DNA photoreactivating enzyme from the cyanobacterium Anacystis nidulans.
Photoreactivating enzyme, which specifically monomerizes pyrimidine dimers in UV-irradiated DNA, was purified 21,000-fold from the cyanobacterium Anacystis nidulans to apparent homogeneity with 41% overall yield. The enzyme consists of a single protein chain with 53,000 molecular weight. Maximal activity was found at pH 6.2 and 0.1 M NaCl. Purified photoreactivating enzyme exhibits a marked absorption spectrum with a main band in the blue region (maximum 437 nm), a protein band (maximum 266 nm), and a low intensity band above 500 nm. The molar extinction coefficient of native enzyme was estimated 53,000 at 437 nm. The action spectrum for photoreactivation shows maximal activity at 440 nm and correlates closely with the 437-nm absorption band. The enzyme contains two different intrinsic chromophores in equimolar amounts, which were identified as 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) and (reduced) FAD. The low intensity absorption band of native photoreactivating enzyme exhibits a shoulder at 498 and maxima at 588 and 634 nm. This band is attributed to a neutral FAD semiquinone radical which accounts for the major part of the FAD present in dark equilibrated enzyme. Preillumination at 585 nm bleaches the semiquinone spectrum due to formation of fully reduced FAD, but exposure to air in the dark restores the spectrum completely. On preillumination at 437 nm the disappearance of FAD semiquinone is more rapid, indicating that the photoreduction is sensitized by the 8-hydroxy-5-deazaflavin chromophore. The 8-hydroxy-5-deazaflavin and possibly also the reduced FAD chromophore appear to act as a primary photon acceptor in the photoreactivation process.


Who's your neighbor? Suggesting alternative assemblies of E/F type bilin lyases from crystal lattice analysis.
Attachment of bilins to phycobiliproteins is performed by dedicated lyases. In this issue of Structure, Kumarapperuma et al., 2022 present the structure of an E/F type lyase-isomerase that identifies the correct biological interface between active domains, suggesting that a previous E/F lyase misidentified the heterodimer structure from the crystal lattice.


Advanced Practice Nurses' Meaningful use of electronic health records.
The aim of this study was to better understand electronic health records (EHRs) use among advanced practice nurses (APNs). EHRs are becoming an integral part of the U.S. health care system. Federal law was enacted with provisions that offer incentive payments to eligible professionals and hospitals who use EHRs. Little is known about APNs' EHR use. A quantitative, non-experimental research design was used. Descriptive and multiple logistic regression analyses were performed. Two thirds of the APNs were EHR-user. Statistically significant differences between EHR-users and non-users were found in age categories, practice setting, practice size, and in tasks related to imagery report review and care coordination. EHR use was associated with higher odds of practicing in hospital, and employment longevity, but with decreased odds in the number of patients seen per day. With one third of the APNs being EHR non-users, more efforts are needed to help guide the adoption and diffusion of EHRs in practice.


Design, synthesis and antitubercular evaluation of novel 2-substituted-3H-benzofuro benzofurans via palladium-copper catalysed Sonagashira coupling reaction.
A series of novel natural product like 2-substiuted-3H-benzofurobenzofurans designed by molecular hybridization were synthesized in very good yields. The key reactions involved in the synthesis are iodination of 2-dibenzofuranol using iodine monochloride followed by palladium-copper catalyzed Sonagashira-coupling of 1-iododibenzofuran-2-ol with various alkyl and aryl acetylenes. Among the all 10 new compounds screened for in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv, 2-(4-methoxy-2-methyl phenyl)-3H-benzofuro[3,2-e]benzofuran (7c) was found to be most active with MIC 3.12 μg/mL and has shown lower cytotoxicity with good therapeutic index.


Role of gabapentin in reducing the need for high-risk medications in patients with stable severe neurological impairment.
The study was aimed at assessing the prevalence of pain behaviors in children with severe neurological impairment (SNI), as well as the use of prescribed pain behavior medications, and the effects of gabapentin initiation on behaviors and use. A pre-post study was conducted on data from 11 patients with SNI who received gabapentin at a children's hospital in Canada. Symptoms and the use of high-risk pain behavior medications were assessed before and after gabapentin initiation and titration. Pain was identified as a primary concern in most patients (8/11 [73%]) before gabapentin initiation. Dystonia was the most prevalent pain behavior (6/11 [55%]). Of the 11 patients, eight (73%) were taking benzodiazepines for symptom management, four (36%) were taking opioids, and one was taking a hypnotic sedative. Symptom improvement was observed in 10/11 (91%) patients after gabapentin initiation and titration. The use of benzodiazepine decreased in 6/8 (75%) patients, opioid use decreased in 3/4 patients, and hypnotic sedative use decreased in 1/1 patient. Successful discontinuation occurred for benzodiazepines in 5/8 (62.5%) patients, opioids in 1/4 (25%) patients, and hypnotic sedatives in 1/1 patient. Prescription medications with substantive risks, including benzodiazepines, opioids, and hypnotic sedatives, were used with high prevalence for pain behaviors in children with SNI. This study revealed an association between gabapentin initiation, and improved symptom burden and decreased use of the three medications.


Bio-array images processing and genetic networks modelling.
The new tools available for gene expression studies are essentially the bio-array methods using a large variety of physical detectors (isotopes, fluorescent markers, ultrasounds...). Here we present first rapidly an image-processing method independent of the detector type, dealing with the noise and with the peaks overlapping, the peaks revealing the detector activity (isotopic in the presented example), correlated with the gene expression. After this primary step of bio-array image processing, we can extract information about causal influence (activation or inhibition) a gene can exert on other genes, leading to clusters of genes co-expression in which we extract an interaction matrix M and an associated interaction graph G explaining the genetic regulatory dynamics correlated to the studied tissue function. We give two examples of such interaction matrices and graphs (the flowering genetic regulatory network of Arabidopsis thaliana and the lytic/lysogenic operon of the phage Mu) and after some theoretical rigorous results recently obtained concerning the asymptotic states generated by the genetic networks having a given interaction matrix and reciprocally concerning the minimal (in the sense of having a minimal number of non-zero coefficients) matrices having given stationary stable states.


Shifting from laparotomy to thoracoscopic repair of congenital diaphragmatic hernia in neonates: early experience.
Thoracoscopic repair of congenital diaphragmatic hernia (CDH) is now widely performed by pediatric surgeons. We compare our experience with this operation versus the results for a group of CDH patients treated by laparotomy at the same center over the same period. From January 2008 to December 2011, we reviewed the medical records of 50 neonates who underwent surgery for posterolateral CDH (34 by laparotomy, 16 by thoracoscopy). Two thoracoscopic operations (12.5 %) were converted to thoracotomy. Eight patients treated with extracorporeal membrane oxygenation (ECMO) underwent laparotomy. There were no significant differences in demographic characteristics between the two groups. Both nitric oxide (p = 0.13) and high-frequency oscillatory ventilation (p = 0.06) tended to be required more frequently in the laparotomy group than in the thoracoscopy group. A patch was applied to nine patients (five laparotomy, four thoracoscopy, p = 0.42). Mean operation time was longer for the thoracoscopy group, but not significantly so (p = 0.06). Times to feeding and lengths of hospital stays were similar, as were days of postoperative ventilator use and of total ventilator use. CDH recurred in two patients, both in the thoracoscopy group (p = 0.08), and intestinal obstruction occurred in five patients in the laparotomy group. Of eight patients who received ECMO treatment, only three survived. Except in patients receiving ECMO treatment, thoracoscopic repair is useful and feasible regardless of defect size or need for patching. Operation time is longer, but cosmetic appearance is better and intestinal obstruction uppers to be less frequent. However, intensive training is needed to prevent the recurrence.


[Functional magnetic resonance imaging for evaluation of radiation-induced renal damage].
The diagnosis of radiation-induced (especially chronic) renal alterations/damage is difficult and currently relies primarily on clinical evaluation. The importance of renal diagnostic evaluation will increase continuously due to the increasing number of long-term survivors after radiotherapy. This article evaluates the potentia diagnostic contribution of magnetic resonance (MR) imaging with a focus on functional MRI. The following functional MRI approaches are briefly presented and evaluated: blood oxygenation level-dependent imaging (BOLD), diffusion-weighted imaging (DWI) or diffusion tensor imaging (DTI), MR perfusion measurements and (23)Na imaging. In summary, only DWI and contrast-enhanced MR perfusion currently seem to be suitable approaches for a broader, clinical implementation. However, up to now valid data from larger patient studies are lacking for both techniques in regard to radiation-induced renal alterations. The BOLD and (23)Na imaging procedures have a huge potential but are currently neither sufficiently evaluated with regard to radiation-induced renal alterations nor technically simple and reliable for implementation into the clinical routine.


Improved technique of intraaortic balloon insertion.
Routine insertion of an intraaortic balloon through the femoral artery may be difficult in the face of obstructive aortoiliac atherosclerosis. Perioperatively, the balloon catheter may be guided through diseased vessels by transabdominal palpation.


Participation rates, response bias and response behaviours in the community survey of the Swiss Spinal Cord Injury Cohort Study (SwiSCI).
Surveying persons with disabilities is challenging, as targeted subjects may experience specific barriers to survey participation. Here we report on participation rates and response behaviour in a community survey of people with spinal cord injury (SCI) in Switzerland. The cross-sectional survey was implemented as part of the Swiss Spinal Cord Injury Cohort Study (SwiSCI) and represents the largest population-based SCI survey in Europe including nearly 2000 persons. Design features to enhance participation rates included the division of the questionnaire volume over three successive modules; recurrent and mixed-mode reminding of non-responders; and mixed-mode options for response. We describe participation rates of the SwiSCI community survey (absolute and cumulative cooperation, contact, response, and attrition rates) and report on response rates in relation to recruitment efforts. Potential non-response bias and the association between responders' characteristics and response behaviour (response speed: reminding until participation; response mode: paper-pencil vs. online completion) were assessed using regression modelling. Over the successive modules, absolute response rates were 61.1, 80.6 and 87.3% which resulted in cumulative response rates of 49.3 and 42.6% for the second and third modules. Written reminders effectively increased response rates, with the first reminder showing the largest impact. Telephone reminders, partly with direct telephone interviewing, enhanced response rate to the first module, but were essentially redundant in subsequent modules. Non-response to the main module was related to current age, membership of Swiss Paraplegic Association (SPA) and time since injury, but not to gender, lesion level and preferred language of response. Response speed increased with household income, but was not associated to other sociodemographic factors, lesion characteristics or health indicators. We found significant associations between online completion and male gender, younger age, higher education, higher income, SPA membership, tetraplegia, longer time since injury, higher quality of life, and more participation restrictions. In this sample with little non-response bias, recurrent and mixed-mode reminding and mixed-mode options for response were key features of optimizing survey design.


