Tuberculous dacryoadenitis: a rare manifestation of tuberculosis.
A 41-year-old Somalian female inhabitant of The Netherlands presented with malaise and cervical lymph node swelling. Enlarged mediastinal, hilar and abdominal lymph nodes were found on CT scan. Subsequently the left lacrimal gland became swollen, accompanied by periostitis of the lateral orbit margin. Mycobacterium tuberculosis was cultured from lymph node tissue and the diagnosis of tuberculous dacryoadenitis with periostitis was made on CT images and histology. All lesions responded well to tuberculostatic treatment. Although tuberculous dacryoadenitis is a very rare manifestation of tuberculosis, it is still important to recognise this presentation, especially since the incidence of tuberculosis continues to increase in Western countries.


Aortic arch debranching: advanced and hybrid techniques.
Aortic arch procedures have traditionally involved complex surgery with increased risk of mortality and morbidity. Throughout the last decade, however, novel and safe surgical approaches aimed at debranching the great vessels with definitive aortic arch repair have been developed. Currently, hybrid arch procedures allow for open or minimally invasive aortic access to be complemented by endovascular stent-graft techniques, which may eliminate the need for prolonged hypothermic circulatory arrest and its associated complications. Hybrid thoracic aortic and arch repairs have become the preferred approach, with open procedures performed only if hybrid approaches are not possible for technical reasons. In the future, aortic pathology may also benefit from the development of branched and fenestrated endografts that would be deployed in a modular fashion. This article describes the rationale, procedural steps, and recent outcomes data of novel aortic arch procedures.


The first Tunisian case of postorgasmic illness syndrome: A case report.
Postorgasmic illness syndrome (POIS) is a rare and singular syndrome. About fifty cases have been reported in the medical literature. Through a clinical observation, we illustrate the first case diagnosed in Tunisia and the difficulties in the etiological diagnosis and the therapeutic management of this syndrome. Given the shortage of cases reported in the literature, the syndrome of POIS remains poorly identified and subsequently misdiagnosed. The clinical diagnosis is relatively simple, yet etiological and therapeutic questions remain to overcome.


Extensive alopecia areata: not necessarily recalcitrant to therapy!
Extensive alopecia areata includes alopecia universalis, alopecia totalis, ophiasis and patients having more than 50% scalp involvement. Alopecia universalis (AU) and totalis (AT) are considered to be resistant to single modalities of treatment. Our study highlights the efficacy and safety of combination therapy in extensive alopecia areata. To evaluate the efficacy and safety of a combination treatment with oral bethametasone mini-pulse, topical minoxidil and short contact anthralin in long-standing, treatment-resistant, extensive alopecia areata. Fifteen patients aged 7 to 45 years with extensive, treatment-resistant alopecia areata (AU: 7; AT: 1; ophiasis: 4; patients with more than 50% scalp involvement: 3) were treated with betamethasone oral mini-pulse (0.1 mg per kg body weight per dose on two consecutive days per week) along with short contact anthralin (1.15%) and 2-5% minoxidil lotion daily, till response. The response was assessed by the severity of alopecia tool (SALT) score. Cosmetic response was defined as regrowth obviating the need of a wig. Failure of treatment was defined as no growth or vellus hair on the scalp. Out of eight patients with AU/AT, two attained cosmetic response as early as three months, two at six months and one had partial response. Cosmetic response was attained in all four patients with ophiasis and all three patients with more than 50% scalp involvement at six months. All responders maintained their response without systemic steroids beyond 12 months. Among a total of twelve responders (80%), two with AU showed a mild relapse and were effectively treated with intralesional steroids. Side effects to therapy were mild and reversible. A combination therapy of oral steroid minipulse with topical anthralin and minoxidil acts synergistically, being effective as well as safe in treatment-resistant, extensive, long-standing alopecia areata.


''Ask the way from those who have walked it before"-Grandmothers' roles in health-related decision making and HIV pre-exposure prophylaxis use among pregnant and breastfeeding women in sub-Saharan Africa.
HIV acquisition among pregnant and breastfeeding women in sub-Saharan Africa and vertical transmission rates remain high despite established strategies for HIV prevention. During the MTN-041/MAMMA study, we explored the influence of grandmothers (mothers and mothers-in-law of pregnant and breastfeeding women) in eastern and southern Africa on the health-related decisions of pregnant and breastfeeding women and their potential to support use of HIV prevention products. To do this we used structured questionnaires and focus group discussions with three stakeholder groups: 1) grandmothers, 2) HIV-uninfected currently or recently pregnant or breastfeeding women and 3) male partners of currently or recently pregnant or breastfeeding women. A total of 23 focus group discussions comprising 68 grandmothers, 65 pregnant or breastfeeding women and 63 male partners were completed across four study sites. Grandmothers were described as important sources of information during pregnancy and breastfeeding playing both supportive and influencer roles due to personal maternal experience and generational knowledge. While pregnant and breastfeeding women were not keen to involve grandmothers in HIV prevention decision making, they were accepting of grandmothers' involvement in a supportive role. Grandmothers expressed willingness to support pre-exposure prophylaxis use and agreed with the other two stakeholder groups that this decision should be made by women themselves or together with partners. These novel data indicate potential for grandmothers' health related supportive roles to be extended to support decision-making and adherence to biomedical HIV prevention options, and possibly contribute to the decline in HIV acquisition among pregnant and breastfeeding women in these communities.


Multiscale Modeling of Superior Cavopulmonary Circulation: Hemi-Fontan and Bidirectional Glenn Are Equivalent.
Superior cavopulmonary circulation (SCPC) can be achieved by either the Hemi-Fontan (hF) or Bidirectional Glenn (bG) connection. Debate remains as to which results in best hemodynamic results. Adopting patient-specific multiscale computational modeling, we examined both the local dynamics and global physiology to determine if surgical choice can lead to different hemodynamic outcomes. Six patients (age: 3-6 months) underwent cardiac magnetic resonance imaging and catheterization prior to SCPC surgery. For each patient: (1) a finite 3-dimensional (3D) volume model of the preoperative anatomy was constructed to include detailed definition of the distal branch pulmonary arteries, (2) virtual hF and bG operations were performed to create 2 SCPC 3D models, and (3) a specific lumped network representing each patient's entire cardiovascular circulation was developed from clinical data. Using a previously validated multiscale algorithm that couples the 3D models with lumped network, both local flow dynamics, that is, power loss, and global systemic physiology can be quantified. In 2 patients whose preoperative imaging demonstrated significant left pulmonary artery (LPA) stenosis, we performed virtual pulmonary arterioplasty to assess its effect. In one patient, the hF model showed higher power loss (107%) than the bG, while in 3, the power losses were higher in the bG models (18-35%). In the remaining 2 patients, the power loss differences were minor. Despite these variations, for all patients, there were no significant differences between the hF and bG models in hemodynamic or physiological outcomes, including cardiac output, superior vena cava pressure, right-left pulmonary flow distribution, and systemic oxygen delivery. In the 2 patients with LPA stenosis, arterioplasty led to better LPA flow (5-8%) while halving the power loss, but without important improvements in SVC pressure or cardiac output. Despite power loss differences, both hF and bG result in similar SCPC hemodynamics and physiology outcome. This suggests that for SCPC, the pre-existing patient-specific physiology and condition, such as pulmonary vascular resistance, are more deterministic in the hemodynamic performance than the type of surgical palliation. Multiscale modeling can be a decision-assist tool to assess whether an extensive LPA reconstruction is needed at the time of SCPC for LPA stenosis.


Granulomatous infections: etiology and classification.
Granulomatous disorders are frequently due to a wide variety of infections. Over the past decade advances in molecular diagnostic techniques have allowed identification of organisms involved in granulomatous disorders that previously were of unknown etiology. On the basis of currently available information, granulomatous infections can now be classified in three categories. Group 1 infections are due to a well-recognized organism. Group 2 comprises infections due to organisms that have been recently identified in granulomas by molecular methods but are not readily isolated by conventional microbiological techniques. Group 3 consists of disorders for which the causal organisms have not yet been identified but are strongly suspected; further advances in diagnostic techniques will lead to reclassification of some of these disorders as group 2. This review describes the etiology, histopathologic features, and classification of granulomatous disorders, with an emphasis on those of groups 2 and 3.


Barley yellow dwarf virus-GAV-derived vsiRNAs are involved in the production of wheat leaf yellowing symptoms by targeting chlorophyll synthase.
Wheat yellow dwarf virus disease is infected by barley yellow dwarf virus (BYDV), which causes leaf yellowing and dwarfing symptoms in wheat, thereby posing a serious threat to China's food production. The infection of plant viruses can produce large numbers of vsiRNAs, which can target host transcripts and cause symptom development. However, few studies have been conducted to explore the role played by vsiRNAs in the interaction between BYDV-GAV and host wheat plants. In this study, small RNA sequencing was conducted to profile vsiRNAs in BYDV-GAV-infected wheat plants. The putative targets of vsiRNAs were predicted by the bioinformatics software psRNATarget. RT-qPCR and VIGS were employed to identify the function of selected target transcripts. To confirm the interaction between vsiRNA and the target, 5' RACE was performed to analyze the specific cleavage sites. From the sequencing data, we obtained a total of 11,384 detected vsiRNAs. The length distribution of these vsiRNAs was mostly 21 and 22 nt, and an A/U bias was observed at the 5' terminus. We also observed that the production region of vsiRNAs had no strand polarity. The vsiRNAs were predicted to target 23,719 wheat transcripts. GO and KEGG enrichment analysis demonstrated that these targets were mostly involved in cell components, catalytic activity and plant-pathogen interactions. The results of RT-qPCR analysis showed that most chloroplast-related genes were downregulated in BYDV-GAV-infected wheat plants. Silencing of a chlorophyll synthase gene caused leaf yellowing that was similar to the symptoms exhibited by BYDV-GAV-inoculated wheat plants. A vsiRNA from an overlapping region of BYDV-GAV MP and CP was observed to target chlorophyll synthase for gene silencing. Next, 5' RACE validated that vsiRNA8856 could cleave the chlorophyll synthase transcript in a sequence-specific manner. This report is the first to demonstrate that BYDV-GAV-derived vsiRNAs can target wheat transcripts for symptom development, and the results of this study help to elucidate the molecular mechanisms underlying leaf yellowing after viral infection.


