by lyophilization, carbonization and thermal treatment in air. Cobalt ions were introduced as a polymerization catalyst to bridge the organogel framework, and finally cobalt species were retained as both metallic cobalt and Co3O4, wrapped by graphitized carbon layers. The material obtained after a thermal treatment in air (CoCA-A) possesses larger BET specific surface area and pore volume, better hydrophilicity and lower leaching of cobalt ions than that without the post-treatment (CoCA). Despite of a lower loading of cobalt content and a larger mass transfer resistance than traditional powder catalysts, CoCA-A can efficiently eliminate organic contaminants by activation of peroxymonosulfate with a low activation energy. CoCA-A can float beneath the surface of aqueous solution and can be taken out completely without any changes in morphology. The monolith is promising to be developed into an alternative water purification technology due to the easily separable feature.


Dynamic left ventricular outflow tract obstruction when the anterior leaflet is retained at prosthetic mitral valve replacement.
Dynamic left ventricular outflow tract obstruction developed in a patient in whom the anterior leaflet was retained at mitral valve replacement. It was caused by systolic anterior movement of the native anterior leaflet. Reduced outflow tract diameter, resulting from both posterior displacement of the septum and anterior displacement of the native anterior leaflet by porcine stents, was likely instrumental in promoting dynamic obstruction.


What kinds of injuries do OSHA inspections prevent?
OSHA's enforcement program is one of the major public efforts to protect American workers. We examine both the scope of injury prevention that inspections can contribute and the types of standards that contribute the most. We linked Pennsylvania Department of Labor and Industry files for lost-time injuries and employment to calculate injury rates for 1998-2005 for all single-establishment manufacturing firms. We linked these to OSHA inspection records. Inspections with penalties did affect injury types unrelated to standards as well as those related. We also found again that citations for violations of the standard requiring personal protective equipment had the largest impact on preventing injuries. Programs requiring protective equipment use deserve added attention from consultants and inspectors. In addition, some inspections spur managers to undertake safety measures that go beyond compliance with standards.


Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis.
Therapeutic angiogenesis is a novel strategy for the treatment of ischemic diseases that involves promotion of angiogenesis in ischemic tissues via the use of proangiogenic agents. However, effective proangiogenic drugs that activate the Ang2/Tie2 signaling pathway remain scarce. We aimed to investigate the proangiogenic activity of notoginsenoside R1 (NR1) isolated from total saponins of Panax notoginseng with regard to activation of the Ang2/Tie2 signaling pathway. We examined the proangiogenic effects of NR1 by assessing the effects of NR1 on the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs). The aortic ring assay and vascular endothelial growth factor receptor inhibitor (VRI)-induced vascular regression in the zebrafish model were used to confirm the proangiogenic effects of NR1 ex vivo and in vivo. Furthermore, the molecular mechanism was investigated by Western blot analysis. We found that NR1 promoted the proliferation, mobility and tube formation of HUVECs in vitro. NR1 also increased the number of sprouting vessels in rat aortic rings and rescued VRI-induced vascular regression in zebrafish. NR1-induced angiogenesis was dependent on Tie2 receptor activation mediated by increased autocrine Ang2 in HUVECs, and inhibition of the Ang2/Tie2 pathway abrogated the proangiogenic effects of NR1. Our results suggest that NR1 promotes angiogenesis by activating the Ang2/Tie2 signaling pathway. Thus, NR1-induced activation of the Ang2/Tie2 pathway is an effective proangiogenic approach. NR1 may be useful agent for the treatment of ischemic diseases.


Receiving Real-Time Clinical Feedback: A Workshop and OSTE Assessment for Medical Students.
Many programs designed to improve feedback to students focus on faculty's ability to provide a safe learning environment, and specific, actionable suggestions for improvement. Little attention has been paid to improving students' attitudes and skills in accepting and responding to feedback effectively. Effective "real-time" feedback in the clinical setting is dependent on both the skill of the teacher and the learner's ability to receive the feedback. Medical students entering their clinical clerkships are not formally trained in receiving feedback, despite the significant amount of feedback received during this time. We developed and implemented a one-hour workshop to teach medical students strategies for effectively receiving and responding to "real-time" (formative) feedback in the clinical environment. Subjective confidence and skill in receiving real-time feedback were assessed in pre- and post-workshop surveys. Objective performance of receiving feedback was evaluated before and after the workshop using a simulated feedback encounter designed to re-create common clinical and cognitive pitfalls for medical students, called an objective structured teaching exercise (OSTE). After a single workshop, students self-reported increased confidence (mean 6.0 to 7.4 out of 10, P<0.01) and skill (mean 6.0 to 7.0 out of 10, P=0.10). Compared to pre-workshop OSTE scores, post-workshop OSTE scores objectively measuring skill in receiving feedback were also significantly higher (mean 28.8 to 34.5 out of 40, P=0.0131). A one-hour workshop dedicated to strategies in receiving real-time feedback may improve effective feedback reception as well as self-perceived skill and confidence in receiving feedback. Providing strategies to trainees to improve their ability to effectively receive feedback may be a high-yield approach to both strengthen the power of feedback in the clinical environment and enrich the clinical experience of the medical student.


[Soft tissue management in knees with varus deformity. Computer-assisted sequential medial ligament release].
Knees with severe varus deformities and contractures of the medial and lateral collateral ligaments and the posterior capsule require special soft tissue management to gain a stable knee over the full range of movement. The introduction of navigation systems into knee surgery has now made precise measurement of the leg axis and gap size possible. Ten knee joints received a computer-assisted total knee replacement (Ci navigation system DePuy) I-Orthopaedics, Munich). The change of the leg axis and the size of the mediolateral gaps were measured and documented when performing a standardized medial ligament release sequence. We found a significant effect after each release step regarding the change of the leg axis as well as the gap width (p<0.001). The highest effect was seen for the 6-cm capsule release in extension and the release of the medial collateral ligament in 90 degrees flexion. Implementation of computer-assisted navigation facilitates visualization and quantification of the effect of the sequential medial soft tissue release in total knee arthroplasty.


New spectrophotometric and smartphone-based colorimetric methods for determination of atenolol in pharmaceutical formulations.
Novel spectrophotometric and smartphone-based colorimetric methods were developed and validated for the estimation of atenolol (ATE) in pharmaceutical formulations. The measurement procedure is based on the de-diazotization reaction, in which ATE is able to inhibit the diazotized sulfanilic acid from reacting with 8-hydroxy quinoline (8-HQ) in a basic medium. As a result, the formation of red-orange color azo-dye is hindered, and the color intensity is decreased proportionally to concentration of ATE. In spectrophotometric method the azo-dye color fate was monitored at 495 nm. While in smartphone-based colorimetric (SBC) method the captured image in the design processed by RGB App and transferred to the absorbance. The reactant concentrations were optimized using a central composite design (CCD) and response surface method. The methods exhibit good linearity in the 8.0 to 60.0 µg mL-1 range with no significant effect of interferences. The spectrophotometric method yields a linear equation with a slope of 0.0187 (R2 = 0.9993), a limit of detection (LOD) of 1.28 µg mL-1, and a limit of quantification (LOQ) of 4.28 µg mL-1. On the other hand, the smartphone-based colorimetric (SBC) method demonstrates a linear equation with a slope of 0.0127 (R2 = 0.9965), an LOD of 2.13 µg mL-1, and an LOQ of 7.09 µg mL-1. Analyzing ATE in pharmaceutical tablets was utilized to validate the applicability of the developed methods, and the results were statistically compared with those obtained by the HPLC method using the t-test and F-test.


The challenges of Covid-19 pandemic on improving plastic waste recycling rates.
The plastic system is burdened with many inefficiencies that have been exposed, and exacerbated, by the outbreak of the coronavirus (SARS-CoV2) pandemic in December 2019, widely known as COVID-19, and which threaten society's commitment to transition to a sustainable plastics economy. This perspective aims to depict the structural and systemic inefficiencies of the plastics system, and illuminate: (a) the vulnerability of the recycling sector to macroeconomic - particularly to oil price - shocks; (b) the economics of the recycling system; (c) the political dimensions of the plastics sector. It emphasises that is unwise to think about plastics recycling as an insular and linear problem, due to the complexity and interconnectedness of different parts of the plastic system that affect and are affected by the intertwined processes, stakeholders and values. That said, the transition to a sustainable plastics system requires an integrated, knowledge-based systems approach that interrogates the dynamics and causal-effect relationships of the interconnected challenges. This analytical scrutiny can indicate where interventions are needed in the plastics system towards creating transformational change.


[Study on genetic mutations of the vWF in type 2A von Willebrand disease].
To study the molecular pathological mechanism of the type 2A von Willebrand disease(vWD) and the relationship of the phenotypes with genotypes. A total of 126 patients with the hereditary hemorrhagic disease were examined using bleeding time, vWF:Ag, FVIII:CAg, ristocentin induced platelet agglutination assay(RIPA) and multimer analysis of plasma. The exon 28 of authenticity vWF gene was studied by PCR, denaturing gradient gel electrophoresis(DGGE) and sequencing in the type 2A vWD. Fourteen cases were diagnosed as type 2A vWD. Four cases of point mutations resulting in single animo acid substitutions, Arg611His, Ala737Glu, Arg834Trp, were identified in 3 families of type 2A vWD. Ala737Glu substitution in vWF is caused by a novel missense mutation. The molecular pathological mechanism of the type 2A vWD is very variant.


Coronary angiography of the ex-situ beating donor heart in a portable organ care system.
To determine safety and feasibility of ex-situ coronary angiography. To cater for the perpetually growing demand for heart donors, interest in donation following circulatory death (DCD) has been rekindled. Further pursuit of donor pool expansion has led to eligibility extension to "marginal" donors who are at higher risk of coronary artery disease (CAD). Excluding CAD in potentially eligible DCD donors, for whom ante-mortem angiography is commonly not permitted, is therefore challenging. Ex-situ coronary angiography serves as an ethical and feasible diagnostic tool to assess for preclusive CAD. We undertook a systematic review of the published literature and institutional retrospective review of case experience with ex-situ coronary angiography of donor hearts, supported by a portable organ care system. Combined literature and institutional case review yielded nine total cases of ex-situ coronary angiography of donor human hearts plus one experimental porcine model. Of the eight cases of ex-situ coronary angiography performed at our institute, all were conducted without complication or injury to the allograft. Two thirds of reported human cases have proceeded to successful transplantation. Diagnostic coronary angiography of the ex-situ beating donor heart is safe, feasible, and demonstrates novel clinical utility in mitigating subsequent transplantation of unsuitable allografts. In the setting of suspected coronary atherosclerosis of the donor heart, which may preclude favorable transplantation outcomes, ex-situ coronary angiography should be considered at eligible transplant centers.


