Pepsin, an aspartic protease, converts porcine big endothelin to 21-residue endothelin.
Porcine big endothelin (big ET-39) at 1 nM, a concentration with no influence on contractile activity in isolated rat aorta, induced a slow-onset and sustained contraction by the pre-incubation with pepsin. When the incubation mixture of big ET-39 with pepsin was analyzed by high-performance liquid chromatography on an octadecyl silica column, two major products of pepsin hydrolysis were obtained; their amino acid sequences were identical with those of 21-residue endothelin (ET-21) and a C-terminal peptide of big ET-39, big ET (22-39), respectively. On the other hand, no degradation of ET-21 was observed by pepsin treatment. These results indicate that pepsin specifically cleaves a Trp21-Val22 bond in the big ET-39 molecule, producing ET-21 and big ET (22-39). Thus, the possibility that pepsin-like aspartic protease may participate in the conversion of big ET-39 to ET-21 in vivo warrants further attention.


Papillary and Follicular Thyroid Cancer in children and adolescents: Current approach and future directions.
An increasing number of children are diagnosed with differentiated thyroid cancer. With an excellent prognosis for the majority of pediatric patients, the goal of therapy is to optimize outcome while reducing complications. Increased knowledge of the somatic, oncogenic driver mutations provides opportunities to improve the accuracy of diagnosis, to stratify surgery, and to treat patients with morbidly invasive or refractory disease. Treatment complications can be reduced by referral to regional, high-volume pediatric thyroid centers.


Indirect determination of chemical shift by coupling evolution during adiabatic pulses.
The use of adiabatic 180 degrees X-pulses within INEPT refocusing periods results in chemical shift-dependent evolution of J-couplings. This has been viewed as a disadvantage and several methods of overcoming it have been suggested. This article shows that there is the potential to use this chemical shift dependence to determine heteronuclear chemical shift without a heteronuclear evolution time. In this way, it possible to estimate heteronuclear chemical shift indirectly from a single one-dimensional proton-observe spectrum and determine it with high accuracy from a extensively-folded two-dimensional proton-observe spectrum.


Does therapeutic use of acetaminophen cause acute liver failure?
To compare the reported occurrence of liver failure in subjects in prospective trials with that in patients in retrospective reports after repeated use of therapeutic dosages of acetaminophen. Systematic review of the medical literature. MEDLINE and EMBASE biomedical and pharmacologic databases. Adults who received repeated dosing of acetaminophen 4 g/day or lower for at least 24 hours. Articles written in several languages were abstracted by trained personnel using a structured abstraction form. Data were categorized by methodology (prospective vs retrospective), acetaminophen dosage, and type of liver effect. A total of 791 articles were identified, which included 30,865 subjects in prospective studies and 9337 patients in retrospective reports. The prospective studies reported no cases of fulminant hepatic injury, liver transplantation, or death due to acetaminophen. Of the 30,865 subjects in these studies, 129 (0.4%) were identified who had a serum aminotransferase level that exceeded the upper limit of normal, including 61 subjects in randomized trials in which the proportion of serum aminotransferase level increase was the same as or less than that in the placebo group and 68 subjects in trials without a placebo group. In addition, 4263 (13.8%) received the maximum recommended therapeutic dosage (3.9-4 g/day). In the retrospective reports, 96 patients (1.0%) had a serum alanine aminotransferase level that exceeded the upper limit of normal, one (0.01%) underwent liver transplantation, and six (0.06%) died. Causality relationship of acetaminophen for each retrospective case was assessed with the Naranjo adverse drug reaction probability scale. The mean +/- SD Naranjo score for all 103 retrospective cases was 3.2 +/- 1.9, indicating a possible relationship between the increased aminotransferase levels and acetaminophen use. Some retrospective reports contained information suggesting that the patient had ingested an overdose despite a history of therapeutic use. Prospective studies indicated that repeated use of a true therapeutic acetaminophen dosage may slightly increase the level of serum aminotransferase activity, but hepatic failure or death was not reported. Retrospective reports indicated a higher rate of increased serum aminotransferase levels, and several reported associated liver injury and death. The differing results and presence of evidence indicating inaccurate acetaminophen dosage information in some case reports suggests that these cases may be inadvertent overdoses, rather than true therapeutic dosages.


A new type of synapse in the ventral cochlear nucleus.
In this paper we report the appearance of flat vesicle-containing endings in aldehyde-fixed ventral cochlear nucleus of rats with qualitative and quantitative properties suggesting they should be identified as calyceal processes. Their synaptic vesicles are elongate and significantly smaller than the vesicles in the calyces of Lenn and Reese (1966). Therefore these endings are flat vesicular calyceal processes, possibly of inhibitory function.


Tutorial review: Enrichment and separation of neutral and charged species by ion concentration polarization focusing.
Ion concentration polarization focusing (ICPF) is an electrokinetic technique, in which analytes are enriched and separated along a localized electric field gradient in the presence of a counter flow. This field gradient is generated by depletion of ions of the background electrolyte at an ion permselective junction. In this tutorial review, we summarize the fundamental principles and experimental parameters that govern selective ion transport and the stability of the enriched analyte plug. We also examine faradaic ICP (fICP), in which local ion concentration is modulated via electrochemical reactions as an attractive alternative to ICP that achieves similar performance with a decrease in both power consumption and Joule heating. The tutorial covers important challenges to the broad application of ICPF including undesired pH gradients, low volumetric throughput, samples that induce biofouling or are highly conductive, and limited approaches to on- or off-chip analysis. Recent developments in the field that seek to address these challenges are reviewed along with new approaches to maximize enrichment, focus uncharged analytes, and achieve enrichment and separation in water-in-oil droplets. For new practitioners, we discuss practical aspects of ICPF, such as strategies for device design and fabrication and the relative advantages of several types of ion selective junctions and electrodes. Lastly, we summarize tips and tricks for tackling common experimental challenges in ICPF.


Visual fatigue in video display terminal operators: objective measure and relation to environmental conditions.
The lighting conditions, luminance, contrast, and design of the workplace were studied in video display terminal (VDT) work stations operated by a group of female VDT data-acquisition clerks. VDT-induced symptoms were assessed by means of subject answers to a questionnaire. To measure VDT-induced ocular fatigue objectively, refraction power was determined before and at the end of workshift by an infrared autorefractometer. Job-induced refraction changes were then related to visual complaints and conditions in the workplace. The results confirmed that VDT data-acquisition work can lead to temporary myopia (myopization) in a remarkable percentage of operators; a significant correlation between eye discomfort, ocular asthenopia, and myopization was also found. Illumination levels, luminance, and contrast seem to be of paramount importance regarding visual symptoms: neither asthenopia nor myopization was observed when all of these conditions were adequate. If the ergonomic design of the workplace and the viewing distance are adequate, there are also usually fewer musculoskeletal symptoms. Our results suggest that changes in the ocular refraction status before and at the end of the work-shift, as determined by an automatic refractometer, provide a good objective index of VDT-induced "ocular fatigue", which in our study proved to be significantly related to workplace conditions.


Effects of cardiopulmonary bypass and prostacyclin on plasma catecholamines, angiotensin II and arginine-vasopressin.
Infusion of prostacyclin during cardiopulmonary bypass (CPB) reduces platelet activation, diminishes postoperative blood loss and decreases arterial blood pressure. In spite of continuous prostacyclin infusion, there is a delayed gradual rise in arterial pressure and resistance from low initial levels. We measured epinephrine (E), norepinephrine (NE), serotonin (5-HT), angiotensin II (ATII) and arginine-vasopressin (AVP) in plasma and carried out hemodynamic studies in 19 patients operated for coronary vascular disease. Eight patients served as a control group and were subjected to routine CPB. Eleven patients received prostacyclin 50 ng/kg/min during CPB. E and NE increased four- to sixfold during CPB from about 0.5 ng/ml (P less than 0.001). There was no difference between the groups. During CPB AVP increased sixfold from about 20 pg/ml in both groups (P less than 0.001), decreased early after CPB and increased again to high levels 3 h after CPB. The combined action of E, NE and AVP is of likely importance for the rise in systemic vascular resistance and/or need of vasodilation during CPB in the control group. ATII did not increase in the control group, but increased fourfold to about 20 pg/ml (P less than 0.01) during CPB in the prostacyclin group. The addition of AT II to E, NE and AVP seems responsible for the gradual return of arterial pressure and resistance during prostacyclin infusion. Postoperative hypertension and/or need of vasodilation 3 h after CPB was associated with high AVP levels in both groups. Hypotension caused by prostacyclin infusion did not increase E, NE or AVP above levels produced by CPB and moderate hypotension alone.


Cyclofenil in childhood scleroderma.
Treatment with cyclofenil for 9 months of a 10-year-old girl with localized scleroderma is reported. No clinical improvement was achieved. The drug was discontinued due to hepatotoxicity.


Epidemiological, clinical characteristics and outcome of severe scorpion envenomation in South Tunisia: multivariate analysis of 951 cases.
The aim of this retrospective descriptive study was to describe both epidemiologically and clinically manifestations following severe scorpion envenomation and to define simple predictive factors which can be used in routine practice in general Intensive Care Units (ICU) as an indicator of poor prognosis. Cases were collected from hospital patients' files during 13-year (1990-2002) period in the medical Intensive Care Unit of a university hospital (Sfax - Tunisia). The diagnosis of scorpion envenomation was based on a history of scorpion sting. Nine hundred fifty-one patients, who were admitted for a scorpion sting, were analyzed. There were 769 patients (80.8%) in the grade III group (with cardiogenic shock and/or pulmonary edema or severe neurological manifestation (coma and/or convulsion)) and 182 patients (19.2%) in the grade II group (with systemic manifestations). Scorpion envenomation is more frequent in summer; indeed 82.3% of our patients were admitted between June and September. The mean age (+/-SD) was 14.7 +/- 17.4 years, ranging from 0.5 to 90 years. In this study 739 patients (77.8%) had neuromuscular signs, 700 patients (73.6%) had gastrointestinal signs and 585 patients (61.5%) had a pulmonary edema, while 195 patients (20.5%) had a cardiogenic shock. The mean blood sugar on admission was at 11.32 +/- 5.66 mmol/l, a high blood sugar level (>11 mmol/l) was observed in 39% of cases. The mean blood urea was at 7.1 +/- 3.2 mmol/l, it was above 10 mmol/l in 10.7% of cases. The mean of leucocytes was at 17 418 +/- 7833 cells/mm(3), it was above 11 000/mm(3) in 80% of cases. In the end of the stay in ICU, evolution was marked by the improvement of 879 patients (92.5%) while 72 patients (7.5%) died. A multivariate analysis found the following factors to be correlated with a poor outcome: age less than 5 years (OR = 2.27), fever >38.5 degrees C (OR = 2.79), coma with Glasgow coma score < or =8/15 (OR = 9.87), pulmonary edema (OR = 8.46), leucocytes >25 000 cells/mm3 (OR = 2.35) and blood urea >8 mmol/l (OR = 4.02). Moreover, in children group, a significant association was found between PRISM score and mortality rate, this model had a high discriminative power with an area under the ROC curve at 0.93. In the adult patients a significant association was found between SAPS II score and mortality rate, this model had a high discriminative power with an area under the ROC curve at 0.82. In summary, in severe scorpion envenomation, age less than 5 years, fever >38.5 degrees C, coma with Glasgow coma score < or =8/15, pulmonary edema, leucocytes >25 000 cells/mm3 and blood urea >8 mmol/l were associated with a poor outcome.


