Carotenoid isolates of Spondias mombin demonstrate anticancer effects in DMBA-induced breast cancer in Wistar rats through X-linked inhibitor of apoptosis protein (XIAP) antagonism and anti-inflammation.
Breast cancer is the most prevalent cancer in women. X-linked inhibitor of apoptosis protein (XIAP) that is constantly overexpressed in cancer is a promising therapeutic target in cancer treatments. The mechanisms of the anticancer effects of carotenoid isolates of Spondias mombim in DMBA-induced breast cancer in Wistar rats through XIAP antagonism were investigated in the present study. Carotenoids isolated from the leaves of Spondias mombim were subjected to Liquid Chromatography/Mass Spectrometry (LC/MS) and Electrospray Ionization (ESI) for characterization. The characterized carotenoid isolates were docked against XIAP BIR2 domain and XIAP BIR3 domain. The anticancer effects of the carotenoid isolates of Spondias mombim in DMBA-induced breast cancer in Wistar rats were also investigated through the expression of XIAP, COX-2, TNF, BCl-2 mRNAs by qRT-PCR and biochemical parameters of catalase, lipid peroxidation, LDH, ALP, and ALT. These show the carotenoid isolates demonstrate anticancer effects by antagonism of XIAP, proapoptotic, and anti-inflammatory properties. PRACTICAL APPLICATIONS: The present study showed that carotenoids (astaxanthin, β-carotene-15,15'-epoxide, and 7,7',8,8'-tetrahydro-β, β-carotene) isolated from the leaves of Spondias mombim are proapoptotic, it further gives credence to the chemopreventive abilities of carotenoids. This study validated XIAP as a druggable target in cancer treatment and hence more phytochemicals should be screened against it, for possible lead compounds of plant origin. Cancer cells often explore XIAP for antiapoptotic and resistance tendencies, hence, β-carotene-15,15'-epoxide and 7,7',8,8'-tetrahydro-β, β-carotene (XIAP antagonists) are promising drug candidates that can withstand resistant and prone cancer cells to apoptotic cell death. There is a need to synthesize β-carotene-15,15'-epoxide and 7,7',8,8'-tetrahydro-β for further investigation in clinical studies.


Thermosensitive Polyester Hydrogel for Application of Immunosuppressive Drug Delivery System in Skin Allograft.
Tacrolimus (FK506) is a common immunosuppressive drug that is capable of suppressing acute rejection reactions, and is used to treat patients after allotransplantation. A stable and suitable serum concentration of tacrolimus is desirable for better therapeutic effects. However, daily drug administration via oral or injection routes is quite inconvenient and may encounter drug overdose or low patient compliance problems. In this research, our objective was to develop an extended delivery system using a thermosensitive hydrogel of poly ethylene glycol, D,L-lactide (L), and ϵ-caprolactone (CL) block copolymer, mPEG-PLCL, as a drug depot. The formulation of mPEG-PLCL and 0.5% PVP-dissolved tacrolimus was studied and the optimal formulation was obtained. The in vivo data showed that in situ gelling is achieved, a stable and sustained release of the drug within 30 days can be maintained, and the hydrogel was majorly degraded in that period. Moreover, improved allograft survival was achieved. Together, these data imply the potential of the current formulation for immunosuppressive treatments.


Using Deep Learning for Classification of Lung Nodules on Computed Tomography Images.
Lung cancer is the most common cancer that cannot be ignored and cause death with late health care. Currently, CT can be used to help doctors detect the lung cancer in the early stages. In many cases, the diagnosis of identifying the lung cancer depends on the experience of doctors, which may ignore some patients and cause some problems. Deep learning has been proved as a popular and powerful method in many medical imaging diagnosis areas. In this paper, three types of deep neural networks (e.g., CNN, DNN, and SAE) are designed for lung cancer calcification. Those networks are applied to the CT image classification task with some modification for the benign and malignant lung nodules. Those networks were evaluated on the LIDC-IDRI database. The experimental results show that the CNN network archived the best performance with an accuracy of 84.15%, sensitivity of 83.96%, and specificity of 84.32%, which has the best result among the three networks.


Polyarticular septic arthritis.
Twenty-five cases of polyarticular septic arthritis (PASA) were observed in our department over a 13-year period. They accounted for 16.6% of all septic arthritis (15% on average in the literature). A male predominance was noted in our patients, as well as in the literature. The knee was the most frequent location followed by the elbow, shoulder, and hip, in varying order depending on the series. An average of 4 joints was involved. The causative microorganism was Staphylococcus aureus in 20/25 of our patients and in about 50% of published cases. Other frequently causative organisms were streptococci and gram-negative bacteria. Blood cultures and joint aspirations were positive in 19/22 and 23/25 of our cases, respectively. Other septic lesions were noted in 10/25 of our cases. Fever and severe leukocytosis were absent at admission in 5/25 (literature, 37%) and 10/25 of our 25 patients, respectively. The underlying disease was rheumatoid arthritis in 13/25, while 9 of the other patients had immunodepression caused by drugs or by concurrent illness. Typically, rheumatoid arthritis was long-standing and erosive, patients having ulcerated calluses on the feet. This skin source was also noted in 23/36 published cases of PASA in rheumatoid arthritis. Systemic lupus erythematosus was an uncommon disease in PASA, but its presence promoted gram-negative infection. Despite effective therapy with 2 antibiotics, 8/25 patients died, a prognosis that is equally severe in cases reported in the literature (30%) and one that has remained surprisingly stable over the last 40 years. For comparison, the death rate was only 4% in our patients with MASA. Factors contributing to a poor prognosis were age greater than 50 years, rheumatoid arthritis as an underlying disease, and disease of staphylococcal origin. Septic polyarthritis should be considered even when the clinical picture is not florid--when patients have low fever and normal white blood cell counts. Nor should the simultaneous involvement of distant joints rule out infection. Indeed, the frequency of underlying rheumatic disease and its treatment may further confuse the clinical presentation. Joints suspected of harboring infection should be aspirated, including those previously affected by the concurrent rheumatism.


Modulation of arm stiffness in relation to instability at the beginning or the end of goal-directed movements.
In reaching to a target, stability near the target may be more critical for success than stability far from the target. Consequently, we postulated that high instability near the start would evoke less compensation than high instability near the target. Three stability conditions were implemented using a robot manipulandum: neutral stability everywhere (null field); high instability along the first half of the trajectory decreasing as the target was approached (start unstable); and instability increasing along the first half of the trajectory and remaining high as the target was approached (end unstable). Under the start unstable condition, the stiffness of the arm in the region of highest instability was significantly less than under the end unstable condition. Furthermore, the stability of the system (manipulandum plus arm) was much lower under the start unstable condition than under the null field condition whereas it was similar under the end unstable and null field conditions.


[Stabilization of the distal radioulnar joint by Hui-Lindscheid ligamentoplasty. Report of 10 cases].
The surgical treatment of chronic sprain of the distal radio-ulnar joint remains a difficult problem. Some authors have proposed a radio-ulnar stabilization procedure which involves some loss of mobility of the forearm. Other, more radical authors, have suggested partial or complete resection of the ulnar head. In this case, they restore mobility in prono-supination, but often with a loss of stability and discomfort or pain. Hui and Lindscheid modified a technique of tenodesis which had been previously proposed by Bunnell. They perfected a tenodesis based on the use of the flexor carpi ulnaris tendon. We feel that this procedure should ensure stability of the distal radio-ulnar joint, while preserving its mobility. We used this technique in 9 patients who were reviewed with a follow-up of 2.7 years. The authors obtained 2/3 of good and very good results. This procedure will be compared with other techniques currently used and differences of the results will be discussed. Unfortunately, few articles have been published on this subject.


Dose response, recovery, and cost of doxacurium as a continuous infusion in neurosurgical intensive care unit patients.
To determine the optimal dosing of doxacurium as a continuous infusion in neurosurgical patients with traumatic brain injury; to determine the effects of bolus administration of doxacurium on heart rate (HR), blood pressure (BP), and intracranial pressure (ICP); to monitor neuromuscular recovery after discontinuation of prolonged doxacurium infusion; and to compare the cost of doxacurium with other current neuromuscular blocking drugs. Prospective, open-label study. Neurosurgical intensive care unit (ICU) of a university-affiliated teaching hospital. Eight critically ill, mechanically ventilated patients with traumatic head injury and normal renal and hepatic function. Patients had ICP monitoring. A bolus injection of doxacurium (0.05 mg/kg) followed by a continuous infusion (0.015 mg/kg/hr), adjusted to maintain one twitch during Train-of-Four nerve stimulation of the adductor pollicis muscle. Bolus injections of doxacurium did not alter the HR, BP, or ICP. Patients were paralyzed 66 +/- 12 (SEM) hrs, with recovery of the fourth twitch occurring 118 +/- 19 mins after infusion of the doxacurium was discontined. There were no incidences of prolonged weakness, myopathy, or other adverse events. Continuous infusion of doxacurium provides stable neuromuscular blockade for neurosurgical patients with traumatic brain injury. Doxacurium is devoid of clinically important interactions with HR, BP, or ICP and is less costly than other neuromuscular blockers used in the ICU.


Treatment Strategy for Dialysis Patient with Urothelial Carcinoma.
To investigate postoperative complications and oncologic outcomes of prophylactic nephroureterectomy and/or cystectomy in dialysis patients with urothelial carcinoma (UC), we retrospectively reviewed the records of dialysis patients with UC and a final status of complete urinary tract extirpation (CUTE, i.e., the removal of both kidneys, ureters, and bladder) between January 2004 and December 2015. Patients undergoing dialysis after initial radical nephroureterectomy and/or cystectomy were excluded. Eighty-four and 27 dialysis patients, undergoing one-stage and multi-stage CUTE, were enrolled in this study, respectively. Demographic, medical, perioperative, and pathologic features were collected to determine variables associated with oncologic outcomes. Although there was no significant difference in mortality between the 2 groups (p = 0.333), all 5 (4.5%) patients with Clavien-Dindo grade 5 complications were from the one-stage CUTE group. On multivariate logistic regression analysis, advanced age (p = 0.042) and high Charlson comorbidity index (CCI) (p = 0.000) were related to postoperative major complications. Compared with multi-stage CUTE, one-stage CUTE had no overall, cancer-specific, and recurrence-free survival benefits (all p > 0.05). According to multivariate analysis with Cox regression, age > 70 years (HR 2.70, 95% CI 1.2-6.12; p = 0.017), CCI ≥ 5 (HR 2.16, 95% CI 1.01-4.63; p = 0.048), and bladder cancer stage ≥ 3 (HR 12.4, 95% CI 1.82-84.7; p = 0.010) were independent, unfavorable prognostic factors for the overall survival. One-stage CUTE is not associated with superior oncologic outcomes, and all perioperative mortalities in our series occurred in the one-stage CUTE group. Our data do not support prophylactic nephroureterectomy and/or cystectomy for uremic patients with UC.