Circulating IL-6 concentrations and abdominal adipocyte isoproterenol-stimulated lipolysis in women.
To examine the association of plasma interleukin-6 (IL-6) concentrations with adiposity and fat cell metabolism in women. Omental (OM) and subcutaneous (SC) adipose tissue samples were obtained from 48 healthy women (age: 47+/-5 years, BMI: 26.9+/-5.3 kg/m(2)) undergoing gynecological surgeries. Total and visceral adiposity were assessed by dual-energy X-ray absorptiometry and computed tomography, respectively. Measures of adipocyte lipolysis (basal, isoproterenol-, forskolin-, and cyclic dibutyryl-adenosine monophosphate (AMP)-stimulated) and adipose tissue lipoprotein lipase (LPL) activity were obtained. Plasma IL-6 was measured by radioimmunoassay. Plasma IL-6 was positively correlated with total body fat mass (r=0.32, P<0.05), SC adipose tissue area (r=0.35, P<0.05), SC adipocyte diameter (r=0.30, P<0.05), and a trend was observed with visceral adipose tissue area (r=0.20, P<0.07). Plasma IL-6 was positively correlated with glycerol released in response to isoproterenol (10(-5) to 10(-8) mol/l) by isolated SC (0.31 <or= r <or= 0.65, P<0.05) and OM (0.36 <or= r <or= 0.40, P<0.02) adipocytes, independent of menopausal status. No correlation was found with LPL activity. A subsample of women with high plasma IL-6 (n=10) was matched with women with low plasma IL-6 (n=10) for total body fat mass. OM adipocyte glycerol release in response to isoproterenol (10(-5) to 10(-8) mol/l) was higher in the subsample of women with elevated plasma IL-6 (P <or= 0.07). We observed that OM lipolysis was significantly higher in women with elevated plasma IL-6 for a similar body fat mass and menopausal status. These results suggest that higher circulating IL-6 concentrations are associated with increased isoproterenol-stimulated lipolysis especially in OM abdominal adipocytes in women.


Effects of Parathyroidectomy on Plasma iPTH and (1-84) PTH Levels in Patients with Stage 5 Chronic Kidney Disease.
Currently, the second-generation intact parathyroid hormone (iPTH) assay is commonly used for measuring PTH levels. The iPTH assay detects both full-length (1-84)PTH and (7-84)PTH fragments, which have antagonistic effects on (1-84)PTH in bones and kidneys. The third-generation PTH assay is specific for (1-84)PTH. This study examined the features of different PTH fragments in stage 5 chronic kidney disease (CKD) and the effects of parathyroidectomy (PTX) on the above markers in severe secondary hyperparathyroidism (SHPT) patients. The cross-sectional study included 262 stage 5 CKD patients and 90 controls. A prospective follow-up study was then conducted in 34 PTX patients. Second- and third-generation assays were used to measure plasma iPTH and (1-84)PTH levels, respectively. Circulating (7-84)PTH levels were calculated by subtracting the (1-84)PTH value from the iPTH value. Different plasma PTH fragments were higher, and (1-84)PTH/iPTH was lower in CKD patients than in controls. Plasma (1-84)PTH and (7-84)PTH concentrations increased as iPTH levels increased, and (7-84)PTH increased more evidently. Plasma iPTH, (1-84)PTH and (7-84)PTH levels were 1530.5 (885.0-2111.5) pg/ml, 683.1 (431.4-1018.0) pg/ml, and 739.3 (452.6-1261.0) pg/ml, respectively, in PTX patients. Plasma iPTH, (1-84)PTH and (7-84)PTH concentrations decreased considerably, and the (1-84)PTH/iPTH ratio increased after PTX (median follow-up interval: 10.9 months). Stage 5 CKD patients had higher plasma levels of different PTH fragments, and lower (1-84)PTH/iPTH ratio. PTX could significantly reverse these abnormalities in severe SHPT patients. The iPTH assay overestimated the function of the parathyroid glands; thus, the third-generation PTH assay is likely better for the management of CKD patients.


Crystallization of human leukocyte elastase with its inhibitor Pro44-eglin c.
Human leukocyte elastase has been crystallized in complex with recombinant Pro44-eglin c in the orthorhombic space group P2(1)2(1)2(1). The cell constants are a = 126.1 A, b = 127.8 A, c = 69.4 A, alpha = beta = gamma = 90 degrees. The crystals diffract to at least 2.5 A resolution and are suitable for crystallographic structure analysis.


Mitoxantrone, etoposide, cytarabine, and melphalan (NEAM) followed by autologous stem cell transplantation for patients with chemosensitive aggressive non-Hodgkin lymphoma.
Patients with chemosensitive aggressive non-Hodgkin lymphoma (NHL) could benefit from high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (auto-SCT). We report clinical outcomes of HDC using a novel regimen consisting of mitoxantrone, etoposide, cytarabine, and melphalan (NEAM) with auto-SCT. A total of 69 patients were consecutively enrolled. Median age was 42 years (range, 20-66 years). Median event-free survival (EFS) was 17.9 months. Median overall survival (OS) has not been reached yet and estimated 2-year OS was 64.2%. Among patients with measurable lesions, response rate was 79.5%. Median time to recovery of neutrophil (>500 mL) and platelet (gt;20,000 mL) was 12.5 and 13.5 days, respectively. Febrile neutropenia developed in 61 patients (88.4%). Grades 3 or 4 hepatic toxicity developed in 7 patients (10.1%), Grades 3 or 4 renal toxicity in 2 patients (2.9%), and Grade 3 or 4 cardiac toxicity in 2 patients (2.9%). Transplant-related mortality (TRM) developed in two patients (2.9%). Multiple prior treatments before transplantation, auxiliary bone marrow harvest for stem cell collection, and high serum lactate dehydrogenase level were related to unfavorable treatment outcomes. In conclusion, NEAM conditioning with auto-SCT demonstrated considerable efficacy with modest toxicity in patients with chemosensitive aggressive NHL.


Influence of the genetic polymorphism in the 5'-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers.
The functional significance of genetic polymorphisms on tobacco smoke-induced CYP1A2 activity was examined. The influence of three polymorphisms of the cytochrome P450 1A2 gene (CYP1A2) (-3860 G-->A (allele *1C), -2467 T-->delT (allele *1D), -163C-->A (allele *1F)), located in the 5'-noncoding promoter region of the gene, on CYP1A2 activity (measured as caffeine metabolic ratio, CMR), was studied in Caucasian current smokers (n=95). Tobacco smoke intake was calculated from the number of cigarettes/day. Also, studied was the influence of these CYP1A2 genotypes on smoking-associated urinary mutagenicity, detected in Salmonella typhimurium strain YG1024 with S9 mix, considering the urinary excretion of nicotine plus its metabolites as an internal indicator of tobacco smoke exposure. Smokers with at least one of the variant alleles CYP1A2 -3860A and -2467 delT showed a significantly increased CYP1A2 CMR (-3860 G/A versus G/G, p<0.05; -2467 delT/delT versus T/delT and T/T, p<0.01). Multiple regression analysis showed that the increase in CYP1A2 CMR (ln values) was again significantly related to the presence of CYP1A2 variants -2467delT and also to variant -163A (p<0.05), but moderately to -3860A (p=0.084). No influence of the number of cigarettes smoked per day by each subject was found. Heavy smokers (n=48, with urinary nicotine plus its metabolites>or=0.69 mg/mmol creatinine) with variant allele -2467delT or -163A had significantly increased urinary mutagenicity (p<0.01 and <0.05). CYP1A2 genetic polymorphisms are shown to influence the CYP1A2 phenotype in smokers, -2467 T-->delT having the main effect. This information is of interest for future studies assessing the possible role of tobacco smoke-inducible CYP1A2 genotypes as individual susceptibility factors in exposure to carcinogens.


Membrane fluidity and fatty acid comparisons in psychrotrophic and mesophilic strains of Acidithiobacillus ferrooxidans under cold growth temperatures.
Psychrotrophic strains of Acidithiobacillus ferrooxidans have an important role in metal leaching and acid mine drainage (AMD) production in colder mining environments. We investigated cytoplasmic membrane fluidity and fatty acid alterations in response to low temperatures (5 and 15°C). Significant differences in membrane fluidity, measured by polarization (P) of 1,6-diphenyl-1,3,5-hexatriene (DPH), were found where the psychrotrophic strains had a significantly more rigid membrane (P range = 0.41-0.45) and lower transition temperature midpoints (T (m) = 2.0°C) and broader transition range than the mesophilic strains (P range = 0.38-0.39; T (m) = 2.0-18°C) at cold temperatures. Membrane remodeling was evident in all strains with a common trend of increased unsaturated fatty acid component in response to lower growth temperatures. In psychrotrophic strains, decreases in 12:0 fatty acids distinguished the 5°C fatty acid profiles from those of the mesophilic strains that showed decreases in 16:0, 17:0, and cyclo-19:0 fatty acids. These changes were also correlated with the observed changes in membrane fluidity (R (2) = 63-97%). Psychrotrophic strains employ distinctive modulation of cytoplasmic membrane fluidity with uncommon membrane phase changes as part of their adaptation to the extreme AMD environment in colder climates.


Mites and birds: diversity, parasitism and coevolution.
Ectoparasites play important roles in the lives of birds. Among these parasites, mites offer unique potential because of their extraordinary ecological and evolutionary diversity. However, the basic biology of most mites is poorly understood, and misleading extrapolations are sometimes made from better studied systems involving lice and fleas. Most importantly, not all bird-associated mites are parasitic; indeed, recent research suggests that some might even be beneficial. Here, we summarize what is known about the diversity of bird-mite relationships, and highlight how mites provide an ideal tool for the study of host life histories, sexual selection, immunocompetence and cospeciation.