[Concerning the administration of pethidine (Dolantin during delivery: discussion to "Analgesia during delivery--delayed effects for the child? by Riegel, Messow and Pielsticker (author's transl)].
The obstetrical problematic of intrapartal infant death following administration of Dolantin were discussed with the help of both of the cases described in the article by Riegel et al. At the same time, the question of analgesia during delivery with pethidine in combination with a respiratory depressant antidote was examined. Lorfalgyl, according to current opinion, cannot compensate the antidepressive effect of pethidine. Instead, the application of pure pethidine is recommended for obstetric analgesia in the first stage of labor. Today, naloxone used as antidote is particularly suitable before delivery or can be injected into the umbilical vein of the child after delivery. A plan of treatment for pathidine therapy during the first stage of labor in combination with the antidepressant was suggested.


Effects of Tai Chi and Qigong on the mobility of stroke survivors: A systematic review and meta-analysis of randomized trials.
Stroke survivors often experience impaired mobility and physical functions. Tai Chi and Qigong have been shown to have physical and psychological benefits for stroke patients. To summarize the evidence on Tai Chi and Qigong for improving mobility in stroke survivors, specifically the ability to walk, dynamic balance, and activities of daily living (ADL). Independent searches of 16 electronic databases in English, Korean, and Chinese from their inception until December 2021 were conducted by two research teams. Methodological quality was assessed using Cochrane's risk of bias tool 2.0. Comprehensive Meta-Analysis 3.0 software was used to calculate effect sizes with subgroup analysis and to assess heterogeneity and publication bias. The meta-analysis included 27 randomized trials (18 with Tai Chi and 9 with Qigong) on stroke survivors (N = 1,919). None of the studies were considered at high risk of bias, about 70% had some concerns, and 30% were considered low risk. Meta-analysis of 27 randomized controlled trials with random-effects models indicated that Tai Chi and Qigong effectively improved mobility, specifically on the ability to walk (Hedges'g = 0.81), dynamic balance (Hedges'g = 1.04), and ADL (Hedges'g = 0.43). The effects of Tai Chi and Qigong were significant for short-term and long-term programs (Hedges'g 0.91 vs. 0.75), and when compared with active controls and no treatment group (Hedges'g 0.81 vs. 0.73). Tai Chi and Qigong performed for 12 weeks or less were effective in improving the mobility of stroke survivors. Further studies are warranted to assess whether Tai Chi and Qigong work best as an adjunct to rehabilitation, an effective alternative to rehabilitation or as a maintenance strategy, and whether the results could be further optimized by assessing different schools of Tai Chi and Qigong, different types of stroke patients, and different points in the post-stroke recovery process. This study has been registered on the UK National Institute for Health Research (http://www.crd.york.ac.uk/PROSPERO) PROSPERO registration number: CRD42020220277.


Clinical efficacy and safety of traditional Chinese medicine Xiao Yao San in insomnia combined with anxiety.
Patients with long-term insomnia generally experience anxiety and depression. Traditional sleeping pills and anti-anxiety drugs have certain limitations. Xiao Yao San (XYS), a complementary and alternative therapy, has been widely used to treat insomnia combined with anxiety. This study aims to evaluate the efficacy and safety of XYS in the treatment of insomnia combined with anxiety. Related literature was retrieved from 8 electronic databases from the establishment time to March 2021. The subjects were diagnosed with insomnia combined with anxiety. We assessed the methodological quality of randomized controlled trials (RCTs) according to the Cochrane Handbook. Data analysis was conducted using RevMan 5.3 software. The analysis includes 9 RCTs involving 681 patients. Meta-analysis supported that as an auxiliary drug for Western medicine (WM), XYS could enhance the clinical efficacy of insomnia calculated according to the traditional Chinese medicine (TCM) syndrome score scale (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 1.13-1.43; P = .0002) and reduced the scores of Hamilton Anxiety Scale (mean difference [MD]: -5.19; 95% CI: -7.78 to -2.60; P < .001), Pittsburgh Sleep Quality Index (MD: -3.35; 95% CI: -4.86 to -1.84; P < .001), Self-rating Anxiety Scale (MD: -9.38; 95% CI: -10.20 to -8.75; P < .001), TCM syndrome score scale for insomnia (MD: -4.45; 95% CI: -6.65 to -2.24; P < .001), and TCM syndrome score scale for anxiety (MD: -5.54; 95% CI: -9.48 to -1.6; P = .006). The summary analysis also shows that the separate use of XYS was advantageous in reducing the scores of the Hamilton Anxiety Scale (MD: -3.70; 95% CI: -6.31 to -1.09; P = .005), Pittsburgh Sleep Quality Index (MD: -1.82; 95% CI: -2.39 to -1.24; P < .001), and Self-rating Anxiety Scale (MD: -10.79; 95% CI: -14.09 to -7.49; P < .001). The incidence of adverse events with XYS as an ancillary drug or used separately was lower than that in the WM. Our systematic evaluation and meta-analysis showed that XYS combined with WM or XYS alone was beneficial for improving sleep quality and relieving anxiety. Due to the low methodological quality, small sample size, and significant heterogeneity of RCTs, more rigorous and scientific clinical trials are required to further evaluate the efficacy and safety of XYS. CRD42020190613.


WT1 immunoreactivity in breast carcinoma: selective expression in pure and mixed mucinous subtypes.
Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (>90% cases) and rarely strong (<10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.


Extension of limb salvage by combined vascular reconstruction and adjunctive free-tissue transfer.
Vascular reconstruction alone can be insufficient for extremity salvage in some patients with severe soft-tissue wounds. We present our experience in 20 patients with vascular reconstruction for ischemic disease and free-tissue transfer for limb-threatening soft-tissue wounds. Nineteen patients underwent autogenous venous bypasses and one patient underwent an aortobifemoral bypass. Ten soft-tissue reconstruction were performed at the time of the vascular reconstruction and 10 were delayed. Free-tissue transferred included muscle, fasciocutaneous flaps, and omentum. Inflow to the flap was from the bypass graft (n = 12) or the distal tibial artery. One free flap and graft failed immediately in the same patient. One successful flap and graft required a below-knee amputation for ongoing infection in the surrounding soft tissues. Eighteen of 20 patients have had free-flap and graft patency during the mean follow-up period of 17 months (range 6 to 33 months). These 18 patients ambulate independently. In patients with arterial insufficiency and severe soft-tissue wounds, combined vascular reconstruction and free-tissue transfer permits extended limb salvage with excellent functional results.


Collagenolytic activity of eosinophilic granuloma in vitro.
Lytic activity of eosinophilic granuloma and other tumours was studied in vitro on collagen substrate. Collagen degradation was measured through the release of hydroxyproline-rich peptides into the medium. The in vitro lytic action was at a maximum in the case of EG and was correlated with the presence of histiocytic cells.


A MATLAB-based app to improve LC-MS/MS data analysis for N-linked glycan peak identification.
Glycosylation is an important modification to proteins that plays a significant role in biological processes. Glycan structures are characterized by liquid chromatography (LC) combined with mass spectrometry (MS), but data interpretation of LC/MS and MS/MS data can be time-consuming and arduous when analyzed manually. Most of glycan analysis requires dedicated glycobioinformatics tools to process MS data, identify glycan structure, and display the results. However, software tools currently available are either too costly or heavily focused on academic applications, limiting their use within the biopharmaceutical industry for implementing the standardized LC/MS glycan analysis in high-throughput manner. Additionally, few tools provide the capability to generate report-ready annotated MS/MS glycan spectra. Here, we present a MATLAB-based app, GlyKAn AZ, which can automate data processing, glycan identification, and customizable result displays in a streamlined workflow. MS1 and MS2 mass search algorithms along with glycan databases were developed to confirm the fluorescent labeled N-linked glycan species based on accurate mass. A user-friendly graphical user interface (GUI) streamlines the data analysis process, making it easy to implement the software tool in biopharmaceutical analytical laboratories. The databases provided with the app can be expanded through the Fragment Generator functionality which automatically identifies fragmentation patterns for new glycans. The GlyKAn AZ app can automatically annotate the MS/MS spectra, yet this data display feature remains flexible and customizable by users, saving analysts' time in generating individual report-ready spectra figures. This app accepts both OrbiTrap and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) MS data and was successfully validated by identifying all glycan species that were previously identified manually. The GlyKAn AZ app was developed to expedite glycan analysis while maintaining a high level of accuracy in positive identifications. The app's customizable user inputs, polished figures and tables, and unique calculated outputs set it apart from similar software and greatly improve the current manual analysis workflow. Overall, this app serves as a tool for streamlining glycan identification for both academic and industrial needs.