TIMELESS regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer.
Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Here, we explored that the expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with specificity protein 1 (Sp1) which contributes to upregulate the expression of alkaline ceramidase 2 (ACER2). Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Collectively, our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer.


Sustained changes in blood alpha amino nitrogen compartmentation during recovery from cafeteria feeding in rats.
We have previously reported that blood urea and blood cell amino acids levels are reduced in rats obese by feeding a palatable cafeteria diet. In order to distinguish whether these changes result from the altered diet, or from the obesity per se, we have studied cafeteria fed rats after returning to standard diet. As in previous studies, obesity induced by cafeteria feeding (for 90 days) was maintained when the cafeteria diet was removed and rats were fed standard diet only. After removal of the cafeteria diet, blood urea levels of 24 h starved obese rats were lower (23%) than those of starved control rats. Blood cell amino acid levels of obese were lower than control ones from day 50 onwards, during and after cafeteria feeding (21% lower on day 100 of life), and thus coincided with divergence of body weights; these differences were maintained despite removal of cafeteria diet. The effects of starvation on plasma amino acid levels were more marked in obese than control rats, during and after cafeteria feeding. Thus the effects on blood amino acids and urea levels in cafeteria diet induced obese rats are related to the obese status rather than to the diet composition.


Relating media with staff development in medical education.
Medical education nowadays experiences an increasing gap between the potential didactic value of educational technology and the practical implementation thereof. One of the important obstacles is the tendency to separate media and media agencies from staff development. A new conceptual model was designed for staff development in medical education, which incorporates media as one of the fundamental components. In application of this model the Bureau for Medical and Dental Education at the University of Stellenbosch medical school directs its media activities and services to the improvement of instruction and learning. For example instead of only offering technical audio-visual production services, medical teachers are also taught how to use different media effectively in teaching and learning. In this way media are directly related to staff development.


Binding interactions between yeast tRNA ligase and a precursor transfer ribonucleic acid containing two photoreactive uridine analogues.
Yeast tRNA ligase, from Saccharomyces cerevisiae, is one of the protein components that is involved in the splicing reaction of intron-containing yeast precursor tRNAs. It is an unusual protein because it has three distinct catalytic activities. It functions as a polynucleotide kinase, as a cyclic phosphodiesterase, and as an RNA ligase. We have studied the binding interactions between ligase and precursor tRNAs containing two photoreactive uridine analogues, 4-thiouridine and 5-bromouridine. When irradiated with long ultraviolet light, RNA containing these analogues can form specific covalent bonds with associated proteins. In this paper, we show that 4-thiouridine triphosphate and 5-bromouridine triphosphate were readily incorporated into a precursor tRNA(Phe) that was synthesized, in vitro, with bacteriophage T7 RNA polymerase. The analogue-containing precursor tRNAs were authentic substrates for the two splicing enzymes that were tested (endonuclease and ligase), and they formed specific covalent bonds with ligase when they were irradiated with long-wavelength ultraviolet light. We have determined the position of three major cross-links and one minor cross-link on precursor tRNA(Phe) that were located within the intron and near the 3' splice site. On the basis of these data, we present a model for the in vivo splicing reaction of yeast precursor tRNAs.


Beliefs about the appropriate age for initiating toilet training: are there racial and socioeconomic differences?
To examine racial and socioeconomic differences in parental beliefs about the appropriate age at which to initiate toilet training. A cross-sectional survey of 779 parents visiting child health providers in 3 clinical sites in Washington, DC and the surrounding metropolitan area completed a self-report survey. The main outcome variable was parental beliefs about the appropriate age at which to initiate toilet training. Using multiple linear regression, differences in beliefs were assessed in relation to race, family income, parental education, parental age, and age of the oldest and youngest children. Among respondents, parents felt that the average age at which toilet training should be initiated was 20.6 months (+/-7.6 months), with a range of 6 to 48 months. Caucasian parents believed that toilet training should be initiated at a significantly later age (25.4 months) compared with both African-American parents (18.2 months) and parents of other races (19.4 months). In the multiple regression model, factors predicting belief in when to initiate toilet training were Caucasian race and higher income. Race and income were independent predictors of belief in age at which to initiate toilet training. More research is needed to determine what factors contribute to toilet training practices in diverse populations.


[Effects of differences in head holder on image quality and radiation dose in head CT].
For emergency or pediatric head CT scans, a simplified pillow made of hard sponge instead of a dedicated head holder may be used if it is difficult to immobilize the head. However, the radiation dose when using a simplified head holder may be increased due to radiation absorption by the patient couch if the automatic exposure control (AEC) system is used. In this phantom study, we compared the radiation dose delivered when using a dedicated and a simplified head holder. We used a dedicated-type and a pillow-type head holder made of hard sponge (simplified head holder). We placed a 20 cm-diameter cylindrical phantom made of water-equivalent material and an anthropomorphic head phantom in the head holders and then scanned them five times with a 64-detector CT scanner (VCT, GE Healthcare). We performed step-and-shoot and helical scanning with AEC; the noise index was set to 2.8. We measured the radiation dose using fluorescent glass dosimeters in the head phantom and the image noise at five sites in the cylindrical phantom. All values were averaged. With step-and-shoot scans, the mean image noise with the dedicated and the simplified head holder was 3.30 ± 0.05 [SD] and 3.20 ± 0.05, respectively. With helical scans they were 3.00 ± 0.09 and 2.88 ± 0.03, respectively. There was no statistically significant difference (p = 0.02 and 0.04, Student's t-test). The radiation doses with the dedicated and the simplified head holder were 58.6 and 70.4 mGy, respectively, for step-and-shoot scanning and 41.8 and 49.0 mGy, respectively, for helical scanning. The doses were thus significantly higher with the simplified head holder for both step-and-shoot and helical scanning (p < 0.01 and < 0.01). We recommend the use of a dedicated head holder for head scanning with AEC since the radiation dose was lower than with the simplified head holder.


Irritable bowel syndrome and diet.
Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and altered bowel habits. The diagnosis of IBS is based on the presence of defined clinical Rome IV criteria in the absence of alarm features. The majority of patients with IBS report of food triggers eliciting typical IBS symptoms and trying to modify their dietary intake. FGID including IBS are defined as disorders of the gut-brain interaction. A large proportion of individuals with IBS link their symptoms to dietary factors, and recent clinical studies have shown benefits of a diet low in FODMAPs (Fermentable Oligo-, Di-, and Monosaccharides and Polyols) on IBS symptoms and quality of life. Dietary interventions mediate directly changes of luminal gut contents affecting chemosensing-enteroendocrine cells in the modulation of the gut brain microbiome axis in IBS patients. Long-term assessment of clinical outcomes in patients on a low FODMAP diet is needed. Professional guidelines have incorporated the suggestion to offer IBS patients a diet low in FODMAPs. The FGIDs, including IBS, are defined as gut-brain disorders. Low FODMAP diet has been shown in clinical trials to reduce IBS symptoms but long-term efficacy and nutritional side-effects remain uncertain.


Retail stores' compliance with a city no-smoking law.
Laws restricting smoking in public places and workplaces can protect the public only if they are obeyed. We sought to assess compliance with a Cambridge, Mass, no-smoking ordinance. We prospectively observed 174 retail stores 1 month before and 3, 11, and 24 months after the law took effect. At 24 months, we interviewed one employee per store. Full compliance with the law was low; at 24 months, only 4% of stores displayed the mandated sign and were free of smokers and smoke. Fewer than half the stores posted any no-smoking sign. Sign prevalence increased over 2 years (22% to 41%, P < .001), but the frequency of smoke or smokers (13% and 10%, respectively, at baseline) did not change. According to employees interviewed at 24 months, 38% of stores illegally permitted customers or employees to smoke. These stores had more smoke and fewer signs than did stores prohibiting smoking. Compliance was poor in liquor and convenience stores. Employees who had been told how to handle customers' smoking were more likely to enforce the law. Compliance with a no-smoking law is not guaranteed. For retail stores, compliance may improve if stores adopt no-smoking policies, post signs, and teach employees to enforce the law.


[The future of pathology--from the viewpoint of clinical pathology].
Pathology is one of the fundamental diagnostic fields of medicine, its position has changed and will undergo transformation in the 21st century due to the introduction of new methods. Theoretically, pathology was based upon 3 pillars: 1. the autopsies, 2. the surgical pathology, i.e. the processing and evaluation of different biopsies and surgically resected specimens and 3. the cytological investigations. The autopsy was the dominant field till the end of the seventies of the 20th century but about the turn of the 20th and 21st century the cytology, first of all the fine needle aspiration cytology took over the leading role in the pathologic diagnostic activity. This displacement resulted in such a high decrease in the number of autopsies that it is impossible to conclude appreciable epidemiological statements. Meanwhile the role and position of the pathologist has changed also substantially. Previously he was regarded often as a prosecuting attorney. At present time this opinion is transformed into clinical pathologist. Errors in the histopathological diagnosis and reporting can occur in the surgical pathology but its number is not high. To detect and to avoid them is attainable by composition of an adequate audit-system. The number of the new investigatory methods is increasing nowadays wide-spreadingly in the medicine and so in the pathology too. The immunocytochemistry is regarded already as a conventional method but the PCR and FISH-technique are applied also on a large scale. At the same time, new tools such as the cDNA microarray technology, the micro-chip based analytical chemistry, the laser capture microdissection and the wireless medical information appear also in the pathology. The modern information technology is impacted more intensively into the day-to-day pathological work. This method enables to develop worldwide communicating systems which can make perfect the diagnostic work. The pathologist has traditionally functioned as a medical consultant to the clinician. The predominant function of the pathologist has to be evolved from that of medical consultant to that of information specialist.


Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias.
M195, a mouse monoclonal antibody reactive with the early myeloid antigen CD33, has been shown to target leukemia cells in patients and to reduce large leukemic burdens when labeled with 131I. A complementarity-determining region-grafted, humanized version (HuM195) has demonstrated similar targeting of leukemia cells without immunogenicity. We have studied two applications of therapy with 131I-M195. First, to intensify therapy prior to bone marrow transplantation (BMT), we combined 131I-M195 with busulfan and cyclophosphamide. Fifteen patients received first BMT for relapsed or refractory acute myelogenous leukemia or accelerated or blastic chronic myelogenous leukemia; four received second BMT for relapsed chronic or accelerated chronic myelogenous leukemia. Doses of 131I-M195 ranged from 120 to 230 mCi/m2. Few toxicities could be attributed to 131I-M195 therapy, and all patients engrafted. Eighteen patients achieved complete remission. Among those patients receiving first BMT, three have remained in unmaintained remission for 18+ to 29+ months. Six patients relapsed, including one with isolated central nervous system disease 32 months after BMT. Ten patients died in complete remission of transplant-related complications. Second, we studied whether 131I-M195 could reduce minimal residual disease and prolong remission and survival durations safely in patients with relapsed acute promyelocytic leukemia after they attained remission with all-trans-retinoic acid. Seven patients were treated with either 50 or 70 mCi/m2 131I-M195. Toxicity was limited to myelosuppression. As a measure of minimal residual disease, we monitored PML/RAR-alpha mRNA by reverse transcription PCR. Six patients had positive reverse transcription PCR assays prior to receiving 131I-M195; two converted transiently to negative. Median disease-free survival and overall survival of the seven patients were 8 (range, 3-14.5) months and 28 (range, 5.5-43+) months, respectively. This regimen compares favorably with others for relapsed acute promyelocytic leukemia. In an effort to avoid nonspecific cytotoxicity associated with 131I in future trials for minimal residual disease, we have conjugated short-range, alpha particle-emitting radioisotopes to HuM195 using a bifunctional chelate, 2-(p-isothiocyanatobenzyl)-cyclohexyldiethyl-enetriaminep entaacetic acid, with high efficiency and specific activities. 212Bi-HuM195 has demonstrated dose- and specific activity-dependent killing of HL60 cells in vitro. Injection of 213Bi-HuM195 into healthy BALB/c mice produced no effects on weight or viability.


[Comparative studies of patient positioning for lumbar intervertebral disk operation].
For surgery on lumbar disks by the posterior route, patients are placed either on a Wilson frame or in genupectoral position. The aim of the prospective study was to record and describe the haemodynamic changes resulting from the patients' position. After written informed consent had been received, 80 neurosurgical patients undergoing lumbar disk surgery were randomly divided into two groups; group I--Wilson frame, group II--genupectoral position. In each group, 20 patients received total intravenous anaesthesia (Alfentanil or Remifentanil, Propofol) and 20 balanced anaesthesia with Isoflurane and Alfentanil or Remifentanil. Haemodynamic parameters (mean arterial pressure--MAP and heart rate--HR) were recorded automatically at three measuring times (MT): firstly, after induction of anaesthesia; secondly, before re-direction; thirdly, after re-direction on the Wilson frame or in the genupectoral position. Induction of anaesthesia did not lead to a significant decrease in MAP (MT 1: 92.5 +/- 15.2 mmHg, MT 2: 89 +/- 13.4 mmHg, n = 80). In group I (n = 40), no significant changes were observed in MAP and HR at MT 3 (p = 0.882, p = 0.051). In comparison to group I, the genupectoral position was associated with significant drops in MAP and HR. The genupectoral position caused a significant decrease in MAP (p < 0.001) and HR (p = 0.016) at MT 3. Our data suggest that body weight or body mass index do not necessarily lead to a preference for one of the two possible positions of the patient. Complications resulting from haemodynamic changes were not seen in either group. We recommend the Wilson frame for neurosurgical lumbar disk surgery in cases of cardiovascular or cerebrovascular disorders. The adaptive capacities in the genupectoral position as a result of the modifying distribution of blood volume are limited in these patients. Furthermore, the dose-dependent effects of different anaesthetics on haemodynamic parameters in these prone positions should be explored.


Macrophage Activation Syndrome Upon Initiation of Adalimumab in a Patient With Longstanding Rheumatoid Arthritis.
Macrophage activation syndrome (MAS) is a subset of hemophagocytic lymphohistiocytosis (HLH) described in patients with rheumatological disorders. Some triggers of MAS and HLH include infection, malignancy, rheumatological disease, HIV, and rarely medications such as immunosuppressants. In recent medical literature, biologic agents are increasingly recognized as a potential trigger, but the mechanism behind this remains poorly understood. We describe the case of a patient who developed MAS after initiating adalimumab and propose a potential pathophysiological link between biologics and this syndrome.


Simultaneous determination of fumonisin B(1) and hydrolyzed fumonisin B(1) in corn products by liquid chromatography/electrospray ionization mass spectrometry.
A method for the simultaneous determination of fumonisin B(1) (FB(1)) and its major hydrolysis product (HFB(1)), which is known to be formed during alkaline treatment of fumonisin-containing corn meal, was devised to analyze the levels of these mycotoxins in corn products available on the German market. Liquid chromatography/electrospray mass spectrometry in combination with selected ion monitoring (SIM) was used for unambiguous detection of FB(1) and HFB(1) after extraction of samples with acetonitrile/methanol/water (25:25:50) and solid-phase C18 cleanup. Quantitation was carried out using labeled fumonisin FB(1)-D(6) as an internal standard. The detection limits achieved with this method were 8 ng/g for HFB(1) (signal-noise ratio = 5:1) and 5 ng/g for FB(1) (s/n = 5:1) using the protonated molecule signals m/z 406 and 722 in the SIM mode. A screening of several corn-containing foodstuffs, among them extrusion products and alkali-processed corn food such as tortilla chips, showed HFB(1) and FB(1) contamination with levels of 8-80 and 5-450 ng/g, respectively.


Clues to VIP function from knockout mice.
We have taken advantage of the availability of vasoactive intestinal polypeptide (VIP) knockout (KO) mice to examine the possible influence of deletion of the VIP gene on: (a) airway reactivity and airway inflammation, as indicators of bronchial asthma; (b) mortality from endotoxemia, a model of septic shock; and (c) the pulmonary circulation. VIP KO mice showed: (a) airway hyperresponsiveness to the cholinergic agonist methacholine, as well as peribronchial and perivascular inflammation; (b) a greater susceptibility to death from endotoxemia; and (c) evidence suggestive of pulmonary hypertension.


Remarkable Diversity and Prevalence of Dagger Nematodes of the Genus Xiphinema Cobb, 1913 (Nematoda: Longidoridae) in Olives Revealed by Integrative Approaches.
The genus Xiphinema includes a remarkable group of invertebrates of the phylum Nematoda comprising ectoparasitic animals of many wild and cultivated plants. Damage is caused by direct feeding on root cells and by vectoring nepoviruses that cause diseases on several crops. Precise identification of Xiphinema species is critical for launching appropriate control measures. We make available the first detailed information on the diversity and distribution of Xiphinema species infesting wild and cultivated olive in a wide-region in southern Spain that included 211 locations from which 453 sampling sites were analyzed. The present study identified thirty-two Xiphinema spp. in the rhizosphere of olive trees, ten species belonging to Xiphinema americanum-group, whereas twenty-two were attributed to Xiphinema non-americanum-group. These results increase our current knowledge on the biodiversity of Xiphinema species identified in olives and include the description of four new species (Xiphinema andalusiense sp. nov., Xiphinema celtiense sp. nov., Xiphinema iznajarense sp. nov., and Xiphinema mengibarense sp. nov.), and two new records for cultivate olives (X. cadavalense and X. conurum). We also found evidence of remarkable prevalence of Xiphinema spp. in olive trees, viz. 85.0% (385 out of 453 sampling sites), and they were widely distributed in both wild and cultivated olives, with 26 and 17 Xiphinema spp., respectively. Diversity indexes (Richness, Hill´s diversity, Hill´s reciprocal of D and Hill´s evenness) were significantly affected by olive type. We also developed a comparative morphological and morphometrical study together with molecular data from three nuclear ribosomal RNA genes (D2-D3 expansion segments of 28S, ITS1, and partial 18S). Molecular characterization and phylogenetic analyses allowed the delimitation and discrimination of four new species of the genus described herein and three known species. Phylogenetic analyses of Xiphinema spp. resulted in a general consensus of these species groups. This study is the most complete phylogenetic analysis for Xiphinema non-americanum-group species to date.


Inter-observer variability in chest radiograph reading for diagnosing acute lung injury in children.
Acute lung injury (ALI), including its most serious form called acute respiratory distress syndrome (ARDS), is a devastating disease that can occur at any age. ALI/ARDS accounts for only 5-8% of admissions to pediatric intensive care units (PICUs) but is fatal in 30-60% of cases. International multicenter prospective studies are needed to better understand pediatric ALI/ARDS. However, a reproducible definition of ALI/ARDS is crucial to ensure that study populations are homogeneous. We designed a retrospective review to test the inter-observer variability of chest radiograph interpretation for presence of the American-European Consensus Conference (AECC) radiographic criterion for ALI/ARDS. The medical files of 24 children ventilated for ALI/ARDS in our PICU between January 1993 and December 2002 were reviewed. Five pediatric radiologists and five pediatric intensivists interpreted one frontal chest radiograph (FCR) per patient taken on the day of ALI/ARDS diagnosis. Each reader indicated whether the radiograph showed the AECC radiographic criterion for ALI/ARDS. Data analysis involved comparing each reader to all the others based on the raw agreement and Kappa coefficient (kappa). Features in the 24 patients were consistent with earlier studies. Global inter-observer agreement beyond chance was fair (kappa = 0.29 +/- 0.02) among the five radiologists (kappa = 0.26 +/- 0.05) and among the five intensivists (kappa = 0.29 +/- 0.05). Thus, considerable inter-observer variability occurred in assessing the radiographic criterion for ALI/ARDS, as previously shown in adults. Given the low incidence of ALI/ARDS in children, this variability may have a large impact in studies of pediatric ALI/ARDS.