Emotion processing in borderline personality disorders.
This study examined relationships between the ability to recognize facial affect and affective intensity in women with Borderline Personality Disorder. Women hospitalized with borderline personality disorder and community women without psychiatric disorder (n s = 35/group) were recruited via convenience sampling. The Pictures of Facial Affect and the Affect Intensity Measure were administered to consenting women. Hypotheses related to differences in recognizing facial affect were supported, but further exploration indicated that selected negative emotions accounted for the statistical significance. Implications for practice and research are explored.


Activity of concanavalin A-induced suppressor cells in human MLR: differential effects on primary MLR, secondary MLR, and memory cell precursors.
The relative sensitivity of the MLR responses of freshly isolated human lymphocytes to Con A-induced suppressor cells (SC) was compared to that of lymphocytes that had been primed previously in vitro. Fresh and primed cells were suppressed 72 and 17%, respectively, when cultured under similar conditions (p less than 0.0005). Titration of SC indicated that equivalent suppression in the two populations would require greater than a 50-fold excess of SC in the primed cells. Neither preincubation of the primed cells for 24 or 72 hr with the SC before restimulation, addition of fresh autologous cells to the primed cells, nor preincubation of the SC with fresh cells before addition to the primed cells increased suppression of primed cells. SC added at the beginning of a primary MLC were, however, very suppressive for both the primary response (67% suppression) and the subsequent secondary response (81% suppression). These data indicate that although the human primary MLR and the precursor of the memory cell are both sensitive to the suppressors induced by Con A, the memory cell itself possess an intrinsic resistance to such suppressors that is not related to simple kinetic phenomena nor to the loss in vitro of an intermediate regulatory cell. Cell depletion experiments suggest that resistance to nonspecific suppression may occur at the level of the helper cell.


Analysis of Maternal and Neonatal Complications in a Group of Patients with Gestational Diabetes Mellitus.
Background and Objectives: Gestational diabetes mellitus (GDM) represents one of the most common complications during pregnancy, being associated with numerous maternal and neonatal complications. The study aimed to analyze maternal and neonatal complications associated with GDM. The risk factors of GDM and of the maternal and neonatal complications were studied in order to prevent their occurrence. Materials and Methods: The study included 97 women in the study, who underwent an oral glucose tolerance test (OGTT) between weeks 24-28 of pregnancy, consequently being divided into two groups: pregnant women with and without GDM. Statistical analysis was performed using the SPSS 26.0 software and MATLAB fitglm, the results being considered statistically significant if p < 0.05. Results: We observed statistically significant differences between the group of women with and without GDM, regarding gestational hypertension (17.6% vs. 0%), preeclampsia (13.72% vs. 0%), and cesarean delivery (96.1% vs. 78,3%). Data on the newborn and neonatal complications: statistically significant differences were recorded between the two groups (GDM vs. no GDM) regarding the average weight at birth (3339.41 ± 658.12 g vs. 3122.83 ± 173.67 g), presence of large for gestational age (21.6% vs. 0%), macrosomia (13.7% vs. 0%), excessive fetal growth (35.3% vs. 0%), respiratory distress (31.4% vs. 0%), hospitalization for at least 24 h in the Neonatal Intensive Care Unit (9.80% vs. 0%), and APGAR score <7 both 1 and 5 min following birth (7.8% vs. 0%). Additionally, the frequency of neonatal hypoglycemia and hyperbilirubinemia was higher among newborns from mothers with GDM. Conclusions: The screening and diagnosis of GDM is vital, and appropriate management is required for the prevention of maternal and neonatal complications associated with GDM. It is also important to know the risk factors for GDM and attempt to prevent their appearance.


"Oxidative stress": effects of mild endurance training and testosterone treatment on rat gastrocnemius muscle.
We evaluated the effects of testosterone overload on mitochondrial superoxide dismutase (MnSOD), cytochrome oxidase (COX) and citrate synthase (CS) activities of the rat superficial gastrocnemius both in non-exercised muscle and following moderate endurance training. Basal (bLPO) and stimulated (sLPO) lipid peroxidation was measured as an index of oxidative tissue damage. Furthermore, to assess the relationship between exercise and testosterone-induced metabolic adaptations and contractile protein expression, the distribution of myosin heavy chain (MHC) isoforms was analysed by SDS-PAGE. Samples were obtained from: controls (C), rats treated with testosterone propionate (Tp) (TP, 5 mg kg(-1) i.m. 6 days/week), trained rats (E, 5 days/week) and rats trained and treated with Tp (ETP). MnSOD significantly increased in E and TP in comparison with C and ETP. Training induced a significant increase in COX activity both in E and ETP whereas a statistical reduction was observed in TP in comparison with the other groups. Moreover, testosterone administration was associated with a significant reduction in CS activity which significantly increased in ETP. A reduction in lipid peroxidation was observed in E and ETP in comparison with controls both in basal and stimulated conditions, whereas TP showed a significant increase of bLPO. In trained rats enzymatic changes were correlated with an increase in the proportion of fast oxidative MHC-2A and MHC-2X with decrease of the proportion of fast MHC-2B. In contrast, Tp treatment induced an increase in the proportion of MHC-2B whereas MHC-2A and MHC-2X disappeared. Finally, ETP showed a reduction in MHC-2B and an increase in MHC-1 and MHC-2X. These data suggest that testosterone supplementation seems not to significantly modify the metabolic adaptation induced by exercise in gastrocnemius muscle. Furthermore, testosterone overload to non-exercised rats seems to reduce the mitochondrial function and increase the lipid peroxidation of the muscle.


The interactions of spore-coat morphogenetic proteins studied by single-molecule recognition force spectroscopy.
Bacillus subtilis can form a spore, which is a dormant type of cell, when its external environment becomes unsuitable for vegetative growth. The spore is surrounded by a multilayered proteinaceous shell called a spore coat, which plays a crucial role in dormancy and germination. Of the over 70 proteins that form the spore coat, only a small subset of them affect its morphogenesis; they are referred to as morphogenetic proteins. How these morphogenetic proteins interact, and furthermore, how they build the ordered, functional coat layers is not well understood. Elucidating the self-assembly mechanism of individual proteins into such a complex structure may contribute to its potential use in nano-biotechnology applications for preparing highly organized, robust, and resistant proteinaceous layers. Herein, direct, noncovalent, low-affinity interactions between the spore-coat morphogenetic proteins SpoIVA, SpoVID, and SafA were studied by using single-molecule recognition force spectroscopy in vitro for the first time. Based on the real-time examination of interactions between these three proteins, a series of dynamic kinetic data were obtained. It was also observed that the SafA-SpoVID interaction was stronger than that of SafA-SpoIVA.


Efficient and accurate diagnosis of otomycosis using an ensemble deep-learning model.
Otomycosis accounts for over 15% of cases of external otitis worldwide. It is common in humid regions and Chinese cultures with ear-cleaning custom. Aspergillus and Candida are the major pathogens causing long-term infection. Early endoscopic and microbiological examinations, performed by otologists and microbiologists, respectively, are important for the appropriate medical treatment of otomycosis. The deep-learning model is a novel automatic diagnostic program that provides quick and accurate diagnoses using a large database of images acquired in clinical settings. The aim of the present study was to introduce a machine-learning model to accurately and quickly diagnose otomycosis caused by Aspergillus and Candida. We propose a computer-aided decision-making system based on a deep-learning model comprising two subsystems: Java web application and image classification. The web application subsystem provides a user-friendly webpage to collect consulted images and display the calculation results. The image classification subsystem mainly trained neural network models for end-to-end data inference. The end user uploads a few images obtained with the ear endoscope, and the system returns the classification results to the user in the form of category probability values. To accurately diagnose otomycosis, we used otoendoscopic images and fungal culture secretion. Fungal fluorescence, culture, and DNA sequencing were performed to confirm the pathogens Aspergillus or Candida spp. In addition, impacted cerumen, external otitis, and normal external auditory canal endoscopic images were retained for reference. We merged these four types of images into an otoendoscopic image gallery. To achieve better accuracy and generalization abilities after model-training, we selected 2,182 of approximately 4,000 ear endoscopic images as training samples and 475 as validation samples. After selecting the deep neural network models, we tested the ResNet, SENet, and EfficientNet neural network models with different numbers of layers. Considering the accuracy and operation speed, we finally chose the EfficientNetB6 model, and the probability values of the four categories of otomycosis, impacted cerumen, external otitis, and normal cases were outputted. After multiple model training iterations, the average accuracy of the overall validation sample reached 92.42%. The results suggest that the system could be used as a reference for general practitioners to obtain more accurate diagnoses of otomycosis.


Impaired upper esophageal sphincter reflexes in patients with supraesophageal reflux disease.
Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, however, abnormal responses have not been characterized. We investigated whether patients with supraesophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events. We performed a prospective study of 25 patients with SERD (age, 19-82 y; 13 women) and complaints of regurgitation and supraesophageal manifestations of reflux. We also included 10 patients with gastroesophageal reflux disease (GERD; age, 32-60 y; 7 women) without troublesome regurgitation and supraesophageal symptoms and 24 healthy asymptomatic individuals (controls: age, 19-49 y; 13 women). UES and esophageal body pressure responses, along with luminal distribution of infusate during esophageal rapid and slow infusion of air or liquid, were monitored by concurrent high-resolution manometry and intraluminal impedance. A significantly smaller proportion of patients with SERD had UES contractile reflexes in response to slow esophageal infusion of acid than controls or patients with GERD. Only patients with SERD had abnormal UES relaxation responses to rapid distension with saline. Diminished esophageal peristaltic contractions resulted in esophageal stasis in patients with GERD or SERD. Patients with SERD and complaints of regurgitation have impaired UES and esophageal responses to simulated liquid reflux events. These patterns could predispose them to esophagopharyngeal reflux.


Use of Predicted Behavior from Accelerometer Data Combined with GPS Data to Explore the Relationship between Dairy Cow Behavior and Pasture Characteristics.
Our aim in this study was to investigate whether the behaviors of dairy cows on pasture, predicted with accelerometer data and combined with GPS data, can be used to better understand the relationship between behaviors and pasture characteristics. During spring 2018, 26 Holstein cows were equipped with a 3D-accelerometer and a GPS sensor fixed on a neck-collar for five days. The cows grazed alternatively in permanent and in temporary grasslands. The structural elements, soil moisture, slope and botanical characteristics were identified. Behaviors were predicted every 10 s from the accelerometer data and combined with the GPS data. The time-budgets expressed in each characterized zone of 8 m × 8 m were calculated. The relation between the time-budgets and pasture characteristics was explored with a linear mixed model. In the permanent grassland, dairy cows spent more time under a tree to ruminate (p < 0.001) and to rest (p < 0.001) and more time to graze in areas with Holcus lanatus (p < 0.001). In the temporary grassland, behavior was influenced by the external environment (presence of other animals on the farm; p < 0.05). Thus, this methodology seems relevant to better understand the relationship between the behaviors of dairy cows and grazing conditions to develop precision grazing.