Mothers' perceptions of the care-by-parent program prior to hospital discharge of their preterm infants.
This research was conducted to gain an understanding of the care-by-parent experience for mothers of preterm infants. Phenomenologic methodology was used to explore the experiences of six mothers. Each participant slept overnight with her infant in a private hospital room. The mother assumed responsibility for her infant's care, knowing that nursing staff assistance was available if needed. Interviews were conducted on the following day and again after the infant had been home at least four days. The participants were six mothers of preterm infants. Mothers' experiences as they assumed responsibility in caring for their preterm infants away from the intensive care nursery. Findings revealed that the care-by-parent experience gives the mother an opportunity to assume full responsibility for her preterm infant's care, tests the reality of caregiving, helps her learn about caregiving activities and her infant's patterns of behavior, and confirms her readiness for independent parenting and the infant's readiness for discharge home. These findings confirm the benefits of rooming-in prior to discharge of preterm infants and provide guidelines for discharge planning.


[Identification of Streptococcus group A in children with pharyngitis, in ambulatory care, through pharyngeal culture].
574 cases of pharyngitis (patients 0.3-14 years aged) were studied. Throat swabs were obtained from all the children, inoculated into blood-agar plates and incubated aerobically at 37 degrees C, in the office, using the bacitracin test for identification of group A streptococci. The 25% of the cultures were positives (80% in the first 24 hours, and the rest in 48 hours). We did not find reliable clinical findings that enable us to diagnose streptococcal pharyngitis accurately. So that we conclude that demonstration of group A streptococcus in patients throat is essential and we find that throat culture is a practical and advisable method for the office practice.


Orbital floor triamcinolone acetonide injections for the management of active non-infectious uveitis.
To evaluate the effect of orbital floor triamcinolone acetonide (OFTA) injections on inflammation and visual acuity in active non-infectious uveitis. Monocentre, retrospective study in 94 eyes (86 patients) with acute non-infectious uveitis receiving a single OFTA (40 mg) injection. Outcome measures were anterior chamber (AC) and vitreous cell counts, laser flare photometry, best-corrected visual acuity (BCVA), and complications over a 6-month follow-up period. The number of patients with >or=1+ cells in AC and vitreous was significantly lower after treatment than at baseline (each, P<0.01 at the follow-up examinations). The anti-inflammatory effect lasted for the 6-month follow-up period. Laser flare photometry values were also significantly lower than the baseline levels at 3 (P<0.01) and 6 (P=0.034) months. BCVA did not differ before and after treatment. Macular oedema was reduced in 27%, unchanged in another 59%, and worse in 14%. Within 6 months, ocular hypertension was observed in up to 8% and progressing cataract was noted in 29%.ConclusionsOFTA injections improved AC and vitreous inflammation, but the effect on visual acuity and macular oedema was limited.


Synaptic vesicle-bound phospholipase(s) acting on phosphatidylinositol exhibit(s) high susceptibility to brain ischemia.
The activity of phospholipase C acting against [3H]-inositol-phosphatidylinositol (PI) and the activity of arachidonic acid (AA) release from [1-14C]arachidonoyl-phosphatidylinositol by enzyme(s) located in synaptic vesicles (SV) isolated from normoxic and ischemic brains was investigated. Brain ischemia significantly activated phospholipase C (PhLC) by about 90% and AA release by about 50%. PhLC and AA release in SV isolated from brain submitted to ischemia were not further activated by 2 mM CaCl2 contrary to the enzymes from normoxic brain. The activation of PhLC and PhLA2 may produce conformational changes and rearrangement of the SV membranes leading to vesicle-membrane fusion and subsequently to massive neurotransmitter release known to occur during ischemia.


The potential role of inflammation in the development of postvaccinal sarcomas in cats.
Epidemiologic evidence shows a strong association between the administration of inactivated feline vaccines (feline leukemia virus and rabies) and subsequent soft tissue sarcoma development at vaccine sites. Although more research is needed to understand the complete pathogenesis of vaccine-induced tumors in cats, good evidence exists that inflammation plays a role.


Improved results of surgical treatment for esophageal and gastroesophageal junction carcinomas after preoperative combined chemotherapy and radiation.
Combined treatment with chemotherapy and radiation (chemoradiation) preceding surgical exploration for esophageal or gastroesophageal squamous cell carcinoma or adenocarcinoma was compared with surgical exploration alone to determine if there was an influence on tumor status at exploration, tumor resectability, disease recurrence, and patient survival. Preoperative chemoradiation resulted in significant tumor response as measured by decreased nodal involvement and 36% incidence of no residual tumor at resection (total response) and was reflected by an improvement in resectability. Local tumor recurrence was eliminated by preoperative chemoradiation preceding resection. Distant recurrence was not reduced and remained the major cause of death. The 2-year survival rate after tumor resection alone was 33% versus 66% after preoperative chemoradiation and resection (p = 0.13). Patient survival after resection alone was predicted by pathologic extent of local disease as measured by lymph node status. In contrast, survival after chemoradiation and resection was not predicted by pathologic extent of local disease. Surgical resection appears to have been an important component of therapy, primarily because survival was improved in patients after resection of residual local disease.


Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies.
2,8-Dihydroxyadenine urolithiasis associated with partial deficiencies of adenine phosphoribosyltransferase (APRT) has been found only among Japanese families. All Caucasian patients with the same lithiasis are completely deficient in this enzyme. Partially purified APRT from one of the Japanese families with the lithiasis associated with a partial deficiency of APRT had a reduced affinity for 5-phosphoribosyl-1-pyrophosphate (PRPP). In the present investigations, we have shown that this characteristic is common in mutant enzymes from all the four separate Japanese urolithiasis families associated with partial APRT deficiencies so far tested. The mutant enzymes also had several other characteristics in common including increased resistance to heat in the absence of PRPP and reduced sensitivity to the stabilizing effect of PRPP. These data suggest that these families have a common mutant allele (APRT*J) at the APRT gene locus.


Protective effect of nitronyl nitroxide-amino acid conjugates on liver ischemia-reperfusion induced injury in rats.
Stable nitroxides are potential antioxidant drugs. In this study, we have linked nitroxide to natural amino acids with the aim to improve therapeutic activity. The radical scavenging activities of two nitronyl nitroxide-amino acid conjugates (NNR and NNK) were evaluated in PC 12 cell survival assays. The NO scavenging activities of these compounds were confirmed in the acetylcholine-induced vasorelaxation assay. In addition, the protective effect of NNR was demonstrated in an in vivo rat model of hepatic ischemia-reperfusion (I/R) induced injury and oxidative change. Because NNR reduced hepatic I/R injury by minimizing oxidative stress, it might be possible to develop it into a possible therapeutic agent for hepatic I/R injury.


[Four "Big" Stereotypes on Nurses in Mass Consciousness: on the Materials of the Moscow People Opinion Analysis in Social Media].
Staffing problems (including staff shortage) in nursing reveal the connection with the stereotypical perception of the profession. The study of stereotypes was limited to Moscow healthcare and was based on downloading messages from social media (31,613 posts), the relevance of their study is determined by the growth of social media influence on public opinion. 24% of messages about nurses in the sample contain "large" stereotypical images (excluding spam). It was studied four "large" stereotypical images of a nurse: "guardian angel", "doctor's assistant", "authoritarian nurse" and "sensual nurse", and each one has negative aspects. Authors considered the specific perception of each of the images in social media. The remaining 76% of messages do not offer an alternative image of a nurse. The conclusion offers recommendations aimed at increasing the prestige of the profession: creating a new positive image of the profession, promoting it, encouraging nurses to join public space and increasing their autonomy.


Microvascular Outcomes in Patients with Type 2 Diabetes Treated with Vildagliptin vs. Sulfonylurea: A Retrospective Study Using German Electronic Medical Records.
Preliminary data suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors may reduce microvascular events, but there is a little evidence to support this from adequate real-world studies. This study aimed to compare microvascular outcomes between patients-prescribed vildagliptin and those prescribed sulfonylurea (SU). This retrospective cohort study was conducted on a large sample from the German electronic medical records database IMS Lifelink Disease Analyzer. We used propensity score-matched samples of patients prescribed either vildagliptin or SU. Exposure was defined as therapy (SU or vildagliptin); primary outcomes were a diagnosis of retinopathy, nephropathy, neuropathy, or diabetic foot ulcer over the observation period in patients with no previous record of these outcomes. Secondary outcome was a composite of any primary outcome occurring in the observation period. In total, 16,321 patients prescribed SU and 4481 prescribed vildagliptin met the inclusion criteria. After propensity score matching, each sample comprised 3015 patients. Mean age was 63.7/64.6 years for SU/vildagliptin, respectively, with mean disease duration of 3.2/3.1 years, and mean treatment duration of 2.5/2.3 years. Treatment with vildagliptin was associated with a significant lower incidence of retinopathy [odds ratio (OR) = 0.55, P = 0.0004], neuropathy (OR 0.71, P = 0.0001), and composite outcome (OR 0.70, P < 0.0001). Incidences of nephropathy and diabetic foot ulcer were lower for vildagliptin, but not significantly so (OR 0.90, P = 0.3920; OR 0.76, P = 0.0742, respectively). There were no significant differences in incident rate ratios (all P > 0.05). Treatment with vildagliptin was associated with a reduced incidence of microvascular complications, especially neuropathy and retinopathy, compared to treatment with SU in this clinical practice setting. Novartis Pharma AG.


Introduction: promoting and maintaining a reflective professional staff in a hospital-based social work department.
Promoting and sustaining a staff of reflective social work practitioners requires a supportive departmental structure and culture. Providing such support is a particular yet necessary challenge to social work administrators in the current health care environment. This article discusses an array of administrative strategies employed in one hospital social work department to promote reflective social work practice. More specifically, it describes the role of practice-based research in enhancing worker reflectiveness.


Minocycline in amyotrophic lateral sclerosis: a pilot study.
Recent studies indicate that minocycline exerts neuroprotective effects in vitro and in vivo, and suggest that the drug may represent a novel therapeutic approach to amyotrophic lateral sclerosis (ALS). In this study we investigated the safety of combined treatment with minocycline and riluzole in ALS. Twenty ALS patients were randomised into two groups and administered either riluzole (50 mg b.i.d.) or riluzole and minocycline (100 mg i.d.) for 6 months. Disease progression was measured by means of the ALS-Functional Rating Scale score at monthly intervals. Respiratory function was measured at the beginning of the study and repeated after 3 and 6 months of treatment. Combined treatment with minocycline and riluzole was not followed by significant side effects. This pilot study shows that minocycline and riluzole can be taken safely together. Further trials are needed to assess efficacy of such treatment.