Fluorosis and caries prevalence in a community drinking above-optimal fluoridated water.
Fluorosis levels and caries prevalence were evaluated in 182 adolescents aged 15-16 yr residing from birth in an area with 5 ppm fluoride in the drinking water. The mean number of surfaces affected by caries in the total study population was 5.46 DMFS. The teeth most susceptible to caries were the first molars. The prevalence of fluorosis was 100% with 53 subjects demonstrating mild fluorosis (according to Dean's index), 83 demonstrating moderate fluorosis, and severe fluorosis diagnosed in 46 subjects. A statistically significant positive association was found between caries prevalence and fluorosis; the more caries experienced, the more severe the fluorosis level. Boys experienced significantly higher fluorosis levels than girls. Further research will investigate the possible variables which may explain this difference in fluorosis by sex.


Envisioning success: the future of the oral health care delivery system in the United States.
The elimination of oral health disparities in the US will require enhancing access to oral health care services. The workshop convened in 2009 by the Institute of Medicine on the "US Oral Health Workforce in the Coming Decade" highlighted both the current workforce's failure to meet the nation's needs as well as the promising opportunities presented by various workforce strategies to significantly enhance access and improve oral health outcomes. In this article, we have briefly reviewed and expanded on the contributions in this special issue of the Journal of Public Health Dentistry, with the goal of identifying common themes and providing a framework for evaluation. There are several key areas where change is critically needed in order to ensure successful implementation of any new workforce models. These areas include a) the public and private financing of dental care, b) the dental educational system, and c) state and federal policies.


[Abiotrophia related endocarditis: contribution of molecular biology].
Former nutritionally-deficient (variant) streptococci were recently separated from other streptococci viridans to constitute a new Abiotrophia genus, subdivided into two species, Abiotrophia defectiva (ex-Streptococcus defectivus) and Abiotrophia adjacens (ex-Streptococcus adjacens). A woman was admitted to the hospital because of purpura and fever. Vegetations were shown by trans-esophageal echocardiography. Although blood samples were positive within 24 hours, accurate identification of the morphologically and biochemically streptococcus-like bacteria that had grown remained impossible. Molecular biology technicals permitted to identify Abiotrophia defectiva, ex-Streptococcus defectivus. This new genus is important to be identified in clinical practice, because of the increased virulence of these bacteria, when compared with Streptococci viridans. They are also frequently penicillin-resistant. Molecular biology technicals allow precocious diagnosis, and make possible the improvement of the prognosis.


Treatment of intractable diseased tissue in the maxillary sinus after endoscopic sinus surgery with high-pressure water jet and preservation of the periosteum.
To describe a new high-pressure water jet (HPWJ) treatment to remove intractable diseased mucosa persisting in the maxillary sinus several months after endoscopic sinus surgery (ESS) while preserving the periosteum. A retrospective review of HPWJ treatment in 45 consecutive patients with at least 12 months follow-up. A private surgicenter in Japan. Patients (25 male and 20 female) ranged in age from 8 to 59 years. All patients had diffuse intractable lesions in the opened maxillary sinus after the initial ESS, with or without disease of the ethmoid and other major sinuses. Resolution of diffuse intractable disease in the maxillary sinus and postoperative change in the size of the cavity were evaluated using nasal endoscopy and computed tomographic scan. Twenty-six (81%) of 32 sides in 25 patients with isolated persistent maxillary sinus disease were restored after HPWJ procedures; 25 (93%) of 27 sides in 20 patients who also had ethmoiditis also were restored. In the latter group, ethmoiditis recurred in 5 sides, which also included 2 sides of unrestored maxillary sinuses. Of the 51 restored sides, 33 (65%) were restored within 3 months after HPWJ treatment under endoscopic observation. No complications were seen during the surgery. Except for 1 side in 1 patient from which all diseased mucosa was removed almost completely, along with the periosteum, no reduction of the cavity by scar tissue formation was observed. This method did not affect the development of the maxillary bone in children. Removing diffuse intractable diseased mucosa in the maxillary sinus while preserving the periosteum with HPWJ treatment is an effective surgical therapy that fulfills the ultimate purpose of ESS.


Chronic intermittent hypoxia alters neurotransmission from lateral paragigantocellular nucleus to parasympathetic cardiac neurons in the brain stem.
Patients with sleep-related disorders, including obstructive sleep apnea (OSA), have an increased risk of cardiovascular diseases. OSA events are more severe in rapid eye movement (REM) sleep. REM sleep further increases the risk of adverse cardiovascular events by diminishing cardioprotective parasympathetic activity. The mechanisms underlying REM sleep-related reduction in parasympathetic activity likely include activation of inhibitory input to cardiac vagal neurons (CVNs) in the brain stem originating from the lateral paragigantocellular nucleus (LPGi), a nucleus that plays a role in REM sleep control. This study tests the hypothesis that chronic intermittent hypoxia and hypercapnia (CIHH), an animal model of OSA, inhibits CVNs because of exaggeration of the GABAergic pathway from the LPGi to CVNs. GABAergic neurotransmission to CVNs evoked by electrical stimulation of the LPGi was examined with whole cell patch-clamp recordings in an in vitro brain slice preparation in rats exposed to CIHH and control rats. GABAergic synaptic events were enhanced after 4-wk CIHH in both male and female rats, to a greater degree in males. Acute hypoxia and hypercapnia (H/H) reversibly diminished the LPGi-evoked GABAergic neurotransmission to CVNs. However, GABAergic synaptic events were enhanced after acute H/H in CIHH male animals. Orexin-A elicited a reversible inhibition of LPGi-evoked GABAergic currents in control animals but evoked no significant changes in CIHH male rats. In conclusion, exaggerated inhibitory neurotransmission from the LPGi to CVNs in CIHH animals would reduce cardioprotective parasympathetic activity and enhance the risk of adverse cardiovascular events.


[Septic arthritis in adult patients in a general hospital in Chile].
Septic arthritis is an infrequent condition of prolonged morbidity and there is no previous publications in Chile that allow orientate therapy. To characterize a group of adult patients with septic arthritis confirmed by culture. Descriptive study of a case series. From 2003 to august 2013, 24 patients with 25 events of septic arthritis were identified in a general hospital. Mean age was 68.3 years old (range 24-94). Predisposing conditions were harbored by 91.7%. Predominant clinical manifestations were pain (92%) and impaired joint movement (95.7%). Fever was present in 64%, hypotension in 28% of events, and C-reactive protein > 100 mg/L in 90.6%. Gram positive cocci were the most frequently isolated microorganisms (81.5%), predominating S. aureus (48.1%), and with 4 isolates methicillin resistant isolates (26.7%). Resistant isolates trend to be associated with previous surgery (p = 0.055) and all cases caused by non-fermentative Gram negative bacilli had recent hospitalization or surgery, a feature that did not reach a significant difference. Nine events were associated to bacteremia (36%). Outcome analysis indicated 32% of events with full recovery, 28% with a favorable evolution, 20% with therapy failure and 16.7% patients that died. A total of 24% of the series remained with significant sequels. Septic arthritis is an infrequent disease that affects in most cases patients with predisposing conditions. Associated symptoms include pain and impaired joint movement, sometimes fever, hypotension, positive blood cultures and frequently a C-reactive protein > 100 mg/L. Predominant agents are Gram positive cocci, specially S. aureus, including methicillin resistant isolates. Case-fatality ratio, treatment failure and sequels are important.


Streptokinase and recombinant tissue plasminogen activator (rt-PA) are equally effective in treating acute myocardial infarction.
In recent trials, patients with myocardial infarction who received either recombinant tissue-type plasminogen activator (rt-PA) or streptokinase showed essentially no difference in the amount of myocardial salvage, in mortality reduction, or in the incidence of bleeding complications. These findings thus failed to fulfill the expectation that rt-PA would be twice as effective as streptokinase as a thrombolytic agent. The basis for this mistaken prediction was an unfortunate overemphasis on an inadequate surrogate endpoint, namely, the patency or reperfusion rate at 90 minutes after the start of therapy. Using the 90-minute patency or reperfusion rate as an endpoint has several serious limitations. First, it is an observation made at only one point in time during a dynamic process that may change even during the infusion proper. Second, a single view at 90 minutes completely disregards the possibility of subsequent reocclusion which often occurs within 1 hour after treatment. Third, an image at 90 minutes is more a reflection of the speed of thrombolysis than of whether lysis will eventually occur; the pace of clot lysis depends on both the agent used and the age of the thrombus. Fourth, lysis at 90 minutes is of minimal relevance for myocardial salvage unless observed within the time frame when infarction size can be limited significantly, which is generally less than 4 hours between symptom onset and the time that reperfusion is accomplished. Fifth, a stable state of vessel patency is meaningful for mortality reduction even if stabilization occurs after completion of the infarction. Such "late," but lasting, patency is a critical component of the "open vessel" principle and explains, at least in part, the survival benefit that accrues to patients treated even 24 hours after the onset of symptoms. There is currently no evidence that rt-PA has a more beneficial effect on survival or function than does streptokinase or any other plasminogen activator used in treating acute myocardial infarction; nor is there any evidence that patients who receive rt-PA therapy show a decreased incidence of bleeding complications compared with those who receive streptokinase, despite the relative fibrinogen-sparing attribute of rt-PA. Given the poor predictive value of the 90-minute angiogram for ultimate clinical advantage of one agent over another, studies that are limited to this endpoint are of marginal use in evaluating treatment regimens used in mortality studies. The best evidence to date indicates that streptokinase and rt-PA are of equivalent value for survival after acute myocardial infarction, a conclusion that can be justifiably challenged only with a valid mortality study.