The predictive value of small versus diminutive adenomas for subsequent advanced neoplasia.
Patients with previous colorectal adenomas are at increased risk of colorectal cancer. Current guidelines for postpolypectomy surveillance intervals treat all tubular adenomas 1 to 9 mm in size with low-grade dysplasia as carrying the same level of risk. We evaluated whether 6 to 9 mm adenomas detected at colonoscopy are associated with greater risk of advanced neoplasia at follow-up compared with baseline 1 to 5 mm adenomas. We retrospectively evaluated a colonoscopy database at a single U.S. academic center. Patients with baseline examinations demonstrating tubular adenomas 1 to 9 mm in size with low-grade dysplasia and no advanced adenomas were included. Follow-up colonoscopies were performed at least 200 days later and were assessed for incident advanced neoplasia (cancer, high-grade dysplasia, adenoma ≥10 mm in size, or villous elements). There were 2477 qualifying baseline colonoscopies. The absolute risk of metachronous advanced neoplasia increased from 3.6% in patients with 1 to 5 mm adenomas to 6.9% in patients with at least 1 adenoma of 6 to 9 mm (P = .001). Patients with 5 or more adenomas 1 of which was at least 6 to 9 mm had the highest risk of advanced neoplasia at follow-up (10.4%, P = .006). When only screening colonoscopies were considered, all baseline groups (1-2 adenomas, 3-4 adenomas, ≥5 adenomas) with adenomas 6 to 9 mm in size had an increased risk for metachronous advanced neoplasia (odds ratio [OR], 4.07; 95% confidence interval [CI], 1.50-11.04; OR, 4.91; 95% CI, 1.44-16.75; OR, 4.71; 95% CI, 1.30-17.05, respectively). Patients with baseline small (6-9 mm) adenomas have an increased risk of advanced lesions on follow-up compared with patients with only diminutive (1-5 mm) adenomas. Postpolypectomy guidelines should consider risk stratification based on small versus diminutive adenomas.


Effect of erosive challenge before and after the restoration of primary teeth.
The aim of this in vitro study was to investigate the erosive effect of a soft drink on primary teeth before and after restoration. Enamel blocks were obtained from 64 primary canines (N = 144) and divided into 3 groups (n = 48): 1, erosive challenge before and after restoration; 2, erosive challenge after restoration; and 3, no erosive challenge (control). The blocks received standardized preparations and were restored with 1 of 4 materials (n = 12): composite resin, bulk-fill composite resin, conventional glass ionomer cement, or resin-modified glass ionomer cement. The erosive challenge consisted of immersing the blocks in a cola soft drink for 1 minute at 25°C, 4 times a day for 5 days. The microhardness, roughness, marginal infiltration, and marginal adaptation of the specimens in all 3 groups were evaluated. Data were analyzed with the Kruskal-Wallis and Bonferroni tests. The results showed that the erosive challenge significantly altered all of the evaluated properties of all of the restorative materials (P < 0.05). The erosive challenge decreased the microhardness and marginal adaptation and increased the roughness and marginal infiltration of the tested materials. Composite resin had the highest values for microhardness and marginal adaptation as well as the lowest roughness value and dye infiltration score both with and without the erosive challenge. Subjecting teeth to erosive challenge before and after restoration altered the enamel microhardness and roughness significantly more than did erosive challenge only after restoration. Composite resin was the material least affected by the erosive challenge.


Psychometric properties of the Arabic version of EPDS and BDI-II as a screening tool for antenatal depression: evidence from Qatar.
The current study aimed to validate and determine the psychometric properties of the Arabic versions of the Beck Depression Inventory-II (BDI-II) and the Edinburgh Postnatal Depression Scale (EPDS) in Qatar. A cross-sectional study design was employed. Antenatal care (ANC) clinics at nine primary healthcare centres. Pregnant women (n=128) aged 15-46 years in different trimesters of pregnancy, attending the ANC clinics as well as capable of reading and writing in the Arabic language. A total of 128 participants were enrolled. On conducting the receiver operating characteristic (ROC) analysis, the EPDS showed a larger area under the curve at 0.951 than the BDI-II tool (0.912). Using Youden's index, a score >13 on the EPDS (87% sensitivity, 90% specificity) and >19 on the BDI-II (96% sensitivity, 73% specificity) allowed for the greatest division between depressed and non-depressed participants. To address the under-recognition of antenatal depression, physicians at primary healthcare centres in Qatar should be encouraged to utilise the EPDS to screen pregnant women seeking ANC services.


One-pot, low-temperature synthesis of self-doped NaTaO3 nanoclusters for visible-light-driven photocatalysis.
Herein we first report the synthesis of self-doped NaTaO3 nanoclusters using a facile and one-pot low-temperature solvothermal method. Ta(4+) in bulk NaTaO3 greatly narrows its band gap from 3.94 to 1.70 eV and thus extends its photoresponse from the UV to the visible light region, which leads to enhanced visible-light photocatalytic activity for water splitting and dye degradation without loading any co-catalysts such as Pt or NiO commonly used in the method described in the literature.


Understanding factors that influence stakeholder trust of natural resource science and institutions.
Building trust between resource users and natural resource institutions is essential when creating conservation policies that rely on stakeholders to be effective. Trust can enable the public and agencies to engage in cooperative behaviors toward shared goals and address shared problems. Despite the increasing attention that trust has received recently in the environmental management literature, the influence that individual cognitive and behavioral factors may play in influencing levels of trust in resource management institutions, and their associated scientific assessments, remains unclear. This paper uses the case of fisheries management in the northeast to explore the relationships between an individual's knowledge of the resource, perceptions of resource health, and participatory experience on levels of trust. Using survey data collected from 244 avid recreational anglers in the Northeast U.S., we test these relationships using structural equation modeling. Results indicate that participation in fisheries management is associated with increased trust across all aspects of fisheries management. In addition, higher ratings of resource health by anglers are associated with higher levels of trust of state and regional institutions, but not federal institutions or scientific methods.


Hydroxyethylamine derivatives as HIV-1 protease inhibitors: a predictive QSAR modelling study based on Monte Carlo optimization.
Application of HIV-1 protease inhibitors (as an anti-HIV regimen) may serve as an attractive strategy for anti-HIV drug development. Several investigations suggest that there is a crucial need to develop a novel protease inhibitor with higher potency and reduced toxicity. Monte Carlo optimized QSAR study was performed on 200 hydroxyethylamine derivatives with antiprotease activity. Twenty-one QSAR models with good statistical qualities were developed from three different splits with various combinations of SMILES and GRAPH based descriptors. The best models from different splits were selected on the basis of statistically validated characteristics of the test set and have the following statistical parameters: r2 = 0.806, Q2 = 0.788 (split 1); r2 = 0.842, Q2 = 0.826 (split 2); r2 = 0.774, Q2 = 0.755 (split 3). The structural attributes obtained from the best models were analysed to understand the structural requirements of the selected series for HIV-1 protease inhibitory activity. On the basis of obtained structural attributes, 11 new compounds were designed, out of which five compounds were found to have better activity than the best active compound in the series.


Human parvovirus B19: historical and clinical review.
Human parvovirus B19 has been associated with disease only for the past few years. First isolated from sera obtained for studies on hepatitis B in 1975, it was not until 1981 that infection with this small, single-stranded DNA virus was related to aplastic crisis associated with hemolytic anemia. A nonspecific viral prodrome, the occurrence in family members, and epidemics of aplastic crisis suggested the infectious etiology. Human parvovirus infection has since been associated with arthritis, erythema infectiosum (fifth disease), fetal death, and hydrops fetalis. Through the use of recently developed serologic tests, epidemics of erythema infectiosum and parvoviral infection have been related not only to aplastic crisis but also to intrauterine infection and hydrops; DNA hybridization studies have allowed the detection of viral DNA in serum and tissue extracts. Studies have been hampered by the lack of an ability to culture the virus, but this is now possible utilizing bone marrow culture and erythropoietin. This article is a historical and clinical review of human parvovirus infection and disease and considers potential questions regarding their consequences.


Extension of a pulmonary blastoma into the left atrium.
Pulmonary tumors of embryonic origin are rare, and pulmonary blastomas are probably the most uncommon. A thorough literature search disclosed no previous reports of extension of this type of tumor into the heart. We describe a patient whose initial clinical presentation suggested an obstructive left atrial mass; however, clinical and histologic findings indicated the mass was a tumor that originated from a pulmonary blastoma that extended into the left atrium through a pulmonary vein. The unique aspect of this case is that the patient's symptoms were related to the obstructive effects of the atrial mass, not to the primary pulmonary tumor.


Genetic control of B cell function. II. Antibody responses of inbred mice to red blood cells are controlled at the B cell level.
Inbred strains of mice can be classified into high and low responders with respect to their antibody responses to RBC. In this paper, we investigate the cellular basis of the difference in responsiveness between high- and low-responder strains. In cell-mixing experiments with purified B cells, T cells, and macrophages from 2 different combinations of H-2-identical high- and low-responder strains, we find that the B cells determine high and low responsiveness, whereas T cells and macrophages from low responders function equally as well as those of high responders. We could also exclude that suppressor T cells play an important role in determining high and low responsiveness. It is therefore suggested that low responsiveness is a defect of B cells to become activated in a T helper cell-dependent antibody response. In the previous paper of this series we showed that a limited number of genes (possibly 2), 1 linked to the Igh gene complex and the other(s) of unknown linkage, control the level of responsiveness. Taken together, we think that this represents a novel example of a genetic polymorphism in B cell function that is sufficiently simple, genetically and functionally, to provide a genetic approach to the study of B cell activation.