[Assessment of intensive therapy: 4-year experience using the Apache II severity score].
To determine the outcome of critically ill patients and to study the characteristics of the population admitted to the intensive care unit. Retrospective chart review. Intensive Care Unit in a civic hospital. The medical records of 1156 patients admitted to the intensive care unit over a period of 4 years were analysed according to the Apache II system on day one of admission. Demographic information, severity of illness, major interventions; mortality rate were examined. Of 1156 patients 888 (76.8%) survived and 268 (23.2%) died. The mean Apache II score was 17 (SD 6), 15 (SD6) and 22 (SD7) for survivors and non-survivors respectively, the mean risk of death was 29 (SD 14), 25 (SD14) for survivors and 43 (SD 21) for nonsurvivors. mortality in emergency surgical admission was 28.3%, in booked elective surgical admission 3.8% and 14.3% in unbooked admission after elective surgery, against a predicted mortality of 34%, 16% and 27% respectively. No significant variations of the number of admissions were observed for each month of the year, day of the week and daily duty. Mortality ratio (actual death/predicted death) was 0.79. Apache II score showed in this series a specificity of 95.72% and a sensitivity of 25.37%. These findings suggest that Apache II score is able to investigate critical ill patients, to stratify patients into disease groups and to quantify correctly the overall risk of death but cannot be used in decision making or to govern admissions in intensive care unit.


Is reduced ornithine-δ-aminotransferase activity the cause of vigabatrin-associated visual field defects?
A gabaergic antiepileptic drug, vigabatrin (VGB), is known to induce bilateral concentric visual field defects (VFD) in 30-40% of treated patients. Although the clinical and electrophysiological features of VFDs are well documented, the mechanism of retinal toxicity is still unclear. To determine if low basal ornithine-δ-aminotranspherase (OAT) activity is implicated in the etiology of VGB retinotoxicity, resulting in a phenotype of a mild form of gyrate atrophy. Assays of OAT activity in lymphocytes and GABA-transaminase activity in platelets were performed, and plasma levels of GABA, ornithine, lysine, glutamic acid and glutamine were measured, and visual fields were examined. A total of 47 subjects, aged 14-78 years, were examined. Twenty-one epileptic patients were off VGB more than 1 year; 11 patients with VGB-induced VFD and 10 with normal visual fields. Ten epileptic patients were on current VGB therapy more than 1 year; four patients with VGB-induced VFD and six with normal visual fields. The results were compared with those of 10 epilepsy patients taking tiagabine and six patients who suffered from gyrate atrophy (GA) or were obligate carriers of the disease. In patients who had stopped VGB and who had VFDs, OAT activity was significantly reduced as compared with those who had normal visual fields (77.4pmol P5C/min/mgPro vs. 181.9pmol P5C/min/mgPro, p=0.002). In patients with ongoing VGB therapy, no difference was found between the patients with and without VFDs (149.4pmol P5C/min/mgPro vs. 159.1pmol P5C/min/mgPro). : The results suggest that VGB retinotoxicity might be associated with elevated retinal ornithine mediated by low basal OAT activity.


Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine.
Summarized are psychonautic bioassays (human self-experiments) of pharmepéna--crystalline 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-Me-bufotenine), at times combined with crystalline beta-carbolines (harmaline or harmine). These substances were administered via intranasal, sublingual and oral routes, by way of pharmacological modeling of diverse South American shamanic inebriants (principally the snuffs epéna/nyakwana, prepared from barks of diverse species of Virola.) Intranasal, sublingual and oral psychoactivity of 5-MeO-DMT, and the 1967 Holmstedt-Lindgren hypothesis of the paricá-effect--intranasal potentiation of tryptamines by concomitant administration of monoamine-oxidase-inhibiting (MAOI) beta-carbolines from stems of Banisteriopsis caapi admixed with the snuffs--have been confirmed by some 17 psychonautic bioassays. Salient phytochemical and psychonautic literature is reviewed.


Factors Associated with Risk of Perinatal Depressive Symptoms Among Puerto Rican Women with Hyperglycemia.
Rates of perinatal depression and pregnancy hyperglycemia are higher in Hispanic women as compared to non-Hispanic white women. In turn, depressive symptoms may reduce a woman's ability to engage in lifestyle changes that could reduce their subsequent diabetes risk. We conducted a secondary analysis using data from Estudio Parto to evaluate sociodemographic, behavioral, psychosocial, and medical factors associated with perinatal depressive symptoms. Estudio Parto was a randomized controlled trial conducted in Western Massachusetts from 2013 to 17. Eligible participants had pregnancy hyperglycemia. The Edinburgh Postnatal Depression Scale (EPDS) was administered at 24-28 weeks gestation and at 6 weeks, 6 months, and 12 months postpartum. An EPDS cutpoint of 10 or greater defined the presence of depressive symptoms. In this sample of Puerto Rican women with pregnancy hyperglycemia, 32% and 27% showed prenatal and postpartum depressive symptoms, respectively. Among participants, 35.5% were diagnosed with GDM, 44.3% with isolated hyperglycemia, and 20.2% with impaired glucose tolerance. In multivariable models, being unmarried (OR 3.87; 95% CI 1.51-9.94), prenatal substance use (smoking or alcohol consumption; OR 2.96; 95% CI 1.41-6.18), and maternal age (1.11 for each year; 95% CI 1.04-1.18) were associated with higher odds of prenatal depressive symptoms. None of the risk factors were associated with subsequent postpartum depression in adjusted analyses. Identifying factors associated with prenatal and postpartum depression in Puerto Rican women with pregnancy hyperglycemia can inform targeted lifestyle interventions in this at-risk group, increase the likely adoption of healthy lifestyle behaviors, and thereby work to address health disparities. gov NCT01679210; date of registration 08/07/2012.


Organochlorine compounds in red deer (Cervus elaphus L.) and fallow deer (Dama dama L.) from inland and coastal Croatia.
Polychlorinated biphenyl (PCB) and organochlorine pesticide (OCP) levels in fat tissue of red and fallow deer (Cervus elaphus L. and Dama dama L.) from two inland and an Adriatic area were established. Of 17 analysed PCBs, PCB-28, PCB-138, PCB-153, PCB-180 and PCB-118 were found in all samples, whilst PCB-101 and PCB-170 were found in more than 50% of samples. They ranged between 0.03 and 5.98 ng g(-1) fat weight. Of seven analysed OCPs, HCB, γ-HCH and 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene (DDE) were found in all samples, whilst β-HCH was found in more than 50% of samples. They ranged between 0.17 and 22.14 ng g(-1) fat weight. The dominating compounds were DDE, PCB-138, PCB153, PCB-118 and PCB-180. According to the Duncan multistage test, the levels of PCB-138, PCB-153, PCB 170 and PCB-180 were significantly higher in perirenal fat samples of specimens taken from the Adriatic area. DDE was significantly higher in the inland deer samples. Some species differences were determined and were mostly related to higher PCB and β-HCH levels in fallow deer samples and higher DDE levels in red deer samples. No sex difference was established. As for age, significantly higher levels of PCB-118 and PCB-52 were found in fawns.


Accumulation of nuclear DNA damage or neuron loss: molecular basis for a new approach to understanding selective neuronal vulnerability in neurodegenerative diseases.
According to a long-standing hypothesis, aging is mainly caused by accumulation of nuclear (n) DNA damage in differentiated cells such as neurons due to insufficient nDNA repair during lifetime. In line with this hypothesis it was until recently widely accepted that neuron loss is a general consequence of normal aging, explaining some degree of decline in brain function during aging. However, with the advent of more accurate procedures for counting neurons, it is currently widely accepted that there is widespread preservation of neuron numbers in the aging brain, and the changes that do occur are relatively specific to certain brain regions and types of neurons. Whether accumulation of nDNA damage and decline in nDNA repair is a general phenomenon in the aging brain or also shows cell-type specificity is, however, not known. It has not been possible to address this issue with the biochemical and molecular-biological methods available to study nDNA damage and nDNA repair. Rather, it was the introduction of autoradiographic methods to study quantitatively the relative amounts of nDNA damage (measured as nDNA single-strand breaks) and nDNA repair (measured as unscheduled DNA synthesis) on tissue sections that made it possible to address this question in a cell-type-specific manner under physiological conditions. The results of these studies revealed a formerly unknown inverse relationship between age-related accumulation of nDNA damage and age-related impairment in nDNA repair on the one hand, and the age-related, selective, loss of neurons on the other hand. This inverse relation may not only reflect a fundamental process of aging in the central nervous system but also provide the molecular basis for a new approach to understand the selective neuronal vulnerability in neurodegenerative diseases, particularly Alzheimer's disease.


Psychoeducational group intervention for intellectually able adults with autism and their close relations (Prisma) - an open feasibility study.
Autism spectrum disorder (ASD) in adulthood is associated with severe impairments in functioning and poor health, while ASD is also affecting close relations. Accessible first-line interventions addressing the complex clinical needs and care coordination are lacking. This study investigated the feasibility and preliminary effects of a new psychoeducational intervention (Prisma) developed for intellectually able adults with ASD and their close relations in an outpatient setting. The manualized Prisma intervention consist of four weekly group sessions guided by trained group leaders and providing information about autism, support, and services. Feasibility was examined through treatment completion rate and group-level comparisons between intervention completers and non-completers (Student's t-test, Fisher's exact test, and Pearson's chi-squared test). Perceived treatment credibility was investigated by within-group comparisons of participant's self-ratings from pre-intervention to post-intervention, as well as by group leaders' ratings using an adjusted questionnaire. Treatment satisfaction was examined quantitatively regarding the session evaluations (Student's t-tests), as well as by a qualitative thematic analysis of participants' feedback. Preliminary efficacy was studied using paired t-tests (pre- and post-intervention). Completion rate was 77% (n = 71 of the 92 adults with ASD) and 73% (n = 69 of the 94 close relations), respectively. Participants considered Prisma to be an acceptable intervention indicated by increases in treatment credibility and expectations from pre- to post-intervention. The group leaders reported treatment credibility in the same range as the participants. Both autistic adults and their close relations reported good treatment satisfaction for each session, while the qualitative thematic analysis indicated that Prisma could be improved by enhancing active participation. This participant feedback will be used to further improve the intervention for an upcoming RCT. Preliminary analyses of effects showed promising results with an increase in knowledge of ASD and some indications for improvements in relationship quality, mental health, quality of life, acceptance of diagnosis and burden of care. Overall, results indicate that the Prisma is a feasible and acceptable first-line intervention in outpatient services. Randomized controlled trials are needed to further corroborate the evidence base of this novel intervention. Clinicaltrials.org NCT0446097, retrospectively registered July 8th 2020.