[The effect of electroacupuncture analgesia on the plasma levels of cortisol and aldosterone in orthopedic operations].
The effects of electroacupuncture on plasma cortisol and aldosterone levels in patients undergoing orthopedic operations were studied. Plasma cortisol and aldosterone levels were measured at three stages. Moderate activation of the hypothalamo-pituitary-adrenal system is considered an adjustment response of the organism to the operative trauma, with stable hemodynamic parameters. The total amount of analgetic drugs which the patients received during the postoperative period was three times lower than that in the control group given neuroleptanalgesia; during electroacupuncture analgesia (EAPA) opioids were not applied. It is considered that the use of EAPA lowers the degree of the stress reaction in surgical trauma, providing adequate analgesia and neurovegetative protection of patients during orthopedic operations and in the early postoperative period.


Phosphorylation of keratin intermediate filaments by protein kinase C, by calmodulin-dependent protein kinase and by cAMP-dependent protein kinase.
Keratins, constituent proteins of intermediate filaments of epithelial cells, are phosphoproteins containing phosphoserine and phosphothreonine. We examined the in vitro phosphorylation of keratin filaments by cAMP-dependent protein kinase, protein kinase C and Ca2+/calmodulin-dependent protein kinase II. When rat liver keratin filaments reconstituted by type I keratin 18 (molecular mass 47 kDa; acidic type) and type II keratin 8 (molecular mass 55 kDa; basic type) in a 1:1 ratio were used as substrates, all the protein kinases phosphorylated both of the constituent proteins to a significant rate and extent, and disassembly of the keratin filament structure occurred. Kinetic analysis suggested that all these protein kinases preferentially phosphorylate keratin 8, compared to keratin 18. The amino acid residues of keratins 8 and 18 phosphorylated by cAMP-dependent protein kinase or protein kinase C were almost exclusively serine, while those phosphorylated by Ca2+/calmodulin-dependent protein kinase II were serine and threonine. Peptide mapping analysis indicated that these protein kinases phosphorylate keratins 8 and 18 in a different manner. These observations gave the way for in vivo studies of the role of phosphorylation in the reorganization of keratin filaments.


Root aeration in rice (Oryza sativa): evaluation of oxygen, carbon dioxide, and ethylene as possible regulators of root acclimatizations.
Adventitious roots of rice (Oryza sativa) acclimatize to root-zone O(2) deficiency by increasing porosity, and induction of a barrier to radial O(2) loss (ROL) in basal zones, to enhance longitudinal O(2) diffusion towards the root tip. Changes in root-zone gas composition that might induce these acclimatizations, namely low O(2), elevated ethylene, ethylene-low O(2) interactions, and high CO(2), were evaluated in hydroponic experiments. Neither low O(2) (0 or 0.028 mol m(-3) O(2)), ethylene (0.2 or 2.0 microl l(-1)), or combinations of these treatments, induced the barrier to ROL. This lack of induction of the barrier to ROL was despite a positive response of aerenchyma formation to low O(2) and elevated ethylene. Carbon dioxide at 10 kPa had no effect on root porosity, the barrier to ROL, or on growth. Our findings that ethylene does not induce the barrier to ROL in roots of rice, even though it can enhance aerenchyma formation, shows that these two acclimatizations for improved root aeration are differentially regulated.


Clinical Outcomes and Capsular Bag Stability of a Four-Point Haptic Bitoric Intraocular Lens.
To evaluate the visual, refractive, and aberrometric outcomes of a bitoric intraocular lens (IOL) and its stability and alignment within the capsular bag. A retrospective study including 41 eyes of 24 patients with preexisting corneal astigmatism of 0.75 diopters or greater undergoing cataract surgery with implantation of the bitoric IOL AT TORBI 709M (Carl Zeiss Meditec, Jena, Germany). Visual and refractive outcomes were evaluated during a 3-month follow-up period. The misalignment between intended and real axis and the levels of corneal, internal, and ocular aberrations (KR-1W; Topcon, Tokyo, Japan) were also evaluated. A total of 76% and 97% of eyes had a postoperative spherical equivalent within ± 0.50 and ± 1.00 diopters of emmetropia, respectively. Likewise, a total of 86% and 95% of eyes had a postoperative absolute value of refractive cylinder of 0.50 or less and 1.00 or less diopters, respectively. Mean postoperative corrected distance visual acuity was 0.00 logMAR (20/20 Snellen). Mean values of postoperative monocular and binocular uncorrected distance visual acuity were 0.10 and 0.00 logMAR (20/25 and 20/20 Snellen), respectively. The aberrometric analysis confirmed that the magnitude of ocular higher-order aberrations was mainly due to corneal optics and that the corneal astigmatism correction was sufficient with the toric IOL. Mean absolute IOL misalignment was 3.5° with values ranging from 0° to 10°. The bitoric IOL AT TORBI 709M is able to provide a predictable correction of corneal astigmatism with low postoperative levels of ocular higher-order aberrations.


NRPS substrate promiscuity diversifies the xenematides.
Xenematide, a cyclic depsipeptide antibiotic produced by Xenorhabdus nematophila, had a candidate nonribosomal peptide synthetase (NRPS) with atypical features. Differential metabolite analysis between a mutant and wildtype validated that this stand-alone NRPS was required for xenematide production, and further analysis led to a series of new xenematide derivatives encoded by the same NRPS. Our results indicate that adenylation domain promiscuity and relaxed downstream processing in the X. nematophila NRPS provide a conduit for xenematide diversification.


Determination of volatile organic compounds in water using ultrasound-assisted emulsification microextraction followed by gas chromatography.
Volatile organic compounds (VOCs) are toxic compounds in the air, water and land. In the proposed method, ultrasound-assisted emulsification microextraction (USAEME) combined with gas chromatography-mass spectrometry (GC-MS) has been developed for the extraction and determination of eight VOCs in water samples. The influence of each experimental parameter of this method (the type of extraction solvent, volume of extraction solvent, salt addition, sonication time and extraction temperature) was optimized. The procedure for USAEME was as follows: 15 μL of 1-bromooctane was used as the extraction solvent; 10 mL sample solution in a centrifuge tube with a cover was then placed in an ultrasonic water bath for 3 min. After centrifugation, 2 μL of the settled 1-bromooctane extract was injected into the GC-MS for further analysis. The optimized results indicated that the linear range is 0.1-100.0 μg/L and the limits of detection (LODs) are 0.033-0.092 μg/L for the eight analytes. The relative standard deviations (RSD), enrichment factors (EFs) and relative recoveries (RR) of the method when used on lake water samples were 2.8-9.5, 96-284 and 83-110%. The performance of the proposed method was gauged by analyzing samples of tap water, lake water and river water samples.


Bacteriocinogenic activity of lactobacilli from fermented sausages.
During the screening of the inhibitory activity of 254 strains of lactobacilli isolated from fermented sausages at different times of ripening, 22% of the strains showed inhibition that was not related to acid or hydrogen peroxide, towards one or more indicator strains. Not all the strains were capable of secreting the inhibitory compound in the supernatant fluid. The characterization of the inhibitory compound from three strains showed that they were bacteriocins with a bactericidal mode of action and a molecular weight exceeding 10,000 Da. Lactobacillus plantarum CTC 305, CTC 306 and Lact. sake CTC 372 inhibited Listeria monocytogenes. Lactobacillus sake CTC 372 was cured of two plasmids of 84.8 kbp and 41.3 kbp, losing the production and the immunity of a bacteriocin as well as the ability to ferment lactose.


Biocompatibility studies of functionalized regioregular poly(3-hexylthiophene) layers for sensing applications.
There is a significant medical and biological need for cheap disposable analytical sensing devices, which can be used in clinical settings or medical research. Organic electronics based on polymeric materials, being suitable for large-area, low-cost, flexible, and maybe even disposable electronics, could satisfy this need in a very elegant way. Unfortunately, the ensurance of biocompatibility and biofunctionalization of conducting and semiconducting polymers is still often lacking. In the present study, we concentrate on one of the most promising polymeric materials, regioregular poly(3-hexylthiophene) (P3HT), being both a reasonably conducting and optically active polymer. To overcome biocompatibility problems, protein-based coatings and oxygen-plasma treatments are performed to enable growth of adherent living cells on those modified surfaces. For our studies, the polymer material is spun or casted onto glass substrates under an inert nitrogen atmosphere. The toxic solvents are removed by thermal treatment with subsequent application of the coating or functionalizing materials. Cell-growth studies and adhesion experiments on the modified P3HT thin-film layers are carried out with mouse fibroblasts. This work demonstrates the biocompatibility and biofunctionalization of an active semiconducting organic polymer, hence opening new possibilities in the realization of biomedical test systems based on organic biosensors in life sciences.


TIR-Domain-Containing Adapter-Inducing Interferon-β (TRIF)-Dependent Antiviral Responses Protect Mice against Ross River Virus Disease.
Ross River virus (RRV) is the major mosquito-borne virus in the South Pacific region. RRV infections are characterized by arthritic symptoms, which can last from several weeks to months. Type I interferon (IFN), the primary antiviral innate immune response, is able to modulate adaptive immune responses. The relationship between the protective role of type I IFN and the induction of signaling proteins that drive RRV disease pathogenesis remains poorly understood. In the present study, the role of TIR-domain-containing adapter-inducing interferon-β (TRIF), an essential signaling adaptor protein downstream of Toll-like receptor (TLR) 3, a key single-stranded RNA (ssRNA)-sensing receptor, was investigated. We found that TRIF-/- mice were highly susceptible to RRV infection, with severe disease, high viremia, and a low type I IFN response early during disease development, which suggests the TLR3-TRIF axis may engage early in response to RRV infection. The number and the activation level of CD4+ T cells, CD8+ T cells, and NK cells were reduced in TRIF-/- mice compared to those in infected wild-type (WT) mice. In addition, the number of germinal center B cells was lower in TRIF-/- mice than WT mice following RRV infection, with lower titers of IgG antibodies detected in infected TRIF-/- mice compared to WT. Interestingly, the requirement for TRIF to promote immunoglobulin class switch recombination was at the level of the local immune microenvironment rather than B cells themselves. The slower resolution of RRV disease in TRIF-/- mice was associated with persistence of the RRV genome in muscle tissue and a continuing IFN response. IMPORTANCE RRV has been prevalent in the South Pacific region for decades and causes substantial economic and social costs. Though RRV is geographically restricted, a number of other alphaviruses have spread globally due to expansion of the mosquito vectors and increased international travel. Since over 30 species of mosquitoes have been implicated as potent vectors for RRV dissemination, RRV has the potential to further expand its distribution. In the pathogenesis of RRV disease, it is still not clear how innate immune responses synergize with adaptive immune responses. Type I IFN is crucial for bridging innate to adaptive immune responses to viral invasion. Hence, key signaling proteins in type I IFN induction pathways, which are important for type I IFN modulation, may also play critical roles in viral pathogenesis. This study provides insight into the role of TRIF in RRV disease development.