Proof-of-concept study of artificial intelligence-assisted review of CBCT image guidance.
Automation and computer assistance can support quality assurance tasks in radiotherapy. Retrospective image review requires significant human resources, and automation of image review remains a noteworthy missing element in previous work. Here, we present initial findings from a proof-of-concept clinical implementation of an AI-assisted review of CBCT registrations used for patient setup. An automated pipeline was developed and executed nightly, utilizing python scripts to interact with the clinical database through DICOM networking protocol and automate data retrieval and analysis. A previously developed artificial intelligence (AI) algorithm scored CBCT setup registrations based on misalignment likelihood, using a scale from 0 (most unlikely) through 1 (most likely). Over a 45-day period, 1357 pre-treatment CBCT registrations from 197 patients were retrieved and analyzed by the pipeline. Daily summary reports of the previous day's registrations were produced. Initial action levels targeted 10% of cases to highlight for in-depth physics review. A validation subset of 100 cases was scored by three independent observers to characterize AI-model performance. Following an ROC analysis, a global threshold for model predictions of 0.87 was determined, with a sensitivity of 100% and specificity of 82%. Inspecting the observer scores for the stratified validation dataset showed a statistically significant correlation between observer scores and model predictions. In this work, we describe the implementation of an automated AI-analysis pipeline for daily quantitative analysis of CBCT-guided patient setup registrations. The AI-model was validated against independent expert observers, and appropriate action levels were determined to minimize false positives without sacrificing sensitivity. Case studies demonstrate the potential benefits of such a pipeline to bolster quality and safety programs in radiotherapy. To the authors' knowledge, there are no previous works performing AI-assisted assessment of pre-treatment CBCT-based patient alignment.


Concentration of ethanol and other volatile compounds in the blood of acutely poisoned alcoholics.
The presence of volatile compounds, such as acetone, acetaldehyde, methanol, ethanol, isopropanol, and n-propanol, in the blood of 169 acutely poisoned alcoholics was determined. The clinical diagnosis of addiction was made on the basis of a patient interview as well as physical, psychological, and psychiatric examination. At the time of the patients' admission to the clinic, the mean concentration of ethanol in blood was 3.14 +/- 1.10 g/l and its elimination rate in the studied group was 0.27 +/- 0.08 g/kg/hr, an elimination rate significantly higher (P <.001) than that of social drinkers, which averages to 0.014 +/- 0.04 g/kg/h. The presence of other volatile compounds in the blood of alcohol-addicted patients is common. The calculated elimination rate constant of methanol was about 0.2 h(-1). This rate seems to indicate that, in heavy drinkers, the elimination of methanol may be relatively fast even if the ethanol concentration is above 1 g/l. The elimination of other volatile compounds can be accelerated by large doses of ethanol, although it is not correlated with actual blood ethanol level. Moreover, in most of the blood samples with a methanol concentration below 10 mg/l, the measured concentration of acetone was below 7 mg/l and that of isopropanol was below 2 mg/l.


Pharmacokinetics and efficacies of obidoxime and atropine in paraoxon poisoning.
The efficacies (ED50) of obidoxime and atropine against paraoxon poisoning in mice were determined by administering the antidotes 5, 20, 40 and 60 min before administration of the organophosphate. With increasing time intervals t between the administration of the antidote and paraoxon, the dose of antidote (ED50), that reduced the lethality of 2 LD50 of paraoxon to 50% increased. The standardized log ED50/t plot was linear and yielded the "efficacy half-life". In addition, the blood concentrations c of the antidotes were measured, resulting in a linear log c/t plot. The "efficacy half-life" was approximately twice the half-life of the antidote in blood. The possible reasons for this phenomenon are discussed.


Lipopolysaccharide-induced production of cytokines by bone marrow-derived macrophages: dissociation between intracellular interleukin 1 production and interleukin 1 release.
We investigated the capacity of mouse bone marrow-derived macrophages (BMDM) to produce interleukin 1 (IL 1), interleukin-6 (IL 6), and tumor necrosis factor (TNF) upon lipopolysaccharide (LPS) stimulation. BMDM were allowed to differentiate either in the presence of conditioned medium (from WEHI-3 or L cells), or in the presence of recombinant cytokines (IL 3, macrophage-colony stimulating factor [M-CSF], or granulocyte/macrophage-colony stimulating factor [GM-CSF]). Cells were maintained in culture up to 3 weeks and tested at different times. Significant spontaneous cytokine production was never observed. BMDM rapidly acquired the capacity to elaborate cytokine upon LPS activation. LPS-triggered BMDM were able to produce IL 1, IL 6, and TNF, throughout the culture period, although 2- to 3-week-old cells lost their ability to release IL 1 while accumulation of intracellular IL 1 remained unchanged. The dissociation between synthesis and release of IL 1 was not correlated with a significant modification of the specific binding of LPS onto the cell surface.


Coexistence of sympatric carnivores in relatively homogeneous Mediterranean landscapes: functional importance of habitat segregation at the fine-scale level.
One of the main objectives of community ecology is to understand the conditions allowing species to coexist. However, few studies have investigated the role of fine-scale habitat use segregation in the functioning of guild communities in relatively homogeneous landscapes where opportunities for coexistence are likely to be the most restrictive. We investigate how the process of habitat use differentiation at the home range level according to the degree of specialism/generalism of species can lead to coexistence between guild species. We examine differences in fine-scale habitat use and niche separation as potential mechanisms explaining the coexistence of five sympatric carnivore species that differ in life history traits (Iberian lynx, Eurasian badger, Egyptian mongoose, common genet and red fox) by collecting data from systematic track censuses in a relatively homogeneous Mediterranean landscape. We found that a higher degree of specialism determines the segregation of species among the fine-scale ecological niche dimensions defined using quantitative elements associated with vegetation, landscape, prey availability and human disturbance. The species with the lowest total performance over the set of variables did not exhibit segregation in the use of habitat at this level. Our study indicates that in relatively homogeneous landscapes, there exist subtle patterns of habitat partitioning over small-scale gradients of habitat determinants as a function of the degree of specialism of carnivore species within a guild. Our results also suggest that coexistence between generalist species may be permitted by fine-scale spatial-temporal segregation of activity patterns or trophic resource consumption, but not fine-scale habitat use differentiation.


Cell number and neuropil alterations in subregions of the anterior hippocampus in a female monkey model of depression.
The anterior hippocampus is associated with emotional functioning and hippocampal volume is reduced in depression. More women are clinically depressed than men, yet the depressed female brain is little studied. We reported reduced anterior hippocampal volume in behaviorally depressed adult female cynomolgus macaques; the mechanisms contributing to that reduction are unknown. The present study represents the first systematic morphological investigation of the entire hippocampus in depressed female primates. Cellular determinants of hippocampal size were examined in subregions of anterior and posterior hippocampus in antidepressant-naïve, adult female monkeys characterized for behavioral depression and matched on variables that influence hippocampal size (n = 8 depressed, 8 nondepressed). Unbiased stereology was used to estimate neuronal and glial numbers, neuronal soma size, and regional and layer volumes. Neuropil and cell layer volumes were reduced in cornu ammonis (CA)1 and dentate gyrus (DG) of the anterior but not the posterior hippocampus of depressed compared with nondepressed monkeys. Glial numbers were 30% lower in anterior CA1 and DG of depressed monkeys, with no differences observed in the posterior hippocampus. Granule neuron number tended toward a reduction in anterior DG; pyramidal neuron number was unchanged in any region. Size of pyramidal neurons and glial densities tended to be reduced throughout the whole hippocampus of depressed monkeys, whereas neuronal densities were unchanged. The reduced size of the anterior hippocampus in depressed female monkeys appears to arise from alterations in numbers of glia and extent of neuropil, but not numbers of neurons, in CA1 and DG.


NMR methods for studying quadruplex nucleic acids.
Solution NMR spectroscopy has traditionally played a central role in examining quadruplex structure, dynamics, and interactions. Here, an overview is given of the methods currently applied to structural, dynamics, thermodynamics, and kinetics studies of nucleic acid quadruplexes and associated cations.


Non-occupational sedentary behaviors: population changes in The Netherlands, 1975-2005.
Evidence is accumulating that sedentary behaviors have detrimental health effects. Comprehensive data on population changes in various sedentary behaviors over time are scarce. This study aimed to determine changes in non-occupational sedentary behaviors in the Dutch adult population between 1975 and 2005. The National Time Use Survey of the Netherlands was used, which has been collected in 5-year intervals since 1975 (seven time points, n range=1017-2845). Adult participants completed a 7-day time-use diary in which they recorded their primary activity in 15-minute intervals throughout or at the end of the day. A validated method was used to determine time spent in various non-occupational sedentary behaviors. Population-weighted analyses determining changes over time in various sedentary behaviors were carried out in 2011 and 2012. Between 1975 and 2005, the proportion of non-occupational time spent sedentary remained relatively constant at ~60%. However, absolute time decreased, because of a 4.7-hour/week increase in occupational time. Sedentary occupational time could not be studied but has likely increased over these 3 decades. Most non-occupational sedentary behavior was during leisure, and the proportion of sedentary leisure time that comes from screen time increased from 26% in 1975 to 43% in 2005. Between 1975 and 2005, sedentary transport increased by 2 hours/week. The nature and distribution of sedentary behaviors in the Dutch adult population changed substantially over 3 decades. Screen-based activities are playing an increasingly dominant role.