Molecular cloning of a tumor promoter-inducible mRNA found in JB6 mouse epidermal cells: induction is stable at high, but not at low, cell densities.
From the mouse JB6 epidermal cell line C122 we have isolated a cDNA clone representing a 1.6-kilobase mRNA, called 2ar, that exhibits a biphasic induction in response to 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The first phase of induction in subconfluent cells is transient, peaking at 6 h after the addition of TPA and returning to noninduced levels by 24 h. When the cells reach plateau density, in the continued presence of TPA, this mRNA is reinduced and remains so upon continued exposure to the tumor promoter. Serum and certain growth factors also induce 2ar mRNA in serum-deprived quiescent fibroblasts. In vitro nuclear "run-on" transcription experiments indicate that the induction of 2ar mRNA is controlled at the transcriptional level.


Predictors of pregnancy and discontinuation of infertility services among women who received medical help to become pregnant, National Survey of Family Growth, 2002.
To determine demographic characteristics associated with pregnancy and, separately, discontinuation of infertility services when unsuccessful at achieving pregnancy, among a national sample of women who received infertility services. Using a log-linear regression model, we examined associations with becoming pregnant among women who had received infertility services; and using a Cox proportional hazards model, we examined associations with earlier infertility service discontinuation. 2002 National Survey of Family Growth, Cycle 6. A total of 530 women aged 18-44 years in the 2002 National Survey of Family Growth who had received infertility services. None. Relative risks for predictors of pregnancy after receiving infertility services; median time to discontinuation of infertility services; hazard ratios for predictors of earlier discontinuation of services. Fifty-nine percent of respondents became pregnant while receiving infertility services, and 32% reported discontinuing infertility services before establishing a pregnancy. Women received infertility services for a median of 8 months; among those who discontinued services, more than half did so within 1 month. Among women who received infertility services, those who were white, nonsmokers, nulliparous, had insurance coverage, and received more than advice had a higher likelihood of pregnancy. Non-whites, parous women, and smokers discontinued infertility services earlier than others. Patients should be adequately counseled regarding modifiable behaviors and the range of services available before making decisions regarding their infertility.


[Pyriform sinus fistulae].
Pyriform sinus fistulae (PSF) are rare branchial pouch anomalies. In most previously described cases the anomaly is located on the left side. PSF should be suspected in cervical inflammatory processes (cervical abscesses and types of suppurative thyroiditis). We report two cases of acute thyroiditis and deep cervical abscesses secondary to PSF, which were diagnosed and treated in our hospital in the last 2 years. Both presented inflammatory cervical masses associated with painful swallowing, high fever and laboratory findings compatible with acute infection. In both cases the diagnosis of PSF was confirmed by barium esophagogram. Cervical ultrasonography and computed tomography were also performed. The treatment of choice consists of broad-spectrum antibiotic therapy during acute exacerbation and subsequent fistulectomy. Definitive surgical treatment prevents recurrences.


Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells.
The RAS-RAF-MEK-ERK and PI3K-AKT-mTOR signaling pathways are activated through multiple mechanisms and appear to play a major role in melanoma progression. Herein, we examined whether targeting the RAS-RAF-MEK-ERK pathway with the RAF inhibitor sorafenib and/or the PI3K-AKT-mTOR pathway with the mTOR inhibitor rapamycin has therapeutic effects against melanoma. A combination of sorafenib (4 microM) with rapamycin (10 nM) potentiated growth inhibition in all six metastatic melanoma cell lines tested. The absolute enhancement of growth inhibition rates ranged from 13.0-27.8% in different cell lines (P<0.05, combination treatment vs monotreatment). Similar results were obtained with combinations of the MEK inhibitors U0126 (30 microM) or PD98059 (50 microM) with rapamycin (10 nM). The combined treatment of melanoma cells with sorafenib and rapamycin led to an approximately twofold increase of cell death compared with sorafenib monotreatment (P<0.05) as assessed by propidium iodide staining and cell death detection ELISA. Moreover, sorafenib in combination with rapamycin completely suppressed invasive melanoma growth in organotypic culture mimicking the physiological context. These effects were associated with complete downregulation of the antiapoptotic proteins Bcl-2 and Mcl-1. Sorafenib combined with rapamycin appears to be a promising strategy for the effective treatment of melanoma and merits clinical investigation.


Accelerated acidification by inoculation with a microbial consortia in a complex open environment.
Bioaugmentation using microbial consortia is helpful in some anaerobic digestion (AD) systems, but accelerated acidification to produce methane has not been performed effectively with corn stalks and cow dung. In this study, the thermophilic microbial consortia MC1 was inoculated into a complex open environment (unsterilized and sterilized systems) to evaluate the feasibility of bioaugmentation to improve acidification efficiency. The results indicated that MC1 itself degraded lignocellulose efficiently, and accumulated more organic acids within 3days. Similar trends were also observed in the unsterilized system, where the hemicellulose degradation rate and organic acid concentrations increased significantly by two-fold and 20.1% (P<0.05), respectively, and clearly reduced the loss of product. Microbial composition did not change obviously after inoculating MC1, but the abundance of members of MC1, such as Bacillus and Clostridium, increased clearly on day 3. Finally, the acidogenic fluid improved methane yield significantly (P<0.05) via bioaugmentation.


Sleep in Normal Aging.
Sleep is a key determinant of healthy and cognitive aging. Sleep patterns change with aging, independent of other factors, and include advanced sleep timing, shortened nocturnal sleep duration, increased frequency of daytime naps, increased number of nocturnal awakenings and time spent awake during the night, and decreased slow-wave sleep. The sleep-related hormone secretion changes with aging. Most changes seem to occur between young and middle adulthood; sleep parameters remain largely unchanged among healthy older adults. The circadian system and sleep homeostatic mechanisms become less robust with normal aging. The causes of sleep disturbances in older adults are multifactorial.


Long-term glycemic control and the rate of progression of early diabetic kidney disease.
In this prospective study of 11.9 years duration (range 9 to 14), we examined the progression of albuminuria prior to and after the onset of microalbuminuria [albumin excretion rate (AER): 20 to 200 micrograms/minute]. Glycated hemoglobin (HbA1), AER and blood pressure were measured every six months. Twenty-two (13 type I, 9 type II) patients were identified in whom AER increased progressively (progressors). These patients were compared with 22 others matched for age, duration and type of diabetes in whom AER did not change significantly during the study period (non-progressors). In the progressors, the rate of increase in AER correlated with mean HbA1 for the study period in patients with type I (r = 0.68, P < 0.01) and type II diabetes (r = 0.71, P < 0.05). Furthermore, AER began increasing well before the conventional 20 micrograms/minute threshold of microalbuminuria had been reached and within the first five years of diagnosis of type I diabetes. We conclude that in predisposed diabetic patients, long-term glycemic control is correlated with the rate of development of early renal abnormalities. Repeated measurements of AER from the time of diagnosis may be useful in the early detection of patients who will develop microalbuminuria and ultimately overt diabetic nephropathy.


[Comparative analysis of the spectrum of radiation-induced structural mutations in diploid and tetraploid cells of mouse bone marrow].
A comparative analysis of the spectrum of radiation-induced mutations was carried out in diploid mouse bone marrow cells and in tetraploid cells obtained from the latter by means of colchicine treatment. It is established that solitary chromatid deletions prevail among aberrations induced at the G2--S stage. This is the difference of the spectrum of induced chromatid rearrangements in animal cells from that in plant cells. It is assumed that the differences observed are caused by the specificity of supramolecular organization of chromatin in animal and plant cells.


Aggressive intervention of previable preterm premature rupture of membranes.
To assess the neonatal and maternal outcomes of pregnancy complicated by previable preterm premature rupture of membranes (PPROM). Retrospective study. Tertiary referral hospital. Sample. Forty-five women having aggressive intervention with antibiotics, amnioinfusion, cerclage and tocolysis. The hospital database between July 2001 and December 2009 was reviewed for women with singleton fetuses and PPROM before 23(+0) weeks of gestation. We analysed maternal and neonatal characteristics. Neonatal survival without major morbidity. Thirty-eight infants were delivered alive and seven were stillborn. Ten infants died in the neonatal intensive care unit and one in the labor ward. Twenty-seven live-born infants survived to discharge from hospital. The survival rate of pregnancies with aggressive management was 60% (27 of 45); that of live-born infants was 71.1% (27 of 38). The median gestational age at PPROM and at delivery were significantly lower in the non-surviving group than the surviving group. Thirty-seven women (82.2%) had an amniotic neutrophil elastase level >0.15 μg/mL. Only four women (8.9%) developed clinical chorioamnionitis. Overall, 90.7% of the women showed histological evidence of chorioamnionitis. Eighty-three per cent of the surviving children had bronchopulmonary dysplasia. Nine infants had serious sequelae at a corrected age of one and a half years. Maternal complications were uncommon. An aggressive treatment protocol for women with previable PPROM resulted in a high neonatal survival rate. Neonatal survival was associated with higher gestational age at delivery and with more frequent use of antenatal corticosteroids. The prognosis is still bad in PPROM before 22(+0) weeks of gestation.