Characterization of an Omnitrap-Orbitrap Platform Equipped with Infrared Multiphoton Dissociation, Ultraviolet Photodissociation, and Electron Capture Dissociation for the Analysis of Peptides and Proteins.
We describe an instrument configuration based on the Orbitrap Exploris 480 mass spectrometer that has been coupled to an Omnitrap platform. The Omnitrap possesses three distinct ion-activation regions that can be used to perform resonant-based collision-induced dissociation, several forms of electron-associated fragmentation, and ultraviolet photodissociation. Each section can also be combined with infrared multiphoton dissociation. In this work, we demonstrate all these modes of operation in a range of peptides and proteins. The results show that this instrument configuration produces similar data to previous implementations of each activation technique and at similar efficiency levels. We demonstrate that this unique instrument configuration is extremely versatile for the investigation of polypeptides.


One cranium, two brains not yet introduced: Distinct but complementary views of the social brain.
Social behavior is pervasive across the animal kingdom, and elucidating how the brain enables animals to respond to social contexts is of great interest and profound importance. Our understanding of 'the social brain' has been fractured as it has matured. Two drastically different conceptualizations of the social brain have emerged with relatively little awareness of each other. In this review, we briefly recount the history behind the two dominant definitions of a social brain. The divide that has emerged between these visions can, in part, be attributed to differential attention to cortical or sub-cortical regions in the brain, and differences in methodology, comparative perspectives, and emphasis on functional specificity or generality. We discuss how these factors contribute to a lack of communication between research efforts, and propose ways in which each version of the social brain can benefit from the perspectives, tools, and approaches of the other. Interface between the two characterizations of social brain networks is sure to provide essential insight into what the social brain encompasses.


Drug targeting to brain: a systematic approach to study the factors, parameters and approaches for prediction of permeability of drugs across BBB.
Drug targeting to brain by circumventing the physiological barriers is a prerequisite for drugs acting on central nervous system (CNS) and therapeutic potential of many drugs can be improved by effectively targeting the drug(s) to brain. Present review describes blood-brain barrier (BBB), drug transport mechanisms and factors affecting drug transportation across BBB along with in vitro BBB models; and the approaches for evaluation of permeability of drug across BBB. The development of a still awaited perfect in vitro model to mimic BBB is a challenging task. System biologist, network biologist and computational technologist should come together to integrate the role of transporters, physiological and pathophysiological complexity of BBB to replicate vascular properties of the brain microcapillaries as a suitable model to facilitate the high-throughput screening of CNS acting biomolecules.


Glycemia and venous thromboembolism in patients with primary brain tumors - A speculative review.
Venous thromboembolism (VTE) is a significant public health issue causing severe morbidity and mortality. One of the most vulnerable populations for VTE development are cancer patients. And among them, patients with brain tumors have arguably the highest risk of developing this often fatal complication. Hyperglycemia is a well-known factor which leads to a wide variety of pro-thrombotic changes. In this article, we review the current literature on the topic of VTE in brain tumor patients. We also discuss the known correlation between VTE and glycemia, as well as the importance and frequency of glycemia dysregulation in brain tumor patients. Based on the already well-known importance of glucose metabolism in cancer patients, as well as the previous research of our group, we hypothesize that there is a significant number of brain tumor patients who have chronically elevated glycemia, a fact that so-far hasn't been reported. We argue that these patients carry a significantly higher risk of VTE development and would benefit greatly from strict glycemic control. We present our hypothesis, the ways in which to test it, as well as the possible counter-arguments against it. Our hope is that other investigators will be inspired by our article to continue this type of research, since we consider the topic of VTE in brain tumor patients highly important and urgent, primarily due to its prevalence and severity.


The effect of a water-soluble tris-galactoside terminated cholesterol derivative on the in vivo fate of small unilamellar vesicles in rats.
When the water-soluble cholesterol derivative, N-[tris [(beta-D-galactopyranosyloxy)methyl]methyl]-N alpha-[4-(5-cholesten-3 beta-yloxy)succinyl]glycinamide (tris-gal-chol) (Kempen et al. (1984) J. Medicin. Chem. 27, 1306-1312) is added as an aqueous micellar solution to a dispersion of small unilamellar phospholipid vesicles it rapidly associates with the vesicles, without causing significant leakage of liposome contents. Incorporation of 10 mol% tris-gal-chol in the liposomal membrane caused a substantial increase in the rate and extent of rat liver uptake and a shift in intrahepatic distribution of an intravenously administered dose of liposomes. For neutral liposomes composed of equimolar amounts of cholesterol and sphingomyelin incorporation of tris-gal-chol led to a 7-fold increase in total liver uptake, which was mainly accounted for by an increase in uptake by the Kupffer cells (12-fold) and by only a small increase in uptake by the hepatocytes (1.4-fold). The increased liver uptake is blocked by preinjection of N-acetyl-D-galactosamine and not affected by preinjection of N-acetyl-D-glucosamine. This indicates that the increased interaction of liposomes as a result of tris-gal-chol incorporation is mediated by galactose-specific recognition sites on both Kupffer cells and hepatocytes. Targeting of liposomes to the asialoglycoprotein receptor of the hepatocytes is thus frustrated by the highly active galactose-specific receptor on Kupffer cells. Comparable results on lactosylceramide incorporation into liposomes were recently reported by us (Spanjer et al. (1984) Biochim. Biophys. Acta 774, 49-55).


Prior Pelvic Osteotomy Affects the Outcome of Subsequent Total Hip Arthroplasty.
Although pelvic osteotomy (PO) is an important surgical procedure that can alleviate symptoms and potentially slow progression of osteoarthritis in patients with development dysplasia of the hip, some patients eventually require conversion to total hip arthroplasty (THA). This study aimed to determine the outcome of conversion THA in patients with prior PO. Forty nine patients with a history of prior PO who underwent conversion THA at a single institution were matched at a 1:3 ratio based on the date of surgery, age, gender, and body mass index with 147 developmental dysplasia of the hip patients who underwent primary THA without prior PO. A retrospective chart review was performed to compare outcomes at a minimum follow-up of 2 years. Patients with prior PO required more supplemental screw fixation for the acetabular component (59.2% vs 38.1%, P = .016), more autologous bone grafting (24.5% vs 11.6%, P = .048), had a longer mean operative time (106.0 vs 79.8 minutes, P < .001), and greater estimated blood loss (350.0 vs 206.8 mL, P = .015). Patients with prior PO had smaller cup version angle (26.0° vs 29.0°, P = .012) and greater discrepancy in the limb length (10.3 vs 7.26 mm, P = .041). Eight hips (16.3%) with prior PO and 6 (4.1%) without osteotomy required reoperation (P = .008). There was no difference in outcome scores at the latest follow-up. THA after prior PO is technically demanding, leading to longer operative times, greater blood loss, and variation in implant placement. Although functional outcomes are similar, THA after a prior PO is more likely to require reoperation. THA after prior PO is technically demanding, leading to longer operative times, greater blood loss, and variation in implant placement. Although functional outcomes are similar, THA after a prior PO is more likely to require reoperation.


Genetically Encoded and Biologically Produced All-DNA Nanomedicine Based on One-Pot Assembly of DNA Dendrimers for Targeted Gene Regulation.
All-DNA nanomedicines have emerged as potential anti-tumor drugs. DNA nanotechnology provides all-DNA nanomedicines with unlimited possibilities in controlling the diversification of size, shape, and loads of the therapeutic motifs. As DNA is a biological polymer, it is possible to genetically encode and produce the all-DNA nanomedicines in living bacteria. Herein, DNA-dendrimer-based nanomedicines are designed to adapt to the biological production, which is constructed by the flexible 3-arm building blocks to enable a highly efficient one-pot DNA assembly. For the first time, a DNA nanomedicine, D4-3-As-DzSur, is successfully genetically encoded, biotechnologically produced, and directly self-assembled. The performance of the biologically produced D4-3-As-DzSur in targeted gene regulation has been confirmed by in vitro and in vivo studies. The biological production capability will fulfill the low-cost and large-scale production of all-DNA nanomedicines and promote clinical applications.


Activation of sodium persulfate by TiO2@MIL-101(Fe): Boosting the Fenton-like process by interfacial charge transfer.
Advanced oxidation processes based on sulfate radicals are considered as a promising approach for environmental remediation. In this study, TiO2@MIL-101(Fe) is successfully fabricated by a facile impregnation method and is used for sodium persulfate (SPS) activation. TiO2@MIL-101@SPS combines the advantages of photocatalysis and SPS activation, which shows high removal efficiency for nitrobenzene and methyl orange. In addition, the effect of multiple factors, including light source, SPS amount and catalyst amount, on nitrobenzene degradation have been investigated. Results show that the nitrobenzene degradation efficiency is up to 66.53 % while that of TOC removal is 32.21 % under 4-h visible light irradiation with 30 mg catalyst and 1.6 mM SPS. Moreover, LC-MS have been carried out to study the route of nitrobenzene degradation. Besides, ESR analysis reveals that both ●SO4- and ●OH radicals are generated sustainably under visible light irradiation, and more ●OH radicals can be detected owing to the synergic effect of photocatalysis and SPS activation. Interfacial charge transfer effect provides photoinduced electrons for the Fe3+/Fe2+ cycle in MIL-101(Fe), which boosts the SPS activation process, resulting in high photocatalytic activity.


Induction of rat muscle insulin resistance by epinephrine is accompanied by increased interstitial glucose and lactate concentrations.
Muscle glucose uptake and lactate release during beta-adrenergic stimulation by epinephrine (epi) and beta-adrenergic blockade by propranolol (prop) were investigated during an euglycaemic hyperinsulinaemic (30 pmol x kg(-1) x min(-1)) with or without added somatostatin (0.1 microg/min; pancreatic) clamp in female rats. To assess the interstitial insulin, glucose and lactate concentrations, microdialysis was done in the medial femoral muscle in both legs. The influence of muscle skeletal blood flow on interstitial insulin, glucose and lactate was examined with the microsphere technique, using 57Co-microspheres. Epinephrine decreased glucose infusion rate by about 75% (p < 0.0001) and increased concentrations of interstitial glucose by about 35% (p < 0.001) and lactate by about 65% (p < 0.01). Plasma insulin concentration increased during beta-adrenergic stimulation by about 25% (p < 0.05) whereas the interstitial insulin concentration was unchanged. Muscle blood flow in the hindlimb was considerably enhanced by about 130%, (p < 0.001) by epinephrine. Infusion of propranolol totally abolished all the above effects induced by epinephrine. The data show that insulin resistance and vasodilation induced by beta-adrenergic stimulation with epinephrine is accompanied by increased interstitial glucose as well as lactate concentrations in muscle. The increased interstitial glucose concentration is the result of a decreased cellular uptake of glucose together with an increased capillary delivery of glucose by vasodilation. It is concluded that the severe cellular resistance to insulin induced by epinephrine could not be overcome either by the increased insulin secretion or by vasodilation.