Vestibular stimulation affects medium latency postural muscle responses.
This study explores whether galvanic vestibular stimulation can alter automatic postural muscle responses triggered 100 ms after surface translations. Our previous study concluded that a step of bipolar, galvanic vestibular stimulation delivered 500 ms prior to a platform translation tilted the internal representation of vertical because subjects' final center of foot pressure and center of mass equilibrium position shifted toward the anode and this tilt was larger than the sum of effects for platform translations and galvanic alone. In the current study, we show that 0.2-0.4 mA of galvanic vestibular stimulation produced significant changes in the tilt of the trunk in space that was realized by changes in the magnitude of the medium latency postural muscle responses at the ankle. The galvanic-induced changes in latency and magnitude of the first 50 ms of gastrocnemius muscle burst in response to the backward surface translation were consistent with changes in background muscle tone induced by the direct vestibulospinal effects of the galvanic current. However, the galvanic-induced changes in the second 50 ms of the gastrocnemius response were in the opposite direction and consistent with the forward- or backward-tilted, final postural equilibrium goal. Kinematic analysis showed that galvanic-induced tilt was first initiated in the trunk and that the shank and thigh segment angles were not altered by galvanic stimulation prior to platform translation such that changes in gastrocnemius and soleus postural responses to translations were not due to an effect of galvanic stimulation on initial ankle angle. More proximal muscles and antagonist muscles involved in the postural response were not altered by the galvanic stimulation. These results suggest that galvanic vestibulospinal stimulation can alter medium latency, automatic postural responses in prime movers by changing the postural equilibrium goal.


Establishing a pediatric interventional radiology inpatient consult service.
To delineate pediatric interventional radiology (IR) inpatient consult growth and resulting collections after implementation of a pediatric IR consult service. An inpatient IR consult process was created at a single academic children's hospital in October 2019. IR consult note templates were created in Epic (Epic Systems Corporation, Verona, Wisconsin) and utilized by 4 IR physicians. Automatic charge generation was linked to differing levels of evaluation and management (E&M) service relating to current procedural terminology (CPT) inpatient consult codes 99251-99255. The children's hospital informatics division identified IR consult notes entered from the implementation of the consult service: October 2019 to January 2022. The university radiology department billing office provided IR service E&M charge, payment, and relative value units (RVU) information during this study period. A chart review was performed to determine the IR procedure conversion rate. Mann-Whitney and a two-sample t-test statistical analyses compared use of the 25-modifier, monthly consult growth and monthly payment growth. P-value < 0.05 was considered statistically significant. RESULTS: Within this 27-month period, a total of 2153 inpatient IR consults were performed during 1757 Epic hospital encounters; monthly consult peak was reached 5 months into the study period. Consult level breakdown by CPT codes: 99251-8.7%, 99252-81.7%, and 99253-8.8%. 69.7% of IR consults had consult-specific billing with payments in 96.4% resulting in $143,976 new revenue. From 2020 to 2021, IR consult volume trended upward by 13.4% (P =0.069), and consult-specific payments increased by 84.1% (P<0.001). IR consult procedure conversion rate was 96.5%. An inpatient pediatric IR consult service was quickly established and maintained by four physicians over a 27-month study period. Annual IR consult volume trended upward and consult-specific payments increased, resulting in previously uncaptured IR service revenue.


Comparison of artificial sebum with human and hamster sebum samples.
To understand drug delivery to the sebum filled hair and sebaceous follicles, it is essential to use an artificial sebum as a surrogate of the human sebum for the investigation of drug transport properties. Artificial sebum L was developed in-house based on the chemical similarity to human sebum. The partition and diffusion of model compounds (ethyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate, and hexyl 4-hydroxybenzoate) were measured in human sebum, hamster ear and body sebum (a commonly used animal model), and four representative artificial sebum samples (N, S, F, and L) in which artificial sebums, N, S and F were selected based on the available literature. DSC and NMR studies were also conducted on all sebums to compare their melting properties and chemical compositions. In vitro studies show that the partition coefficients of the three model compounds in artificial sebum L were similar to that of human sebum, whereas the hamster ear and body sebum, and other three artificial sebum samples were different from that of human sebum. Additionally, the in vitro sebum flux (microg/(cm(2)min) of three model compounds through artificial sebum L was closer to that of human sebum when compared with the other three artificial sebum (N, S and F), hamster body and hamster ear sebum. The results of this study indicate that the artificial sebum L could be used as an alternative to human sebum, as the physicochemical properties of this artificial sebum is relatively similar to human sebum.


No evidence for the involvement of the argasid tick Ornithodoros faini in the enzootic maintenance of marburgvirus within Egyptian rousette bats Rousettus aegyptiacus.
The cave-dwelling Egyptian rousette bat (ERB; Rousettus aegyptiacus) was recently identified as a natural reservoir host of marburgviruses. However, the mechanisms of transmission for the enzootic maintenance of marburgviruses within ERBs are unclear. Previous ecological investigations of large ERB colonies inhabiting Python Cave and Kitaka Mine, Uganda revealed that argasid ticks (Ornithodoros faini) are hematophagous ectoparasites of ERBs. Yet, their potential role as transmission vectors for marburgvirus has not been sufficiently assessed. In the present study, 3,125 O. faini were collected during April 2013 from the rock crevices of Python Cave, Uganda. None of the ticks tested positive for marburgvirus-specific RNA by Q-RT-PCR. The probability of failure to detect marburgvirus at a conservative prevalence of 0.1 % was 0.05. The absence of marburgvirus RNA in O. faini suggests they do not play a significant role in the transmission and enzootic maintenance of marburgvirus within their natural reservoir host.


Behavioural responses and expression of P2X3 receptor in trigeminal ganglion after experimental tooth movement in rats.
To explore the role of P2X(3) receptor in pain induced by experimental tooth movement. Male Sprague-Dawley rats weighing 200-300g were used. P2X(3) receptor distribution in the caudal one-third portion of the trigeminal ganglion (TG) was studied by IHC. Next, the changes of P2X(3) expression were detected by Western blotting 4h, 1d, 2d, 3d, 5d, 7d, 14d after tooth movement. We then developed a behaviour pain model associated with directed mouth wiping. Finally, the effect of TNP-ATP on nociceptive-like behaviour was evaluated. Our results showed that P2X(3) receptors were expressed mainly in small- and medium-sized cells and experimental tooth movement led to an increase in staining of mandibular P2X(3) receptors. In addition, following experimental tooth movement, the expression of P2X(3) receptor in TG was statistically significantly up-regulated from days 1 to 5, with a peak on day 3. It was also found that the time spent on directed mouth wiping was dramatically increased by experimental tooth movement from days 1 to 7. The rhythm change of P2X(3) receptor expression in TG and the mouth wiping behaviour were in concert with the initial orthodontic pain responses. The directed mouth wiping behaviour was modulated in a force-dependent manner and could be attenuated by peripheral and systemic morphine. Furthermore, peripherally administered TNP-ATP could exert an analgesic effect on this pain model. These results suggest that directed mouth wiping behaviour can be a reliable measurement of pain following experimental tooth movement in rats. The P2X(3) receptor is important in the development and maintenance of tooth movement pain and thus may be peripheral targets for analgesics in orthodontic pain control.


Latex hypersensitivity: the IgE response.
The IgE-mediated allergic response involves a series of physiological pathways that result in the array of symptoms commonly associated with allergy. This article describes the mediators that prompt specific clinical responses and identifies those at risk for latex hypersensitivity.


Recognition of lectin with a high signal to noise ratio: carbohydrate-tri(ethylene glycol)-alkanethiol co-adsorbed monolayer.
Densely packed co-adsorbed ultrathin mono molecular layers of short tri(ethylene glycol)-alkanethiolate (for repelling proteins) and maltoside terminated alkanethiolate (for capturing lectin) provided an extremely high signal to noise ratio surface: the repelling molecules, which had two different functions (highly flexible-hydrophilic arm and rigid packing tail group), worked as "nano barriers" in the recognition monolayer.


Determination of imipenem in human plasma, urine and tissue by high-performance liquid chromatography.
A simple and reliable HPLC method is described for the new beta-lactam antibiotic imipenem; suitable extraction procedures for the drug in human plasma, urine and prostatic tissue are described. The figures of merit for the assays are reported and examples given of their application.


Excystation of five digenean metacercariae in vitro and in the peritoneal cavity of the mouse.
Excystation of metacercariae of Parorchis acanthus, Posthodiplostomum nanum, Posthodiplostomum sp., Posthodiplostomoides leonensis and Clinostomum tilapiae in mammalian saline at 39 degrees C was similar to their excystation in mouse peritoneal cavity. Extrinsic enzymes were not needed for C. tilapiae excystation but were an absolute necessity for P. acanthus excystation. Extrinsic pepsin enhanced P. nanum excystation but was not obligatory. Acid pepsin was an absolute requirement for Posthodiplostomum sp. and Posthodiplostomoides leonensis excystation. It was noted that acid saline could not be substituted for acid pepsin and that there was diversity in the condition involved in digenean excystation.


Ultrasound-enabled topical anesthesia for pain reduction of phlebotomy for whole blood donation.
Ultrasound-facilitated delivery of topical anesthetics has been used to achieve effective anesthesia within 5 minutes for venipuncture and the insertion of intravenous access devices, but has never been studied for blood donation. This study was a single-center, prospective, randomized, sham treatment-controlled, single-blinded clinical evaluation. Repeat donors were randomly assigned to undergo treatment with ultrasound and topical anesthetic or sham ultrasound and placebo anesthetic before phlebotomy for whole blood donation. The primary outcome measures were pain assessments using the Verbal Categorical Scale (VCS) and the Visual Analogue Scale and the assessment of skin irritation at the target site. One-hundred subjects were enrolled and all completed the study. Compared to the sham/placebo control group, donors receiving ultrasound/anesthetic had lower pain scores on the VCS (1.81 +/- 0.67 vs. 2.17 +/- 0.68; p = 0.01) and Visual Analog Scale (17.2 +/- 15.5 vs. 27.6 +/- 19.5; p = 0.006). The proportion of subjects in the treatment group who experienced skin irritation (8%) was similar to that in the control group (2%; p = 0.20). Ultrasound-enhanced delivery of topical anesthetic was demonstrated to be a safe means of quickly achieving clinically meaningful reduction in the pain of phlebotomy for whole blood donation compared to sham/placebo treatment.


Synaesthesia: supernormal integration?
Synaesthesia has been known to scientific research for over 100 years but has undergone something of a renaissance recently as new investigations begin to uncover its neurological basis. Rather than being an anomaly, it might offer beneficial insights into the basis of normal perception. A new study by Esterman et al. epitomises this current trend and claims to show that the posterior parietal cortex is a crucial locus of synaesthetic experience. As the posterior parietal cortex is commonly linked to normal sensory integration, Esterman et al.'s finding might lend support to the claim that synaesthesia is an extension of the normal perceptual processes assumed to occur in binding.