The effects of a soy rich diet on serum lipids: the Menfis randomized trial.
To assess beneficial effects of a soy rich diet on the main biomarkers of cardiovascular health in menopause, compared with the effects of the hormone replacement therapy (HRT). 187 healthy asymptomatic postmenopausal women, aged 39-60, were recruited and randomized into three groups: a soy rich diet group, a HRT group, and a control group. Lipid profile, body mass index, blood pressure, endometrial thickness, uterine artery resistance index (RI), were evaluated in all the participants at the baseline, after 6 months, and at the end of the study. After a 6-month intervention period, the lipid profile in the soy rich diet group showed a favourable outcome, similar to that observed in the HRT group, but compliance to the diet was low. Soy products may be used in the prevention of cardiovascular risk in postmenopausal women because of their efficacy in contrasting the negative effects of menopause on the cardiovascular system, but our findings should be confirmed; moreover, suitable strategies to improve the compliance have to be considered.


Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population.
Little is known about the trace element profile differences between Schizophrenia patients and healthy controls; previous studies about the association of certain elements with Schizophrenia have obtained conflicting results. To identify these differences in the Han Chinese population, inductively coupled plasma-mass spectrometry was used to quantify the levels of 35 elements in the sera of 111 Schizophrenia patients and 110 healthy participants, which consisted of a training (61/61 for cases/controls included) and a test group including remaining participants. An orthogonal projection to latent structures model was constructed from the training group (R(2)Y = 0.465, Q(2)cum = 0.343) had a sensitivity of 76.0% and a specificity of 71.4% in the test group. Single element analysis indicated that the concentrations of cesium, zinc, and selenium were significantly reduced in patients with Schizophrenia in both the training and test groups. The meta-analysis including 522 cases and 360 controls supported that Zinc was significantly associated with Schizophrenia (standardized mean difference [SMD], -0.81; 95% confidence intervals [CI], -1.46 to -0.16, P = 0.01) in the random-effect model. Information theory analysis indicated that Zinc could play roles independently in Schizophrenia. These results suggest clear element profile differences between patients with Schizophrenia and healthy controls, and reduced Zn level is confirmed in the Schizophrenia patients.


Removal and regeneration of the endothelium of the left common carotid artery of rats with induced hypercholesterolemia compared with normocholesterolemic animals. Experimental model to quantify the endothelial layer.
Male Wistar rats were used in a study of removal of the endothelium and endothelial regeneration in the large arteries. The endothelium was stripped completely by surgery from a well-defined segment, with no branches, of the left common carotid artery of rats, drying the vessel by blowing a gentle air stream through the lumen. The animals were fed the normocholesterolic or hypercholesterolic diets. The conditions of the denuded arterial segment were checked histologically at various intervals after the operation. The exposed area became covered with new endothelial cells growing from the two margins of the damaged area; regeneration was complete by about 20 days in normocholesterollemic rats (99.06%) and in a slightly lower proportion of the rats on the atherogenic diet (90.56%). The animals with induced hypercholesterolemia, however, had a significantly larger amount of missing endothelium on day 11 after surgery than the controls. This suggests that hypercholesterolemia affects not only the severity of the lesion but also the rate of endothelial repair.


Pregnancy and COVID-19: what anesthesiologists should know.
Anesthetic management of parturients with COVID-19 is a big challenge to anesthesiologists. Limited data are available about COVID-19 during pregnancy; however, information on illnesses associated with SARS and MERS might provide insights into COVID-19's effects during pregnancy. Evidence from previous reports from SARS and MERS, and from COVID-19 cases were reviewed. Concepts from guidelines from the government and academic societies were collected as well. The evidence was described and summarized. Principles to minimize the risk of infection as well as optimize patients' safety during obstetric anesthesia were found to include careful evaluation, tight protection, and multi-discipline-based strategy. Though vertical transmission of COVID-19 still needs more definitive evidence, strict isolation is necessary for the newborn of COVID-19 mothers. Psychological support for the parturients is also an important issue during COVID-19 pandemic.


[Effect of E-selectin A561C (S128R) polymorphism on blood pressure].
To investigate the effect of E-selectin A561C (S128R) polymorphism on blood pressure. 347 essential hypertensive patients (male 163 and female 184, age 46.08 +/- 12.49 y, and body mass index 26.13 +/- 3.14 kg/m(2)) and 315 normal controls (male 93 and female 222, age 42.21 +/- 14.67 y, and body mass index 25.66 +/- 3.19 kg/m(2)) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Phenotypic measurements included blood pressure, blood glucose, serum triglycerides, serum total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, serum uric acid, blood urea nitrogen, nitric oxide, endothelin, angiotensin I, and II and plasma aldosterone. The frequencies of the AC and CC genotypes (6.92%) and C allele (4.76%) were significantly (P = 0.029 and 0.013) higher in hypertensive patients than normal controls (3.17% and 2.22%). The relative risk of hypertension associated with the C allele was 2.197 (95% CI: 1.164-4.144). Both diastolic blood pressure and mean arterial pressure were higher in C allele carriers than AA subjects (P = 0.049 and 0.024). Furthermore, C allele carriers, compared with AA subjects, had higher concentrations of blood glucose, and total and LDL cholesterol (P = 0.031, 0.046, and 0.003) and lower concentrations of nitric oxide (P = 0.036). The E-selectin A561C (S128R) polymorphism might affect blood pressure in Chinese.


Protective immunity against plague.
Plague, an infectious disease that reached catastrophic proportions during three pandemics, continues to be a legitimate public health concern worldwide. Although antibiotic therapy for the causative agent Yersinia pestis is available, pharmaceutical supply limitations, multi-drug resistance from natural selection as well as malicious bioengineering are a reality. Consequently, plague vaccinology is a priority for biodefense research. Development of a multi-subunit vaccine with Fraction 1 and LcrV as protective antigens seems to be receiving the most attention. However, LcrV has been shown to cause immune suppression and Y. pestis mutants lacking F1 expression are thought to be fully virulent in nature and in animal experiments. The LcrV variant, rV10, retains the well documented protective antigenic properties of LcrV but with diminished inhibitory effects on the immune system. More research is required to examine the molecular mechanisms of vaccine protection afforded by surface protein antigens and to decipher the host mechanisms responsible for vaccine success.


A Systematic Review of Family Victimization Experiences Among Sexual Minority Youth.
Sexual minority youth experience substantially higher rates of family victimization than their heterosexual peers. No systematic review has yet identified the predictors and consequences in this vulnerable population of childhood abuse, exposure to sibling abuse and domestic violence, and sibling aggression. This systematic review aims to (a) describe differences in these family victimization rates by sexual orientation, gender, and race/ethnicity; (b) identify potential sexual minority and non-sexual minority-specific risk factors; and (c) identify physical, mental, and behavioral health and extrafamilial victimization correlates. The systematic review, which followed PRISMA guidelines, yielded 32 articles that met study inclusion criteria. Rates of childhood physical, sexual, and emotional abuse were consistently higher for sexual minority youth than for their heterosexual peers. Bisexual youth appear to be at greater risk for physical abuse than their gay and lesbian peers. Younger age at sexual minority milestones (first awareness, disclosure, and same-sex sexual contact) and higher levels of sexual minority-specific (sexuality disclosure, gender non-conformity) and non-sexual minority-specific (delinquent behaviors, parental drinking) risk factors were associated with higher rates of family victimization. Sexual minorities who experienced some form of childhood abuse reported more frequent physical (higher rates of HIV, higher BMIs, lower levels of perceived health), mental (higher rates of depression, PTSD symptoms, experiential avoidance, internalized homophobia), and behavioral (higher rates of suicidality, substance misuse, earlier sexual debut, unprotected anal sex) health problems relative to heterosexual or non-abused sexual minority peers. Sexual minority females who experienced childhood physical or sexual abuse were at greater risk than abused sexual minority males for sexual assault later in life. We conclude this systematic review with recommendations for future research, including the necessity for longitudinal research that utilizes a poly-victimization conceptual framework to identify the developmental pathways connecting risk factors, different types of family victimization, and health and extrafamilial victimization consequences.


Cloning studies on the gene coding for L-(+)-lactate dehydrogenase of Plasmodium falciparum.
We show that the L-(+)-lactate dehydrogenase (EC 18.104.22.168;L-lactate: NAD+-oxidoreductase) of Plasmodium falciparum (LDH-P) is encoded in the parasite genome. A monoclonal antibody (McAb 7.2) has been shown to bind the LDH-P subunit which has an apparent molecular mass of 35 kDa. A polyclonal antiserum raised against affinity purified LDH-P has been used to isolate cDNA clones containing LDH-P epitopes from a lambda gt11Tn5 expression library. DNA sequence analysis of one clone, lambda LDH-P.1, reveals a single open reading frame which shows a degree of homology to the N-terminal domain of known LDH amino acid sequences.


Antibodies to guanosine. Fractionation and specificities.
Bovine serum albumin conjugates of guanosine prepared by the periodate method was used as immunogen to elicit guanosine antibodies in rabbits. The specificities of the antibodies were studied by the inhibition of their binding to [3H]Gox-red, [32P]DNA and [3H]RNA by related non-radioactive compounds. A population of antibodies is specific to Gox-red with an average association constant of around 10(7) M-1 at 4 degrees C. There are a population of antibodies which bind to [32P]ssDNA and [3H]RNA specifically at guanosine residues. RNA binding antibodies were separated into two populations by affinity chromatography.


Time course of caspase activation in selectively vulnerable brain areas following global cerebral ischemia due to cardiac arrest in rats.
This study evaluated the time course of caspase activation in selectively vulnerable brain areas (hippocampus, nucleus reticularis thalami (NRT), cortex and striatum) following cardiopulmonary resuscitation (CPR) after global cerebral ischemia due to cardiac arrest (CA) in rats. Caspases are well known to play a crucial role in the apoptotic cascade and inflammatory syndromes and, therefore, represent potential therapeutic postischemic targets. Given the delayed neurodegeneration following CA, it is highly important to study the time course of caspase activation in regard to therapeutic interventions after CA. To assess caspase activity, in situ staining was applied to detect general caspase activity at 6h, 3d and 7d and caspase-3 activity at 3d after return of spontaneous circulation (ROSC). For detection of neuronal apoptosis, TUNEL staining was applied at 7d after ROSC. Distinct patterns of early caspase activation were observed at 6h and 3d in the NRT and striatum and of late activation at 7d in the hippocampal CA-1 sector. General caspase and caspase-3 activity correlated strongly at 3d after ROSC in all areas studied. At 7d, the TUNEL-positive neuron counts in the hippocampal CA-1 sector correlated strongly with caspase activation. In conclusion, general caspase and caspase-3 activity after 6 min of CA and the delayed occurrence of TUNEL-positive neurons strongly indicate that neuronal degeneration after CA is at least strongly associated with apoptosis. Therefore, postischemic antiapoptotic interventions might offer potential future therapeutic opportunities global cerebral ischemia due to CA.