Hierarchical MnO2/SnO2 heterostructures for a novel free-standing ternary thermite membrane.
We report the synthesis of a novel hierarchical MnO2/SnO2 heterostructures via a hydrothermal method. Secondary SnO2 nanostructure grows epitaxially on the surface of MnO2 backbones without any surfactant, which relies on the minimization of surface energy and interfacial lattice mismatch. Detailed investigations reveal that the cover density and morphology of the SnO2 nanostructure can be tailored by changing the experimental parameter. Moreover, we demonstrate a bottom-up method to produce energetic nanocomposites by assembling nanoaluminum (n-Al) and MnO2/SnO2 hierarchical nanostructures into a free-standing MnO2/SnO2/n-Al ternary thermite membrane. This assembled approach can significantly reduce diffusion distances and increase their intimacy between the components. Different thermite mixtures were investigated to evaluate the corresponding activation energies using DSC techniques. The energy performance of the ternary thermite membrane can be manipulated through different components of the MnO2/SnO2 heterostructures. Overall, our work may open a new route for new energetic materials.


Redox regulation of the intrinsic pathway in neuronal apoptosis.
Two principal pathways exist by which cells can undergo apoptotic death, known as the extrinsic and the intrinsic pathways. Binding of a ligand to a death receptor activates the extrinsic pathway. In the intrinsic pathway, an apoptotic stimulus, such as neurotrophin withdrawal or exposure to a toxin, causes a proapoptotic member of the Bcl-2 family of proteins, such as Bax, to permeabilize the outer mitochondrial membrane. This allows redistribution of cytochrome c from the mitochondrial intermembrane space into the cytoplasm, where it causes activation of caspase proteases and, subsequently, cell death. A dramatic increase occurs in mitochondria-derived reactive oxygen species (ROS) during the apoptotic death of sympathetic, cerebellar granule, and cortical neurons. These ROS lie downstream of Bax in each cell type. Here I review possible mechanisms by which Bax causes increased ROS during neuronal apoptosis. I also discuss evidence that these ROS are an important part of the apoptotic cascade in these cells. Finally, I discuss evidence that suggests that neurotrophins prevent release of cytochrome c in neurons through activation of an antioxidant pathway.


Corona virus disease bring a new challenge for the dentistry: A review.
An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. While human strains of coronavirus (CoV) are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly CoV strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes, and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Common clinical signs of the infection comprises of respiratory symptoms in the form of fever, cough, shortness of breath, and breathing difficulties. In more severe cases, infection results in pneumonia, severe acute respiratory syndrome, kidney failure, and even death. Standard recommendations advocated to prevent spread of infection consist of frequent hand washing, covering mouth and nose when coughing and sneezing. This article, based on our experience and relevant guidelines and research, introduces essential knowledge about CoV in dental settings and provides recommended management protocols for dental practitioners affected areas.


Copper-Catalyzed [5 + 1] Cyclization of o-Pyrrolo Anilines and Heterocyclic N-Tosylhydrazones for Access to Spiro-dihydropyrrolo[1,2-a]quinoxaline Derivatives.
An inexpensive copper-catalyzed sequential reaction process, proceeding via a nucleophilic attack of amine to Cu-carbene generated in situ from heterocyclic N-tosylhydrazone precursors followed by a 1,2-H shift/oxidative cyclization cascade of N-ylides, has been described, smoothly generating the corresponding structurally various spiro-dihydropyrrolo[1,2-a]quinoxaline derivatives. Furthermore, the significance of this protocol can be also highlighted by its diverse conversions of the synthetic compounds to the potentially bioactive molecules such as the 2-substituted pyrrolo[1,2-a]quinoxalins.


Stability of colorimetric results in the detection of urine biomarkers using a paper-based analytical device.
Urinalysis allows obtaining information about many of the body's functions. Normally, urine is a very easily collected specimen, but in some cases, it can be an uncomfortable process. Moreover, standard methods such as microscopic examination or urine culturing represent time-consuming procedures. In this regard, this work explores the design of a device that combines disposable diapers, as a platform for sample collection, with part of the dipsticks method. Even though this is a desirable combination for a faster and comfortable approach, it is also convenient to extend the prescribed time, provided by the dipstick manufacturer, to read the results. This allows the stability and validity of the results for longer, preferably until the moment of the diaper changing, and it was also considered in the design. The desired conditions were reproduced for the reagent pads of glucose and nitrite. The results show that the RGB profile, obtained in glucose detection, varied after approximately 60 min. However, when the developed colors are visually compared with the reference colors, the results suggest that there were not significant variations. In the nitrite assay, by analyzing the RGB profile or by visual comparison with the reference colors, the color does not appear to change over time, but the results were not the expected. It seems that the proposed design is promising regarding results stability, but more experiments need to be done to check if the variations are constant for more biomarkers in the conditions provided by the device.


Budesonide versus placebo in high-risk population with screen-detected lung nodules: rationale, design and methodology.
Screening-CT is able to discover small peripheral lung nodules. The nature of these nodules is uncertain but it is reasonable that some of them, in particular the non-solid ones, could represent precancerous lesions. A previous trial showed a reduction in size of peripheral nodules by inhaled budesonide in subjects with bronchial dysplasia. The primary objective of the study was the evaluation of the effect of budesonide as a chemopreventive agent for lung lesions. The primary endpoint was the modification of lung lesions at ld-CT scan (according to RECIST criteria) after one year of treatment in a person-specific analysis. We performed a randomized, double-blind, placebo controlled trial to evaluate whether inhaled budesonide was able to reduce size and number of persistent, undetermined CT-detected lung nodules in high-risk asymptomatic subjects currently undergoing a five-year CT scan screening program at the European Institute of Oncology. Trial enrollment started in April 2006 and ended in July 2007 with the randomization of 202 current or former smokers with stable CT-detected lung nodules set to receive budesonide 800 μg or placebo twice daily for 12 months. Our trial represents the first phase II study of a chemopreventive intervention focusing on the peripheral lung, where the majority of lung cancers arise. The research was nested into a screening project with clear advantages in participant accrual and reduction of costs. This paper describes the rationale and design of the study, thus focusing on the methodology and operational aspects of the clinical trial. (Clinicaltrials.gov number. NCT00321893).


Glucose-6-phosphate dehydrogenase deficiency and the use of primaquine: top-down and bottom-up estimation of professional costs.
The aim of this study has been to study whether the top-down method, based on the average value identified in the Brazilian Hospitalization System (SIH/SUS), is a good estimator of the cost of health professionals per patient, using the bottom-up method for comparison. The study has been developed from the context of hospital care offered to the patient carrier of glucose-6-phosphate dehydrogenase (G6PD) deficiency with severe adverse effect because of the use of primaquine, in the Brazilian Amazon. The top-down method based on the spending with SIH/SUS professional services, as a proxy for this cost, corresponded to R$60.71, and the bottom-up, based on the salaries of the physician (R$30.43), nurse (R$16.33), and nursing technician (R$5.93), estimated a total cost of R$52.68. The difference was only R$8.03, which shows that the amounts paid by the Hospital Inpatient Authorization (AIH) are estimates close to those obtained by the bottom-up technique for the professionals directly involved in the care.


Abortive base-excision repair of radiation-induced clustered DNA lesions in Escherichia coli.
It has been postulated that ionizing radiation produces a unique form of cellular DNA damage called "clustered damages" or "multiply damaged sites". Here, we show that clustered DNA damages are indeed formed in Escherichia coli by ionizing radiation and are converted to lethal double-strand breaks during attempted base-excision repair. In wild-type cells possessing the oxidative DNA glycosylases that cleave DNA at repairable single damages, double-strand breaks are formed at radiation-induced clusters during postirradiation incubation and also in a dose-dependent fashion. E. coli mutants lacking these enzymes do not form double-strand breaks postirradiation and are substantially more radioresistant than wild-type cells. Furthermore, overproduction of one of the oxidative DNA glycosylases in mutant cells confers a radiosensitive phenotype and an increase in the number of double-strand breaks. Thus, the effect of the oxidative DNA glycosylases in potentiating DNA damage must be considered when estimating radiation risk.


Combinatorial delivery of CPI444 and vatalanib loaded on PEGylated graphene oxide as an effective nanoformulation to target glioblastoma multiforme: In vitro evaluation.
Glioblastoma multiforme (GBM) is known as the primary malignant and most devastating form of tumor found in the central nervous system of the adult population. The active pharmaceutical component in current chemotherapy regimens is mostly hydrophobic and poorly water-soluble, which hampers clinical implications. Nanodrug formulations using nanocarriers loaded with such drugs assisted in water dispersibility, improved cellular permeability, and drug efficacy at a low dose, thus adding to the overall practical value. Here, we successfully developed a water-dispersible and biocompatible nanocargo (GO-PEG) based on covalently modified graphene oxide (GO) with a 6-armed poly(ethylene glycol) amine dendrimer for effective loading of the two hydrophobic anticancer drug molecules, CPI444 and vatalanib. These drug molecules target adenosine receptor (A2AR), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and type III stem cell receptor tyrosine kinase (c-KIT), which plays a crucial role in cancers. The effective cellular delivery of the drugs when loaded on GO-PEG is attributed to the increased permeability of the drug-nanoconjugate formulation. We observed that this combinatorial drug treatment with nanocargo resulted in a significant reduction in the overall cell survival as supported by reduced calcium levels and stem cell markers such as Oct4 and Nanog, which are two of the prime factors for GBM stem cell proliferation. Furthermore, reduced expression of CD24 upon treatment with nanoformulation impeded cellular migration. Cellular assays confirmed inhibition of cell proliferation, migration, and angiogenic potential of GBM treated with GO-PEG-Drug conjugates. Ultimately, GBM U87 cells assumed programmed cell death at a very low concentration due to nanocarrier-mediated drug delivery along with the chosen combination of drugs. Together, this study demonstrated the advantage of GO-PEG mediated combined delivery of CPI444 and vatalanib drugs with increased permeability, a three-pronged combinatorial strategy toward effective GBM treatment.


Cell cycle regulation of a human cyclin-like gene encoding uracil-DNA glycosylase.
The predicted amino acid sequence of a human cDNA encoding uracil-DNA glycosylase activity shows striking similarity to the cyclin protein family. To characterize the expression of this DNA repair enzyme, we have isolated the corresponding genomic clone. This gene is contained within 4.2 kilobases and is composed of only two exons. Sequence analysis of the upstream region shows that it contains two cell cycle box (CCB) regulatory elements which are also found in yeast cyclin genes. Deletional analysis of the promoter reveals the presence of a repressor region located from position -812 to -603. An inverted CCB element (alpha-CCB) and an SP1-like binding site are contained within this region. When uracil-DNA glycosylase mRNA levels are examined in vivo, a 2-3-fold increase is associated with G1 phase in both HeLa S3 and WI38 cells. To examine the role of the 209-base pair repressor region in mediating cell cycle regulation, this fragment was used in gel shift assays with cellular extracts prepared from various stages of the cell cycle. Several specific complexes are formed during S and G2 phases which are not present during M and G1 phases. Two of the complexes are the result of alpha-CCB binding as they can be specifically disrupted by the addition of an oligonucleotide containing the alpha-CCB binding site. Immunoprecipitation studies reveal that uracil-DNA glycosylase protein levels are also elevated during G1 phase. Additionally, we show that the 36-kDa uracil-DNA glycosylase protein is turned over during the course of one cell cycle. These results demonstrate coordinate regulation of uracil-DNA glycosylase at both the transcriptional and the post-transcriptional levels as a function of the cell cycle.