Impact of alarm management and automation on abnormal operations: A human-in-the-loop simulation study.
Process control consists of complex states of performance that require a significant amount of operator attention and skill to manage. Automation and smart alarms can enhance these processes. This study investigated the effects of alarm management and automation on process control operator workload (NASA-TLX) and performance via material lost through flaring outcomes. Eleven console qualified operators participated in a human-in-the-loop, high-fidelity simulation-based training exercise. Three levels of alarm management (no rationalization, rationalization, and state-based smart alarm) and two levels of automation (no automation and automation) conditions were implemented using six scenarios. A repeated measures two-way MANOVA indicated that both alarm management schema and automation significantly affected operator workload and performance. These results indicate that state-based smart alarm management and automation schemas may assist operators in reducing workload and material lost through flare release during abnormal operating conditions.


Effect of immediate postoperative physical therapy on length of stay for total joint arthroplasty patients.
The isolated effect of physical therapy (PT) on total joint arthroplasty hospital length of stay (LOS) has not been studied. A prospective cohort study was conducted on 136 primary total joint arthroplasties (58 hips, 78 knees). The LOS was determined by the operative start time until the time of discharge. On postoperative day (POD) 0, 60 joints remained in bed, 51 moved to a chair, and 25 received PT (22 ambulated, 3 moved to a chair). Length of stay differed for patients receiving PT on POD 0 (2.8 ± 0.8 days) compared with POD 1 (3.7 ± 1.8 days) (P = .02). There was no difference in PT treatment based on nausea/vomiting, pain levels, or discharge location. Isolated PT intervention on POD 0 shortened hospital LOS, regardless of the intervention performed.


A comparative study of postoperative complications associated with the modified Indiana pouch in elderly versus younger patients.
We defined the nature and risk of complications associated with the modified Indiana pouch in patients older than 75 years. We analyzed the clinical course of 25 elderly patients and a control group of 25 selected randomly from the cohort of those younger than 75 years. All patients underwent the modified Indiana pouch procedure. Charts were reviewed for type of operation, mean patient age, length of hospital stay, medical conditions, and early and late morbidity and mortality. Comparisons were made between the 2 groups. Simultaneous cystectomy or anterior exenteration was performed in 84% and 95% of patients in the elderly and younger groups, respectively. Mean age was 78.5 years in the elderly and 59.3 years in the younger group. Medical illnesses and early postoperative complication rates did not differ significantly between the 2 groups. Mean hospital stay was increased but not significantly in the elderly group (12.4 versus 11.1 days). There were 2 perioperative deaths in the elderly group (8%) and 1 in the control group (4%). Mean followup was 24.5 months (range 4 to 64) in the elderly versus 29.5 months (range 6 to 69) in the younger group. Late complications with the pouch were also similar (16% in the elderly and 12% in the control group). Of the elderly patients 9 died (intercurrent medical disease in 1 and cancer progression in 8) compared to 4 in the younger group (intercurrent medical disease in 1 and cancer progression in 3). Of the elderly patients 13 are alive (mean age 81 years) with a well functioning continent diversion. The modified Indiana pouch can be created with acceptable postoperative morbidity and mortality in elderly patients, and it provides an excellent functional result.


Substance P in the rat parotid gland: evidence for a dual origin from the otic and trigeminal ganglia.
The substance P innervation of the rat parotid was investigated using retrograde tracing with the fluorescent dye True Blue, in combination with the immunohistochemical localization of substance P. Retrogradely-labelled cells were seen in the otic, trigeminal, superior cervical and nodose ganglia. A proportion of the True Blue-labelled cells in the otic and trigeminal ganglia also contained substance P-like immunoreactivity providing direct evidence for a dual origin of substance P in the rat parotid. In addition, these results imply that in the rat otic ganglion substance P and acetylcholine coexist.


Current recommendations for imaging in the management of urologic traumas.
Three percent to 10% of trauma patients have genitourinary tract injuries. Radiologic imaging is essential for making the correct diagnosis and managing it appropriately. Which modality is appropriate is based on the mechanism of injury and patient presentation. Patients with pelvic injuries and gross hematuria should undergo either CT cystography or conventional cystography. Ultrasound is warranted in patients with scrotal trauma when physical exam is inconclusive. Patients with penetrating trauma to the external genitalia, who suffer blunt trauma to the penis, or who present with gross hematuria, blood at the meatus, inability to void, perineal/scrotal ecchymosis, or abnormal digital rectal exam should undergo retrograde urethrography. Using these criteria for imaging should lead to the proper diagnosis and minimize patient morbidity.


Cyclic nucleotide phosphodiesterase in silkworm. Separation and characterization of multiple forms of the enzyme.
The existence of two forms of cyclic AMP phosphodiesterase (3',5'-cyclic AMP 5'-nucleotidohydrolase, EC 184.108.40.206) was demonstrated in silkworm larvae by kinetic analysis and DEAE-cellulose column chromatography. The two forms of the enzyme (phosphodiesterase II and III) differ apparently in their characteristics from the previously reported cyclic nucleotide phosphodiesterase (phosphodiesterase I) of silkworm. The higher K-m form (phosphodiesterase II) has a molecular weight of approx. 50 000 and optimum pH of 7.8, and requires Mn-2-+ for maximum activity. The lower K-m form (phosphodiesterase III) has a molecular weight of approx. 97 000 and optimum pH of 7.2, and requires Mg-2-+ for maximum activity. Phosphodiesterase II and probably phosphodiesterase III are specific enzymes for the hydrolysis of cyclic AMP.


Serum Oxytocin in Cows Is Positively Correlated with Caregiver Interactions in the Impossible Task Paradigm.
This study explored a possible relationship between the circulating oxytocin, cortisol, and the willingness of dairy cows to engage in social behaviors with humans in an experimental context. The behaviors of twenty-nine cows were recorded during the impossible task paradigm, a procedure aimed at creating a violation of expectancy, in the presence of the caregiver and a stranger. The results showed that serum oxytocin levels were positively correlated with duration and negatively correlated with the latency of the cows' social interactions with the caregiver. This research provides a clear correlation between circulating oxytocin and a willingness to engage in social contact with the caregiver, excluding the possible effect of different cortisol levels on such behavior.


15(S)-HETE production in human retinal microvascular endothelial cells by hypoxia: Novel role for MEK1 in 15(S)-HETE induced angiogenesis.
To examine for the expression of 15-lipoxygenase 1 (15-LOX1) and 15-LOX2 in human retinal microvascular endothelial cells (HRMVECs) and study the role of arachidonic acid metabolites of these enzymes in angiogenesis. Quantitative RT-PCR and reverse-phase HPLC analyses were used to determine 15-LOX1/2 expression and their arachidonic acid metabolites in HRMVECs. The role of MEK1 in 15(S)-HETE-induced angiogenesis was studied using HRMVEC migration, tube formation, and basement membrane matrix plug angiogenesis. HRMVECs expressed both 15-LOX1 and 15-LOX2. Hypoxia induced the expression of 15-LOX1 and the production of its arachidonic acid metabolites 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). 15(S)-HETE stimulated HRMVEC migration and tube formation as potently as 20 ng/mL fibroblast growth factor-2 (FGF-2). In addition, 15(S)-HETE stimulated the phosphorylation of ERK1/2, JNK1, p38 MAPK, and MEK1 in a time-dependent manner in these cells. Inhibition of MEK1 by pharmacologic and dominant-negative mutant approaches attenuated 15(S)-HETE-induced phosphorylation of ERK1/2 and JNK1 but not p38 MAPK. Blockade of ERK1/2 and JNK1 activation suppressed 15(S)-HETE-induced HRMVEC migration and tube formation and basement membrane matrix plug angiogenesis. Inhibition of p38 MAPK attenuated 15(S)-HETE-induced HRMVEC migration only. Inhibition of MEK1 also blocked 15(S)-HETE-induced HRMVEC migration and tube formation and basement membrane matrix plug angiogenesis. These results suggest that hypoxia, through the induction of 15-LOX1 expression, leads to the production of 15(S)-HETE in HRMVECs. In addition, 15(S)-HETE, through MEK1-dependent activation of ERK1/2 and JNK1, stimulates the angiogenic differentiation of HRMVECs and basement membrane matrix plug angiogenesis.


Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice.
Diabetic skin ulcers are difficult to heal spontaneously due to the reduced levels and activity of endogenous growth factors. Recombinant human vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are known to stimulate cell proliferation and accelerate wound healing. Direct delivery of VEGF and bFGF at the wound site in a sustained and controllable way without loss of bioactivity would enhance their biological effects. The aim of this study was to develop a poly(ether)urethane-polydimethylsiloxane/fibrin-based scaffold containing poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with VEGF and bFGF (scaffold/GF-loaded NPs) and to evaluate its wound healing properties in genetically diabetic mice (db/db). The scaffold application on full-thickness dorsal skin wounds significantly accelerated wound closure at day 15 compared to scaffolds without growth factors (control scaffold) or containing unloaded PLGA nanoparticles (scaffold/unloaded NPs). However, the closure rate was similar to that observed in mice treated with scaffolds containing free VEGF and bFGF (scaffold/GFs). Both scaffolds containing growth factors induced complete re-epithelialization, with enhanced granulation tissue formation/maturity and collagen deposition compared to the other groups, as revealed by histological analysis. The ability of the scaffold/GF-loaded NPs to promote wound healing in a diabetic mouse model suggests its potential use as a dressing in patients with diabetic foot ulcers.


Breaking dormancy is spores of the arbuscular mycorrhizal fungus Glomus intraradices: a critical cold-storage period.
To elucidate the effect of cold storage on spore dormancy in the arbuscular mycorrhizal (AM) fungus Glomus intraradices, spores were cold stratified at 4 degrees C, for either 0, 3, 7, 14, 90 or 120 days, prior to germination tests at 25 degrees C. The results showed that cold stratification longer than 14 days significantly increased spore germination. Moreover, the longer cold storage periods clearly reduced spore mortality from 90% to 50% and considerably altered the hyphal growth pattern. Long polarized hyphae were only observed after cold stratification periods longer than 14 days, involving consequences for root infectivity. The results clearly show that environmental factors, e.g., coldness, can affect the physiology of AM fungal spores.