Ransomware Attack Associated With Disruptions at Adjacent Emergency Departments in the US.
Cyberattacks on health care delivery organizations are increasing in frequency and sophistication. Ransomware infections have been associated with significant operational disruption, but data describing regional associations of these cyberattacks with neighboring hospitals have not been previously reported, to our knowledge. To examine an institution's emergency department (ED) patient volume and stroke care metrics during a month-long ransomware attack on a geographically proximal but separate health care delivery organization. This before and after cohort study compares adult and pediatric patient volume and stroke care metrics of 2 US urban academic EDs in the 4 weeks prior to the ransomware attack on May 1, 2021 (April 3-30, 2021), as well as during the attack and recovery (May 1-28, 2021) and 4 weeks after the attack and recovery (May 29 to June 25, 2021). The 2 EDs had a combined mean annual census of more than 70 000 care encounters and 11% of San Diego County's total acute inpatient discharges. The health care delivery organization targeted by the ransomware constitutes approximately 25% of the regional inpatient discharges. A month-long ransomware cyberattack on 4 adjacent hospitals. Emergency department encounter volumes (census), temporal throughput, regional diversion of emergency medical services (EMS), and stroke care metrics. This study evaluated 19 857 ED visits at the unaffected ED: 6114 (mean [SD] age, 49.6 [19.3] years; 2931 [47.9%] female patients; 1663 [27.2%] Hispanic, 677 [11.1%] non-Hispanic Black, and 2678 [43.8%] non-Hispanic White patients) in the preattack phase, 7039 (mean [SD] age, 49.8 [19.5] years; 3377 [48.0%] female patients; 1840 [26.1%] Hispanic, 778 [11.1%] non-Hispanic Black, and 3168 [45.0%] non-Hispanic White patients) in the attack and recovery phase, and 6704 (mean [SD] age, 48.8 [19.6] years; 3326 [49.5%] female patients; 1753 [26.1%] Hispanic, 725 [10.8%] non-Hispanic Black, and 3012 [44.9%] non-Hispanic White patients) in the postattack phase. Compared with the preattack phase, during the attack phase, there were significant associated increases in the daily mean (SD) ED census (218.4 [18.9] vs 251.4 [35.2]; P < .001), EMS arrivals (1741 [28.8] vs 2354 [33.7]; P < .001), admissions (1614 [26.4] vs 1722 [24.5]; P = .01), patients leaving without being seen (158 [2.6] vs 360 [5.1]; P < .001), and patients leaving against medical advice (107 [1.8] vs 161 [2.3]; P = .03). There were also significant associated increases during the attack phase compared with the preattack phase in median waiting room times (21 minutes [IQR, 7-62 minutes] vs 31 minutes [IQR, 9-89 minutes]; P < .001) and total ED length of stay for admitted patients (614 minutes [IQR, 424-1093 minutes] vs 822 minutes [IQR, 497-1524 minutes]; P < .001). There was also a significant increase in stroke code activations during the attack phase compared with the preattack phase (59 vs 102; P = .01) as well as confirmed strokes (22 vs 47; P = .02). This study found that hospitals adjacent to health care delivery organizations affected by ransomware attacks may see increases in patient census and may experience resource constraints affecting time-sensitive care for conditions such as acute stroke. These findings suggest that targeted hospital cyberattacks may be associated with disruptions of health care delivery at nontargeted hospitals within a community and should be considered a regional disaster.


A new formula for rapid assessment of pericardial effusion volume by computed tomography.
The aim of this study was to evaluate a new formula for the rapid assessment of pericardial effusion (PE) volume by computed tomography. Twenty computed tomographic scans positive for PE were reviewed by two observers. Diameters of PE were measured at four locations. Additionally, PE volume was assessed by volumetry. The correlation between PE diameters and volume was evaluated, and a linear equation was derived for each diameter location. To test validity and reliability of the measurements, intraclass correlation and Bland-Altman analysis were performed. Good validity was expressed by strong correlations between diameter measurements at all four locations and PE volume (all R values >0.80 and P values <.0001). Intraclass correlation (all coefficients >0.75) and Bland-Altman analysis revealed good interobserver and intraobserver reliability of diameter measurements. The best values were observed for apical diameter measurements. The following linear equation was derived for apical diameter measurements: PE volume = 296 (mL/cm) × apical diameter (cm) - 32 mL. PE volume can rapidly be assessed by apical PE diameter measurement using the simplified formula PE volume = 0.3 (L/cm) × apical diameter (cm).


Autoimmune encephalitis with posterior reversible encephalopathy syndrome: A case report.
Posterior reversible encephalopathy syndrome (PRES) is a neuroimaging-based syndrome and is associated with multifocal vasogenic cerebral edema. Patients with PRES frequently demonstrate headache, seizure, encephalopathy, altered mental function, visual loss and so on. We here report a patient who showed persistent neurologic deficits after PRES and was ultimately diagnosed with autoimmune encephalitis (AE). This case exhibits a rare imaging manifestation of anti-casper 2 encephalitis which was initially well-matched with PRES and associated vasogenic edema. AE should be further considered when the etiology, clinical manifestations, and course of PRES are atypical.


Exploring the reciprocal relationship between activities of daily living disability and depressive symptoms among middle-aged and older Chinese people: a four-wave, cross-lagged model.
Early studies have shown a relationship between activities of daily living (ADL) disability and depressive symptoms in older people. However, discussions on the direction of this relationship are insufficient. The study's objective was to assess the reciprocal relationship between ADL disability and depressive symptoms among middle-aged and older Chinese people. Data was collected in four waves of a nationwide survey, the China Health and Retirement Longitudinal Study (CHARLS), which was carried out in 2011, 2013, 2015, and 2018. In total, this study included 4,124 participants aged ≥ 45 years at baseline. A summing score of the eleven items for basic activities of daily living (BADL) and instrumental activities of daily living (IADL) was calculated to indicate the degree of ADL disability. The 10-item Centre for Epidemiological Studies Depression Scale (CESD-10) was adopted to measure depressive symptoms. The reciprocal relationship between ADL disability and depressive symptoms was tested by cross-lagged models. At baseline, 911 (22.1%) participants were classified as having difficulties with ADL, and the prevalence of depressive symptoms was 34.4% (1,418). Among middle-aged and older people in China, there was a significant reciprocal and longitudinal relationship between ADL disability and depressive symptoms. People who had difficulty with ADL faced a higher risk of depressive symptoms, and those who suffered from depressive symptoms were accompanied by an increase in ADL disability in the following years. The subgroup analysis on age also showed that ADL disability was reciprocally and longitudinally related to depressive symptoms. However, only women showed similar results in the subgroup analysis on gender. This study shows that ADL disability is bi-directionally related to depressive symptoms in middle-aged and older Chinese people over time. The results suggest we should identify ADL disability and bad psychological conditions in time to prevent subsequent mutual damage among middle-aged and older Chinese people, a vulnerable group rising in the future.


Insights into the Hydrolytic Polymerization of Trimethoxymethylsilane. Crystal Structure of (MeO)2MeSiONa.
The commercially practiced conversion of trimethoxymethylsilane (MTM) to [OSi(OMe)Me)]n polymers and resins is assumed to proceed via the silanol (MeO)2MeSiOH. Access to this crucial silanol is gained via the synthesis of (MeO)2MeSiONa, the first methoxysilanoate to be crystallographically characterized. Mild protonation of this silanoate gives (MeO)2MeSiOH, which is shown to condense with (MeO)2MeSiOH but not with MTM. Condensation generates reactive disiloxanols but does not produce symmetric disiloxanes. Parallel results were obtained with (MeO)2PhSiOH.


Sorption of selenium(IV) onto magnetite in the presence of silicic acid.
Sorption of selenium(IV) and silicic acid onto magnetite (Fe(3)O(4)) was investigated in binary systems, with concentrations of silicic acid under the solubility limit of amorphous silica. Using the double diffuse layer model (DDLM), surface complexation constants of selenium(IV) and H(4)SiO(4) onto magnetite were extracted using Fiteql 4.0. Then, prediction curves of the sorption of selenium(IV) in the presence of silicic acid onto magnetite were obtained, using the calculated surface complexation constants. Finally, laboratory experiments were performed and showed a competition between selenium(IV) and silicic acid for the surface sites of magnetite. Experimental results matched the model predictions, confirming its ability to model qualitatively and quantitatively the ternary system.


Spatiotemporal dynamics of nanowire growth in a microfluidic reactor.
Co-integration of nanomaterials into microdevices poses several technological challenges and presents numerous scientific opportunities that have been addressed in this paper by integrating zinc oxide nanowires (ZnO-NWs) into a microfluidic chamber. In addition to the applications of these combined materials, this work focuses on the study of the growth dynamics and uniformity of nanomaterials in a tiny microfluidic reactor environment. A unique experimental platform was built through the integration of a noninvasive optical characterization technique with the microfluidic reactor. This platform allowed the unprecedented demonstration of time-resolved and spatially resolved monitoring of the in situ growth of NWs, in which the chemicals were continuously fed into the microfluidic reactor. The platform was also used to assess the uniformity of NWs grown quickly in a 10-mm-wide microchamber, which was intentionally chosen to be 20 times wider than those used in previous attempts because it can accommodate applications requiring a large surface of interaction while still taking advantage of submillimeter height. Further observations included the effects of varying the flow rate on the NW diameter and length in addition to a synergetic effect of continuous renewal of the growth solution and the confined environment of the chemical reaction.


The application of theory to triage decision-making.
Theory in nursing is frequently thought of as being a mainly academic exercise with little relevance to the everyday practice of nursing. In nursing there is disagreement about what theory is and what it is not. Scientific theory is an abstract systematic explanation of how concepts are related to each other. Many nursing theories do not fit this description and should therefore, in the opinion of the authors, be thought of as models. Nursing knowledge has been described as the knowledge that is useful to nurses, whether it is derived from the discipline of nursing or other disciplines. Decision-making (DM) and triage nursing have been investigated by several nurse researchers, however, most have not clearly articulated a theoretical or conceptual framework. The recognition primed decision (RPD) model is based on research about DM under uncertain conditions such as time pressure, limited time available, high stakes, and changing cues. The context of emergency triage nursing DM is congruent with the RPD model. The authors propose that the RPD model can serve as a foundation for research that seeks to understand DM by triage nurses with the aim of yielding new knowledge that is useful for their practice.


Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2).
Lp-PLA2 has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery of a new fragment derived chemotype that interacts with the active site of Lp-PLA2. The starting fragment hit was discovered through an X-ray fragment screen and showed no activity in the bioassay (IC50 > 1 mM). The fragment hit was optimized using a variety of structure-based drug design techniques, including virtual screening, fragment merging, and improvement of shape complementarity. A novel series of Lp-PLA2 inhibitors was generated with low lipophilicity and a promising pharmacokinetic profile.


18F-FDG PET/CT in the diagnosis of prosthetic valve endocarditis.
Recent studies have shown promising results using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the diagnosis of prosthetic valve endocarditis (PVE). However, previous studies did not include negative controls. The aim of this study was to compare (18)F-FDG-uptake around prosthetic aortic valves in patients with and without PVE and to determine the diagnostic performance of (18)F-FDG PET/CT in the diagnosis of PVE. (18)F-FDG PET/CT examinations in patients with a prosthetic aortic valve performed 2008-2014 were retrieved. Eight patients with a final diagnosis of definite PVE were included in the analysis of the diagnostic performance of (18)F-FDG PET/CT. Examinations performed on suspicion of malignancy in patients without PVE (n = 19) were used as negative controls. Visual and semi-quantitative analysis was performed. Maximal standardized uptake value (SUVmax) in the valve area was measured and SUVratio was calculated by dividing valve SUVmax by SUVmax in the descending aorta. The sensitivity was 75 %, specificity 84 %, positive likelihood ratio [LR(+)] 4.8 and negative likelihood ratio [LR(-)] 0.3 on visual analysis. Both SUVmax and SUVratio were significantly higher in PVE patients [5.8 (IQR 3.5-6.5) and 2.4 (IQR 1.7-3.0)] compared to non-PVE patients [3.2 (IQR 2.8-3.8) and 1.5 (IQR 1.3-1.6)] (p < 0.001). ROC-curve analysis of SUVratio yielded an area under the curve of 0.90 (95 % CI 0.74-1.0). (18)F-FDG-uptake around non-infected aortic prosthetic valves was low. The level of (18)F-FDG-uptake in the prosthetic valve area showed a good diagnostic performance in the diagnosis of PVE.


Prolonged analgesia from Bupisome and Bupigel formulations: from design and fabrication to improved stability.
There is a compelling need for an ultralong-acting local anesthetic. Previously, we demonstrated in mice and humans that encapsulation of bupivacaine into large multivesicular liposomes (Bupisome) prolongs drug residence time and analgesic duration at the injection site while reducing peak plasma concentration. However, we observed considerable leakage of bupivacaine from the liposomes during storage at 4 °C. This deficiency was overcome by modifying the lipid composition of Bupisome and by entrapping them in a Ca-alginate cross-linked hydrogel (Bupigel), forming stable, soft, injectable (3-5 mm) beads. Bupisome are not released from Bupigel, but their encapsulated bupivacaine is released into the bulk solution. Adding 0.5% to 2.0% free bupivacaine to the Bupigel prevented net loss of bupivacaine from the Bupisome after storage at 4 °C for 2 years, and at 37 °C enough bupivacaine was released to prolong analgesia. For injection subcutaneously into mice, the beads are drawn into a syringe, leaving the small amount of free bupivacaine behind. Both Bupisome and Bupigel formulations significantly prolonged analgesia in mice compared to standard bupivacaine, with Bupigel performing better than Bupisome.


Train accidents and orthopaedic morbidity. The Groote Schuur Hospital experience.
The Department of Orthopaedic Surgery at Groote Schuur Hospital, Cape Town, treats a disturbingly large number of train-associated injuries. The magnitude of the problem, the associated high morbidity and the serious socio-economic implications are outlined.


Severe malaria.
Malaria represents a medical emergency. Without rapid diagnosis and treatment, it can progress and lead to severe complications and, eventually, death. Severe malaria is almost always caused by Plasmodium falciparum. Here, we present an image showing a set of hematological findings associated with severe malaria, highlighting the importance of a correct morphological diagnosis.


Effect of chain unsaturation on the structure and thermotropic properties of galactocerebrosides.
Differential scanning calorimetry (DSC) and x-ray diffraction have been used to study the effect of increasing chain-unsaturation on the structure and properties of the hydrated cerebrosides N-stearoyl, -oleoyl, and -linoleoyl galactosylsphingosine (NSGS, NOGS, and NLnGS, respectively). DSC of hydrated (70 wt% water) NSGS shows an endothermic transition at 85 degrees C (delta H = 18.0 kcal/mol NSGS) and a broad exothermic transition at 40-60 degrees C, the latter being dependent upon the previous cooling rate. X-Ray diffraction patterns recorded at 21, 61, and 86 degrees C provide evidence for interconversions between metastable and stable crystalline NSGS bilayer phases. The properties of the unsaturated-chain cerebrosides are more complex. Hydrated NOGS shows a single endothermic transition at 44.8 degrees C (delta H = 11.5 kcal/mol NOGS). However, incubation of NOGS at 49 degrees C for 24 h results in a second transition at 55.5 degrees C. By cycling NOGS between 0 and 49 degrees C complete conversion into this higher melting phase (delta H = 12.1 kcal/mol NOGS) is achieved. X-ray diffraction confirms a bilayer phase at all temperatures and delineates the conversions between a crystalline phase at 21 degrees C (bilayer period d = 56.5A), a second crystalline phase at 47 degrees C (d = 69.9A), and a liquid crystalline phase at 59 degrees C (d = 52.0A). The more unsaturated NLnGS shows two transitions, a sharp transition at 28 degrees C (delta H = 8.0 kcal/mol NLGS) and a broad, low-enthalpy transition at 42 degrees C (delta H = 0.4 kcal/mol NLGS). Again, incubation between the two transitions leads to a single transition at 44 degrees C (delta H = 9.3 kcal/mol NLGS). X-ray diffraction demonstrates conversions between two crystalline bilayer phases (d = 55.2A and d = 68.4A), and a liquid crystalline bilayer phase (d = 51.8A). Thus, increased unsaturation in the amide-linked fatty acyl chain of cerebrosides results in decreased chain-melting temperatures (NSGS greater than NOGS greater than NLnGS) and has marked effects on their structural properties.


Stakeholder Perspectives on the School Experiences of Students With Traumatic Brain Injury: The Effects of COVID-19 Pandemic on Service Delivery.
For students with traumatic brain injury (TBI), the COVID-19 pandemic exacerbated challenges they were already experiencing at school. This qualitative study employed focus groups and interviews with students, parents, school, and medical personnel to explore the school experiences of students with TBI. Thematic qualitative analyses were used. Key themes from the analysis include (a) incidence of brain injuries decreased; (b) screen time for students with TBI exacerbated symptoms; (c) COVID protocols at school made it difficult for educators to identify and provide accommodations for students with TBI; (d) COVID protocols at school could inadvertently exacerbate mental health difficulties after a TBI; and (e) COVID-related logistics increased the time between an injury and return to school or return to play. The results from this study suggest that professional development for teachers supporting students with TBI is needed, especially for online learning environments. Additionally, because mental/behavioral health concerns may arise for students with TBI in online learning environments, school health care providers can work with families to assess a student's mental health, making referrals to appropriate supports. There is a significant need for professional development and school-wide infrastructure supportive of students with TBI.


Technical note: Determining the applicability of a clinical knowledge-based learning model via prospective outlier detection.
Knowledge-based planning (KBP) is increasingly implemented clinically because of its demonstrated ability to improve treatment planning efficiency and reduce plan quality variations. However, cases with large dose-volume histogram (DVH) prediction uncertainties may still need manual adjustments by the planner to achieve high plan quality. The purpose of this study is to develop a data-driven method to detect patients with high prediction uncertainties so that intentional effort is directed to these patients. We apply an anomaly detection method known as the local outlier factor (LOF) to a dataset consisting of the training set and each of the prospective patients considered, to evaluate their likelihood of being an anomaly when compared with the training cases. Features used in the LOF analysis include anatomical features and the model-generated DVH principal component scores. To test the efficacy of the proposed model, 142 prostate patients were retrieved from the clinical database and split into a training dataset of 100 patients and a test dataset of 42 patients. The outlier identification performance was quantified by the difference between the DVH prediction root-mean-squared errors (RMSE) of the identified outlier cases and that of the remaining inlier cases. With a predefined LOF threshold of 1.4, the inlier cases achieved average RMSEs of 5.0 and 6.7 for bladder and rectum, while the outlier cases have substantially higher RMSEs of 6.7 and 13.0 in comparison. We propose a method that can determine the prospective patient's outlier status. This method can be integrated into existing automated treatment planning workflows to reduce the risk of generating suboptimal treatment plans while providing an upfront alert to the treatment planner.


Atrial signal variations and pacemaker malsensing during exercise: a study in the time and frequency domain.
To give some explanation for atrial malsensing in dual chamber pacing that occurs only during exercise, atrial electrograms from 33 patients were telemetrically recorded and analyzed in both the time and frequency domains. During exercise, an overall decrease from 6.4 +/- 1.9 to 5.6 +/- 1.9 mV (-11%) in the atrial signal amplitude was noted. Despite considerable variability among patients, marked changes occurred in 15 patients whose signals diminished by 11 to 49%. Slew rates showed a similar decrease from 1.35 +/- 0.45 to 1.18 +/- 0.45 V/s (-10.8%), with individual changes of as much as -51%. Signal attenuation in the time domain correlated well with frequency data, exhibiting a highly significant reduction of signal energy between 25 and 105 Hz. However, spectral distribution changed from rest to exercise, with a relative increase of signal energy in the range between 5 and 25 Hz and a decrease at higher frequencies. Individual changes differed widely when low (15 to 65 Hz) and high (65 to 115 Hz) frequencies were compared, but in a group of 11 patients signal attenuation in the high frequency band was more pronounced (-45%) than in the low frequency band (-23%). The clinical impact of the change in frequency distribution during ergometry was visualized by computer simulation of two different (low and high bandpass) filters. Although in individual patients, both characteristics may be favorable with respect to atrial sensing, it was observed in 11 patients that high pass filtering attenuates signal amplitudes by 10 to 24% in excess of the variation without filtering.(ABSTRACT TRUNCATED AT 250 WORDS)


Diterpenoid Alkaloids and One Lignan from the Roots of Aconitum pendulum Busch.
Diterpenoid alkaloids have neroprotective activity. Herein, three napelline-type diterpenoid alkaloids 1-3, two aconitine-type diterpenoid alkaloids 4-5, and one isoquinline-type alkaloid 6, as well as one lignan glycoside 7, have been isolated from the roots of Aconitum pendulum Busch. Compounds 1 and 7 were new compounds, and their chemical structures were determined on the basis of nuclear magnetic resonance (NMR) spectra and mass spectrometry analysis. A ThT assay revealed that compound 2 showed significant disaggregation potency on the Aβ1-42 aggregates.