Peyer's patches: organized lymphoid structures for the induction of mucosal immune responses in the intestine.
Peyer's patches (PP) comprise transmucosal clusters of lymphoid follicles overlaid with a specialized lympho-epithelium and consequently play a central role in the induction of mucosal immune responses in the gut. Despite considerable achievements in the last 3 decades, in our understanding of how PP are involved in the induction of immune responses, much remains to be learned about these major organized lymphoid organs. The history and current status of PP termed 'the major inductive site of immune responses' is reviewed. The present understanding of PP biology and function, taking into account their preferential and unique retention of immune competent cells at specific sites, is discussed.


Cisatracurium besilate enhances the TRAIL-induced apoptosis of gastric cancer cells via p53 signaling.
Cisatracurium besilate is the most commonly used non-depolarizing muscle relaxant in general anesthesia and in intensive care units. Studies have indicated that the proliferation of gastric cancer (GC) cells can be restrained by cisatracurium besilate. The present study aimed to investigate the mechanism underlying the role of cisatracurium besilate in TNF-related apoptosis-inducing ligand (TRAIL)-induced GC. The AGS cell line was exposed to cisatracurium besilate, and then cell viability, colony formation and apoptosis were assessed by performing Cell Counting Kit-8, colony formation, TUNEL and Western blot assays, respectively. Furthermore, the expression levels of p53 and p53 upregulated modulator of apoptosis (PUMA) were measured by Western blotting to determine the effect of cisatracurium besilate on p53/PUMA signaling. After co-treatment with p53 inhibitor, cisatracurium besilate and pifithrin-α/TRAIL, cell apoptosis was detected. Finally, cisatracurium besilate and pifithrin-α were used to co-treat TRAIL-induced AGS cells followed by apoptosis detection. Cisatracurium besilate treatment restrained the proliferation and promoted the apoptosis of AGS cells. Cisatracurium besilate also promoted the expression of p53 and PUMA in AGS cells. Furthermore, TRAIL induced the apoptosis of AGS cells, which was aggravated by cisatracurium besilate treatment. However, pifithrin-α reversed the synergistic effects of cisatracurium besilate and TRAIL on the activities of AGS cells. Therefore, the present study suggested that cisatracurium besilate enhanced the TRAIL-induced apoptosis of GC cells via p53 signaling, and the synergistic effects of cisatracurium besilate and TRAIL may achieve maximal therapeutic efficacy in GC management.


Building Your Peripheral Artery Disease Toolkit: Medical Management of Peripheral Artery Disease in 2022.
Peripheral artery disease (PAD) is associated with substantial morbidity, including a high risk of cardiovascular and limb events and death. A growing body of evidence has demonstrated the benefits of antithrombotic therapy, lipid lowering, blood pressure control, diabetes management, smoking cessation, and exercise programs on improving symptoms and reducing these complications. Guidelines make specific recommendations on how to use these strategies to prevent adverse cardiovascular and limb outcomes in patients with PAD. Unfortunately, antithrombotic therapies, statins, optimal antihypertensives, smoking cessation counselling and therapies, and exercise programs have all been consistently shown to be underutilised in PAD patients both in Canada and globally. A variety of barriers to optimal utilisation of evidence-based medical therapies have been described at the patient, health care provider, and system levels. These include lack of knowledge among patients and health care providers, and lack of access to secondary prevention programs. We review the evidence for preventive therapies in PAD, evidence for underutilisation of these therapies, and barriers to their use. Core elements of PAD secondary prevention clinics are proposed, and a summary of optimal medical therapies and relevant tools is provided. This review may help clinicians who treat patients with PAD to develop a toolkit to overcome these barriers in order to improve utilisation of medical therapies, with the ultimate goal of improving outcomes for PAD patients.


The glutamatergic system outside the CNS and in cancer biology.
Glutamate is a major excitatory neurotransmitter in the CNS. The signalling machinery consists of: glutamate receptors, which are responsible for signal input; plasma glutamate transporters, which are responsible for signal termination; and vesicular glutamate transporters for signal output through exocytic release. Recently, data have suggested that the glutamatergic system plays an important role in non-neuronal tissues. In addition, the expression of glutamatergic system has been implicated in tumour biology. This review outlines the evidence, which suggests that the glutamatergic system may have an important role in cancer biology.


The Study of Developmental Risk Factors for Early Fire Involvement.
Child fireplay may be regarded as developmentally appropriate, yet can negatively impact those who engage in it and those around them. This study discusses the mental health, fire-specific, and psychosocial risk factors of children who set fires. Fifty-seven caregivers reported on their children's demographics, firesetting behaviors, mental health symptoms, and family history. Children were aged 2-6 years and the majority were male. Most children used lighters and matches on paper and small objects. The majority of the children were motivated by curiosity. Children who set more fires had more externalizing symptoms, and were more likely to have accomplices, to have been exposed to firesetting media, and to have been disciplined or punished for their firesetting behaviors. The study identifies important psychosocial risk factors among young children who set fires. Given the long-term implications of firesetting, understanding firesetting in children will set the foundation of intervention and prevention models.


Diagnostic and therapeutic characteristics of diabetes mellitus and risk of out-of-hospital cardiac arrest.
This study aimed to evaluate the risks of diabetes mellitus (DM) on out-of-hospital cardiac arrest (OHCA) and to investigate whether the risks of DM on OHCA varied according to the diagnostic and therapeutic characteristics of diabetes. We conducted a multicenter prospective case-control study in 17 University hospitals in Korea from September 2017 to December 2020. Cases were EMS-treated OHCA patients aged 20 to 79 with a presumed cardiac etiology. Community-based controls were recruited at a 1:2 ratio after matching for age, sex, and urbanization level of residence. A structured questionnaire and laboratory findings were collected from cases and controls. Multivariable conditional logistic regression analyses were conducted to estimate the risk of DM on OHCA by characteristics. A total of 772 OHCA cases and 1544 community-based controls were analyzed. A total of 242 (31.3%) OHCAs and 292 (18.9%) controls were previously diagnosed with DM. The proportions of type I DM (10.7% vs. 2.1%) and insulin therapy (15.3% vs. 6.5%) were higher in OHCAs with DM than in controls with DM. The duration of DM was longer in OHCAs than in controls (median 12 vs. 7 years). DM was associated with an increased risk of OHCA (aOR (95% CI), 2.13 (1.64-2.75)). Compared to the no diabetes group, the risks of OHCA increased in the diabetes patients with type I DM (5.26 (1.72-16.08)) and type II DM group (1.63 (1.18-2.27)), a long duration of DM prevalence (1.04 (1.02-1.06) per 1-year prevalence duration), and a high HbA1c level (1.38 (1.19-1.60) per 1% increase). By treatment modality, the aOR (95% CI) was lowest in the oral hypoglycemic agent (1.47 (1.08-2.01)) and highest in the insulin (6.63 (3.04-14.44)) groups. DM was associated with an increased risk of OHCA, and the risk magnitudes varied according to the diagnostic and therapeutic characteristics.


Photochromic properties of [2.2]paracyclophane-bridged imidazole dimer with increased photosensitivity by introducing pyrenyl moiety.
The photochromic [2.2]paracyclophane-bridged imidazole dimers show instantaneous coloration upon exposure to UV light and rapid fading in the dark. A new [2.2]paracyclophane-bridged imidazole dimer, pseudogem-PPI-DPI[2.2]PC, with high photosensitivity to UVA radiation was developed. To enhance the photosensitivity, we introduced pyrenyl moieties to the [2.2]paracyclophane-bridged imidazole dimer. The localized π-π* transition of pyrenyl moieties appears in the UVA radiation region by introducing a pyrenyl moietiy on the 4-position of the imidazole rings. The expansion of the π-electron system also affects the absorption spectrum of the colored species. The broad absorption band of the colored species covers the whole range of visible light region and its absorbance is approximately equal throughout the visible light region. Thus, pseudogem-PPI-DPI[2.2]PC shows the photochromic reaction coloring black upon light irradiation and successive fast thermal bleaching following the monoexponential kinetics with a time constant of 12 ms at room temperature.


Origin of Orthogonality of Strain-Promoted Click Reactions.
Site-specific labeling of biomolecules is rapidly advancing due to the discovery of novel mutually orthogonal reactions. Quantum chemistry studies have also increased our understanding of their relative rates, although these have until now been based on highly simplified reactants. Here we examine a set of strain-promoted click-type cycloaddition reactions of n-propyl azide, 3-benzyl tetrazine and 3-benzyl-6-methyl tetrazine with cyclooctenes/ynes, in which we aim to address all relevant structural details of the reactants. Our calculations have included the obligatory handles used to attach the label and biomolecule as these can critically influence the stereochemistry and electron demand of the reaction. We systematically computed orbital gaps, activation and distortion energies using density functional theory and determined experimental rates for validation. Our results challenge the current paradigm of the inverse electron demand for this class of reactions. We found that the ubiquitous handles, when next to the triple bond of cyclooctynes, can switch the Diels-Alder type ligations to normal electron demand, a class we term as SPINEDAC reactions. Electron donating substituents on tetrazine can enhance normal demand but also increase distortion penalties. The presence and isomeric configuration of handles thus determine the reaction speed and regioselectivity. Our findings can be directly utilized in engineering genuine cycloaddition click chemistries for biological labeling.