Partners in community health: the Baltimore City Health Department, the Johns Hopkins School of Hygiene and Public Health, and the Eastern Health District, 1932-1992.
The Eastern Health District of Baltimore was established in 1932 as an early partnership between the Baltimore City Health Department and the Johns Hopkins School of Hygiene and Public Health. Although its heydey occurred in the thirties and forties, for 51 years the district has provided data for researchers studying community health problems; learning opportunities for students in medicine, nursing, and public health administration; and a wide array of clinical and public health services to urban residents. The Eastern Health District concept has been copied worldwide, and although the partnership between the health department and the school of public health has changed over the years, some collaborative activities continue the tradition of research and service provision.


Describing the component dynamics in miscible polymer blends: towards a fully predictive model.
We have recently proposed [D. Cangialosi et al., J. Chem. Phys. 123, 144908 (2005)] an extension of the Adam-Gibbs [J. Chem. Phys. 43, 139 (1965)] theory, combined with the concept of self-concentration, to describe the temperature dependence of the relaxation time for the component segmental dynamics in miscible polymer blends. Thus, we were able to obtain the dynamics of each component in the blend starting from the knowledge of the dynamic and thermodynamic data of the pure polymers, with a single fitting parameter (alpha) which had to be obtained from the fitting of the experimental data. In the present work we demonstrate that this model is also suitable to describe the polymer segmental dynamics in concentrated polymer solutions. From this result we have developed a new route for determining the value of the alpha parameter associated with any given polymer. Once this value is known for the two components of a possible polymer blend, our model for polymer blends dynamics becomes fully predictive.


Pressure bandage as an effective treatment for intralymphatic histiocytosis associated with rheumatoid arthritis.
The patient is a 71-year-old male who has been suffering from rheumatoid arthritis for over 20 years. He first noticed the erythema on his right forearm in 2008, which got worse in 2009. Topical corticosteroids were not effective, and a skin biopsy was performed. Histopathologic examination showed aggregation of the inflammatory cells in the dermal vessels. Those cells were positive for CD68 and CD31 and all the surrounding vessels expressed D2-40 and CD31. We diagnosed him with intralymphatic histiocytosis. One week after the skin was biopsied, only the part of the erythematous lesion covered by skin tape had improved, suggesting that pressure on the lesion might improve the erythematous eruption. We therefore used a pressure bandage elbow supporter in addition to topical treatment. The lesion improved 3 months later and was totally diminished after 9 months. Combined with previously reported cases, our case suggested that intralymphatic histiocytosis is closely related to lymphostasis.


Investigation of Teamwork Quality of Healthcare Professionals Providing Care for Women during Childbirth.
Background A successful delivery depends on the coordinated work of all medical personnel. Compliance with the basic principles of teamwork is the key to the quality of medical care. The purpose of this study was to investigate the issues of teamwork of healthcare professionals during delivery. Methods This descriptive study was conducted in 2019 in Almaty, Republic of Kazakhstan. A total of 40 doctors and 40 midwives who provide inpatient care for women during childbirth took part in the study. Based on the questionnaire, the authors conducted a standardized survey. The tools for statistical processing of the obtained data were Microsoft Excel and Software IBM SPSS Statistics 25.0. The authors used the Student's t-test to calculate the significance of differences. Results The results of the study showed that 85% of the respondents believed that the size of the team did not require changes. Approximately 2/3 of the respondents evaluated the efficacy of delivery techniques used by the team as "medium" and "low". Compliance with the general approach based on mutually agreed principles was partial. The opinions of the doctors and midwives differed significantly regarding fair distribution of responsibilities in the team and the level of trust in the team. Conclusion As a result of the study, it was concluded that there is an urgent need to introduce modern team-building technologies into the daily practice of healthcare professionals of the obstetrician-gynecological service.


Securing the second front: achieving first receiver safety and security through competency-based tools.
Limited research has focused on the safety and security of First Responders and Receivers, including clinicians, hospital workers, public safety officials, community volunteers, and other lay personnel, during public health emergencies. These providers are, in some cases, at greater peril during large-scale disasters due to their lack of training and inadequate resources to handle major influxes of patients. Exemplified in the 1995 Tokyo sarin gas attacks and the 2008 Wenchuan earthquakes, lack of training results in poor outcomes for both patients and First Receivers. The improvement of knowledge and comfort level of First Receivers preparing for a medical disaster via an affordable, repeatable emergency preparedness training (EPT) curriculum. A 5-hour EPT curriculum was developed including nine learning objectives, 18 competencies, and 34 performance objectives. Following brief didactic and small group sessions, interprofessional teams of four to six trainees were observed in a large patient simulator designed to recreate environmentally challenging (ie, flood evacuation), multi-patient scenarios using a novel technique developed to utilize trainees as actors. Trained observers assessed successful completion of 16 individual and 18 team performance objectives. Prior to training, team members completed a 24-question knowledge assessment, a demographic survey, and a comfort level self-assessment. Following training, trainees repeated the 24 questions, self-assessment, and course assessment. One hundred ninety-five participants completed the course between November 2012 and August 2013. One hundred ninety-one (98.5%), 150 (76.9%), and 66 (33.8%) participants completed the pretest, post-test, and course assessment, respectively. The mean (SD) percentage of correct answers between the pretest and post-test increased from 46.3 (13.4) to 75.3 (12.2), P < .0001. Thirty-eight participants (19.5%) reported more than three hours of disaster EPT each year while 157 participants (80.5%) reported three hours or less of yearly EPT. Sixty-six (100%) reported the course relevant to care providers and 61 (92.4%) highly recommended the course. Comfort level increased from 37.0/100 (n = 192) before training to 76.3/100 (n = 145) after training. The Center for Health Professional Training and Emergency Response's (CHPTER's) 5-hour EPT curriculum for patient care providers recreates simultaneous multi-actor disasters, measures EPT performance, and improves trainee knowledge and comfort level to save patient and provider lives during a disaster, via an affordable, repeatable EPT curriculum. A larger-scale study, or preferably a multi-center trial, is needed to further study the impact of this curriculum and its potential to enhance the safety and security of the "Second Front.


Identification of noble candidate gene associated with sensitivity to phytotoxicity of etofenprox in soybean.
Phytotoxicity is caused by the interaction between plants and a chemical substance, which can cause critical damage to plants. Understanding the molecular mechanism underlying plant-chemical interactions is important for managing pests in crop fields and avoiding plant phytotoxicity by insecticides. The genomic region responsible for sensitivity to phytotoxicity of etofenprox (PE), controlled by a single dominant gene, was detected by constructing high density genetic map using recombination inbred lines (RILs) in soybean. The genomic region of ~ 80 kbp containing nine genes was identified on chromosome 16 using a high-throughput single nucleotide polymorphism (SNP) genotyping system using two different RIL populations. Through resequencing data of 31 genotypes, nonsynonymous SNPs were identified in Glyma.16g181900, Glyma.16g182200, and Glyma.16g182300. The genetic variation in Glyma.16g182200, encoding glycosylphosphatidylinositol-anchored protein (GPI-AP), caused a critical structure disruption on the active site of the protein. This structural variation of GPI-AP may change various properties of the ion channels which are the targets of pyrethroid insecticide including etofenprox. This is the first study that identifies the candidate gene and develops SNP markers associated with PE. This study would provide genomic information to understand the mechanism of phytotoxicity in soybean and functionally characterize the responsive gene.


Diel regulation of photosynthetic activity in the oceanic unicellular diazotrophic cyanobacterium Crocosphaera watsonii WH8501.
The oceanic unicellular diazotrophic cyanobacterium Crocosphaera watsonii WH8501 exhibits large diel changes in abundance of both Photosystem II (PSII) and Photosystem I (PSI). To understand the mechanisms underlying these dynamics, we assessed photosynthetic parameters, photosystem abundance and composition, and chlorophyll-protein biosynthesis over a diel cycle. Our data show that the decline in PSII activity and abundance observed during the dark period was related to a light-induced modification of PSII, which, in combination with the suppressed synthesis of membrane proteins, resulted in monomerization and gradual disassembly of a large portion of PSII core complexes. In the remaining population of assembled PSII monomeric complexes, we detected the non-functional version of the D1 protein, rD1, which was absent in PSII during the light phase. During the dark period, we also observed a significant decoupling of phycobilisomes from PSII and a decline in the chlorophyll a quota, which matched the complete loss of functional PSIIs and a substantial decrease in PSI abundance. However, the remaining PSI complexes maintained their photochemical activity. Thus, during the nocturnal period of nitrogen fixation C. watsonii operates a suite of regulatory mechanisms for efficient utilization/recycling of cellular resources and protection of the nitrogenase enzyme.


Understanding low dose radiation exposure effects: MELODI's views on developing international cooperation.
The paper presents, from a European point of view, the combined scientific and sociological rationale for further development of research into the biological effects and risks related to population exposures to low dose/low dose rate ionizing radiation. It further explains how this rationale led to the constitution, at European level, of the MELODI Association, to foster innovative and multidisciplinary research programs dedicated to this objective, and driven by a consensus-based Strategic Research Agenda (SRA). Finally, the paper suggests that this evolution towards a more integrated and multi-disciplinary approach to research in the field of low dose/dose rate radiation exposure effects and related risks could lead to new research opportunities also at an international level.