γδ T cells augment rejection of skin grafts by enhancing cross-priming of CD8 T cells to skin-derived antigen.
Gamma delta T cells (γδ T cells) possess innate-like properties and are proposed to bridge the gap between innate and adaptive immunity. In this study, we explored the role of γδ T cells in cutaneous immunity using a skin transplantation model. Following engraftment of skin expressing cell-associated model antigen (Ag) (ovalbumin) in epithelial keratinocytes, skin-resident γδ T cells enhanced graft rejection. Although the effector function of CD8 T cells was intact in the absence of γδ T cells, cross-priming of CD8 T cell to graft-derived Ag was impaired in the absence of γδ T cells. The reduced graft rejection and graft priming of γδ T-cell-deficient mice was evident in both acutely inflamed and well-healed grafting models. Furthermore, expression of the CD40 activation marker on migrating dendritic cells was lower in TCRδ(-/-) mice compared with wild-type mice, regardless of the presence or absence of inflammation associated with grafting. These results indicate that γδ T cells enhance graft priming and consequently the likelihood of a successful immune outcome in the context of skin graft rejection, suggesting that γδ T cells may be an important component of immunity to epithelial cancers or infection.


Enhanced Proton Transport of β″-Al2O3 Modified by LiAlO2 as a High-Performance Electrolyte for a Low-Temperature Solid Oxide Fuel Cell and an Electrolyzer.
β″-Al2O3 has been proven as a fast ionic conductor in solid batteries due to its unique structure. In this work, β″-Al2O3 was further modified by LiAlO2 and employed as the electrolyte material for low-temperature solid oxide fuel cells and electrolyzers, i.e., proton-conducting ceramic fuel cells and electrolysis cells, named as PCFC and PCEC, respectively. At 550 °C, thanks to this superior electrolyte with a remarkable conductivity of 0.161 S·cm-1, the PCFC reached a high power density up to 1029 mW·cm-2, and the PCEC demonstrated a significant current density of 1.49 A·cm-2 at a low operation voltage of 2.0 V. It has been found that the introduction of the LiAlO2 phase into β″-Al2O3 reduces the total impedance, while it increases the oxygen vacancy concentration and thus promotes the proton transport process with the reduced activation energy. This work provides a new approach for exploring two-dimensional materials with high-ionic conductivity that can be applied for solid oxide fuel cells and water electrolyzers and more wider power-to-X devices such as electrosynthesis for green ammonia production.


HER1/EGFR tyrosine kinase inhibitors for the treatment of glioblastoma multiforme.
Glioblastoma multiforme (GBM) is a highly malignant brain tumor with limited therapeutic options, a high recurrence rate and mortality. Standard therapy is maximal surgical resection and radiotherapy (RT). Recent data suggest combining temozolomide with RT is better than RT alone. Adjuvant chemotherapy has a modest impact on survival. For relapsed patients there is no standard therapy, but options include chemotherapeutic agents or new agents in development. One approach to improve outcome is using targeted agents that interfere with cell-surface receptors or intracellular signaling pathways. Between 40% and 50% of GBM tumors show HER1/EGFR dysregulation, and almost half co-express the constitutively active mutant receptor subtype EGFRvIII, which may contribute to the aggressive and refractory course of GBM. Numerous studies show a relationship between aberrant HER1/EGFR biology and tumorigenicity in GBM cells. Two available HER1/EGFR tyrosine kinase inhibitors (TKIs) are gefitinib (Iressa) and erlotinib (Tarceva); both show antitumor and radiosensitization effects in vitro and in animal models of GBM. Clinical trials in patients with GBM and other gliomas are ongoing. Preliminary and published results from trials of gefitinib in recurrent GBM show no increased time to progression or overall survival (OS) compared with historical controls. Studies with erlotinib show greater antitumor activity in patients with GBM than with gefitinib, although the impact of both agents on OS remains unclear. GBM treatment with HER1/EGFR TKIs alone or combined with other targeted therapies and conventional modalities deserve further investigation and refinement, as does our understanding of their mechanisms of action and the role of genetics.


The protracted exodus of migrants from Hyderabad in the time of COVID-19.
The immediate aftermath of the COVID-19 pandemic in India saw a mass movement of people, mainly from the cities and large towns to the villages. The lockdown announced by the government abruptly suspended the instrumental value of the city for the millions of migrant workers inhabiting these. As the lockdown period extended, with very uncertain means of inter-state public transport, desperate migrant workers took to the streets in large numbers undertaking arduous and often dangerous journeys to their places of origin. The media highlighting the plight of the migrants elicited responses from different sections. This paper is an exploration of the role of the state and its institutions, civil society and the judiciary in responding to the migrant crisis in the city of Hyderabad, a hub of migrant workers. Closely following the silences and pronouncements of the institutions and analysing the role of each of these over the different phases of the migrant crisis, the paper asserts the need for a closer scrutiny of the universal role of the state response during the migrant crisis.


Cellular electrophysiological effects of D- and DL-sotalol in guinea-pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity.
The effects of racemic DL-sotalol and D-sotalol on guinea-pig sino-atrial node, atrium and ventricle and on human atrium were studied using standard microelectrode techniques. Both compounds increased spontaneous sinus node cycle length largely by prolonging the repolarization phase of the action potentials. This effect was attributed to blockade of outward potassium current. Ventricular action potential duration was similarly prolonged by DL-sotalol at concentrations of 5-50 microM. DL-Sotalol 1-50 microM had no effect on guinea-pig atrial action potential duration and D-sotalol produced minor prolongation only at the highest concentration (50 microM). Human atrial action potentials were, however, significantly prolonged by both DL- and D-sotalol 10 microM. This indicates differential sensitivities to sotalol for human and guinea-pig atrium and explains the ability of sotalol to prolong atrial monophasic action potential duration in clinical studies.


Costs associated with transfusion therapy in patients with myelodysplastic syndromes in Sweden: a nationwide retrospective cohort study.
Blood transfusion is a cornerstone therapy for many patients with myelodysplastic syndromes (MDS), but ranges from few to no transfusions to intensive transfusion therapy. To date, no large studies have described transfusion use or costs for patients with MDS, accounting for the range of disease severity. A nationwide cohort study was conducted with all patients diagnosed with MDS in Sweden between 2008 and 2017, based on the Swedish MDS register and the Swedish part of the Scandinavian Donations and Transfusions Database 3 (SCANDAT3-S). Patients were followed from diagnosis until death, emigration, allogeneic hematopoietic stem cell transplantation or end of follow-up. Average cumulative transfusion count and costs over time were calculated, stratified by the revised international prognostic scoring system (IPSS-R) and age at diagnosis. Costs calculations used data on incident transfusions and laboratory testing and were divided into: direct material costs, direct labour costs and laboratory costs. In total, 2311 patients were included in the cohort. In the first four years after diagnosis, patients in the very low IPSS-R category received on average 25 red cell (95% confidence interval, 20-32) and 4 (3-7) platelet transfusions. Conversely, patients in the very high-risk category received on average 171 (135-200) red cell and 66 (51-78) platelet transfusions. Correspondingly, transfusion costs ranged from $8805 ($6482-$11 625) to $80 106 ($61 460-$95 792). Transfusion count and costs for patients with MDS increased markedly with IPSS-R risk category, but were similar across age groups. Transfusion costs were considerable for the highest IPSS-R risk categories.


Favourable clinical outcomes following cemented arthroplasty after metal-on-metal total hip replacement: a retrospective study with a mean follow-up of 10 years.
Given the unexpected high rate of failure following metal-on-metal total hip replacement (MoM-THR), it is expected that more MoM-THR patients will experience revision. The long-term outcomes regarding the primary MoM-THR revised to cemented THR (CTHR) remain controversial. The purpose of this retrospective review was to evaluate the long-term outcomes of patients who underwent conversion from MoM-THR to CTHR. A total of 220 patients (220 hips) who underwent a conversion of primary MoM-THR to CTHR from March 2006 to October 2016 were retrospectively reviewed. The primary outcomes were the functional outcomes assessed using the Harris hip scores (HHS) and major radiographic outcomes. Follow-ups occurred at 3 months, 6 months, 1 year, 2 years, and then every two years after revision. Mean follow-up was 10.1 years (5-13 years). Distinct improvements were detected in the mean HHS between the preoperative and last follow-up analysis (62.35[±8.49] vs. 84.70[±14.68], respectively, p < 0.001). The key orthopaedic complication rate was 18.2% (27/148). Seven (4.7%) cases experienced a CTHR failure at a mean of 3.4 (±1.2) years after revision MoM-THR, mostly attributed to recurrent dislocation. CTHR might yield an acceptable functional score and a low rate of the key orthopaedic complications.


An ultrastructural classification of the neuronal cell bodies of the rat dorsal root ganglion using zinc iodide-osmium impregnation.
Zinc iodide-osmium (ZIO) impregnation of rat dorsal root ganglia differentially stained various elements in the neuronal cells, particularly their Golgi bodies. On the basis of this differential ZIO staining dorsal root ganglion neurones have been classified into seven types. The ultrastructure of these is described and the numbers of each type in the L4 dorsal root ganglion have been determined. Prolonged nerve stimulation did not change the relative numbers of the different cell types suggesting that none of the differences between cell types represents differences in their state of activity. The possibility is discussed that differences in morphology may reflect differences in neurotransmitter function.


Bioactive diterpenoids from Octocorallia, 2. Deoxyxeniolide B, a novel ichthyotoxic diterpenoid from the soft coral Xenia elongata.
An ichthyotoxic diterpenoid, deoxyxeniolide B [1], was isolated from the soft coral Xenia elongata. It has also been shown that deoxyxeniolide B [1] is gradually oxidized in solution to give the oxidation products 2 and 3. The structures of these compounds were elucidated on the basis of spectral analysis.