Vertebrobasilar Junction Angle Over 90°: A Potential Imaging Marker Associated With Vertebrobasilar Atherosclerosis.
Objective: Whether the cerebral vascular variations play an important role in the progression of intracranial atherosclerosis is yet largely unclear. We aimed to investigate the relationship between the magnitude of the vertebrobasilar junction (VBJ) angle and the imaging features of vertebrobasilar artery atherosclerosis. Methods: Adult patients with acute ischemic stroke or transient ischemic attack undergoing a 3.0-tesla vessel wall magnetic resonance imaging (VW-MRI) scanning were consecutively included. Imaging features of vertebrobasilar artery atherosclerosis were assessed on the reconstructed short axis of VW-MRI at the most stenotic site. The VBJ angle degree was measured on magnetic resonance angiography and classified into the angle ≥90° or <90°. Results: Among 68 patients (mean age = 63.5 ± 9.4 years old; 63.2% were male) with vertebrobasilar atherosclerosis, 33 had a VBJ angle ≥90° and 35 had a VBJ angle <90°. Compared to the vertebrobasilar plaques with VBJ angle <90°, those with VBJ angle ≥90° had a heavier plaque burden (84.35 vs. 70.58%, p < 0.001) and higher prevalence of intraplaque hemorrhage (17.1 vs. 3.3%, p = 0.01). In the regression analyses, the VBJ angle ≥90° was also robustly associated with plaque burden (odds ratio, 1.11; 95% confidential interval, 1.043-1.18; p = 0.001) and intraplaque hemorrhage (odds ratio, 5.776; 95% confidential interval, 1.095-30.46; p = 0.039) of vertebrobasilar atherosclerosis. Conclusion: The VBJ angle over 90° might aggravate the vessel wall condition of the atherosclerotic vertebrobasilar arteries, which might serve as a potential risk factor for vertebrobasilar atherosclerosis.


A novel murine model of cerebral scedosporiosis: lack of efficacy of amphotericin B.
Cerebral scedosporiosis is a life-threatening infection that is difficult to treat. The aim of this work was to develop a murine model of cerebral infection by Scedosporium apiospermum using intracranial inoculation and to use this model to evaluate the efficacy of amphotericin B deoxycholate and liposomal amphotericin B. Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous (iv) 5-fluorouracil administration. Animals were infected with iv or intracranial inoculation of 1 x 10(4), 5 x 10(4) or 5 x 10(5) cfu of a clinical strain of S. apiospermum. Tissue burden reduction was determined in kidneys and brain 4 days after the infection. Efficacy of amphotericin B and liposomal amphotericin B (0.8 mg/kg/day intraperitoneally and 40 mg/kg/day iv, respectively) was evaluated in neutropenic mice infected iv or intracranially with 5 x 10(4) cfu. Survival was analysed with the log-rank test. Fungal burden values of different groups were compared using the Mann-Whitney U-test. In our model, intracranial infection produced a higher fungal load in the brain and a lower fungal load in the kidney than iv inoculation. Survival of animals infected intracranially and treated with amphotericin B or liposomal amphotericin B (mean survival time = 8.3 and 9.2 days, respectively) was not different from the control group (P=0.58 and 0.85, respectively). We have developed a murine model of cerebral scedosporiosis, which may be useful for studying various pathological aspects of this infection and evaluating new therapeutic approaches. Amphotericin B and liposomal amphotericin B were unable to resolve the infection.


Recent Advances in Higher-Order, Multimodal, Biomedical Imaging Agents.
Advances in biomedical imaging have spurred the development of integrated multimodal scanners, usually capable of two simultaneous imaging modes. The long-term vision of higher-order multimodality is to improve diagnostics or guidance through the analysis of complementary, data-rich, co-registered images. Synergies achieved through combined modalities could enable researchers to better track diverse physiological and structural events, analyze biodistribution and treatment efficacy, and compare established and emerging modalities. Higher-order multimodal approaches stand to benefit from molecular imaging probes and, in recent years, contrast agents that have hypermodal characteristics have increasingly been reported in preclinical studies. Given the chemical requirements for contrast agents representing various modalities to be integrated into a single entity, the higher-order multimodal agents reported so far tend to be of nanoparticulate form. To date, the majority of reported nanoparticles have included components that are active for magnetic resonance. Herein, recent progress in higher-order multimodal imaging agents is reviewed, spanning a range of material and structural classes, and demonstrating utility in three (or more) imaging modalities.


Significant Difference in Acute Coronary Lesions in Patients on Therapeutic Statin Therapy Compared to Those Without.
Background Statin therapy has been shown to alter coronary plaque via decreasing lipid-rich pools, substituting with fibrocalcific plaque. We propose that acute coronary lesions in patients on therapeutic statin therapy, compared with patients not on statin therapy with elevated low-density lipoprotein (LDL) levels, will have features typically not associated with lipid-rich disease, such as lengthy fibrocalcific lesions, stent failure (in-stent restenosis and stent thrombosis), and/or bypass graft degeneration. Methods Charts and coronary angiograms of 143 consecutive patients from May 2016 to December 2018 with Type 1 Myocardial Infarction Fourth Universal Definition were retrospectively reviewed. Patients were divided into two groups: group 1, those on statin therapy with an LDL < 100 mg/dL, and group 2, those not on statin therapy with an LDL ≥ 100 mg/dL at the time of an acute coronary syndrome. Acute lesion characteristics and angioplasty techniques/equipment were recorded. Results There were 56 patients in group 1 and 39 patients in group 2. Group 1 patients, compared with group 2, were more likely to have moderate-severe vessel calcification (55.4% vs 10.3%; p < 0.01), lesion length greater than 20 mm (51.8% vs 23.1%; p = 0.019), stent failure (39.3% vs 7.7%; p < 0.01), and bypass graft failure (23.2% vs 7.7%; p = 0.04). Coronary interventions in group 1, compared with group 2, more often required adjunctive angioplasty techniques, including the need for multiple coronary wires, guide extender, thrombectomy, and circulatory support (51.8% vs 7.7%; p < 0.01). There was no significant difference between the number of culprit vessels, including the specific coronary culprit vessel identified between both groups. Conclusion Acute coronary lesions in patients on therapeutic statin therapy, compared to those not on statin therapy with an elevated LDL, tend to be longer, more calcific with increased vessel tortuosity and angulation, as well as from a stent or bypass graft failure mechanism. Furthermore, there is a signal for heightened procedural complexity in the arm with statin therapy. These clinical findings are likely the result of the altered natural history of plaque pathophysiology seen with statin therapy.


Expression of neurotrophic factor genes by human adipose stem cells post-induction by deprenyl.
Human adipose stem cells (hASCs) were introduced as appropriate candidate due to advantages like ease of isolation, in vitro expansion and lack of immune response. Deprenyl (Dep) was used to induce bone marrow stem cells into neuron-like cells. We investigated the Dep effect on neurotrophin genes expression in hASCs and their differentiation into neuron-like cells. The cells were isolated from small pieces of abdominal adipose tissue and subjected to flow cytometry to confirm purification. The osteogenic and adipogenic differentiation were identified. The proliferation rate and neurotrophin genes expression of treated cells were evaluated by MTT, TH immunostaining and RT-PCR. hASCs had positive response to CD44, CD73, CD90, CD105 markers and negative response to CD34 and CD45 markers and differentiated into adipocytes and osteocytes. Exposure to 10-7 M of Dep for 24 hours caused a significant increase of viable cells and BDNF, NTF-3 genes expression as compared to cultured cells in serum free medium and had no effect on the expression of NGF and GDNF genes. Based on our results, Dep is able to induce BDNF, NTF-3 and NTF-4 genes expression and neroun-like morphology in hASCs.


[The detection and clinical feature of HcoV-nL63 in children with acute respiratory tract infection in Lanzhou city].
To investigate the prevalence and clinical characterization of HCoV-NL63 (NL63) in children with acute respiratory tract infections (ARTIs) in Lanzhou with other respiratory viruses. The prevalence of HBoV1 in ALRTI was obviously city,China. From November 2006 to October 2009,1169 nasopharyngeal aspirates (NPA) were collected from children under 14 years old with ARTIs. Samples were screened for NL63 using a reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. Demography and clinical information were recorded. NL63 was detected in 35 (2.99%) of the 1169 children. The peak of the positive rate were in August, September 2007, July, August 2008 (23.53%,17.65%, 50%, 33.33% separately). There are no NL63 positive samples was detected in December, 2007 to February 2009. 25 (25/35, 71.43%) were co-infected with other respiratory viruses, and human rhinovirus (HRV) were the most common additional respiratory virus. No significant differences of infective rate of NL63 was found between < or = 3 years age group and > 3 years age group. Bronchiolitis and pneumonia were the most frequent diagnoses in NL63 positive patients and the major symptoms were fever and cough in our study. Between the monoinfection group and the coinfection group of NL63-positive patients, no differences were found in symptoms and clinical diagnoses except symptoms of gastrointestinal. HCoV-NL63 is an important pathogen of acute respiratory tract infection in children in Lanzhou city. The peak of HCoV-NL63 infections was in summer. There were annual differences in the prevalence of HCoV-NL63. HCoV-NL63 infections existed a high rate of mixed infection, and mixed infection does not increase the severity of the disease.


[Apoptosis during embryo development].
The development of human embryo includes two essential processes, i.e., rapid mitotic activity of cells and gradual differentiation of tissues and organs. The latter process is very often characterized by extensive migration of cells from their site of origin to the site of definitive location, inductive action of the neighboring germ layers and programmed cell death (apoptosis). This paper describes examples of proliferative and apoptotic processes during the development of human embryo. The development of trilaminar germ disk, skin, gonads, central and peripheral nerve system as well as limbs provides instructive examples of how apoptosis regulates the development and differentiation of cells.


Acetaldehyde enhances acquisition of nicotine self-administration in adolescent rats.
Tobacco use has one of the highest rates of addiction and relapse of any abused drug. Paradoxically, however, in animal models of reinforcement nicotine appears weak compared to other abused drugs. We report here that acetaldehyde, a major component of tobacco smoke, enhances nicotine self-administration. Juvenile and adult male rats were implanted with intravenous catheters and tested for self-administration 4 days later at postnatal day 27 or 90, respectively. Animals were tested, without prior response training, in five daily 3-h sessions where each nose-poke delivered an intravenous injection followed by a 60-s timeout. Animals (11-13/group) were offered one of the following solutions: nicotine (30 microg/kg/injection), acetaldehyde (16 microg/kg/inj), nicotine (30 microg/kg/inj)+acetaldehyde (16 microg/kg/inj), or saline. The youngest animals responded significantly more for nic+acet than for saline or for either drug alone. Responding at the reinforced hole was significantly higher than at the nonreinforced hole or at the reinforced hole during noncontingent injections of nic+acet. Tests with receptor antagonists indicated that these drug effects are mediated by central, but not peripheral, nicotinic receptors. There was an age-related decline in self-administration of nic+acet, but not for cocaine. Taken together, these results indicate that acetaldehyde, at the low concentrations found in tobacco smoke, interacts with nicotine to increase responding in a stringent self-administration acquisition test where nicotine alone is only weakly reinforcing, and that adolescent animals are more sensitive to these actions than adults. Animal models of tobacco addiction could be improved by combining acetaldehyde, and possibly other smoke components, with nicotine to more accurately reflect the pharmacological profile of tobacco smoke.