Use of tandem carbon microfiber columns for on-line fractionation strategy of reducing ion suppression effects in electrospray ionization-mass spectrometry.
As we all know, the complexity and diversity of complex sample are confronting with challenge of high-sensitive mass spectrometry analysis, especially direct mass spectrometry. The work proposed a two-dimensional carbon microfiber fractionation (2DμCFs) system for the reduction of ion suppression effects in electrospray ionization mass spectrometry (ESI-MS). The 2DμCFs system can on-line fractionated the complex sample into strong-polar, medium-polar and weak-polar fractions for sequential MS analysis. Direct analysis brings about the strong ion suppression effect up to 85%, but the fractionated analysis of 2DμCFs system can distinctly reduce the ion suppression effect to less than 43%, even close to none. And the fractionated analysis not only decrease the number of analytes of direct analysis, but also narrows down the polarity range of analytes within the droplets of ESI, contributing to the homogeneous distribution to reduce the ion suppression effect. As an example, the 2DμCFs system coupled with tandem mass spectrometry (MS/MS) was applied for fractionated analysis of Radix Puerariae extract in 4.5 min. Compared with direct MS/MS, the 2DμCFs-MS/MS shows the lower ion suppression and the more ionic species (m/z). In addition, and most of ionic species detected by the 2DμCFs-MS/MS, are the same as those by HPLC MS/MS. Furthermore, the 2DμCFs-MS/MS exhibit the good analysis repeatability of real sample with the RSDs less than 10.32% (intra-day), 7.12% (inter-day) and 14.28% (inter-batch of CFs and ACFs). The carbon fibers (CFs) and active carbon fibers (ACFs) columns, as the key parts, are conducive to achieve on-line fractionation of compounds based on the difference of polarity. The 2DμCFs system has the merits of on-line, speediness, low-pressure and recycle. More importantly, such fast and high-throughput method is advantageous for comprehensive screening of complex samples in drug, clinical, environment and plant.


[Xerosis].
The clinical characteristic of xerosis is rough or coarse skin. Physiopathologically, the structure of the stratum corneum is modified and abnormalities in keratinization, proliferation, surface lipid, water metabolism and also pH and sebum exist. There are two forms of xerosis: dry skin forms and ichtyosis or ichtyosis-like forms. Xerosis has many etiologies including external aggression, senescence, drugs, infection, atopy, deficiencies, malignant diseases, endocrine affections, eating disorders and renal failure in dialyzed patients. It provokes cutaneous discomfort and unaesthetic appearance that justify appropriate treatment. Treatment is essentially local, symptomatic and must be accompanied by general measures. Many products include moisturizers and emollients (keratolytics: salicylic acid, urea and alpha-hydroxy acid).


Data on antioxidant activity in grapevine (Vitis vinifera L.) following cryopreservation by vitrification.
Cryopreservation is used for the long-term conservation of plant genetic resources. This technique very often induces lethal injury or tissue damage. In this study, we measured indicators of viability and cell damage following cryopreservation and vitrification-cryopreservation in Vitis vinifera L. axillary buds cv. "Flame seedless" stored in liquid nitrogen (LN) for: three seconds, one hour, one day, one week and one month; after LN thawed at 38 °C for three minutes. The enzymatic activity of catalase (CAT) and superoxide dismutase (SOD), as well as the amount of malondialdehyde (MDA), total protein and viability were assayed.


Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility.
Fatty acids induce cholecystokinin (CCK) secretion and modify gastric motility, but the chain length requirements for these effects are not known. Nor is it clear whether the effects of fatty acids on gastric motility in humans are CCK mediated or directly exerted. The aim of this study was to determine the role of fatty acyl chain length in CCK secretion and in influencing gastric motility. Fatty acids were infused into the upper gut in healthy volunteers; plasma CCK was determined by radioimmunoassay. Effects of fatty acids on antral contractility were determined by percutaneous ultrasonography; effects on proximal gastric tone were studied during fundal distention. Plasma CCK concentration was consistently and similarly elevated by fatty acids with a chain of 12 carbon atoms or longer, whereas those of 11 or fewer carbon atoms failed to increase plasma CCK. A 12-carbon but not a 10-carbon-long chain fatty acid reduced antral contractile amplitude, an effect that was abolished by loxiglumide (a specific CCK-A receptor antagonist). The 12-carbon fatty acid also reduced proximal gastric tone more than the 10-carbon fatty acid. A highly specific, chain length-sensitive fatty acid recognition system exists in the proximal gut mediating CCK secretion and gastric motility. An additional, probably CCK-independent, effect of fatty acid also regulates proximal gastric tone.


A severe myopathy case in aged patient treated with high statin dosage.
Statins (S) are widely used drugs for cardiovascular prevention however their utilization may cause a various grade of muscle toxicity. Sometime S discontinuation alone is not sufficient to revert muscle injury and this can evolve in serious inflammatory muscle disease. In this case immunosuppressive medications are required to achieve remission. This case report describes a patient who developed rhabdomyolysis after recent S treatment initiation and the diagnostic work up have lead to the diagnosis of necrotizing autoimmune myopathy (NAM). We believe that the clinical case described here is a useful report of this rare toxicity and we aim to highlight the importance of its prompt recognition and treatment.


Applications of cognitive testing to group therapies with the chronically mentally ill.
Appreciation of the various cognitive deficits displayed by many chronic patients offers an alternative way of understanding each patient's predicament and an alternative way of approaching group and milieu therapies with chronic patients. Case examples taken from a test protocol based on neuropsychological testing procedures illustrate the clinical information that can be obtained in this important, but relatively unexplored area.


Toward a complete decision model of item and source recognition.
In a recognition memory test, subjects may be asked to decide whether a test item is old or new (item recognition) or to decide among alternative sources from which it might have been drawn for study (source recognition). Confidence-rating-based receiver operating characteristic (ROC) curves for these superficially similar tasks are quite different, leading to the inference of correspondingly different decision processes. A complete account of source and item recognition will require a single model that can be fit to the entire data set. We postulated a detection-theoretic decision space whose dimensions, in the style of Banks (2000), are item strength and the relative strengths of the two sources. A model that assumes decision boundaries of constant likelihood ratios, source guessing for unrecognized items, and nonoptimal allocation of attention can account for data from three canonical data sets without assuming any processes specifically devoted to recollection. Observed and predicted ROCs for one of these data sets are given in the article, and ROCs for the other two may be downloaded from the Psychonomic Society's Archive of Norms, Stimuli, and Data, www.psychonomic.org/archive.


High blood pressure in the young: why should we care?
While primary hypertension (HTN) clearly occurs in children and adolescents, the approach of many providers to such patients can best be described as ambivalent: the condition may be recognised, but is not acted upon. Such ambivalence may stem from incomplete understanding of the effects of high blood pressure in the young, which in turn is related to the shortage of information on long-term outcomes of primary childhood HTN. However, other evidence on the short- and long-term effects of blood pressure elevation in childhood clearly shows that it is not a benign condition at all. Childhood HTN warrants action to prevent adult cardiovascular disease.


[Influence of partial intraspecies deprivation on short-term image-driven memory in rats].
Behavior and short-term memory function were studied in adult rats risen under conditions of partial intraspecies social deprivation. Testing of delayed responses (and emotional state) showed that the partial deprivation of intraspecies communication at the early stage of postnatal ontogeny led not only to disorders of short-term memory in the adult rats, but also to behavioral alterations, which may be due to impaired development of the regulatory mechanisms of motivation and emotions.


Hypertension and age at onset of natural menopause in Korean postmenopausal women: Results from the Korea National Health and Nutrition Examination Survey (2008-2013).
Menopause is a natural phenomenon of aging, although the timing and management of menopause can significantly affect a woman's quality of life. It is therefore important to identify measures to ensure a healthy menopause. We set out to investigate the association between hypertension and early menopause in Korean women. This cross-sectional study was based on 2008-2013 data from the Korea National Health and Nutrition Examination Survey (KNHANES). Of the 53,829 participants surveyed, 13,584 women were selected. We analyzed the contents of the health interview, health examination, and nutrition survey. The main outcome was defined based on hazard ratios (HR) to identify the effects of hypertension on age at onset of menopause. Among postmenopausal women (n=6650), the mean age at onset of menopause was 50.4 years. Premenopausal hypertension was statistically significantly associated with age at menopause, oral contraceptive usage, household income, education level, occupation, marital status and smoking and drinking habits. With lower age at diagnosis of hypertension, HRs for menopause tended to be higher, and hypertension diagnosed before age 40 years conferred a statistically significantly higher HR (Model 1, HR=2.32, 95% CI=1.87-2.88; Model 2, HR=2.31, 95% CI=1.86-2.86; Model 3, HR=2.23, 95% CI=1.80-2.77; Model 4, HR=2.00, 95% CI=1.52-2.63). Premature menopause is strongly associated with lifestyle factors, in combination with incomplete management of chronic diseases. Our findings support the hypothesis that younger age at diagnosis of hypertension is associated with younger age at onset of menopause in Korean women.


Effect of propranolol on mepivacaine serum concentrations in dental practice.
The objective of this study was to determine the effect of propranolol pretreatment on mepivacaine serum concentrations in dental patients. In a double blind, randomized, 2-way crossover study, 10 patients ingested 30 mg propranolol or placebo, 2 hours before local anesthesia for dental scaling. Each subject received a single dose of 51 mg mepivacaine for posterior superior alveolar nerve block. Mepivacaine in venous serum was measured for up to 1 hour, after 5, 15, 30, 45, and 60 minutes from injection. Serum concentrations of mepivacaine were determined by gas chromatography. Blood pressure and heart rate were measured before and after propranolol or placebo and after each sampling. Peak serum concentrations of mepivacaine, C(max) (1.214 +/- 0.746 microg/mL(-1)), were significantly increased by propranolol (2.249 +/- 1.559 microg/mL(-1), P < .05). Propranolol pretreatment reduced blood pressure and heart rate. Although propranolol pretreatment increased almost doublefold mepivacaine serum concentrations and reduced blood pressure and heart rate, mepivacaine can be used safely in dental patients taking propranolol for short-duration interventions.