Digital health competencies for primary healthcare professionals: A scoping review.
Despite digital health providing opportunities to enhance the quality, efficiency and safety of primary healthcare, the adoption of digital tools and technologies has been slow, partly because of poor digital health literacy. For primary healthcare systems to take full advantage of these technologies, a capable, digitally literate workforce is necessary. Still, the essential digital health competencies (DHCs) for primary healthcare have not been explored. This review aims to examine the broad literature on DHCs as it applies to Primary Care (PC) settings. We performed a scoping review on all types of research linking DHCs to PC. We searched all major databases including Medline, Embase, CINAHL, and Cochrane Library in November 2019. Concurrently, a thorough grey literature search was performed through OpenGrey, ResearchGate, Google Scholar, and key government and relevant professional associations' websites. Screening and selection of studies was performed in pairs, and data was analysed and presented using a narrative, descriptive approach. Thematic analysis was performed to identify key DHC domains. A total of 28 articles were included, most of them (54 %) published before 2005. These articles were primarily aimed at PC physicians or general practitioners, and focused on improving knowledge about information technologies and medical informatics, basic computer and information literacy, and optimal use of electronic medical records. We identified 17 DHC domains, and important knowledge gaps related to digital health education and curriculum integration, the need for evidence of the impact of services, and the importance of wider support for digital health. Literature explicitly linking DHCs to PC was mostly published over a decade ago. There is a need for an updated and current set of DHCs for PC professionals to more consistently reap the benefits of digital technologies. This review identified key DHC domains and statements that may be used to guide on the development of a set of DHC for PC, and critical knowledge gaps and needs to be considered. Such a DHC set may be used for curricula development and for ensuring that the essential DHC for PC are met at a clinical or organizational level, and eventually improve health outcomes.


Male reproductive traits are differentially affected by dietary macronutrient balance but unrelated to adiposity.
Dietary factors influence male reproductive function in both experimental and epidemiological studies. However, there are currently no specific dietary guidelines for male preconception health. Here, we use the Nutritional Geometry framework to examine the effects of dietary macronutrient balance on reproductive traits in C57BL/6 J male mice. Dietary effects are observed in a range of morphological, testicular and spermatozoa traits, although the relative influence of protein, fat, carbohydrate, and their interactions differ depending on the trait being examined. Interestingly, dietary fat has a positive influence on sperm motility and antioxidant capacity, differing to typical high fat diet studies where calorie content is not controlled for. Moreover, body adiposity is not significantly correlated with any of the reproductive traits measured in this study. These results demonstrate the importance of macronutrient balance and calorie intake on reproductive function and support the need to develop specific, targeted, preconception dietary guidelines for males.


Cathepsin D activity of venous and polyester vascular grafts implanted in the abdominal aorta of the dog.
Autogenous veins and polyester prostheses were implanted in the abdominal aorta of dogs. The venous or polyester grafts were removed together with sections of the normal arteries and veins 1 month, 4 months, and 3 years after the operation. This material was then dissected into the intimal, medial, and adventitial layers, and homogenized after which their cathepsin D activity was determined. It was found that the cathepsin D activity was far higher in all the layers of the venous grafts, particularly in the polyester grafts, than in the corresponding layers of the normal arteries and veins.


Activity of cholinesterases, pyruvate kinase and adenosine deaminase in rats experimentally infected by Fasciola hepatica: Influences of these enzymes on inflammatory response and pathological findings.
The aim of this study was to investigate acetylcholinesterase (AChE) in total blood and liver tissue; butyrylcholinesterase (BChE) in serum and liver tissue; adenosine deaminase (ADA) in serum and liver tissue; and pyruvate kinase (PK) in liver tissue of rats experimentally infected by Fasciola hepatica. Animals were divided into two groups with 12 animals each, as follows: group A (uninfected) and group B (infected). Samples were collected at 20 (A1 and B1;n=6 each) and 150 (A2 and B2; n=6 each) days post-infection (PI). Infected animals showed an increase in AChE activity in whole blood and a decrease in AChE activity in liver homogenates (P<0.05) at 20 and 150 days PI. BChE and PK activities were decreased (P<0.05) in serum and liver homogenates of infected animals at 150 days PI. ADA activity was decreased in serum at 20 and 150 days PI, while in liver homogenates it was only decreased at 150 days PI (P<0.05). Aspartate aminotransferase and alanine aminotransferase activities in serum were increased (P<0.05), while concentrations of total protein and albumin were decreased (P<0.05) when compared to control. The histological analysis revealed fibrous perihepatitis and necrosis. Therefore, we conclude that the liver fluke is associated with cholinergic and purinergic dysfunctions, which in turn may influence the pathogenesis of the disease.


The crosstalking immune cells network creates a collective function beyond the function of each cellular constituent during the progression of hepatocellular carcinoma.
Abundance of data on the role of inflammatory immune responses in the progression or inhibition of hepatocellular carcinoma (HCC) has failed to offer a curative immunotherapy for HCC. This is largely because of focusing on detailed specific cell types and missing the collective function of the hepatic immune system. To discover the collective immune function, we take systems immunology approach by performing high-throughput analysis of snRNAseq data collected from the liver of DIAMOND mice during the progression of nonalcoholic fatty liver disease (NAFLD) to HCC. We report that mutual signaling interactions of the hepatic immune cells in a dominant-subdominant manner, as well as their interaction with structural cells shape the immunological pattern manifesting a collective function beyond the function of the cellular constituents. Such pattern discovery approach recognized direct role of the innate immune cells in the progression of NASH and HCC. These data suggest that discovery of the immune pattern not only detects the immunological mechanism of HCC in spite of dynamic changes in immune cells during the course of disease but also offers immune modulatory interventions for the treatment of NAFLD and HCC.


Short- and long-term corneal vascular effects of tafluprost eye drops.
Prostaglandin analogs are first line therapy in the treatment of glaucoma, but also display side effects during ocular inflammation. In this context, the potential side effects of prostaglandin analogs on the normally avascular cornea, the main application route for eye drops, are so far not fully defined. Therefore, the aim of this study was to evaluate the vascular effects of the prostaglandin analog tafluprost on the healthy and inflamed cornea. For in vitro studies, blood and lymphatic endothelial cells were treated with tafluprost; cell proliferation was assessed after 48 h. For long-term in vivo studies under healthy conditions, naïve corneas of BALB/c mice were treated with tafluprost eye drops for 4 weeks. For short-term in vivo studies under inflammatory conditions, corneal inflammation was induced by suture placement; mice then received tafluprost eye drops for 1 week. Afterwards, corneas were stained with CD31 as panendothelial and LYVE-1 as lymphendothelial (and macrophage) marker. In vitro, tafluprost did not alter blood or lymphatic endothelial cell proliferation. In vivo, there was no change in limbal blood or lymphatic vessel anatomy after long-term treatment with tafluprost. Short-term treatment with tafluprost under inflammatory conditions did not influence the recruitment of LYVE-1 positive macrophages into the cornea. Moreover, treatment of inflamed corneas with tafluprost did not significantly influence corneal hem- and lymphangiogenesis. Tafluprost does not affect blood and lymphatic vessel growth, neither under resting nor under inflammatory conditions. These findings suggest a safe vascular profile of tafluprost eye drops at the inflammatory neovascularized cornea.


[The Principle of Genome Complementarity in the Enhancement of Plant Adaptive Capacities].
In the present work, the potential for the enhancement of the adaptive capacity of microbe-plant systems (MPSs) through the integration of the symbiosis partners' genomes is considered on the example of different types of symbiotic relationships. The accumulated data on the genetic control of interactions for both the plant and microbe, which are discussed in the paper with respect to signaling genes, suggest that it is the complementarity of genetic determinants that underlies the successful formation of MPSs. A eukaryotic genome with limited information content, which is stable throughout a generation, is complemented by a virtually unlimited prokaryotic metagenome. The microsymbiont's ability to adapt to different living conditions is based on the restructuring of the accessory genome by different mechanisms, which are likely to be activated under the influence of plants, although the details of such a regulation remain unknown. Features of the genetic control of the interaction, particularly its universal character for different symbionts, allow us to formulate a principle of genome-complementarity with respect to interacting organisms and consider it an important factor, an adaptation that enhances the abilities of M PSs for their sustainable development in natural ecosystems and for high plant productivity in agrocenoses.


LipoxinA4 attenuates acute pancreatitis-associated acute lung injury by regulating AQP-5 and MMP-9 expression, anti-apoptosis and PKC/SSeCKS-mediated F-actin activation.
An essential component of acute pancreatitis(AP)-induced acute lung injury(ALI) is the inflammation that is part of the body's systemic inflammatory response to a variety of systemic stimuli. Lipoxins(LXs) are considered important endogenous lipids that mediate the resolution of inflammation. In previous studies, we found that Lipoxin A4 (LXA4) reduced AP-induced pulmonary oedema and TNF-α production in lung. However, the underlying mechanism remains unclear. Due to the above studies, we investigated the aquaporin, matrix metalloprotein, apoptosis and PKC/SSeCKS signal pathway in cellular and animal models of AP-associated lung injury following LXA4 intervention. In this study, we first proved LXA4 could effectively promote F-actin reconstruction and regulate its expression in pulmonary microvascular endothelial cells both in vivo and vitro via suppressing PKC/SSeCKS signalling pathway. Next, we found that LXA4 attenuated cell growth inhibition and apoptosis in lung tissues of AP-ALI mice and HPMECs. Additionally, we demonstrated that LXA4 could regulate the expression of AQP-5 and MMP-9 to stabilize the permeability of pulmonary microvascular endothelial cell. In summary, our results suggest that the anti-inflammatory eff ;ects of LXA4 may be due to the inhibition of both the PKC/SSeCKS pathway and apoptosis to reduce alveolar fluid exudation and to the regulation of AQP-5 and MMP-9 expression to maintain the clearance of alveolar fluid. Thus, LXA4 is capable of exerting protective eff ;ects on AP-induced ALI.