Redescription of Admete sadko Gorbunov, 1946 (Gastropoda: Cancellariidae).
Five species of the family Cancellariidae are currently known from Arctic seas: Admete contabulata Friele, 1879, A. clivicola Høisæter, 2011, A. solida (Aurivillius, 1885), A. viridula (Fabricius, 1780) and Iphinopsis inflata (Friele, 1879) (Golikov et al. 2001; Kantor Sysoev 2006; Høisæter 2011). Admete contabulata, A. clivicola and Iphinopsis inflata are only known from the Atlantic part of the Arctic, i.e. Norwegian and southwestern Barents seas (Høisæter 2011; Nekhaev 2014). Admete solida has been rarely reported since its first description from the Bering Strait (Sysoev Kantor 2002), however Nekhaev Krol (2017) recently reported a specimen from the eastern region of the Barents Sea that is similar in morphology to the holotype of this species. Admete viridula is the only representative of Admete reported from Siberian seas (Golikov et al. 2001; Lyubin 2003; Kantor Sysoev, 2006).


[Peroral cholangioscopy].
Peroral cholangioscopy has been used since the 1970'es and provides direct visualization of the biliary tree, possibility of electrohydraulic or laser lithotripsy and visually guided biopsies. This paper presents an overview of the existing literature focusing on the Spyglass single-operator cholangioscopy system. Several studies indicate that cholangioscopy can improve therapy of difficult accessible biliary stones and histological diagnosis in patients with indeterminate bile duct stenoses.


Accommodative function of eyes in persons exposed to ionizing radiation.
Results of a comparative study of accommodative capability of eyes in individuals exposed to various doses of ionizing radiation and in a control group are presented. The mean values for ranges of accommodation in the control group were consonant with previous data. However, the range of accommodation was found to be reduced in exposed patients from younger age groups. It has been established that the ranges of accommodation depended, besides the age, on the absorbed dose of ionizing radiation: the greater the dose absorbed, the lesser the range of accommodation in the same age group. The effect of ionizing radiation seems to be additive to that of age.


An enhanced procedure for urban mobile methane leak detection.
Leaked methane from natural gas distribution pipelines is a significant human and environmental health problem in urban areas. To assess this risk, urban mobile methane leak surveys were conducted, using innovative methodology, on the streets of Hartford, Danbury, and New London, Connecticut, in March 2019. The Hartford survey was done to determine if results from a 2016 survey (Keyes et al., 2019) were persistent, and surveys in additional towns were done to determine if similar findings could be made using an identical approach. Results show that Hartford continues to be problematic, with approximately 3.4 leaks per road mile observed in 2016 and 4.3 leaks per mile estimated in 2019, similar to that previously found in Boston, Massachusetts (Phillips et al., 2013). A preliminary estimate of methane leaks in Hartford is 0.86 metric tonnes per day (or 313 metric tonnes per year), equivalent to 42,840 cubic feet per day of natural gas, and a daily gas consumption of approximately 214 U.S. households. Moreover, the surveys and analyses done for Danbury and New London also reveal problematic leaks, particularly for Danbury with an estimated 3.6 leaks per mile. Although road miles covered in New London were more limited, the survey revealed leak-prone areas, albeit with a range of methane readings lower than those in Hartford and Danbury. Data collection methods for all studies is first reported here and are readily transferable to similar urban settings. This work demonstrates the actionable value that can be gained from data-driven evaluations of urban pipeline performance, and if supplemented with a map of leak-prone pipe geo-location, and information on pipeline operating pressures, will provide a spatial database facilitating proactive repair and replacement of leak-prone urban pipes, a considerable improvement compared to reactive mitigation of human-reported leaks. While this work pertains to the selected urban towns in the Northeast, it exemplifies issues and opportunities nationwide in the United States.


Physician leadership: a roadmap for health-system change.
Physician involvement in health-system decision making and their support of health-system initiatives can be critical to a health system's success. Many physicians, however, do not have the business skills or perspective to be effective contributors. This paper identifies three levels of physician leader development: awareness and head knowledge; creating an "us" culture; and taking ownership of the marketplace. It also identifies three physician leader-development methods that health systems can use to reach these points: integrated executive education; project-based learning; and facilitating ownership. Based on health-system objectives, top management should choose an appropriate level of physician leader development and then implement an appropriate change plan by using the proposed physician leader-development methods.


Liver function in workers exposed to N,N-dimethylformamide during the production of synthetic textiles.
In a factory producing synthetic fibers the hepatotoxic effects of the solvent N,N-dimethylformamide (DMF) were investigated in 126 male employees, especially with regard to the combination effects of DMF exposure and ethyl alcohol consumption. A collective of similar structure from the same factory served as a control collective. Reference is made to the results of air measurements and biological monitoring presented in a previous publication. The DMF concentrations in the air ranged from < 0.1 (detection limit) to 37.9 ppm (median 1.2 ppm). Concentrations of the DMF metabolite N-methylformamide (NMF) in urine were 0.05-22.0 mg/l (preshift) and 0.9-100.0 mg/l (postshift), corresponding to 0.02-44.6 mg/g creatinine (preshift) and 0.4-62.3 mg/g creatinine (postshift). A standardized anamnesis was drawn up for relevant previous illnesses and other factors influencing liver function. The laboratory tests included parameters especially relevant to the liver (e.g., AST, ALT, gamma-GT, hepatitis B and C antibodies, and carbohydrate-deficient transferrin). The results indicate a statistically significant toxic influence of DMF on liver function. Alcohol has a synergistic effect. The effects of DMF and those of alcohol are dose-dependent. Under the existing workplace conditions the hepatotoxic effects of alcohol are more severe than those of DMF. In the exposed group there was a statistically significantly greater number of persons who stated that they had drunk less since the beginning of exposure (13% versus 0). This corresponded with the data on symptoms occurring after alcohol consumption (71% versus 4%). In the work areas with lower-level exposure to DMF there was greater alcohol consumption. It corresponded to that of the control collective not exposed to DMF. In this study we tried to differentiate and quantify the interaction between DMF exposure and alcohol consumption and the influence of both substances on liver function. The experience gained from former occupational health surveillance in DMF-exposed persons and from the present study show that there are individual differences in tolerance of interactions between DMF and ethyl alcohol. Further studies are necessary for the evaluation of these individual degrees of susceptibilitiy.


Underlying potential: cellular and molecular determinants of adult liver repair.
The liver has a unique and extraordinary capacity for regeneration, even in adult organisms. This regenerative potential has traditionally been attributed to the replicative capabilities of mature hepatocytes and cholangiocytes, though emerging evidence suggests that other resident liver cell types such as progenitors, liver sinusoidal endothelial cells, and hepatic stellate cells respond to liver injury and contribute to repair. These other cells types are also associated with liver scarring, dysfunction, and carcinogenesis, which suggests that appropriate regulation of these cells is a major determinant of response to liver injury. The Reviews in this series explore possible contributions of liver progenitor cells, liver sinusoidal endothelial cells, and hepatic stellate cells to liver homeostasis and repair and highlight how these processes can go awry in chronic liver injury, fibrosis, and liver cancer.


Evaluation of organic light-emitting diodes as light sources for a compact optoelectronic integrated neural coprocessor.
Organic light-emitting diodes (OLEDs) are a most promising candidate for light sources of the compact optoelectronic integrated neural (COIN) coprocessor because of their easy integration with the silicon electronics. However, the optical properties of OLEDs are different from those of vertical-cavity surface-emitting lasers, which were previously used in the COIN system. The interconnect behavior of the COIN coprocessor is unknown if OLEDs are employed. In this paper, we build a mathematical model of the interconnect scheme of the COIN coprocessor and investigate the influence of the spectral bandwidth, light-emitting area, and angular emission profile of OLEDs by numerical simulations. The simulation results show that OLEDs with properly selected properties can be used as the light sources for the COIN coprocessor.


Effect of a Nurse-Managed Telemetry Discontinuation Protocol on Monitoring Duration, Alarm Frequency, and Adverse Patient Events.
Telemetry monitoring is a limited resource. This quality improvement project describes a nurse-managed telemetry discontinuation protocol aimed at stopping telemetry monitoring when it is no longer indicated. After implementing the protocol, data were collected for 6 months and compared with a preintervention time frame. There was a mean decrease in telemetry monitor usage and a decreased likelihood of remaining on a telemetry monitor until discharge. A nurse-managed telemetry discontinuation protocol was effective in decreasing overmonitoring and ensuring telemetry availability.


Repeat presentations to the emergency department for non-fatal suicidal behaviour: Perceptions of patients.
Presentations to emergency departments (EDs) for non-fatal suicidal behaviour (NFSB) are increasing in Australia and overseas. Our understanding of the factors contributing to this trend remains unclear. In this qualitative phenomenological study, we explored patient perceptions of their ED experience and the interventions provided. The study group comprised 10 adults who had had 3 or more presentations to the ED in a 12-week period for NFSB. Individual interviews were conducted in person with participants and transcribed verbatim. Three broad themes emerged from analysis of the transcripts: ED - a safety net; 'treatment - what treatment!'; and maintaining ED dependence. The findings highlight a failure to understand the needs of those with NFSB and establish better ED treatment strategies and models of aftercare for this sub-group of patients. The findings have implications for mental health nurses working with consumers in the ED and in broader case management roles.