Pediatric columnar lined esophagus vs Barrett's esophagus: is it the time for a consensus definition.
We describe the clinical, endoscopic, and histological features of all cases of Barrett's esophagus (BE) diagnosed at our institution between 2000 and 2007 following the criteria of the British Society of Gastroenterology. This society defines BE as a segment of columnar metaplasia (CLO) (whether intestinalized or not) of any length, visible endoscopically above the gastroesophageal junction and confirmed histologically. The diagnosis was challenged after immunostaining for Cdx2 (marker of intestinal differentiation). Information was collected with respect to age, symptoms, treatment, and endoscopic and histological features. Twelve children (10 males and 2 females) with a median age of 11.7 (2 to 17) years had been diagnosed with CLO-BE. Histology confirmed BE in 31 of 38 endoscopies. The initial diagnosis was reviewed according to Cdx2 results in 10 of 12 patients: Cdx2 strongly expressed in 4 cases with intestinal metaplasia (the diagnosis of BE was maintained); was negative in 4 other patients with "CLO" mucosa (reviewed diagnosis was that of expansion of the gastric cardia into the distal esophagus); and 2 patients had occasional Cdx2-positive cells showing cardia-type mucosa with goblet cells (early BE?). The estimated prevalence of CLO-BE in the pediatric population of South Yorkshire (United Kingdom) is 0.0024%, 0.8% in children referred for endoscopy and 5.5% in the children with reflux esophagitis. Characterization of the BE and confirmation of intestinal differentiation may have prognostic implications that can impact the surveillance program. Our results showed that intestinal differentiation as demonstrated with Cdx2 was only seen if goblet cells were present. A consensus definition and further studies to understand the molecular mechanisms involved in the development of BE at this age are needed.


Community based study on married couples' family planning knowledge, attitude and practice in rural and urban Gambia.
Family planning services have been free of charge and available in all the health facilities in the Gambia since 1975 yet contraceptive prevalence is only 17.5% and even 6% in some areas. Since the last census in 2003, there existed no available data on married couples' contraception status. To explore married couples' family planning knowledge, attitudes, and practices in rural and urban Gambia and to analyze what factors may affect such knowledge, attitudes and practices. Quantitative cross-sectional study design was used. Through convenience sampling, 176 men and 235 women representing a total of 176 couples participated. A structured questionnaire was used for data collection. The mean scores of the married couples family planning knowledge, attitudes, and practices were 19.00 ± 6.11(ranging from 0 to 64), 6.90 ± 3.08 (0 to 14) and 4.69 ± 3.3 (0 to 19) respectively. Urban residents had higher scores on family planning practice than rural residents (p<.05). Attitude is the strongest predictor of practice (accounted for 34.6% of variance). These findings offer a descriptive answer to "what are married couples' family planning knowledge, attitude and practice in Gambia", as well as suggesting broader health intervention programs in health education and promotion.


201T1 and 99Tcm-J001X macrophage scintigraphy: two radionuclide imaging techniques for the surveillance of acute localized radiation over-exposures.
The therapeutic or surgical management of acute localized irradiation is very complicated due to the delayed occurrence of ionizing radiation effects. There is a great need for non-invasive imaging techniques to delineate healthy from exposed tissues. Such a technique should be of value considering that spread of damage can occur from apparently silent fibrotic foci. Of the scintigraphic procedures, 99Tcm first-pass scintigraphy has already been recommended by the International Atomic Energy Agency (IAEA) for the evaluation of irradiated tissues. In order to improve the scintigraphic surveillance of accidental over-exposures, the potentials of 201T1 and 99Tcm-J001X were evaluated on an experimental porcine model reproducing the late fibrotic effect encountered after localized irradiation. J001X, an acylated poly-(1,3)-galactoside of bacterial origin, was used for the functional imaging of the inflammatory reaction which took place after irradiation. This scintigraphy, based on targeting of activated macrophages recruited by lesions, was performed together with 201T1 scans for the assessment of blood perfusion and cellular metabolism. Our results demonstrate that these two radiopharmaceuticals provide reliable information for the management of accidental localized over-exposure, J001X allowing the assessment of the inflammatory reaction and 201T1-chloride being mainly useful for imaging the delayed onset of fibrosis.


[Gynecomastia and chronic renal insufficiency in periodic hemodialysis. Demonstration of a decrease in the free fraction of testosterone].
Gynecomastia is frequently observed in male patients undergoing hemodialysis; however, its mechanism is still unclear. Hormonal studies were performed in a group of 39 men, aged 50 +/- 14 years, dialysed for 2.8 +/- 2 years. 23 (59 p. 100) of them had gynecomastia. Peripheral hypogonadism and hyperprolactinemia were found in all the hemodialysed patients. Whether gynecomastia was present or not, no significant difference was observed for gonadotropins, prolactin, testosterone, estradiol 17 beta and testosterone-estradiol binding globulin levels. In contrast, the urinary output (p less than 0,05) and free testosterone (p less than 0,05) were significantly lower in the group with gynecomastia. Gynecomastia occurring in hemodialysed patients is probably due to a decrease of the testosterone/estrogen ratio. If so, percutaneous treatment with 5 alpha dihydrotestosterone might improve this type of gynecomastia.


A new day dawns: women without oestrogen or is a balance best?
Building on the 30-year success story with tamoxifen, the question now is whether one agent can be used for treatment and prevention or should new medicines be targeted to specific applications? The early results with anastrozole suggest it could replace tamoxifen for treatment and should be tested as a preventive. Unfortunately, long-term testing of aromatase inhibitors will be required to avoid concerns about osteoporosis, Alzheimer's disease and coronary heart disease. Most importantly, the knowledge gained with tamoxifen has resulted in a new generation of selective oestrogen receptor modulators that can be used to prevent osteoporosis, breast cancer and uterine cancer. It is now clear that strategies utilising aromatase inhibitors and selective oestrogen receptor modulators will provide much needed options for individualised treatments.


Optimization and photomodification of extremely broadband optical response of plasmonic core-shell obscurants.
Plasmonic resonances of the metallic shells depend on their nanostructure and geometry of the core, which can be optimized for the broadband extinction normalized by mass. The fractal nanostructures can provide a broadband extinction. It allows as well for a laser photoburning of holes in the extinction spectra and consequently windows of transparency in a controlled manner. The studied core-shell microparticles synthesized using colloidal chemistry consist of gold fractal nanostructures grown on precipitated calcium carbonate (PCC) microparticles or silica (SiO2) microspheres. The optimization includes different core sizes and shapes, and shell nanostructures. It shows that the rich surface of the PCC flakes is the best core for the fractal shells providing the highest mass normalized extinction over the extremely broad spectral range. The mass normalized extinction cross section up to 3m2/g has been demonstrated in the broad spectral range from the visible to mid-infrared. Essentially, the broadband response is a characteristic feature of each core-shell microparticle in contrast to a combination of several structures resonant at different wavelengths, for example nanorods with different aspect ratios. The photomodification at an IR wavelength makes the window of transparency at the longer wavelength side.


Ultrasound for nurses in reproductive medicine.
Nurses are in an ideal position to perform pelvic ultrasound evaluations, and appropriately trained nurses can perform limited ultrasound evaluations as part of the assessment and treatment of infertility. In this article, the author provides detailed descriptions and accompanying ultrasonic images illustrating the use of ultrasound in providing vital clinical information in reproductive medicine and in the assessment of the first trimester of pregnancy.


Cyclic voltammetry: a new strategy for the evaluation of oxidative damage to bovine insulin.
Research on protein oxidative damage may give insight into the nature of protein functions and pathological conditions. In this work, the oxidative damage of bovine insulin on Au electrode was investigated by cyclic voltammetry (CV). The experimental results show that there are two anodic peaks for the oxidative damage of bovine insulin, which arise from the oxidation of the exposed disulfide bond S--S(CYS7A,CYS7B), forming sulfenic acid RSOH (1.20 V, vs. SCE), sulfinic acid RSO(2)H and sulfonic acid RSO(3)H (1.35 V, vs. SCE). These in vitro findings not only demonstrate the applicability of CV in simulating/evaluating the oxidative damage of nonredox proteins but also find two promising candidates (two anodic peaks) for measuring insulin.


Postconditioning against ischaemia-reperfusion injury: ready for wide application in patients?
Ischaemic postconditioning (IPOC) is an intervention in which brief, intermittent periods of reocclusion at the onset of reperfusion (i.e. stuttering reperfusion) protect myocardium from lethal reperfusion injury. The mechanism underlying the cardioprotective effects of IPOC is incompletely understood. However, it is perceived that IPOC begins with specific cell-surface receptors responsible for activating a number of signalling pathways, many of which appear to converge at the mitochondrial level. IPOC has been demonstrated both in animal models and in patients with acute myocardial infarction (AMI) in small proof-of-concept trials. This intervention offers the possibility of further limiting infarct size in patients undergoing primary percutaneous coronary intervention (PCI). Here, we provide a brief overview of the concept of IPOC and the mechanisms underlying this phenomenon. (Neth Heart J 2010;18:389-93.).


[Expert systems in gastroenterology].
Expert systems are the software systems developed by the application of the various intelligence, which could successfully compete to peoples-experts, and have the consultant function with the characteristics of the explanations and the advices in some specific domain. These are, in essence, the intelligent information systems, which consists several thousands of the rules from the definite problem field and which are capable to explain their decisions. The knowledge systems are lesser software systems, also developed by means of the technique of the artificial intelligence which are usually less successful in some field of knowledge of the experts. In the paper are presented the basic characteristics three most often applied expert systems in gastroenterology: Quick Medical Reference (QMR), HEPAT, ILIAD.


Evaluation of HE4, CA-125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) in the Preoperative Assessment of Patients with Adnexal Mass.
To evaluate the validity and compare the performance of cancer antigen-125 (CA-125), human epididymis protein 4 (HE4), the risk of malignancy index (RMI), and the risk of ovarian malignancy algorithm (ROMA) in the diagnosis of ovarian cancer in patients with ovarian lesions discovered during their preoperative work-up investigations. This prospective, cross-sectional study looked at patients who attended the gynecology department at the Royal Hospital, Muscat, from 1 March 2014 to 30 April 2015, for the evaluation of an ovarian lesion. The inclusion criteria included women who underwent surgical intervention and who had a preoperative pelvic ultrasound with laboratory investigation for CA-125 and HE4. The study validated the diagnostic performance of CA-125, RMI, HE4, and ROMA using histopathological diagnosis as the gold standard. The study population had a total of 213 cases of various types of benign (77%) and malignant (23%) ovarian tumors. CA-125 showed the highest sensitivity (79%) when looking at the total patient population. When divided by age, the sensitivity was 67% in premenopausal women. In postmenopausal women, CA-125 had lower sensitivity (89%) compared to RMI, HE4, and ROMA (93% each). A high specificity of 90% was found for HE4 in the total patient population, 93% in premenopausal women and 75% in postmenopausal women. CA-125 had the highest specificity (79%) in postmenopausal women. Both CA-125 and RMI were frequently elevated in benign gynecological conditions particularly in endometriosis when compared to HE4 and ROMA. We also studied modifications of the optimal cut-offs for the four parameters. Both CA-125 and RMI showed a significant increase in their specificity if the cut-off was increased to ≥ 60 U/mL for CA-125 and to ≥ 250 for RMI. For HE4, we noted an improvement in its specificity in postmenopausal women when its cut-off was increased to140 pmol/L. HE4 and ROMA showed a very high specificity, but were less sensitive than CA-125 and RMI in premenopausal women. However, they were of comparable sensitivity in postmenopausal women and were valuable in distinguishing benign ovarian tumors or endometriosis from ovarian cancer. Modifying the cut-off values of the different markers resulted in a higher accuracy compared to the standard cut-offs, but at the expense of reduced sensitivity.