A direct role of the homeodomain proteins Phox2a/2b in noradrenaline neurotransmitter identity determination.
Development of noraderenergic (NA) neurons in the vertebrate brain is dependent on the homeodomain proteins Phox2a and 2b. Here, we show that Phox2a directly controls the NA identity by activating NA-synthesizing dopamine beta-hydroxylase (DBH ) gene. Single point mutations in the homeodomain of Phox2a resulted in a failure to transactivate the DBH promoter in vitro and resulted in the loss of NA neurons in vivo. In addition, injection of Phox2a-specific antisense oligonucleotide induced the loss of NA neurons in developing zebrafish. Phox2a and 2b activate the DBH promoter and bind to three domains (PBD1-3). PBD1 is composed of two overlapping sites with which monomers of Phox2a can interact. In contrast, PBD2 and 3 interact with the dimeric form of Phox2a. Mutations in three or four, but not one or two, of the binding sites completely abolished activation of the DBH promoter by Phox2a or 2b, while the conversion of PBD3 to a consensus motif (ATTA) improved the DBH promoter activity by > 10-fold. Taken together, these findings establish that Phox2a and 2b control the development of NA neurons in part by directly transactivating DBH transcription through interactions with four binding sites clustered in the proximal promoter.


[Percutaneous coronary revascularization in patients with renal insufficiency].
An ideal strategy of percutaneous coronary revascularization in patients with renal insufficiency has not been established yet. Our aim was to compare in this group the clinical results of bare metal stents and drug-eluting stents, and identify predictors. In a group of 200 patients with renal disease, 93 received bare metal stents and 107 drug-eluting stents; for over 2 years we studied rates of a combined event: death, non fatal myocardial infarction, or target lesion revascularization. We did not identify differences in the combined event. With multivariate analysis, peripheral arterial disease, left ventricular ejection fraction <45% and treatment with statins were predictor factors. We had no evidence of the superiority of any type of stent in the revascularization in patients with chronic renal insufficiency.


Sperm selection: effect on sperm DNA quality.
The selection of spermatozoa without DNA fragmentation and chromosomal diseases prior to assisted reproductive techniques helps to optimize the outcome of the treatment; in particular, sperm selection prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is crucial. In fact, although ICSI has been successfully and safely applied worldwide for almost 20 years, at the present time we have no real knowledge regarding the hypothetical long-term side effects on ICSI adults, given the increased likelihood of spermatozoa with defective nuclear content fertilizing oocytes.In the case of DNA damage, the basal sperm DNA fragmentation rate can be significantly reduced by some sperm processing procedures that improve the percentage of spermatozoa with normal chromatin structure by filtering out DNA-damaged spermatozoa. After this first step, new advances in micromanipulation can be performed to choose the "ideal" mature spermatozoa for ICSI, reducing potential damage to the gametes. In fact, it is possible to prevent fertilization by DNA-damaged and chromosomal-unbalanced spermatozoa by selecting ICSI sperm by maturation markers such as hyaluronic acid or other zona pellucida receptors. Furthermore, novel noninvasive imaging techniques can be valid tools for helping in the morphological selection of ICSI spermatozoa.


Soil quality assessment using GIS-based chemometric approach and pollution indices: Nakhlak mining district, Central Iran.
This paper is a comprehensive assessment of the quality of soil in the Nakhlak mining district in Central Iran with special reference to potentially toxic metals. In this regard, an integrated approach involving geostatistical, correlation matrix, pollution indices, and chemical fractionation measurement is used to evaluate selected potentially toxic metals in soil samples. The fractionation of metals indicated a relatively high variability. Some metals (Mo, Ag, and Pb) showed important enrichment in the bioavailable fractions (i.e., exchangeable and carbonate), whereas the residual fraction mostly comprised Sb and Cr. The Cd, Zn, Co, Ni, Mo, Cu, and As were retained in Fe-Mn oxide and oxidizable fractions, suggesting that they may be released to the environment by changes in physicochemical conditions. The spatial variability patterns of 11 soil heavy metals (Ag, As, Cd, Co, Cr, Cu, Mo, Ni, Pb, Sb, and Zn) were identified and mapped. The results demonstrated that Ag, As, Cd, Mo, Cu, Pb, Sb, and Zn pollution are associated with mineralized veins and mining operations in this area. Further environmental monitoring and remedial actions are required for management of soil heavy metals in the study area. The present study not only enhanced our knowledge regarding soil pollution in the study area but also introduced a better technique to analyze pollution indices by multivariate geostatistical methods.


Tracking the progression of the human inner cell mass during embryonic stem cell derivation.
The different pluripotent states of mouse embryonic stem cells (ESCs) in vitro have been shown to correspond to stages of mouse embryonic development. For human cells, little is known about the events that precede the generation of ESCs or whether they correlate with in vivo developmental stages. Here we investigate the cellular and molecular changes that occur during the transition from the human inner cell mass (ICM) to ESCs in vitro. We demonstrate that human ESCs originate from a post-ICM intermediate (PICMI), a transient epiblast-like structure that has undergone X-inactivation in female cells and is both necessary and sufficient for ESC derivation. The PICMI is the result of progressive and defined ICM organization in vitro and has a distinct state of cell signaling. The PICMI can be cryopreserved without compromising ESC derivation capacity. As a closer progenitor of ESCs than the ICM, the PICMI provides insight into the pluripotent state of human stem cells.


[A computer system for the synchronous staged analysis of the indices of bioelectrical activity and systemic hemodynamics].
Programmes have been designed for computerized assessment of bioelectrical impulse amplitude, duration and frequency, simultaneously with instant indexes of systolic, diastolic arterial pressure and heart rate.


3 '2' 1: Orthodontic re-positioning of canines into central incisors.
Resorption of lateral incisors caused by impacted maxillary canines is frequently reported. However, resorption of the central incisor is less common and management of such a finding can prove to be a challenge for the clinician. This article reviews the literature of impacted canines and incisor resorption. The management of two cases of severe central incisor resorption caused by an impacted maxillary canine is also described.


Resolving the profile of metabolites generated during oxidation of dibenzofuran and chlorodibenzofurans by the biphenyl catabolic pathway enzymes.
Although the metabolism of dibenzofuran by the biphenyl catabolic enzymes had been inferred in previous reports, the metabolic pattern has never been determined unambiguously. In this work, we describe the evolved biphenyl dioxygenase (BPDO) RR41 that exhibits a higher turnover rate of metabolism toward dibenzofuran and chlorodibenzofurans than the parental Burkholderia xenovorans LB400 BPDO. We used RR41 BPDO to identify unambiguously the metabolites produced from the oxygenation of dibenzofuran by LB400 BPDO, and we evaluated their further metabolism by the biphenyl catabolic pathway enzymes of strain LB400. RR41 BPDO was obtained by saturation mutagenesis of targeted amino acid residues. I335F336N338I341L409 of LB400 BphA were replaced by A335M336Q338V341F409 in RR41 BphA. Data confirm the critical role played by these amino acid residues for substrate specificity and regiospecificity.


Repurposing small-molecule drugs for modulating toxic protein aggregates in neurodegenerative diseases.
Neurodegenerative diseases (NDs) are often age-related disorders that can cause dementia in people, usually over 65 years old, are still lacking effective therapies. Some NDs have recently been linked to toxic protein aggregates, for example Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington disease; therefore, mulating toxic protein aggregates would be a promising therapeutic strategy. Moreover, drug repurposing, in other words exploiting drugs that are already in use for another indication, has been attracting mounting attention for potential therapeutic purposes in NDs. Thus, in this review, we focus on summarizing a series of repurposed small-molecule drugs for eliminating or inhibiting toxic protein aggregates and further discuss their intricate molecular mechanisms to improve the current ND treatment. Taken together, these findings will shed new light on exploiting more repurposed small-molecule drugs targeting different types of toxic proteins to fight NDs in the future.


Determination of partition coefficients n-octanol/water for treosulfan and its epoxy-transformers: an example of a negative correlation between lipophilicity of unionized compounds and their retention in reversed-phase chromatography.
For the last decade an alkylating agent treosulfan (TREO) has been successfully applied in clinical trials in conditioning prior to hematopoietic stem cell transplantation. Pharmacological activity of the pro-drug depends on its epoxy-transformers, monoepoxide (S,S-EBDM) and diepoxide (S,S-DEB), which are formed in a non-enzymatic consecutive reaction accompanied by a release of methanesulfonic acid. In the present study partition coefficient n-octanol/water (POW) of TREO as well as its biologically active epoxy-transformers was determined empirically (applying a classical shake-flask method) and in silico for the first time. In vitro the partition was investigated at 37°C in the system composed of the pre-saturated n-octanol and 0.05 M acetate buffer pH 4.4 adjusted with sodium and potassium chloride to ionic strength of 0.16 M. Concentration of the analytes was quantified by reversed-phase high performance liquid chromatography (RP-HPLC) method in which retention time increased from S,S-DEB to TREO. It was shown that neither association nor dissociation of the tested compounds in the applied phases occurred. Calculated logPOW (TREO: -1.58±0.04, S,S-EBDM: -1.18±0.02, S,S-DEB: -0.40±0.03) indicate the hydrophilic character of the all three entities, corresponding to its pharmacokinetic parameters described in the literature. Experimentally determined logPOW of the compounds were best comparable to the values predicted by algorithm ALOGPs. Interestingly, the POW values determined in vitro as well as in silico were inversely correlated with the retention times observed in the endcapped RP-HPLC column. It might be explained by the fact that a cleavage of methansulfonic acid from a small molecule of TREO generates significant changes in the molecular structure. Consequently, despite the common chemical origin, TREO, S,S-EBDM and S,S-DEB do not constitute a 'congeneric' series of compounds. We concluded that this might occur in other low-weight species, therefore measurement of their POW by RP-HPLC had to be applied with a special care.