Influence of age on 13C-urea breath test results in children.
The 13C-urea breath test for diagnosis of Helicobacter pylori infection has not been validated in infants and young children. The influence of age on the test results was studied by conventional validation against invasive methods and by mathematical estimation in a large pediatric population. The breath test was performed in 1499 children aged 2 months to 18 years. After a fasting period of 4 hours or more, 75 mg 13C-urea was ingested with cold apple juice, breath samples were taken at baseline and at 15 and 30 minutes. The distribution of the natural logarithms of the delta-over baseline (DOB) values were calculated, and the optimal cutoff values between positive and negative test results and gray zones with a risk of misclassification more than 10% were determined for both time points. In a subgroup of 149 children results of the breath test were compared with concordant results of histology and rapid urease test; 53 of them were less than 6 years of age. Logarithmic results of 1499 breath tests revealed two normally distributed subgroups with minimal overlap. The calculated optimal cutoff values were 4.7/1000 at 15 minutes and 5.0/1000 at 30 minutes. At 30 minutes, only 2.6% of all results were in the calculated gray zone (2.6-6.5/1000). Age was negatively correlated to DOB values of both negative (r = -0.223) and positive results (r = -0.291; P < 0.001). Breath test-negative and -positive children 6 or less years of age had significantly higher mean DOB values (P < 0.02) and a larger proportion of results within the gray zone than older children. Compared with biopsy-based results, the least discrepancies occurred at a cutoff of 5.0/1000: 0 of 61 infected (sensitivity 100%) and 6 of 88 noninfected children. Because five of the false-positive results were obtained in children less than 6 years of age, specificity and positive predictive values were lower in this age group than in older patients (88.1% vs. 97.8% and 68.8% vs. 98.0%, respectively). Under the applied conditions, the 13C-urea breath test shows an excellent separation between positive and negative results. Because of some overlap and a strong age effect, definition of a gray zone appears more meaningful than a threshold value. Because infants and young children have a high risk for false-positive breath test results, the values for cutoff and gray zones may have to be adapted. Further validation studies against invasive methods are warranted in this age group.


Radiodermatitis prevention with sucralfate in breast cancer: fundamental and clinical studies.
Acute radiodermatitis induced by radiotherapy may affect the quality of life and in some cases requires withholding treatment. The present study concerns the protective effect of a 1% sucralfate lotion. We propose joint fundamental and clinical points of view. The free radical scavenging capacity of sucralfate was measured with electron spin resonance and was supported by theoretical calculations. The clinical effects of sucralfate lotion were evaluated on 21 women treated for breast cancer. Breast skin response was evaluated at 0, 10, 20, 30, 40, and 50 Gy, according to (1) the radiation therapy oncology group (RTOG) acute toxicity scale and (2) spectrophotometry data obtained with X-Rite SP60. Sucralfate appeared as a relatively poor free radical scavenger (compared to reference compounds such as vitamin E). The sucralfate-containing lotion used in the present study did not provide systematic radiodermatitis prevention. Spectrophotometric evaluation of the skin response to irradiation appeared to be a very effective and more sensitive technique than the RTOG scale. Its use should be recommended to study cutaneous radioprotective action.


The rat liver ecto-ATPase is also a canalicular bile acid transport protein.
A approximately 110-kDa glycoprotein purified from canalicular vesicles by bile acid affinity chromatography has been identified as the canalicular bile acid transport protein. Internal amino acid sequence and chemical and immunochemical characteristics of this protein were found to be identical to a rat liver canalicular ecto-ATPase. In order to definitively determine whether these were two activities of a single polypeptide, we examined the possibility that transfection of cDNA for the ecto-ATPase would confer bile acid transport characteristics, as well as ecto-ATPase activity, on heterologous cells. The results show that transfection of the ecto-ATPase cDNA conferred on COS cells de novo synthesis of a approximately 110-kDa polypeptide, as immunoprecipitated by antibody to the purified canalicular bile acid transport protein and conferred on COS cells the capacity to pump out [3H]taurocholate with efflux characteristics comparable with those previously determined in canalicular membrane vesicles (Km = 100 microM; Vmax = 200 pmol/mg of protein/20 s). A truncated ecto-ATPase cDNA, missing the cytoplasmic tail, was targeted correctly to the cell surface but did not confer bile acid transport activity on COS cells. The results of this study also show that the canalicular ecto-ATPase/bile acid transport protein is phosphorylated on its cytoplasmic tail and that its phosphorylation is stimulated by activation of protein kinase C and inhibited by inhibitors of protein kinase C activation. Moreover, inhibition of protein kinase C activation by staurosporine completely abrogates bile acid transport but does not affect ATPase activity. This study, therefore, demonstrates that the rat liver canalicular ecto-ATPase is also a bile acid transport protein, that the capacity to pump out bile acid can be conferred on a heterologous cell by DNA-mediated gene transfer, and that phosphorylation within the cytoplasmic tail of the transporter is essential for bile acid efflux activity but not for ATPase activity.


Density functional theory study of the adsorption of formaldehyde on Pd4 and on Pd4/gamma-Al2O3 clusters.
B3LYP/LANL2DZ and B3LYP/6-31G(d)-restricted and -unrestricted calculations are employed to calculate energies and adsorption forms of formaldehyde adsorbed on planar and on tetrahedral Pd4 clusters and on a Pd4 cluster supported on Al10O15. Formaldehyde adsorbs on planar Pd4 in the eta(2)(C,O)-di-sigma adsorption mode, while on tetrahedral Pd4, it adsorbs in the eta(2)(C,O)-pi adsorption mode. The adsorption energy on planar Pd4 is -21.4 kcal x mol(-1), whereas for the tetrahedral Pd4 cluster, the adsorption energy is -13.2 kcal x mol(-1). The latter value is close to experimental findings (-12 to -14 kcal x mol(-1)). Adsorption of formaldehyde on Pd4 supported on an Al10O15 cluster leads essentially to the same result as that found for adsorption on the tetrahedral Pd4 cluster. Charge density analysis for the interaction between formaldehyde and the Pd4 clusters indicates strong backdonation in the eta(2) adsorption mode, leading to positive charge on the Pd4 cluster. NBO analysis shows that the highly coordinated octahedral aluminum atoms of Al10O15 donate electron density to the supported Pd4 cluster, while tetrahedral aluminum atoms with lower coordination number have acidic nature and therefore act as electron acceptors.


A nonsense mutation in CRYBB1 associated with autosomal dominant cataract linked to human chromosome 22q.
Autosomal dominant cataract is a clinically and genetically heterogeneous lens disorder that usually presents as a sight-threatening trait in childhood. Here we have mapped dominant pulverulent cataract to the beta-crystallin gene cluster on chromosome 22q11.2. Suggestive evidence of linkage was detected at markers D22S1167 (LOD score [Z] 2.09 at recombination fraction [theta] 0) and D22S1154 (Z=1.39 at theta=0), which closely flank the genes for betaB1-crystallin (CRYBB1) and betaA4-crystallin (CRYBA4). Sequencing failed to detect any nucleotide changes in CRYBA4; however, a G-->T transversion in exon 6 of CRYBB1 was found to cosegregate with cataract in the family. This single-nucleotide change was predicted to introduce a translation stop codon at glycine 220 (G220X). Expression of recombinant human betaB1-crystallin in bacteria showed that the truncated G220X mutant was significantly less soluble than wild type. This study has identified the first CRYBB1 mutation associated with autosomal dominant cataract in humans.


Nitrate Accumulation, Assimilation, and Transport by Decapitated Corn Roots : EFFECTS OF PRIOR NITRATE NUTRITION.
The effects of accumulated [(14)N]nitrate and its utilization in decapitated, 5-day-old dark-grown corn roots on influx, accumulation, xylem deposition, and reduction of concurrently absorbed nitrate during an 18-hour exposure to 0.5 millimolar K(15)NO(3) nutrient solution were examined. A 20-hour pretreatment in 15.0 millimolar K(14)NO(3) high nitrate (HN) resulted in a 2-fold greater tissue nitrate level than pretreatment in 0.5 millimolar K(14)NO(3) low nitrate (LN). Upon transfer to the 0.5 millimolar K(15)NO(3) solution, the net nitrate uptake rate in HN roots after 2 hours was 52% of the LN rate, but increased to 93% at the end of the uptake period. Despite an enhanced [(14)N]nitrate efflux from HN roots to the uptake solution, the efflux differences between the two pretreatments did not compensate for the decrease in net nitrate uptake. The [(15)N]nitrate influx rate was initially restricted by 33% in the HN roots compared to LN roots, but it had decreased to 7% by the end of the 18-hour uptake period. At this time, the total tissue nitrate levels were similar for both pretreatments. The rate of accumulation of [(15)N]nitrate in the tissue was relatively constant for both pretreatments, but was 25% less in HN roots. Of the previously accumulated [(14)N]nitrate, 52 and 46% remained after 18 hours in the LN and HN roots, respectively. The [(14)N]nitrate decline for HN roots was initially more rapid than in the LN roots which was linear over time. Xylem transport and efflux more than accounted for the decline in [(14)N]nitrate of LN roots and all but 4% in the HN roots which was attributed to reduction. Compartmentation of the previously accumulated nitrate was evident from the higher atom per cent (15)N of xylem nitrate compared to that of the tissue nitrate of both LN and HN roots. During the first 2 hours, xylem transport of [(14)N]nitrate by the HN roots was 49% greater than for LN roots, while [(15)N]nitrate transport was 9% less in HN roots compared to LN roots. Even though the reduction of [(15)N]nitrate in HN roots was 31% less than LN roots during the first 2 hours, [(15)N]nitrate was reduced more rapidly than the previously accumulated [(14)N]nitrate. After the first 4 hours, the relative partitioning of absorbed [(15)N]nitrate between accumulation, reduction, and translocation was similar regardless of pretreatment.


Assessment of oral mucosal lesions with autofluorescence imaging and reflectance spectroscopy.
The aim of this prospective study was to evaluate the efficacy of a new form of autofluorescence imaging and tissue reflectance spectroscopy (Identafi, DentalEZ) in examining patients with oral mucosal lesions. The authors examined 88 patients with 231 oral mucosal lesions by conventional oral examination (COE) using white-light illumination and ×2.5 magnification loupes, followed by examination using Identafi. The authors noted fluorescence visualization loss, the presence of blanching, and diffuseness of vasculature. They performed incisional biopsies to provide definitive histopathologic diagnosis. Identafi's white light produced lesion visibility and border distinctness equivalent to COE. Identafi's violet light displayed a sensitivity of 12.5% and specificity of 85.4% for detection of oral epithelial dysplasia (OED). The authors noted visible vasculature using the green-amber light in 40.9% of lesions. Identafi's intraoral white light provided detailed visualization of oral mucosal lesions comparable with examination using an extraoral white-light source with magnification. A high level of clinical experience is required to interpret the results of autofluorescence examination as the violet light displayed low sensitivity for detection of OED. The green-amber light provided additional clinical information in relation to underlying vasculature and inflammation of lesions. Examination using Identafi can provide clinicians with more clinical data than a standard COE with yellow incandescent light, but the clinical and optical findings should be interpreted as a whole and not in isolation. Clinicians should use the light features of Identafi in a sequential and differential manner.