Long-term recovery of upper limb motor function and self-reported health: results from a multicenter observational study 1 year after discharge from rehabilitation.
Impaired motor functions after stroke are common and negatively affect patients' activities of daily living and quality of life. In particular, hand motor function is essential for daily activities, but often returns slowly and incompletely after stroke. However, few data are available on the long-term dynamics of motor recovery and self-reported health status after stroke. The Interdisciplinary Platform for Rehabilitation Research and Innovative Care of Stroke Patients (IMPROVE) project aims to address this knowledge gap by studying the clinical course of recovery after inpatient rehabilitation. In this prospective observational longitudinal multicenter study, patients were included towards the end of inpatient rehabilitation after ischemic or hemorrhagic stroke. Follow-up examination was performed at three, six, and twelve months after enrollment. Motor function was assessed by the Upper Extremity Fugl-Meyer Assessment (FMA), grip and pinch strength, and the nine-hole peg test. In addition, Patient-Reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) was included. Linear mixed effect models were fitted to analyze change over time. To study determinants of hand motor function, patients with impaired hand function at baseline were grouped into improvers and non-improvers according to hand motor function after twelve months. A total of 176 patients were included in the analysis. Improvement in all motor function scores and PROMIS-10 was shown up to 1 year after inpatient rehabilitation. FMA scores improved by an estimate of 5.0 (3.7-6.4) points per year. In addition, patient-reported outcome measures increased by 2.5 (1.4-3.6) and 2.4 (1.4-3.4) per year in the physical and mental domain of PROMIS-10. In the subgroup analysis non-improvers showed to be more often female (15% vs. 55%, p = 0.0155) and scored lower in the Montreal Cognitive Assessment (25 [23-27] vs. 22 [20.5-24], p = 0.0252). Continuous improvement in motor function and self-reported health status is observed up to 1 year after inpatient stroke rehabilitation. Demographic and clinical parameters associated with these improvements need further investigation. These results may contribute to the further development of the post-inpatient phase of stroke rehabilitation. The trial is registered at ClinicalTrials.gov (NCT04119479).


Suicidal burn in Hong Kong.
The aim of our study is to review our experience in the management of patients who sustained burns associated with suicidal attempts over a 10-year period. In particular, we look into the outcome and incidence of self-harm/suicide after discharge among the survivors. Thirty-one patients with median age 36 years, ranging from 10 to 74, were included. Twenty-three (74%) were males and eight (26%) were females. Nearly three quarters (74%) of our patients had a known history of psychiatric illness: 11 had known history of substance abuse; 3 of them had drug-induced psychosis; 6 had schizophrenia; 5 had depression; 4 had personality disorders; 1 had pathological gambling and another one had adjustment disorder. Relationship problems and work/financial difficulties were the commonest reason for the suicidal attempts. Self-inflicted flame burn was the most frequent (39%; 12 patients) method of burning. Six patients (19%) died. The remaining 25 patients healed and were discharged. Seventeen patients required ICU care. The median length of stay in ICU was 7 days. The overall median length of stay was 35 days. The median follow up time for those survived is 63 months. Only 4 of these patients had further suicidal/parasuicidal attempts. Despite the high mortality, once these patients survived the initial injury, they are unlikely to commit suicide again. Thus, we believe that aggressive resuscitation should therefore be advocated for all suicidal burn patients.


An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) is complex, chronic, and relapsing gastrointestinal inflammatory disorders, which includes mainly two conditions, namely ulcerative colitis (UC) and Crohn's disease (CD). Development of IBD in any individual is closely related to his/her autoimmune regulation, gene-microbiota interactions, and dietary factors. Dietary tryptophan (Trp) is an essential amino acid for intestinal mucosal cells, and it is associated with the intestinal inflammation, epithelial barrier, and energy homeostasis of the host. According to recent studies, Trp and its three major metabolic pathways, namely kynurenine (KYN) pathway, indole pathway, and 5-hydroxytryptamine (5-HT) pathway, have vital roles in the regulation of intestinal inflammation by acting directly or indirectly on the pro/anti-inflammatory cytokines, functions of various immune cells, as well as the intestinal microbial composition and homeostasis. In this review, recent advances in Trp- and its metabolites-associated intestinal inflammation are summarized. It further discusses the complex mechanisms and interrelationships of the three major metabolic pathways of Trp in regulating inflammation, which could elucidate the value of dietary Trp to be used as a nutrient for IBD patients.


Relationship between psychiatric illness and conduct disorder in adolescents.
Ninety-six psychiatrically ill adolescents admitted to an adolescent inpatient service were systematically assessed to determine the morbidity of conduct disorder (CD), with other Axis I psychiatric disorders. Twenty-six (27%) met DSM-111 criteria for CD in addition to other Axis I disorders. A CD diagnosis was significantly associated with substance abuse, and attention deficit disorder with hyperactivity. Although CD was found in 21% of depressives it was more commonly found in patients with psychotic disorders (25%) and bipolar (42%) disorders. These findings suggest that CD may be commonly found in a variety of adolescent psychiatric disorders. The implications of this finding for pharmacologic treatment of CD, the clinical assessment of the CD patient, and possible relationships between CD and adolescent psychiatric disorders are discussed.


Performance of Clinical Screening Algorithms for Tuberculosis Intensified Case Finding among People Living with HIV in Western Kenya.
To assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya. Prospective cohort study. PLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms [World Health Organization (WHO), Ministry of Health (MOH), and "Improving Diagnosis of TB in HIV-infected persons" (ID-TB/HIV) study], underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey. Overall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9-12.7). Sensitivity of the three screening algorithms was similar [WHO, 74.1% (95% CI, 64.1-82.2); MOH, 77.5% (95% CI, 68.6-84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9-81.7)]. Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women [28.2% (95% CI, 14.9-46.7)] compared to non-pregnant women [78.3% (95% CI, 67.3-86.4)] and men [77.2% (95% CI, 68.3-84.2)]. Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4-93.9) and 96.1% (95% CI, 94.4-97.3), respectively, among asymptomatic men and non-pregnant women. Clinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services.


MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets.
c-MYC (MYC) is a major driver of prostate cancer tumorigenesis and progression. Although MYC is overexpressed in both early and metastatic disease and associated with poor survival, its impact on prostate transcriptional reprogramming remains elusive. We demonstrate that MYC overexpression significantly diminishes the androgen receptor (AR) transcriptional program (the set of genes directly targeted by the AR protein) in luminal prostate cells without altering AR expression. Analyses of clinical specimens reveal that concurrent low AR and high MYC transcriptional programs accelerate prostate cancer progression toward a metastatic, castration-resistant disease. Data integration of single-cell transcriptomics together with ChIP-seq uncover an increase in RNA polymerase II (Pol II) promoter-proximal pausing at AR-dependent genes following MYC overexpression without an accompanying deactivation of AR-bound enhancers. Altogether, our findings suggest that MYC overexpression antagonizes the canonical AR transcriptional program and contributes to prostate tumor initiation and progression by disrupting transcriptional pause release at AR-regulated genes.


Sarafotoxin expression in the bronchopulmonary tract: immunohistochemical occurrence and colocalization with endothelins.
The immunohistochemical occurrence of sarafotoxin (SRTX), a snake venom peptide under strong evolutionary control, was investigated in the pulmonary diffuse neuroendocrine system (PDNES) of newborn cats and rats. By applying the avidin-biotin-peroxidase complex method on serial lung sections, we have demonstrated its distribution and colocalization with different endothelin (ET) isoforms. A light microscopic study revealed apparent immunostaining for SRTX in neuronal components and smooth muscle tissue and in neuroepithelial bodies (NEB), while isolated neuroendocrine cells (NEC) remain unlabelled. Comparison of the SRTX reactivity pattern with that of different ET peptides on adjacent lung sections showed colocalization of SRTX-b with ET-3 in NEB, intrapulmonary ganglion cells and nerve fibres, on the one hand, and with ET-1 in airway and vascular smooth muscle cells, on the other. These findings, in addition to the remarkable functional and structural similarities between SRTX and ET peptides, suggest a common evolutionary origin and biological significance of sarafotoxin and endothelins. Moreover, this is the first time that a toxic peptide has been demonstrated in the PDNES.


Characterization of whole blood transcriptome and early-life fecal microbiota in high and low responder pigs before, and after vaccination for Mycoplasma hyopneumoniae.
We investigated gene expression patterns in whole blood and fecal microbiota profile as potential predictors of immune response to vaccination, using healthy M. hyopneumoniae infection free piglets (n = 120). Eighty piglets received a dose of prophylactic antibiotics during the first two days of life, whereas the remaining 40 did not. Blood samples for RNA-Seq analysis were collected on experimental Day 0 (D0; 28 days of age) just prior to vaccination, D2, and D6 post-vaccination. A booster vaccine was given at D24. Fecal samples for microbial 16SrRNA sequencing were collected at 7 days of age, and at D0 and D35 post-vaccination. Pigs were ranked based on the levels of M. hyopneumoniae-specific antibodies in serum samples collected at D35, and groups of 'high' (HR) and 'low' (LR) responder pigs (n = 15 each) were selected. Prophylactic antibiotics did not influence antibody titer levels and differential expression analysis did not reveal differences between HR and LR at any time-point (FDR > 0.05); however, based on functional annotation with Ingenuity Pathway Analysis, D2 post-vaccination, HR pigs were enriched for biological terms relating to increased activation of immune cells. In contrast, the immune activation decreased in HR, 6 days post-vaccination. No significant differences were observed prior to vaccination (D0). Two days post-vaccination, multivariate analysis revealed that ADAM8, PROSER3, B4GALNT1, MAP7D1, SPP1, HTRA4, and ENO3 genes were the most promising potential biomarkers. At D0, OTUs annotated to Prevotella, CF21, Bacteroidales and S24-7 were more abundant in HR, whereas Fibrobacter, Paraprevotella, Anaerovibrio, [Prevotella], YRC22, and Helicobacter positively correlated with the antibody titer as well as MYL1, SPP1, and ENO3 genes. Our study integrates gene differential expression and gut microbiota to predict vaccine response in pigs. The results indicate that post-vaccination gene-expression and early-life gut microbiota profile could potentially predict vaccine response in pigs, and inform a direction for future research.