Management of nonpalpable breast lesions in a modern functional breast unit.
During the last 20 years an ever increasing number of nonpalpable breast lesions (NPBL) have been identified. A cytohistological definition is required to establish the correct diagnostic classification of these lesions and the suitable therapy to be used. The Fine-Needle Aspiration Cytology (FNAC), the Advanced Breast Biopsy Instrumentation (ABBI) system or the Vacuum Assisted Core Biopsy (VACB) represent valid alternatives to the surgical excision with needle localisation. 591 NPBL have been included in the present study. The suspected grade of each lesion was then assigned according to the Breast Imaging Reporting and Data System (BI-RADS) of the American College of Radiology. All the BI-RADS 4 and 5, and all the BI-RADS 3 lesions, which after 6-month follow-up showed altered morphology, were sampled for cytological and/or histological examinations by FNAC, VACB or biopsy by ABBI system. The diagnostic algorithm used in this study obviated a surgical procedure in 574 women (97.1%), yielding a 73.9% decrease in the cost of diagnosis compared with surgical biopsy, and a 48.1% decrease in cost if all lesions had been histologically tested using ABBI or VACB procedure. Compared to surgical biopsy, VACB and ABBI system are less expensive, and have smaller emotional and aesthetical impact on patients; however they retain the same sensitivity and specificity.


Conversion to Resectability Using Transarterial Chemoembolization Combined With Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma.
To evaluate whether this conversion rate to resectability could be increased when patients are treated with transarterial chemoembolization and hepatic arterial infusion chemotherapy (TACE-HAIC) using oxaliplatin plus fluorouracil/leucovorin. Conventional TACE (c-TACE) is a common regimen for initially unresectable hepatocellular carcinoma (HCC), which converts to curative-intent resection in about 10% of those patients. It is urgent need to investigated better regimen for those patients. The data of 83 initially unresectable HCC patients were examined, including 41 patients in the TACE-HAIC group and 42 patients in the c-TACE group. Their response rate, conversion rate to resection, survival outcome, and adverse events were compared. The conversion rate was significantly better in the TACE-HAIC group than in the c-TACE group (48.8% vs 9.5%; P < 0.001). The TACE-HAIC had marginal superiority in overall response rate as compared to c-TACE (14.6% vs 2.4%; P = 0.107 [RECIST]; 65.9% vs 16.7%; P < 0.001 [mRECIST], respectively). The median progression-free survival was not available and 9.2 months for the TACE-HAIC and cTACE groups, respectively (hazard rate [HR]: 0.38; 95% confidence interval [CI], 0.20-0.70; P = 0.003). The median overall survival was not available and 13.5 months for the TACE-HAIC and c-TACE groups, respectively (HR, 0.63; 95% CI, 0.34-1.17; P = 0.132). The 2 groups had similar rates of grade 3/4 adverse events (all P > 0.05). TACE-HAIC demonstrated a higher conversion rate and progression-free survival benefit than c-TACE and could be considered as a more effective regimen for patients with initially unresectable HCC. Future prospective randomized trials are needed to confirm it.


Biosynthetic conclusions from the functional dissection of oxygenases for biosynthesis of actinorhodin and related Streptomyces antibiotics.
Actinorhodin (ACT) produced by Streptomyces coelicolor A3(2) belongs to the benzoisochromanequinone (BIQ) class of antibiotics. ActVA-ORF5, a flavin-dependent monooxygenase (FMO) essential for ACT biosynthesis, forms a two-component enzyme system in combination with a flavin:NADH oxidoreductase, ActVB. The genes for homologous two-component FMOs are found in the biosynthetic gene clusters for two other BIQs, granaticin (GRA) and medermycin (MED), and a closely related antibiotic, alnumycin (ALN). Our functional analysis of these FMOs (ActVA-ORF5, Gra-ORF21, Med-ORF7, and AlnT) in S. coelicolor unambiguously demonstrated that ActVA-ORF5 and Gra-ORF21 are bifunctional and capable of both p-quinone formation at C-6 in the central ring and C-8 hydroxylation in the lateral ring, whereas Med-ORF7 catalyzes only p-quinone formation. No p-quinone formation on a BIQ substrate was observed for AlnT, which is involved in lateral p-quinone formation in ALN.


A radioimmunoassay method for urinary catechol estrogens.
A radioimmunoassay method for urinary catechol estrogens is described; The specific nature of the antisera allows direct analyses of acid hydrolyzed urine. A LH-20 Sephadex column chromatography can be employed for individual determinations of 2-hydroxyestrone and 2-hydroxyestradiol. The excretion of catechol estrogens during menstrual cycles ranged from 14.48 to 50.15 microgram per 24 hours, whereas, during the last trimester of pregnancies, the values ranged from 129.30 to 1758. 20 microgram per 24 hours.


Prevesical xanthogranulomatous pseudotumor.
We describe a patient who was referred to our hospital because of dysuria, frequency and a palpable mass in the suprapubic area. A specimen obtained at suprapubic exploration consisted of fatty tissue and tentative diagnosis was pelvic lipomatosis. The symptoms persisted and the entire mass was removed from its prevesical pelvic position. The pathological report was xanthogranuloma. Postoperatively, the symptoms disappeared.


Safety and quality of the green tide algal species Ulva prolifera for option of human consumption: A nutrition and contamination study.
This study sampled U. prolifera and surface seawater from the same locations where green tide broke out in the southern Yellow Sea, in both the year 2016 and 2017. The revealed nutritive components of U. prolifera samples characterized U. prolifera as a high-protein, high-Fe, high ratio of unsaturated lipid acids and low-fat seaweed food, with an ideal ratio of essential and nonessential amino acids. The concentrations and health risk assessment of major micropollutants (heavy metals, pesticides and polycyclic aromatic hydrocarbon (PAHs)) in U. prolifera were also analyzed, respectively. The results showed that the Target Hazard Quotient values of five heavy metals (<1.0 × 10-1) and the total hazard index of 13 pesticides (<1.5 × 10-8) were lower than the unity, respectively, and the incremental lifetime cancer risk values of PAHs (<7.4 × 10-7) were lower than the USEPA limit (1.0 × 10-6). It suggested that consuming U. prolifera is safe as a food-source option, with PAHs causing relatively higher risks. PAHs from the sites closer to the shore were also found more originated from pyrolysis. We further confirmed the PAH congeners were partly in equilibrium between seawater and U. prolifera. It suggested the possibility that the food safety-risk turned to be above the USEPA limit was not high regardless of the sample collecting time. However, the sources of PAHs and their contributions to the accumulation in U. prolifera need further investigation. This study favored that U. prolifera of the green tide from the southern Yellow Sea has a potential for a nutritious-food production.


Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension.
This study investigated the effect of catheter-based renal sympathetic denervation (RD) on left ventricular hypertrophy (LVH) and systolic and diastolic function in patients with resistant hypertension. LVH and diastolic dysfunction are associated with elevated sympathetic activity and increased morbidity and mortality. The effect of RD on LVH and LV function is unclear. Forty-six patients underwent bilateral RD, and 18 patients served as controls. Transthoracic echocardiography was performed at baseline, and after 1 month and 6 months. Besides reduction of systolic and diastolic blood pressure (-22.5/-7.2 mm Hg at 1 month and -27.8/-8.8 mm Hg at 6 months, p < 0.001 at each time point), RD significantly reduced mean interventricular septum thickness from 14.1 ± 1.9 mm to 13.4 ± 2.1 mm and 12.5 ± 1.4 mm (p = 0.007), and LV mass index from 53.9 ± 15.6 g/m(2.7) (112.4 ± 33.9 g/m(2)) to 47.0 ± 14.2 g/m(2.7) (103.6 ± 30.5 g/m(2)) and 44.7 ± 14.9 g/m(2.7) (94.9 ± 29.8 g/m(2)) (p < 0.001) at 1 month and 6 months, respectively. The mitral valve lateral E/E' decreased after RD from 9.9 ± 4.0 to 7.9 ± 2.2 at 1 month and 7.4 ± 2.7 at 6 months (p < 0.001), indicating reduction of LV filling pressures. Isovolumic relaxation time shortened (baseline 109.1 ± 21.7 ms vs. 85.6 ± 24.4 ms at 6 months, p = 0.006), whereas ejection fraction significantly increased after RD (baseline: 63.1 ± 8.1% vs. 70.1 ± 11.5% at 6 months, p < 0.001). No significant changes were obtained in control patients. Besides the known effect on blood pressure, our study showed for the first time that RD significantly reduces LV mass and improves diastolic function, which might have important prognostic implications in patients with resistant hypertension at high cardiovascular risk.


Expression and enzymatic activity of small intestinal tissue transglutaminase in celiac disease.
The molecular and functional properties of small intestinal tissue transglutaminase are largely unknown despite growing interest because of its role in celiac disease (CD). In this study, we aimed to evaluate tissue transglutaminase expression and enzymatic activity in bioptic fragments obtained from the duodenum of untreated individuals with CD and from control subjects. Analysis of tissue transglutaminase mRNA expression was performed by reverse transcription-polymerase chain reaction (RT-PCR). The presence of the enzyme in bioptic fragments as well as in homogenates from CD patients and controls was revealed by immunohistochemistry and Western blot, respectively, using the antitissue transglutaminase CUB 7402 clone. To evaluate in situ transglutaminase activity, sections of bioptic fragments were incubated in the presence of 5 mmol/L CaCl(2) with 5-(biotinamido)pentylamine or, alternatively, with a biotinylated glutamine-containing hexapeptide (TVQQEL) and the biotinylated 31-43 A-gliadin-derived peptide. Tissue transglutaminase mRNA levels were 1.0-fold higher (p < 0.05) in CD patients than in controls. Immunohistochemistry and in situ demonstration of enzymatic activity in celiac mucosa clearly showed an increased expression of active tissue transglutaminase in the extracellular matrix of the subepithelial region and in the enterocytes. Staining of the biotinylated 31-43 A-gliadin peptide in the same area of tissue transglutaminase suggested the presence of lysine-donor substrates in intestinal mucosa. Tissue transglutaminase is more expressed and active in defined areas of the small intestinal mucosa from patients with CD. The presence in the celiac mucosa of proteins able to act as amine-donor substrates suggests that tissue transglutaminase-mediated post-translational modification of proteins cross-linked with gliadin peptides may represent a pathogenic mechanism of CD.