Adiponectin affects lung epithelial A549 cell viability counteracting TNFα and IL-1ß toxicity through AdipoR1.
Adiponectin (Acrp30) exerts protective functions on metabolic and cellular processes as energy metabolism, cell proliferation and differentiation by two widely expressed receptors, AdipoR1 and AdipoR2. To date, the biological role of Acrp30 in lung has not been completely assessed but altered levels of Acrp30 and modulated expression of both AdipoRs have been related to establishment and progression of chronic obstructive pulmonary disease (COPD) and lung cancer. Here, we investigated the effects of Acrp30 on A549, a human alveolar epithelial cell line, showing how, in a time and dose-dependent manner, it decreases cell viability and increases apoptosis through ERK1/2 and AKT. Furthermore, we examined the effects of Acrp30 on A549 cells exposed to TNFα and/or IL-1ß, two potent lung inflammatory cytokines. We showed that Acrp30, in dose- and time-dependent manner, reduces cytotoxic effects of TNFα and/or IL-1ß improving cell viability and decreasing apoptosis. In addition, Acrp30 inhibits NF-κB nuclear trans-activation and induces the expression of the anti-inflammatory IL-10 cytokine without modifying that of pro-inflammatory IL-6, IL-8, and MCP-1 molecules via ERK1/2 and AKT. Finally, specifically silencing AdipoR1 or AdipoR2, we observed that NF-κB inhibition is mainly mediated by AdipoR1. Taken together, our data provides novel evidence for a direct effect of Acrp30 on the proliferation and inflammation status of A549 cells strongly supporting the hypothesis for a protective role of Acrp30 in lung. Further studies are needed to fully elucidate the Acrp30 lung effects in vivo but our results confirm this adipokine as a promising therapeutic target in lung diseases.


Cold ischemia >4 hours increases heart transplantation mortality. An analysis of the Spanish heart transplantation registry.
Cold ischemia time (CIT) has been associated to heart transplantation (HT) prognosis. However, there is still uncertainty regarding the CIT cutoff value that might have relevant clinical implications. We analyzed all adults that received a first HT during the period 2008-2018. CIT was defined as the time between the cross-clamp of the donor aorta and the reperfusion of the heart. Primary outcome was 1-month mortality. We included 2629 patients, mean age was 53.3 ± 12.1 years and 655 (24.9%) were female. Mean CIT was 202 ± 67 min (minimum 20 min, maximum 600 min). One-month mortality per CIT quartile was 9, 12, 13, and 19%. One-year mortality per CIT quartile was 16, 19, 21, and 28%. CIT was an independent predictor of 1-month mortality, but only in the last quartile of CIT >246 min (odds ratio 2.1, 95% confidence interval 1.49-3.08, p < .001). We found no relevant differences in CIT during the study period. However, the impact of CIT in 1-month and 1-year mortality decreased with time (p value for the distribution of ischemic time by year 0.01), particularly during the last 5 years. Although the impact of CIT in HT prognosis seems to be decreasing in the last years, CIT in the last quartile (>246 min) is associated with 1-month and 1-year mortality. Our findings suggest the need to limit HT with CIT > 246 min or to use different myocardial preservation systems if the expected CIT is >4 h.


Targeted gene disruption in Epstein-Barr virus.
We report the development of a method that should allow the insertion of a selective marker into any region of the Epstein-Barr virus (EBV) genome of strain B95-8 through homologous recombination with plasmids. In this method, EBV recombinants are isolated as G418-resistant, immortalized B-cell clones or as G418-resistant, latently infected subclones of Burkitt lymphoma cell lines. The presence of the productive replication origin of EBV, oriLyt, on the plasmid was found to increase the number of observed recombinant viruses by approximately 100-fold; this stimulation was observed when oriLyt was separated from the sites of recombination by several kilobases of nonhomologous DNA. Long segments of EBV DNA flanking the marker on the plasmid and/or a large plasmid size were inferred to be important for obtaining a high proportion of recombinant genomes that had recombined on both sides of the selective marker; otherwise, the recombinants that predominated had acquired the entire plasmid by recombining only on one side of the inserted marker. Therefore, to facilitate targeted insertion of genetic markers into the EBV genome, a cosmid vector carrying oriLyt was constructed and tested by using it to generate EBV mutants with the BALF2 open-reading frame disrupted.


Clinical evaluation of irreversible data compression for computed radiography of the chest.
Efficient data compression is essential for practical daily operation of computed radiography (CR) systems. In this study the clinical applicability of type III irreversible high data compression using an FCR 9501 chest unit (Fuji Photo Film, Tokyo, Japan) was evaluated. Sixty-eight normal and 93 various abnormal cases, with an additional 15 cases of lung cancers with solitary lung nodules, were selected from the file. A pair of hard copies of original images and images reconstructed using type III compression was made for each case. Six radiologists evaluated the image quality by visual rating and receiver operating characteristic (ROC) curve analysis. For all five anatomic regions of normal cases, "original equal to compressed" was the most common response, followed by "original significantly better than compressed." When abnormal cases were evaluated for diagnostic information, there was no significant difference between the compressed and original images. ROC curve analysis on lung nodules with lung cancer showed no significant difference between the two. Compressed CR images using the type III irreversible technique are clinically applicable and acceptable despite slight degradation of image quality.


ISHLT International Registry for Heart and Lung Transplantation - three decades of scientific contributions.
The International Registry for Heart and Lung Transplantation (Registry) was established by the International Society for Heart and Lung Transplant (ISHLT) in 1983. It has since become the largest repository of heart and lung transplant data in the world. The continued relevance of the Registry and its high impact scientific contributions have been possible through accountability and responsible governance. This manuscript describes the logistics of the Registry's operations, its goals and future directions.


The esterase-like activity of covalently bound human third complement protein.
The acyl ester bond between the third complement protein, C3, and a variety of molecules is hydrolyzed spontaneously at neutral pH (Venkatesh et al., 1984). Modification of the free, single sulfhydryl group of bound C3 by thiol reagents suggested that a functional group other than the -SH acts as a "catalytic" group in this intramolecular hydrolytic reaction. Complete inhibition of the esterase-like activity is observed with stoichiometric amounts of mercuric chloride, palladium chloride, and the bifunctional organic mercurial, 3,6-bis-(acetoxymercuri)-o-toluidine [BAMT]. Since alkyl and aryl mercuric ions do not inhibit the esterase-like activity of C3-[3H]glycerol, it is conjectured that divalent mercury, palladium, and BAMT will form a complex with the -SH group and an atom of the "catalytic" group X having a lone pair of electrons. The structural features of C3 that are essential for the esterase-like activity remain intact after subjecting C3-[3H]glycerol to covalent chromatography on organomercurial agarose. Based on the observed effects of chemical reagents and the kinetic deuterium solvent isotope effect on the esterase-like activity, a general-base mechanism is proposed for the intramolecular hydrolysis of the acyl ester bond in covalently bound C3. The "catalytic" group X is located in the C3d region (residues 317-632 of the alpha chain), since C3d-[3H]glycerol also has esterase-like activity. A general-base mechanism mediated by the same "catalytic" group X may also apply to the formation of acyl ester bonds following the hydrolysis of the internal thiolester bond in native C3.


Temperature-insensitive label-free SARS-CoV-2 spike protein detection based on complementary refractive index and temperature dependence of multi-mode interference and grating resonance.
We demonstrated temperature-insensitive, label-free detection of SARS-CoV-2 spike protein (SSP) by harnessing the complementary refractive index and temperature dependence of multi-mode interference (MMI) created by a no-core fiber (NCF) and phase-matched resonance generated by a long-period fiber grating (LPFG). To combine MMI and grating resonance, primarily sensitive to the surrounding medium refractive index (SMRI) and ambient temperature, respectively, a fiber-optic transducer was fabricated by splicing an NCF segment with an LPFG inscribed on double-clad fiber. The transducer was functionalized with human ACE2 receptors to selectively capture SSP. The functionalized sensor head exhibited high SSP selectivity, with overall average wavelength displacements of ∼253.33 and ∼160.00 pm in PBS and saliva, respectively, for SSP with concentrations ranging from 1 to 104 ng/mL. These spectral shifts are associated with localized SMRI modulations on the sensor surface induced by specific binding between SSP and ACE2. We also examined the cross-reactivity of the sensor head for MERS-CoV spike protein to confirm its SSP specificity. Moreover, we proved the capability of temperature-independent SSP detection and ambient temperature measurement by scrutinizing the temperature effect on the sensor performance. Our functionalized fiber transducer showed great promise as a temperature-insensitive and portable platform for rapid SSP detection.


Mechanism and function of Drosophila capa GPCR: a desiccation stress-responsive receptor with functional homology to human neuromedinU receptor.
The capa peptide receptor, capaR (CG14575), is a G-protein coupled receptor (GPCR) for the D. melanogaster capa neuropeptides, Drm-capa-1 and -2 (capa-1 and -2). To date, the capa peptide family constitutes the only known nitridergic peptides in insects, so the mechanisms and physiological function of ligand-receptor signalling of this peptide family are of interest. Capa peptide induces calcium signaling via capaR with EC₅₀ values for capa-1 = 3.06 nM and capa-2 = 4.32 nM. capaR undergoes rapid desensitization, with internalization via a b-arrestin-2 mediated mechanism but is rapidly re-sensitized in the absence of capa-1. Drosophila capa peptides have a C-terminal -FPRXamide motif and insect-PRXamide peptides are evolutionarily related to vertebrate peptide neuromedinU (NMU). Potential agonist effects of human NMU-25 and the insect -PRLamides [Drosophila pyrokinins Drm-PK-1 (capa-3), Drm-PK-2 and hugin-gamma [hugg]] against capaR were investigated. NMU-25, but not hugg nor Drm-PK-2, increases intracellular calcium ([Ca²⁺]i) levels via capaR. In vivo, NMU-25 increases [Ca²⁺]i and fluid transport by the Drosophila Malpighian (renal) tubule. Ectopic expression of human NMU receptor 2 in tubules of transgenic flies results in increased [Ca²⁺]i and fluid transport. Finally, anti-porcine NMU-8 staining of larval CNS shows that the most highly immunoreactive cells are capa-producing neurons. These structural and functional data suggest that vertebrate NMU is a putative functional homolog of Drm-capa-1 and -2. capaR is almost exclusively expressed in tubule principal cells; cell-specific targeted capaR RNAi significantly reduces capa-1 stimulated [Ca²⁺]i and fluid transport. Adult capaR RNAi transgenic flies also display resistance to desiccation. Thus, capaR acts in the key fluid-transporting tissue to regulate responses to desiccation stress in the fly.