Burnout and Psychological Distress Among Pediatric Critical Care Physicians in the United States.
To estimate the prevalence of physician burnout, psychological distress, and its association with selected personal and practice characteristics among pediatric critical care physicians and to evaluate the relationship between burnout and psychological distress. Cross-sectional, online survey. Pediatric critical care practices in the United States. Pediatric critical care physicians. None. A nonrandom sample of 253 physicians completed an online survey consisting of personal and practice characteristics, the Maslach Burnout Inventory, and the General Health Questionnaire. Nearly half of the participants (49%; 95% CI, 43-55%; n = 124) scored high burnout in at least one of the three subscales of the Maslach Burnout Inventory and 21% reported severe burnout. The risk of any burnout was about two times more in women physicians (odds ratio, 1.97; 95% CI, 1.2-3.4). Association between other personal or practice characteristics and burnout was not evident in this study, while regular physical exercise appeared to be protective. One third of all participants (30.5%) and 69% of those who experienced severe burnout screened positive for psychological distress. About 90% of the physicians reporting severe burnout have considered leaving their practice. Burnout is high among pediatric critical care physicians in the United States. About two thirds of the physicians with severe burnout met the screening criteria for psychological distress that suggests possible common mental disorders. Significant percentages of physicians experiencing burnout and considering to leave the profession has major implications for the critical care workforce.


[Echocardiogram in atrial fibrillation].
The echocardiogram should be performed in the patients with atrial fibrillation to detect cardiac structurally abnormality and assess left ventricular systolic and diastolic functions. Parameters that reflect left atrium (LA) size such as LA dimension and LA volume have been proposed as predictors of success of the radiofrequency catheter ablation. The transthoracic echocardiogram can provide useful information to guide the management of atrial fibrillation, but cannot exclude thrombus in the left atrial appendage (LAA). The transesophageal echocardiography must be used to rule out intra LA thrombus especially prior to cardioversion and the radiofrequency catheter ablation. The smoke-like echo and sludge in the LA or LAA and the decreased LAA flow velocity are associated with high risk for LA thrombus.


Electrospun Nanofibers Revisited: An Update on the Emerging Applications in Nanomedicine.
Electrospinning (ES) has become a straightforward and customizable drug delivery technique for fabricating drug-loaded nanofibers (NFs) using various biodegradable and non-biodegradable polymers. One of NF's pros is to provide a controlled drug release through managing the NF structure by changing the spinneret type and nature of the used polymer. Electrospun NFs are employed as implants in several applications including, cancer therapy, microbial infections, and regenerative medicine. These implants facilitate a unique local delivery of chemotherapy because of their high loading capability, wide surface area, and cost-effectiveness. Multi-drug combination, magnetic, thermal, and gene therapies are promising strategies for improving chemotherapeutic efficiency. In addition, implants are recognized as an effective antimicrobial drug delivery system overriding drawbacks of traditional antibiotic administration routes such as their bioavailability and dosage levels. Recently, a sophisticated strategy has emerged for wound healing by producing biomimetic nanofibrous materials with clinically relevant properties and desirable loading capability with regenerative agents. Electrospun NFs have proposed unique solutions, including pelvic organ prolapse treatment, viable alternatives to surgical operations, and dental tissue regeneration. Conventional ES setups include difficult-assembled mega-sized equipment producing bulky matrices with inadequate stability and storage. Lately, there has become an increasing need for portable ES devices using completely available off-shelf materials to yield highly-efficient NFs for dressing wounds and rapid hemostasis. This review covers recent updates on electrospun NFs in nanomedicine applications. ES of biopolymers and drugs is discussed regarding their current scope and future outlook.


Optical purification of a mixture of chiral forms by dimer formation.
We introduce a readily executable method for the optical purification of "scalemic" (non 50%-50%) mixtures of chiral molecules of opposite handedness ("enantiomers"). The method relies on the formation of two types of dimers, (R-R or S-S) "homodimers" and (R-S) "heterodimers." The selectivity is linked to the difference in sign recently discovered by us to exist between certain transition-dipole matrix elements of opposite enantiomers. This sign difference results in differences in spectral propensity rules: In homodimers, transitions from the ground state can only take place to inversion symmetric excited states, while in the heterodimer the transitions are much more likely to proceed to antisymmetric excited states (although for heterodimers weak transitions to symmetric states might exist). These opposing propensity rules fully explain the observed large differences in the spectra of homodimers vs. heterodimers, which exist despite the almost identical energy levels positions. We illustrate the general concepts by computationally demonstrating the optically induced enantio-purification of scalemic mixtures of the hydropropionic C(3)H(6)O(3) (lactic) acid.


COVID-19 and Extracorporeal Membrane Oxygenation.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. In SARS-CoV-2 patients with refractory respiratory failure, there may be a role for veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a life-saving rescue intervention. This review summarizes the evidence gathered until June 12, 2020; electronic databases were screened for pertinent reports on coronavirus and V-V ECMO. Search was conducted by two independent investigators; keywords used were SARS-CoV-2, COVID-19, ECMO, and extracorporeal life support (ECLS). Many patients with COVID-19 experience moderate symptoms and a relatively quick recovery, but others must be admitted into the intensive care unit due to severe respiratory failure and often must be mechanically ventilated. Further deterioration may require institution of extracorporeal oxygenation. Infection mechanisms may trigger "cytokine storm," an inflammatory disorder notable for multi-organ system failure; together with other metabolic and hematological changes, these amplify the changes pertinent to ECMO therapy, often exaggerating blood coagulation disorders. Thirty-two studies were found describing experiences with ECMO in the treatment of COVID-19. Of 4,912 COVID-19 patients, 2,119 (43%) developed ARDS and 2,086 (42%) were transferred to the ICU; 1,015 patients (21%) were treated with ECMO. While in an overall cohort, observed mortality was 640 (13%), the mortality within ECMO subgroups reached up to 34.6% (range 0-100%). The efficacy of ECMO treatment for COVID-19 is largely dependent on the expertise of the center in ECLS due to the interplay between the changes in hematological and inflammatory modulators associated with both COVID-19 and ECMO. In order to support gas exchange during early infection with SARS-CoV-2, ECMO has a strong rationale for the treatment of the most critically ill patients. Due to the limited resources during a global pandemic, ECMO should be reserved for only the most severe cases of COVID-19.


[Arbuscular mycorrhizal fungi enhanced cadmium uptake in Photinia frase through altering root transcriptomes and root-associated microbial communities].
As a non-essential metal, cadmium (Cd) pollution poses severe threats to plant growth, environment, and human health. Phytoextraction using nursery stocks prior to their transplantation is a potential useful approach for bioremediation of Cd contaminated soil. A greenhouse pot experiment was performed to investigate the growth, Cd accumulation, profiles of transcriptome as well as root-associated microbiomes of Photinia frase in Cd-added soil, upon inoculation of two types of arbuscular mycorrhizal fungi (AMF) Sieverdingia tortuosa and Funneliformis mosseae. Compared with the control, inoculation of F. mosseae increased Cd concentrations in root, stem and leaf by 57.2%, 44.1% and 71.1%, respectively, contributing to a total Cd content of 182 μg/plant. KEGG pathway analysis revealed that hundreds of genes involved in 'Mitogen-activated protein kinase (MAPK) signaling pathway', 'plant hormone signal transduction', 'biosynthesis of secondary metabolites' and 'glycolysis/gluconeogenesis' were enriched upon inoculation of F. mosseae. The relative abundance of Acidobacteria was increased upon inoculation of S. tortuosa, while Chloroflexi and Patescibacteria were increased upon inoculation of F. mosseae, and the abundance of Glomerales increased from 23.0% to above 70%. Correlation analysis indicated that ethylene-responsive transcription factor, alpha-aminoadipic semialdehyde synthase, isoamylase and agmatine deiminase related genes were negatively associated with the relative abundance of Glomerales operational taxonomic units (OTUs) upon inoculation of F. mosseae. In addition, plant cysteine oxidase, heat shock protein, cinnamoyl-CoA reductase and abscisic acid receptor related genes were positively associated with the relative abundance of Patescibacteria OTUs upon inoculation of F. mosseae. These finding suggested that AMF can enhance P. frase Cd uptake by modulating plant gene expression and altering the structure of the soil microbial community. This study provides a theoretical basis for better understanding the relationship between root-associated microbiomes and root transcriptomes of P. frase, from which a cost-effective and environment-friendly strategy for phytoextraction of Cd in Cd-polluted soil might be developed.


Identifying molecular targets mediating the anticancer activity of histone deacetylase inhibitors: a work in progress.
The anticancer properties of histone deacetylase inhibitors have been known for some time. However, it is only recently that the functional identities of the intracellular targets mediating the anticancer properties have started to be revealed. These targets appear to play significant roles in cell cycle control, apoptosis and differentiation. Importantly, the modulation of these activities is likely to be mediated by alterations in the acetylation status of both histone and non-histone targets. Identification of these targets, and the specific histone deacetylase enzymes that modulate them, is an important step in designing rational-based therapies for the treatment of cancer. In this review we discuss the state of progress in identifying the molecular pathways/events mediating the anticancer activity of histone deacetylase inhibitors.