A Multi-Scale Approach for Modeling the Optical Response of Molecular Materials Inside Cavities.
The recent fabrication advances in nanoscience and molecular materials point toward a new era where material properties are tailored in silico for target applications. To fully realize this potential, accurate and computationally efficient theoretical models are needed for: a) the computer-aided design and optimization of new materials before their fabrication; and b) the accurate interpretation of experiments. The development of such theoretical models is a challenging multi-disciplinary problem where physics, chemistry, and material science are intertwined across spatial scales ranging from the molecular to the device level, that is, from ångströms to millimeters. In photonic applications, molecular materials are often placed inside optical cavities. Together with the sought-after enhancement of light-molecule interactions, the cavities bring additional complexity to the modeling of such devices. Here, a multi-scale approach that, starting from ab initio quantum mechanical molecular simulations, can compute the electromagnetic response of macroscopic devices such as cavities containing molecular materials is presented. Molecular time-dependent density-functional theory calculations are combined with the efficient transition matrix based solution of Maxwell's equations. Some of the capabilities of the approach are demonstrated by simulating surface metal-organic frameworks -in-cavity and J-aggregates-in-cavity systems that have been recently investigated experimentally, and providing a refined understanding of the experimental results.


Developmental exposure to thyroid disrupting chemical mixtures alters metamorphosis and post-metamorphic thymocyte differentiation.
While there is some evidence to suggest that disruption of the thyroid hormone (TH)-axis during perinatal development may weaken T cell immunity later in life, data are currently lacking on whether environmentally relevant thyroid disrupting chemicals (TDCs) can induce similar outcomes. To fill this gap in knowledge, X. laevis tadpoles were exposed to an environmentally relevant mixture of TDCs, either during early tadpole development, or immediately before and during metamorphosis, to assess T cell differentiation and anti-viral immune response against FV3 infection after metamorphosis. Extending our previous study showing a delay in metamorphosis completion, here we report that TDC exposure prior to metamorphosis reduced the frequency of surface MHC-II + splenic lymphocytes and weakened some aspects of the anti-viral immune response. TDC exposure during metamorphosis slowed post-metamorphic migration of the thymus reduced the renewal of cortical thymocytes and splenic CD8 + T cells. The results indicate that TDC exposure during perinatal development may perturb the formation of T cell immunity later in life.


Spotlight on ocular Kaposi's sarcoma: an update on the presentation, diagnosis, and management options.
Kaposi's sarcoma (KS) is a multifocal low-grade vascular neoplasm that can affect the skin, mucus membranes, visceral organs, and lymph nodes. KS can also affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis. In this review, the manifestations of ocular KS are discussed along with theories for pathogenesis, common risk factors, and management options. KS is caused by the oncogenic human herpesvirus 8 (HHV8). Immunosuppression in patients with HIV and AIDS contributes to the development of KS but conjunctival and ocular adnexal KS lesions are now uncommon in the era of anti-retroviral therapy. A high index of suspicion is required to diagnose ocular KS as these lesions can be mistaken for alternative entities. Prompt diagnosis can reduce significant morbidity and mortality by prompting a multidisciplinary systemic evaluation, particularly in immunosuppressed individuals. While surgical excision, cryotherapy, intralesional or systemic chemotherapy, and radiation are all viable treatment options, ongoing research to identify novel therapies and molecular treatment targets will help expand the armamentarium of therapeutics available for this disease.


Influence of Diabetes Mellitus on Glaucoma-Relevant Examination Results in Primary Open-Angle Glaucoma.
Primary open-angle glaucoma (POAG) is no longer considered an isolated eye pressure-dependent optic neuropathy, but a neurodegenerative disease in which oxidative stress and neuroinflammation are prominent. These processes may be exacerbated by additional systemic diseases. The most common are arterial hypertension, dyslipidemia, and diabetes mellitus. Using diabetes mellitus as an example, it will be shown how far-reaching the influence of such a systemic disease can be on both the functional and the structural diagnostic methods for POAG. This knowledge is essential, since these interferences can lead to misinterpretations of POAG, which can also affect therapeutic decisions.


Ten-Year Outcomes of Hypofractionated Postmastectomy Radiation Therapy of 26 Gy in 6 Fractions.
To investigate the efficacy and long-term side effects of hypofractionated postmastectomy radiation therapy (HFRT-PM) of 26 Gy in 6 fractions over 5 weeks. We retrospectively reviewed characteristics and outcomes of patients with stage I to III breast cancer treated with HFRT-PM between 2000 and 2009. Treatment provided 4 fractions of 4 Gy (days 1, 3, 15, 17) and then 2 fractions of 5 Gy (days 29 and 31) over 5 weeks. The treatment techniques were applied by using 3-dimensional conformal radiation therapy of the chest wall with regional nodal volume if required. We identified 454 patients with a median follow-up of 10.6 years (range, 0.5-22.9). Regional nodal irradiation was done in 84.1% of patients. At 10 years, the cumulative incidence of locoregional relapse was 15.1%. In multivariate analysis, regional lymph node involvement (≥4 nodes) was associated with worse locoregional control (hazard ratio, 1.68; 95% confidence interval, 1.06-2.67; P = .03) and overall survival (hazard ratio, 2.16; 95% confidence interval, 1.59-2.95; P < .001). The toxicities were acceptable. The incidence of cardiac disorders (3.3%), and symptomatic lung fibrosis (1.5%) was low during follow-up. At 10 years, the cumulative rate of arm lymphedema was 9.5% and considered severe in 20 patients (4.4%). The long-term results of this study show that HFRT-PM of 26 Gy in 6 fractions over 5 weeks seems safe, but locoregional recurrence seems slightly higher than that observed in the literature, highlighting the need for long-term follow-up and for randomized trials for hypofractionated radiation therapy postmastectomy.


Ptosis and vertical diplopia after ligation of ethmoidal arteries.
The treatment of epistaxis is well codified, ligation of the ethmoidal arteries being the last resort. We report the case of a 25-year-old pregnant patient, who has had a ligation of the anterior and posterior ethmoidal arteries after a persistent epistaxis. Postoperatively, she presented a complete ptosis and an impaired eye elevation without any visual acuity disorders, evoking a lesion of the upper branch of the common oculomotor nerve (third cranial nerve). The patient totally recovered after 3 months. Anatomical study shows that the upper branch of the third cranial nerve is lying very close to the optic nerve and cannot be affected by surgery without any associated damage of the optic nerve. Thus, a vascular etiology seems to be the best explanation of the complication experienced by our patient. Ligation of the posterior ethmoidal artery should be done with caution.


Subcutaneous injection of inhaled anesthetics produces cutaneous analgesia.
Previous investigations suggest that inhaled anesthetics may produce cutaneous analgesia. The objective of this study was to evaluate whether inhaled anesthetics have a direct analgesic effect on skin. We conducted subcutaneous injections of one of three inhaled anesthetics (halothane, isoflurane, and enflurane) or one of two local anesthetics (lidocaine and procaine) at various dosages in rats (n=6 rats, for each dose of each drug). Subcutaneous injections of vehicles (saline or olive oil) were used as controls (n=6 rats for each vehicle). We constructed concentration-response curves, wherein the concentrations of drugs tested in subcutaneous tissue fluid were estimated by calculation, and the cutaneous analgesic effects of drugs were evaluated by pinprick tests on skin. Like local anesthetics, subcutaneous injection of inhaled anesthetics produced concentration-dependent, cutaneous analgesia which attained maximum (complete cutaneous analgesia) at high concentration. This effect was reversible and localized in the area of injection. On the basis of 50% effective concentration, the ranking of potencies was lidocaine>halothane>isoflurane>enflurane>procaine (P<0.05 for all differences). Subcutaneous injections of vehicles did not produce cutaneous analgesia. Like local anesthetics (lidocaine and procaine), subcutaneous injections of inhaled anesthetics (halothane, isoflurane, and enflurane) produced a concentration-dependent, cutaneous, analgesic effect at the site of injection. Inhaled anesthetics have a direct analgesic effect on skin.


The relationship between cyclic AMP changes and histamine release from basophil-rich human leucocytes.
Histamine release and changes in cyclic AMP levels induced by a variety of stimuli have been measured in isolated human leucocytes from a patient with 40-70% basophilia. Adenosine and sodium fluoride induced early monophasic rises in cyclic AMP which peaked at 1 min, but they did not release histamine. 2',5'-Dideoxyadenosine (DDA) caused a transient fall in cyclic AMP levels. Anti-IgE, polylysine and calcium ionophore A23187 induced a slow release of histamine commencing 2-5 min after addition of secretagogue. With polylysine and A23187, release was still proceeding 45 min after challenge. In contrast, the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe) induced a rapid secretion of histamine which was complete within 2 min. Anti-IgE induced a rapid monophasic rise in cyclic AMP which reached a maximum at 45 sec and was inhibited by pretreatment with DDA. Cyclic AMP rises induced by polylysine and f-met-leu-phe were kinetically similar but smaller in magnitude. A23187 caused a later rise in cyclic AMP which peaked 3 min after challenge. A high concentration (50 microM) of compound 48/80 induced a slow cytotoxic release of histamine which was not accompanied by changes in cyclic AMP levels. The inconsistent quantitative and kinetic relationships of histamine release and cyclic AMP production suggest that changes in cyclic AMP levels may not play a key role in the biochemical events leading to mediator secretion from human basophil leucocytes.


Learning not to fear: neural correlates of learned safety.
The ability to recognize and properly respond to instances of protection from impending danger is critical for preventing chronic stress and anxiety-central symptoms of anxiety and affective disorders afflicting large populations of people. Learned safety encompasses learning processes, which lead to the identification of episodes of security and regulation of fear responses. On the basis of insights into the neural circuitry and molecular mechanisms involved in learned safety in mice and humans, we describe learned safety as a tool for understanding neural mechanisms involved in the pathomechanisms of specific affective disorders. This review summarizes our current knowledge on the neurobiological underpinnings of learned safety and discusses potential applications in basic and translational neurosciences.