Target action of antioxidants using iontophoresis.
The use of antioxidants in applications for topical use seems promising, however, many studies must be performed to ensure processes and products that can effectively bring benefits to combat the action of free radicals in the skin. For topical antioxidants to be effective against free radicals from the skin, it is essential that the antioxidants compounds permeate the different skin layers, to reach deeper layers of the epidermis in active form and stay there for a sufficient time to cause the beneficial effects. This work aimed to evaluate the antioxidant action of formulations with phenolic compounds as well as to comprehend the skin retention profile of these actives. The antioxidant potential was recognized with isolated phenolic acids (gallic, caffeic, and ferulic acid) or in combinations, using different in vitro methods (DPPH ABTS , FRAP , β-carotene/linoleic acid system and ORAC). The skin retention study was performed through in vitro assay with Franz's diffusion cell associating, or not, the cathodic iontophoresis. Gallic acid showed the greatest antioxidant activity and was selected for a study of skin permeation following gel application to porcine skin, with or without cathodic iontophoresis. Gallic acid retention in deeper skin layers was promoted by iontophoresis, and increased skin antioxidant activity was detected after only 20 min of iontophoresis. The present study demonstrated the importance of polymeric gelling agents for optimizing the antioxidant activity. The cathodic iontophoresis represents a promising strategy to promote a target action of antioxidants in the skin.


Hemiparesis with multiple periventricular enhancing lesions on cranial CT.
A 23-year-old woman had progressive right hemiparesis followed by spontaneous clinical remission. The clinical profile and multifocal contrast-enhancing CT lesions in the periventricular region of the cerebrum favored the diagnosis of an acute demyelinating process. Serial examinations showed resolution of CT abnormalities. Right internal carotid angiography showed prominent deep draining medullary veins with fleck-like stains. The angiographic appearances might reflect vascular involvement in the demyelinating process.


Purification and identification of antioxidant peptides from egg white protein hydrolysate.
Egg white proteins were hydrolysed separately using five different proteases to obtain antioxidant peptides. The antioxidant activity of egg white protein hydrolysates was influenced by the time of hydrolysis and the type of enzyme. Of the various hydrolysates produced, papain hydrolysate obtained by 3-h hydrolysis (PEWPH) displayed the highest DPPH radical scavenging activity. PEWPH could also quench the superoxide anion and hydroxyl radicals, effectively inhibit lipid peroxidation and exhibit reducing power. Then, PEWPH was purified sequentially by ultrafiltration, gel filtration, RP-HPLC and two fractions with relatively strong antioxidant activity were subsequently subjected to LC-MS/MS for peptide sequence identification. The sequences of the two antioxidant peptides were identified to be Tyr-Leu-Gly-Ala-Lys (551.54 Da) and Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe-Gln (974.55 Da), and they were identified for the first time from food-derived protein hydrolysates. Last, the two purified peptides were synthesized and they showed 7.48- and 6.02-fold higher DPPH radical scavenging activity compared with the crude PEWPH, respectively. These results indicate that PEWPH and/or its isolated peptides may be useful ingredients in food and nutraceutical applications.


[Nosocomial catheter-related sepsis secondary to central venous catheters].
To study bacteria and drug sensitivity of catheter-related sepsis (CRS). Between February 1993 and December 1997, 52 patients with central venous catheter-related sepsis were studied retrospectively. The most common organisms were staphylococcus aureus and staphylococcus epidermis. The bacterial pathogens isolated demonstrated a marked pattern of antibiotic resistance. Gram-positive cocci were sensitive to vancomycin with a sensitivity of 93.3%, and gram-negative bacilli were sensitive to amikacin and ceftazidine with a sensitivity of 51.7%. The effective treatment of catheter-related sepsis is removal of infected catheters. Vancomycin and (or) amikacin may be first chosen to treat CRS.


Cross-border reproductive care in the USA: Who comes, why do they come, what do they purchase?
This article explores the participation of non-US-resident patients/clients in the US reproductive market, garnering a picture of cross-border reproductive care (CBRC) into the USA by drawing on the existing literature, identifying the frequency of and motivations for such arrangements, the primary sending countries, and the reproductive services sought. I find that although the expense of US CBRC necessarily limits the patient/client pool, it is largely non-economic factors that drive CBRC into the USA. The US CBRC patient/client base, which is diverse in terms of national origin, race and sexual orientation, is recruited by the US fertility industry and drawn to the full range of assisted reproductive technology (ART) services, such as in-vitro fertilization, surrogacy, oocyte donation and preimplantation genetic screening/preimplantation genetic diagnosis, available in the US market which are often restricted or limited in their countries of origin. CBRC patients/clients enjoy the legal clarity for establishing parentage and citizenship for their children available in the USA, as well as what some view as a medically and ethically superior ART market.


A three-year prospective study of rearrests for driving under influence of alcohol or drugs.
Fifty drunken drivers and 50 drivers with high blood drug concentrations arrested during the first four months of 1983 were selected for a study of rearrests for driving under influence of alcohol or drugs. Of the drugged drivers selected, 32 had been driving with high blood concentrations of diazepam (greater than 1.0 microM). 50% of these drivers were rearrested during the subsequent three years. The rearrest rate was low (6%) among those who had been driving with high blood concentrations of amphetamine (greater than 2.0 microM) or THC (greater than 0.010 microM). Among the drunken drivers arrested (BAC greater than 0.05%), the rearrest rate was 20%. The drivers were mostly rearrested for driving under the influence of alcohol.


Concurrent Chemotherapy Improves the Overall Survival of Patients Irradiated for Locally Recurrent Bladder Cancer.
To investigate the predictive value of several factors, including concurrent chemotherapy, for overall survival of patients irradiated for locally recurrent bladder cancer. Thirty patients irradiated for local recurrence of bladder cancer were included; 14 received concurrent chemotherapy. Ten factors were analyzed for overall survival: gender, age, period from bladder cancer diagnosis to irradiation of local recurrence, Karnofsky performance scale, tumour grading, pack-years smoked, smoking during radiotherapy, radiation dose, interruption of radiotherapy and concurrent chemotherapy. On univariate analyses, significantly longer overall survival was found for those with age ≤76 years (p=0.024), better performance status (p<0.001) and those treated with concurrent chemotherapy (p<0.001). On Cox regression analysis, concurrent chemotherapy remained significantly associated with survival (risk ratio 3.82, p=0.013); a trend for association was found for performance status (risk ratio 2.50, p=0.076). Addition of concurrent chemotherapy to radiotherapy for locally recurrent bladder cancer resulted in improved overall survival. Concurrent radiochemotherapy should be considered when this is clinically reasonable for such patients.


Incidence of ras gene mutations in neuroblastoma.
Using a rapid dot-blot screening procedure based on DNA amplification and hybridization to synthetic oligonucleotide probes, we investigated 18 neuroblastomas in various clinical stages for the presence of ras mutations. In none of the samples was a mutation in the relevant codons 12, 13 or 61 of Ha-ras, Ki-ras or N-ras found. These data virtually exclude the participation of mutated ras genes in the genesis of neuroblastoma.


Biochemical biomarkers and hydrocarbons concentrations in the mangrove oyster Crassostrea brasiliana following exposure to diesel fuel water-accommodated fraction.
Understanding the toxic mechanisms by which organisms cope to environmental stressful conditions is a fundamental question for ecotoxicology. In this study, we evaluated biochemical responses and hydrocarbons bioaccumulation of the mangrove oyster Crassostrea brasiliana exposed for 96 h to four sublethal concentrations of diesel fuel water-accommodated fraction (WAF). For that purpose, enzymatic activities (SOD, CAT, GPx, GR, G6PDH, GST and GGT), HSP60 and HSP90 immunocontent and lipid peroxidation (LPO) levels were determined in the gill and digestive gland of oysters and related to the hydrocarbons accumulated in the whole soft tissues. The results of this study revealed clear biochemical responses to diesel fuel WAF exposure in both tissues of the oyster. The capacity of C. brasiliana to bioaccumulate aliphatic and aromatic hydrocarbons in a dose-dependent manner is a strong indication of its suitability as a model in biomonitoring programs along the Brazilian coast, which was also validated by the response of the antioxidant defenses, phase II biotransformation and chaperones. HSP60 levels and GGT activity were the most promising biomarkers in the gill, while GST and GR activities stood out as suitable biomarkers for the detection of diesel toxicity in the digestive gland. The decrease of SOD activity and HSP90 levels may also reflect a negative effect of diesel exposure regardless the tissue. The present results provide a sound preliminary report on the biochemical responses of C. brasiliana challenged with a petroleum by-product and should be carefully considered for use in the monitoring of oil and gas activities in Brazil.


Initial studies on the implanting sites of high and low ventricular septa using leadless cardiac pacemakers.
To study the safety and electrical characteristics of various implanting sites of the Micra pacemaker. A total of 15 patients from Beijing Anzhen Hospital, Capital Medical University, were included, who were implanted with Micra leadless pacemakers and allocated to either the high ventricular septum group (eight patients) or the low ventricular septum group (seven patients) based on their individual patient factors and clinical conditions. The baseline of the patients, the implanting area, the electrocardiogram change after implantation, the implantation data, the threshold, R wave, impedance, and the date of the 1-month follow-up were then analyzed. With all of the data, the characteristics of different implantation sites of the Micra pacemaker were determined. Overall, the thresholds were low at implantation and remained stable over the 1-, 3-, 6-month, 1-, 2-, 3-, and 4-year follow-ups. On comparing the two groups, there was no difference in QRS duration at pacing (140.00 [40.00] ms vs. 179.00 [50.00] ms), threshold at implantation (0.38 [0.22] mV vs. 0.63 [1.00] mV), R wave at implantation ([10.85 ± 4.71] V vs. [7.26 ± 2.98] V), or impedance at implantation ([906.25 ± 162.39] Ω vs. [750.00 ± 173.40] Ω). While the difference in QRS duration between the two groups was not significant, the QRS duration of the high ventricular septum group exhibited a reduced tendency compared with that of the low ventricular group. The corrected QT interval during pacing exhibited a significant difference (440.00 [80.00] ms vs. 520.00 [100.00] ms; p < .05). For the 1-, 3-, 6-month, 1-, 2-, 3-, and 4-year follow-ups, there was no difference between the threshold of the high ventricular septum group and that of the low ventricular septum group (p > .05). High ventricular septum pacing appears to be a safe site for implantation of the Micra pacemaker. It could entail a shorter QRS duration at pacing and could be more physiological than low ventricular septum pacing.


Optimizing Crops for Biocontrol of Pests and Disease.
Volatile compounds and extrafloral nectar are common defenses of wild plants; however, in crops they bear an as-yet underused potential for biological control of pests and diseases. Odor emission and nectar secretion are multigene traits in wild plants, and thus form difficult targets for breeding. Furthermore, domestication has changed the capacity of crops to express these traits. We propose that breeding crops for an enhanced capacity for tritrophic interactions and volatile-mediated direct resistance to herbivores and pathogens can contribute to environmentally-friendly and sustainable agriculture. Natural plant volatiles with antifungal or repellent properties can serve as direct resistance agents. In addition, volatiles mediating tritrophic interactions can be combined with nectar-based food rewards for carnivores to boost indirect plant defense.